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Phytochemistry, Pharmacological Properties, and Recent Applications of Ficus benghalensis and Ficus religiosa

Suganya murugesu.

1 Institute of Tropical Agriculture and Food Security (ITAFoS), Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia; ym.ude.mpu@aynagus

Jinap Selamat

2 Faculty of Food Science and Technology, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia

Vikneswari Perumal

3 Faculty of Pharmacy & Health Sciences, University of Kuala Lumpur Royal College of Medicine Perak, Ipoh 30450, Perak, Malaysia; ym.ude.lkinu@irawsenkiv

Ficus is one of the largest genera in the plant kingdom that belongs to the Moraceae family. This review aimed to summarize the medicinal uses, phytochemistry, and pharmacological actions of two major species from this genus, namely Ficus benghalensis and Ficus religiosa . These species can be found abundantly in most Asian countries, including Malaysia. The chemical analysis report has shown that Ficus species contained a wide range of phytoconstituents, including phenols, flavonoids, alkaloids, tannins, saponins, terpenoids, glycosides, sugar, protein, essential and volatile oils, and steroids. Existing studies on the pharmacological functions have revealed that the observed Ficus species possessed a broad range of biological properties, including antioxidants, antidiabetic, anti-inflammatory, anticancer, antitumor and antiproliferative, antimutagenic, antimicrobial, anti-helminthic, hepatoprotective, wound healing, anticoagulant, immunomodulatory activities, antistress, toxicity studies, and mosquitocidal effects. Apart from the plant parts and their extracts, the endophytes residing in these host plants were discussed as well. This study also includes the recent applications of the Ficus species and their plant parts, mainly in the nanotechnology field. Various search engines and databases were used to obtain the scientific findings, including Google Scholar, ScienceDirect, PMC, Research Gate, and Scopus. Overall, the review discusses the therapeutic potentials discovered in recent times and highlights the research gaps for prospective research work.

1. Introduction

Ficus have been known for their vast number of species, consisting of more than 800 species in the form of trees, vines, shrubs, epiphytes, and hemiphytes. Ficus genera belong to the Moraceae family of Urticales order under the classification of Dicotyledone and Spermatophyte phylum of the Plantae kingdom. There are more than 800 species of Ficus that have been discovered. Ficus plants are generally known as figs or fig trees. The genus is distributed in various regions across the tropical and sub-tropical areas, mainly in Asia, America, Australia, and Africa [ 1 ].

In India, some of the species are considered sacred, especially Ficus benghalensis , which is referred to as India’s National Tree that signifies spiritual knowledge and eternal life [ 2 ]. Some of the species are edible, while some are used as ornamental plants, especially Ficus lyrata , commonly known as the fiddle-leaf fig [ 3 ]. The common fig or Ficus carica Linnaeus is the most popular species of Ficus , known for its remarkable commercial importance, with multiple vernacular names such as Anjir (Hindi, Sanskrit, Malay, etc.), Fagari (Northern India), Thaphan (Burmese), Qua Va (Vietnamese), etc. [ 4 ]. Typically, all Ficus spp. have latex-like gummy material within the vasculatures that plays a role in the defense system and self-healing upon physical assaults. The latex is generally used as household detergents. Most species of this genus are characterized by their syconia, fleshy receptacles with ostioles at the apex that come in various shapes that develop into multiple fruits with duplets collection. Generally, the fresh fruits are sweet and juicy once ripe, containing thin and tender skin with a fleshy wall of different color variants such as red, pink, purple, etc., depending on the species [ 1 ].

Some of the species do not bear fruit, however they possess similar morphological features that are difficult to be distinguished from their species and variants. The veins’ ornamentation and traces in the lamina are added characteristics that aid in the species’ identification. Mainly, this genus grows with auxiliary root structures extended from their tree trunks or branches into the ground. As one of the diverse species, Ficus trees are some of the highest oxygen generators with the highest photosynthesis rate. The deeply lobed leaves were reported to contribute to the three major types of leaf minerals, namely calcium oxalates, amorphous calcium carbonate cystoliths, and silica phytoliths [ 5 ].

The genus displays various unique features that can be morphologically observed in its species. This review will highlight the two most abundant Ficus spp. available in Asian countries, especially in Malaysia, Ficus benghalensis and Ficus religiosa. Apart from those, F. benghalensis and F. religiosa are the two species that were explored extensively for their biological functions and bioactive compounds, besides their traditional applications. Thus, the review intends to update on the latest scientific findings of the two species, and thus indicate a gap in the research that may potentially be fulfilled in future studies.

Literature Search

Various search engines and databases were used to obtain the scientific findings on both the selected Ficus spp., including Google Scholar, ScienceDirect, PMC, Research Gate, and Scopus. Some of the terms or keywords used to search for potential publications included Ficus spp., Ficus benghalensis , Ficus religiosa , pharmacological activities, botany, nanotechnology, traditional uses, bioactivity, phytoconstituents, phytochemistry, etc. The total search yielded about 402 publications, that included research articles, review papers, book chapters, proceeding papers, and online notes. However, only research and review papers retrieved were used to present a comprehensive and updated review on the subject matter: about 38 papers of Ficus benghalensis , 40 of Ficus religiosa , 19 scientific findings on Ficus spp. and the rest are of nanotechnologyfollowed by publications on pharmacological activities and their definitions. One of the citations includes a plant database (Natural Resources Conservation Service). The rest of the documents were excluded considering the validity of the content with scientific proof. Figure 1 below shows the sources and number of publications used for this review. The chemical structures were generated using the ChemSketch software.

The sources and number of publications used.

3. Morphological Description and Traditional Uses

3.1. ficus benghalensis.

Some of the common synonyms of the F. benghalensis plant include the Banyan tree, Indian fig, and Nyagrodha. The sacred Banyan tree of India, that comes from the Urostigma subgenus, branches into a great number of shoots that take roots and become a new trunk, and thus are grown mainly in gardens and on roadsides for shade. The tree is known to be epiphytic when young, with petioles of 1.25 to 5 cm length, ovate lamina sessile, and reddish hypanthodia upon maturation. The female flowers are pedicellate, elongated with about 3 to 5 mm in length. However, male flowers are absent in the same stalk [ 5 ]. Typically, the plant parts are used in the preparation of Ayurvedic remedies in India [ 6 ]. The plant parts are known for their astringency due to the presence of tannins. Despite its astringency, it is also known for its cooling effect, as alterative and demulcent. F. benghalensis ( Figure 2 ) root and stem bark are typically prepared in decoction form to treat a variety of conditions, such as dysentery, diarrhea, skin disorders, inflammation, and diabetes [ 6 , 7 ]. Meanwhile, the leaf portion is consumed to boost the immune system, and as a remedy for leucorrhea and other vaginal discharges [ 7 , 8 ]. Latex produced by this plant is utilized in promoting conception, as a blood purifier in urinary and urinogenital disorders [ 9 , 10 ]. The seeds of F. benghalensis are prescribed as a dietary supplement for peptic ulcers by traditional medicine practitioners [ 11 ]. However, the fleshy fruit of F. benghalensis is not edible for humans due to its laxative nature [ 12 ].

Ficus benghalensis tree, leaves, and fruits. Adapted from CalPhotos (2012) © 2021 Zoya Akulova [ 13 ].

3.2. Ficus religiosa

Ficus religiosa is one of the widely planted species of Ficus in the tropics, with various traditional applications. It belongs to the subgenus of Urostigma and is locally known as the Peepal tree (synonym: Pimpala). It is a large tree ( Figure 3 ) and epiphytic when young, containing petioles of 5 to 10 cm in length, aspen-like lamina, sessile, and paired hypanthodia, with no male flowers and pedicellate or sessile [ 5 ]. Its bitter-sweet and acrid nature is the reason for its use as an astringent, refrigerant, purgative, aphrodisiac, and laxative [ 9 ]. The root bark is often used to treat stomatitis, ulcers, and other inflammatory conditions such as gout [ 14 ]. The laxative young fruit is known to promote digestion and treat vomiting [ 15 ]. The ripe fruit of this species is edible and commonly used in food preparation. The fruits are rich in antioxidants, minerals, and vitamins [ 16 ]. The leaves are usually applied to wounds, skin diseases, and scabies [ 15 ]. The leaves are also prepared as a tonic for ulcers and constipation [ 14 ]. The young shoots are purgative and are thus used in the treatment of various conditions, including urinary vaginal discharge, asthma, cracked foot, toothache, snake bite, pimples, otitis, sores, etc. [ 9 ].

Ficus religiosa tree, leaves, and fruits. Adapted from CalPhotos (2012) © 2021 Zoya Akulova [ 13 ].

4. Phytochemical Constituents

Plants are the source of various phytochemical constituents that are functional as a remedy for health defects that occur in humans, and the diversity of the plant metabolites benefits humans in treating those conditions [ 1 , 2 ]. Ficus species is one of the largest genera of the plant kingdom, with promising phytoconstituents from various classes of compounds, including phenols, flavonoids, sterols, alkaloids, tannins, saponin, terpenoids, etc. Table 1 displays the phytoconstituents of the discussed Ficus species and the plant parts containing them. Some of the distinct compounds identified from both species are displayed in Figure 4 .

Distinctive compounds present in Ficus benghalensis ( 1 – 5 ) and Ficus religiosa ( 4 , 6 , 7 ).

Phytochemical constituents present in Ficus benghalensis and Ficus religiosa plant parts.

The leaves and bark of F. benghalensis are rich in flavonoids, phenols, terpenoids, and terpenes [ 17 , 18 , 19 , 20 ]. Besides that, the leaves also contain quinone and furanocoumarin derivatives, namely rhein, psoralen, and bergapten ( Figure 5 ) [ 17 ]. The root extract consists of sterols and organic and fatty acids, while the fruit was reported to be rich in fatty acids [ 21 ]. As for F. religiosa , the fruits mainly contain terpenes [ 23 ]. The leaves are rich in amino and fatty acids, as well as terpenoids [ 23 , 24 ]. The latex of F. religiosa contains serine protease named Religiosin B and C [ 30 , 31 ].

Chemical structure of bioactive compounds reported from Ficus benghalensis ( 2 – 5 , 8 – 10 , 11 – 13 ) and Ficus religiosa ( 1 , 6 – 10 , 11 , 14 – 16 ).

Apart from these plant parts, Ficus species are known for their parasitic host effect in the ecosystem for various endophytic fungi. These fungi inhabit the host plant by living in their tissues, exhibiting a mutual relationship without causing any disease to the host. The parasitic fungi play a role in the host plants’ defense mechanism by producing bioactive secondary metabolites. Some of these metabolites possess similar functions as the ones produced by the plants [ 32 ]. Some of the fungi were analyzed for their metabolites with medicinal effects, which will also be highlighted ( Table 2 ) in this review. Apart from the fungi, Bacillus subtilis , a catalase-positive bacterium, was identified and isolated from the aerial root of F. benghalensis . Two anti-fungal compounds (surfactins and iturins) produced by the bacterium were isolated ( Table 2 ) [ 33 ]. The screening analysis has revealed the presence of phenols, flavonoids, alkaloids, terpenes, and terpenoids from the fungi extracts [ 32 , 34 , 35 ].

Microorganisms isolated from Ficus religiosa and Ficus benghalensis .

5. Pharmacological Actions

Ficus species have been vastly studied for multiple pharmacological effects ( Figure 6 ), as discussed below. All the plant organs, including leaves, stem bark, root, latex, and fruits, were investigated for their potential bioactivities. Some of the bioactivities researched include antioxidants, antidiabetic, anti-inflammatory, anticancer, antitumor and antiproliferative, antimutagenic, antimicrobial, anti-helminthic, hepatoprotective, wound healing, anticoagulant, immunomodulatory activities, antistress, and toxicity studies. The plants are also utilized as insect repellents.

Pharmacological activities of Ficus benghalensis and Ficus religiosa .

5.1. Antioxidants

Plants are typically rich in diverse antioxidant compounds, which contribute to most of their biological effects in the human system. Antioxidants can inhibit oxidation via termination of radical reaction by donating at least one hydrogen atom to the free radical or by preventing the initiation of radical chain reaction via a substitutive reaction. Therefore, cells must preserve the levels of antioxidants through dietary and de novo synthesis [ 36 , 37 , 38 ].

The presence of antioxidants has been studied extensively in Ficus species using various antioxidant assays. F. benghalensis root’s aqueous extract was reported to possess the highest scavenging activity and reducing power compared to its methanolic and ethanolic extracts [ 21 ]. The phytochemical screening of the F. benghalensis root revealed the presence of steroids, flavonoids, tannins, phenolic compounds, and anthraquinone glycoside as its major constituents [ 39 ]. Meanwhile, the aqueous extract of F. benghalensis stem bark displayed a significant inhibition (IC 50 = 80.24 μg/mL) compared to the standard reference used, tetraethoxypropane. The measurement was performed based on the thiobarbituric acid reactive substances (TBARS) value that measures the lipid peroxide generation as tested on microsomal lipid peroxidation [ 40 ]. Besides that, F. benghalensis latex methanolic extract showed potential scavenging activity of 1-1-diphenyl-2-picrylhydrazyl (DPPH), ferric chloride (FeCl 3 ) reducing antioxidant power (FRAP), and phosphomolybdenum (IC 50 = 28.63, 49.82, and 31.84 µg/mL, respectively) as compared to the reference compounds (ascorbic acid and Trolox). The activity is reportedly due to abundance in flavonoids and phenolics, corresponding to their preliminary phytochemical screening [ 41 ].

Apart from those plant parts, the leaves’ extracts (hydroethanolic and hexane) of F. benghalensis have also shown potential DPPH scavenging activity (IC 50 = 32.3 and 28.2 µg/mL) that are comparable with the reference compounds used (ascorbic acid 11.5 µg/mL and quercetin 15.4 µg/mL) [ 42 ]. In addition, the ethanolic extract of F. benghalensis seed was reported to possess potential antioxidant capacity with a high abundance in tannins, flavonoids, and phenolics content [ 10 ]. F. benghalensis plant parts were reported to contain carbohydrates, phenolic compounds, oil, fats, saponins, flavonoids, alkaloids, proteins, and tannins as major constituents that contribute to their antioxidant capacity, which subsequently influences the pharmacological effects [ 17 ].

F. religiosa , the sacred fig, is known to exhibit potent antioxidant capacity contributed by phenolic and flavonoids (1032 mg GAE/g extract and 63.31 mg QE/g extract, respectively) in its fruit [ 43 ]. Meanwhile, the n -hexane, dichloromethane, and ethyl acetate fractions of the F. religiosa stem bark were reported to possess high scavenging activity with >90% inhibition compared to the crude methanol and n -butanol fraction [ 44 ]. Similarly, Ashraf et al. [ 45 ] reported that the ethanolic extract of the F. religiosa exhibits strong scavenging activity compared to other extracts analyzed. Added to this, the methanolic extract of F. religiosa bark displayed a significant antioxidant activity with the IC 50 value of 48 μg/mL [ 46 ]. Another study was conducted using the combined methanolic extracts of F. religiosa and F. benghalensis leaves, which exhibited significantly good scavenging activity of DPPH with an inhibition percentage slightly higher than the standard (ascorbic acid) used. The study also displayed the hydrogen peroxide scavenging ability of the extract with the IC 50 value of 49.85 µg/mL, much lower compared to the standard (80.09 µg/mL). The activity may be contributed by the extract’s constituents identified via GC/MS by the same team, reportedly comprised of amine, aldehyde, and aromatic groups, with squalene and amyrin acetate as the major compounds [ 47 ].

One of the recent studies by Jayant and Vijayakumar [ 32 ] has shown the pharmacological activity of the secondary metabolites extracted from the endophytic fungi isolated from F. religiosa . Among the ten fungi isolated and tested, Curvularia lunata displayed the highest radical scavenging activity with the lowest IC 50 value of 0.42 mg/mL.

5.2. Antidiabetic

The management of diabetes involves multiple mechanisms that biologically affect the pathogenesis of the disorder. These include the inhibition of glucose hydrolyzing enzymes to reduce the postprandial glucose level [ 48 , 49 , 50 ]. Both the Ficus species observed in this study have been explored for their antidiabetic effects using an in vitro assay and various animal models.

The in vitro study analyzing the carbohydrate hydrolyzing enzyme inhibition activity using F. benghalensis bark powder extract demonstrated potential activity. The aqueous extract of the bark powder measured IC 50 values of 77 and 141 µg/mL, against both α-glucosidase and sucrose enzymes, respectively [ 51 ]. Meanwhile, in an in vivo study using the ethanolic leaves’ extract (200 mg/kg, 400 mg/kg body weight) from F. benghalensis on alloxan-induced diabetic albino rats, the extract reportedly reduced the triglycerides, cholesterol, and glucose levels, signifying the traditional use of plant leaves as antidiabetic agents [ 52 ]. In another study, oral administration of F. benghalensis bark extract was reported to lower blood glucose in streptozotocin (STZ)-induced diabetic rats through the stimulation of insulin secretion from beta cells of Islets of Langerhans [ 53 ]. Apart from that, an in silico study has revealed the potential α-glucosidase inhibitors reported in F. benghalensis that can inhibit the aldose reductase enzyme. The aldose reductase is the enzyme involved in the glucose metabolism pathway that is crucial in the management of diabetes mellitus. The three flavonoids (apigenin, 3,4’,5,7-tetrahydroxy-3’-methoxy flavone, and kaempferol) investigated showed a high affinity towards the enzyme observed and were predicted to modulate most protein molecules via the p53 signaling pathway [ 54 ].

The aqueous extract of F. religiosa bark has successfully reduced the blood glucose level in a STZ-induced diabetic rat model in a dose-dependent manner. The extract also improved the insulin level and glycogen content in the liver and skeletal muscle. Besides that, a significant reduction in serum triglyceride and total cholesterol along with reduced lipid peroxidation were observed upon treatment. The extract displayed blood glucose normalization within four hours of treatment in all treated groups [ 55 ]. Another study using the methanolic extract of the F. religiosa bark reported a strong antidiabetic activity with the IC 50 value of 83.72 μg/mL, displaying potential antihyperglycemic activity [ 56 ].

The bioactivity determined in the metabolites extracted from the endophytic fungus ( Curvularia lunata ) isolated from F. religiosa exhibited good α-amylase inhibition activity (80%) [ 32 ]. Another similar study isolated nine endophytic fungi which were then colonized and extracted using three different solvents: petroleum ether, diethyl ether, and ethyl acetate. All the recovered extracts were analyzed via α-amylase and α-glucosidase inhibition assays, followed by a glucose diffusion assay. The isolated fungi that displayed good inhibition were suggested to be Aspergillus species based on their microscopic view. The petroleum ether extract of the fungi showed 91% inhibition against α-amylase and average α-glucosidase inhibition (42%). The same extract managed to prevent glucose efflux via maximum inhibition of the glucose movement outside the membrane [ 57 ]. Another species of fungus isolated and extracted was the Aspergillus species, which yields two naphthoquinones, namely naphthoquinone antibiotic herbarin and herbaridine A. The first compound was reported to induce glucose uptake in rat skeletal muscles in the presence of insulin at a low concentration (EC 50 : 0.8 µM) compared to the standard, Rosiglitazone (EC 50 : 3.0 µM), thus indicating its potential to be developed as an antidiabetic drug [ 35 ].

5.3. Anti-Inflammatory

Inflammation is a defense mechanism towards harmful stimuli, such as pathogens, injured or damaged cells, irradiation, or toxic compounds, thus initiating the healing process [ 58 , 59 ]. Inflammation is often associated with major diseases including cancer, diabetes, heart diseases, etc., via multiple mechanisms. Various phytoconstituents have the potential to interfere with the mechanisms and combat a series of inflammation [ 60 ]. One of the mechanisms that involves inflammation is an injury to the skin and other soft tissues, and the wound healing process. An inflammatory response occurs upon injury that subsequently induces the cells underlying the dermis layer to increase collagen production, followed by epithelial tissue regeneration in response to healing [ 61 ].

F. benghalensis is one of the Ficus spp. that is widely used for wound healing. The healing property of this species was investigated using its leaves’ ethanolic extract on excision and incision wound models [ 62 ]. The extract (200 mg/kg dose) had effectively accelerated wound healing through a decreased epithelization period, increased wound contraction rate, and skin breaking tensile, along with the absence of mortality and toxicity signs at a 2000 mg/kg dose. The root’s ethanolic extract has also exhibited wound healing properties. The extract has significantly increased the closure of the excision wound on the rat by enhancing the epithelization. The extract also increased the granuloma tissue-breaking strength, indicating progressive healing [ 63 ].

Meanwhile, another study investigated the antiulcer activity of F. benghalensis leaves’ methanolic extract using the gastric ulcer rat model at the dosage of 250 and 500 mg/kg via oral administration [ 14 ]. The extract was measured to effectively reduce the ulcer index in the aspirin-induced gastric ulcer model, thus indicating its anti-ulcerogenic potential. It is suggested that the gastro-protective effect of the extract is exhibited through the action against the 5-lipoxygenase pathway induced by aspirin. The disruption of this pathway stimulates the prostaglandin synthesis, which eventually protects the gastric mucosa [ 14 ]. Similarly, another antiulcer study used three different animal model to test the F. benghalensis leaves’ methanolic (50%) extract was conducted. The first model is of pylorus ligation and aspirin-induced gastric ulcer where 100, 200 and 400 mg/kg were orally administered for three days. The treatment showed reduction of damage in the mucosa with reduced ulcer indices and increased protection percentage in dose-dependent manner. The second model is acetic acid- induced gastric ulcer with ten days intervention while the third model is of ethanol-hydrochloric acid-induced gastric ulcer for eight days treatment with the same dosages. Both models displayed potential antiulcer activity with improved damage in the mucosa and ulcer indices and protection percentage [ 64 ].

Arthritis is a chronic inflammatory disorder that occurs in the joints and may progress with age [ 60 ]. The aqueous and ethanol extracts of F. benghalensis bark were shown to exhibit anti-arthritic activity, that was displayed via stabilization of protein denaturation in a dose-dependent manner [ 65 ]. The bark extracts showed the presence of a significant amount of terpenoids, saponin, flavonoids, and phenol [ 65 ]. F. religiosa leaves’ ethanolic extract (200–400 mg/kg) was analyzed for its anti-arthritic effect in Freund’s complete adjuvant-induced arthritis rat. The treatment was conducted for 21 days and multiple parameters were measured, including body weight, arthritic score, ankle diameter, and paw volume, which were normalized after the treatment with protective effects exerted by the extract on the primary and secondary lesions [ 24 ].

Pain is a sensation caused by any intense or damaging stimulation that occurs in response to tissue damage and inflammation. Pain can be blocked using anti-inflammatory or analgesic drugs [ 66 ]. The analgesic effect of F. benghalensis aqueous root extract (100 and 200 mg/kg) was tested using Swiss albino mice. Some of the tests carried out include the hot-plate, tail-flick, and writhing tests. A significant observation was recorded in the writhing test upon treatment with the root extract, indicating the potential analgesic effect of the plant root [ 66 ].

The anti-inflammatory potential of another Ficus spp. was investigated using its latex on cisplatin-induced liver injury. An in vivo study carried out by Yadav and Srivastava [ 67 ] has demonstrated the hepato-curative and nephroprotective effects of F. religiosa latex (defatted) methanolic extract. The latex-treated group with cisplatin-induced liver injury has shown protective and curative symptoms upon treatment with 200 and 300 mg/kg, with an observable reduction in the hyaline droplets, tubular dilation, and recovery. The negative impacts caused by cisplatin were reversed upon treatment with the latex. The elevated serum urea and creatinine, as well as lipid peroxidation, were normalized. Besides that, normalization of the renal biomarkers, namely glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and ATPase (Na + /K + , Ca 2+ , and Mg 2+ ), were observed. They have concluded that the antioxidant content in the latex has played an important role in the protective and curative effects of the liver injury and renal profile.

The anti-inflammatory activity of two naphthoquinones extracted from Dendryphion nanum (Nees), an endophytic fungus isolated from F. religiosa leaves, was reported by Mishra et al. [ 35 ]. Compound 1 was identified as naphthoquinone antibiotic herbarin, which effectively inhibits the TNF-α (IC 50 : 0.06 µM) and IL-6 (IC 50 : 0.01 µM) cytokines’ production in the LPS-induced human mononuclear cell line, which was similar to that of the standard drug used in the assay, Dexamethasone. Meanwhile, the other compound isolated and identified as herbaridine A was found to be inactive against the same activity.

The wound healing properties of aqueous extracts obtained from F. religiosa bark, leaves, and aerial roots were tested using cell culture, real-time polymerase chain reaction (PCR), astringent activity, and the wound healing assay. Downregulation of the metalloproteinase-1 (MMP) matrix was observed in the PCR analysis using the bark and aerial root extracts. The bark and leaf extracts were found to enhance the wound healing area [ 46 ].

Recently, the bark extract and ash were tested on the burned wound on Sprague Dawley rats. Different extracts of ointment were formulated for topical application, of which the ash and the aqueous extract formulation were found to be effective in healing the burned wound. The methanolic and chloroform extract formulation was found to be the least reactive. The 100% wound contraction was observed after 15 days of treatment in both the bark ash and aqueous extract ointments, leading to a lower wound closure time, indicating healing. A progressive re-epithelization, formation of granulation tissues, followed by cellular proliferation was observed in the plant-treated wound [ 68 ].

5.4. Antitumor, Antimitotic, and Antiproliferative

Tumor formation is an early stage of cancer evolution. However, a tumor can be benign, forming a mass that enlarges, is localized, and is treatable. A malignant tumor is referred to as cancer that can be deadly. The continual proliferation of the malignant cells is the mechanism by which cancer cells metastasize in no time, and it leads to mortality if not detected [ 69 ]. Therefore, finding novel antitumor, antimitotic, and antiproliferative agents would be of help to the communities that are uncertain about the mass formation and effects. Ficus spp. has been investigated for their antitumor activity as well. F. benghalensis stem bark butanol fraction was shown to possess the strongest antiproliferative activity with the lowest viability of 8% at 4 mg/mL [ 70 ]. The same study has investigated the antimitotic action of the crude methanol and fractions from stem bark. Similarly, the n -butanol fraction showed the strongest antimitotic activity, with a mitotic index of 28% at the same concentration. The mechanism involved the induction of chromosomal and mitotic aberrations, which can be observed through the accumulation of prophases, sticky chromosomes at metaphase, followed by spindle disturbance at prophase and anaphase bridges.

5.5. Anticancer

The search for an anticancer plant and its constituents is ongoing, extensively applying various cell lines.

F. benghalensis latex extracted in various solvents was screened for its antiproliferative activity on multiple cell lines, including colorectal, human breast, neuroblastoma, and lymphocytes [ 71 ]. Ethanol extract has shown promising results against colorectal and neuroblastoma cells, while ethyl acetate extract against the human breast cell lines. Both the extracts were also discovered to exert lesser toxic effects on peripheral blood lymphocytes [ 72 ]. Another study investigated the ethyl acetate extract of F. benghalensis aerial roots to assess its anticancer activity on lung cancer (A549), breast cancer (MDA-MB-231), and cervical cancer (Hela) cell lines. The extract showed potential activity with the IC 50 values of 17.81, 97.89, and 49.27 µg/mL, respectively [ 73 ].

Besides that, F. religiosa plant parts were also investigated for their anticancer activity using various cancer cell lines. The aqueous extract of F. religiosa bark reduced the growth of the cervical cancer cell lines (SiHa and HeLa). The mechanism of action involves upregulating the expression of p53, p21, and pRb proteins. This was followed by downregulation of the phospho Rb (ppRb) protein expression, that subsequently terminates the cell cycle progression at the G1/S phase in SiHa. On the other hand, the extract was found to induce apoptosis in HeLa by increasing the intracellular Ca 2+ level, which results in the loss of mitochondrial membrane potential. It also promoted the release of cytochrome-c and upregulated the caspase-3 expression. Overall, the mechanism of action involved the downregulation of MMP-2 and Her-2, as well as viral oncoproteins E6 and E7 expression in both the cell lines [ 74 ]. The results are in accordance with those reported by El-Hawary et al. [ 75 ] and Kumaresan et al. [ 48 ] on the same cell line, however, using the methanolic extract.

Gulecha and Sivakumar [ 76 ] have reported the F. religiosa leaves’ extract and fraction to be effective in attenuating the viable breast cancer cells. The extract caused apoptosis in breast cancer cells (MCF-7) via multiple cellular signaling mechanisms. Cell cycle analysis showed that cell arrest occurs in the G1 phase. The extract was observed to induce chromatin condensation, resulting in the apoptotic population being increased, as well as causing the loss of mitochondrial membrane potential in the cells. Subsequently, the extract upregulated caspase 9 expression and accelerated mitochondria-mediated cell death.

Recently, F. religiosa latex’s ethanol extract was tested against three different cell lines, namely human neuroblastoma IMR 32, human colorectal HCT 116, and human breast adenocarcinoma MDA MB 231. The extract was found to be toxic against all the cell lines observed in this study, with the lowest inhibitory value of 4.8 μg/mL measured against the neuroblastoma cell line. The mechanism of action observed via cell cycle analysis revealed cell arrest and accumulation at the G1 phase in both adenocarcinoma and colorectal cell lines, whereas similar actions were observed in the G2/M phase of IMR 32 cells. The extract induced apoptosis action, which indicates the upregulation of pro-apoptotic (caspase-3 and p53) and downregulation of anti-apoptotic (Bcl-2, AKT) genes [ 77 ]. A similar study using the methanolic bark extract (91 µg/mL) on human breast adenocarcinoma was conducted by Shankar et al. [ 78 ]. The study revealed that maximum cell death was observed in the treated cells; in contrast, minimal apoptosis or necrosis was observed in the non-cancerous cell line (HEK 293 T) tested, simultaneously. This indicates the selectivity of the potential compound(s) in targeting cancerous cells. The extract stimulated early apoptosis and apoptosis in cells, with about 86.3% apoptotic cells in the G0/G1 population. The gene expression indicates that the mechanisms involved were upregulation of BAX and proteolytic cleavage of PARP-1, and downregulated Bcl-2 genes. The anticancer activity of the bark extract is reportedly due to the presence of potential metabolites, which include rutin, 3-caffeoylquinic acid, luteolin 7-O-rutinoside, 6-C-glucosyl-8-C-arabinosylapigenin, and kaempferol-3-O-rutinoside ( Figure 5 ), detected from the UPLC-MS analysis.

5.6. Antimutagenic

Mutagenicity is described as the induction of permanent transmissible changes in the structure or quantity of the genetic material of cells or organisms that consequently lead to certain diseases. Antimutagenic agents can prevent this in the first place before the phenomenon could take place by inhibiting and suppressing the known mutagens [ 79 ]. Some of the plant metabolites can act as antimutagens that can prevent mutagenicity in certain cells and their genetic materials. F. benghalensis aqueous stem bark demonstrated a potential antimutagenic effect on Salmonella typhimurium TA100 strains with the IC 50 value of 70.24 mg/mL [ 40 ].

5.7. Antimicrobial

Microbes are microorganisms, including bacteria, viruses, fungi, and others, that may cause infectious and deadly diseases if acquired into any biological system. An antimicrobial agent refers to natural or synthetic components that can kill or inhibit the growth of those microorganisms. The increased multi-drug resistance organisms have increased the search for novel antimicrobial agents from the natural source, plants [ 80 ].

The ethanolic extract of F. benghalensis root showed good growth inhibition with increased concentration (25, 50, and 75 mg/mL) in three strains of bacteria ( Staphylococcus aureus, Escherichia coli , and Klebsiella pneumonia ), as reported by Murti and Kumar [ 19 ]. The extract has effectively inhibited the S. aureus, E. coli , and K. pneumonia with the diameter of inhibition zones 30, 24, and 22 mm respectively, at its highest concentration compared to the standard drug (Ampicillin) used, with 40, 35, and 35 mm inhibition zones. A similar study using methanol and ethanol extracts of F. bengalensis aerial root suggested that the extract is more sensitive against Vibrio anguillarum and Enterococcus faecalis with the diameter of the zone of inhibition of more than 20 mm [ 21 ]. Previous studies using alcohol extract of F. bengalensis plant parts (leaf, root, and fruit) against S. aureus , E. coli , Pseudomonas protobacteria , and Bacillus cereus showed moderate activity [ 81 ].

In recent times, F. bengalensis leaves’ aqueous extract showed moderate activity upon investigation for its antiviral activity, which was screened using both cell-free and cell-associated assays against primary isolates of Human Immunodeficiency Virus (HIV), HIV-1UG070, and HIV-1VB59 in TZM-bl and PM1 cell lines [ 82 ].

The Gram-negative K. pneumonia showed more sensitivity towards the ethanolic extract of F. religiosa fruits’ extract (15 mg/mL) than S. epidermidis with the inhibition zones of 21 and 19 mm, respectively. The other two strains of bacteria were less vulnerable towards the extract, even at 30 mg/mL [ 83 ]. The antifungal activity was reported on F. religiosa bark ethanol extract, which exhibited moderate activity against Candida albicans , an opportunistic pathogenic yeast [ 84 ].

5.8. Anti-Helminthic Activity

Helminth infections are parasitic infestations in the human system that affect the world’s populations, mostly in developing countries with poor sanitation. Humans can become infected through ingestion or skin penetration. The parasite could deprive the host of food, resulting in blood loss, organ and intestinal damage, or lymphatic obstruction, that eventually causes death. Anti-helminthic drugs react by killing or expelling the infesting helminth from the host body. Generally, helminthiasis is not fatal, however, it can cause morbidity. The medications may cause some side effects, including fever, dizziness, nausea, severe allergies, and headache [ 85 , 86 ]. In most developing countries, medicinal plants are used as anti-helminthic agents. F. bengalensis aerial roots’ methanol and leaves’ ethanol extract exhibit the same action against the same species analyzed [ 87 , 88 , 89 ]. Meanwhile, for the latex of F. bengalensis and F. religiosa , the latter exhibits the most effective activity with a much faster time to cause paralysis in the earthworms analyzed, eventually leading to death [ 90 ]. Both the plants can be utilized as anti-helminthic in communities with less access to proper medications.

5.9. Hepatoprotective

The liver is the key organ that is responsible for regulating metabolism, secretion, storage, and detoxifying activity in the body, which will distort those functions if the organ is affected in any way [ 91 ]. Therefore, it is crucial to ensure the liver is protected from various kinds of toxic components acquired via food, synthetic medicines, and other factors.

F. bengalensis latex was orally administered to CCl 4 -induced hepatotoxicity in albino rats and paracetamol-induced hepatic damage in rats. The latex treatment showed improvement to liver function with a significant reduction in the serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), and bilirubin and alkaline phosphate (ALP) levels, and improvement in the total protein level [ 92 ]. The investigation of the hepatoprotective effect of the F. bengalensis fruit extract on goat liver assessed through catalase activity showed that the ethanol extract of the fruit at the dose of 50 mg/kg could significantly reduce the hepatoxicity effect against Silymarin [ 93 ].

Recently, the fruit of F. benghalensis was evaluated for its hepatoprotective effects via in vitro assays. The fruit was extracted using different solvent systems, namely ethanol, water, chloroform, ethyl acetate, and petroleum ether. The hepatotoxicity condition was induced using carbon tetrachloride, acetaminophen, and erythromycin in the liver extracted from goat, Capra Capra , and treated with 100, 250, and 500 mg/kg of the fruit extracts. Of all the extracts tested, the ethanol extract was found to be most effective in reducing the hepatotoxic activity at the dose of 500 mg/kg of fruit extract against Silymarin, the control drug [ 94 ]. This finding is supported by an in vivo study conducted recently using the fruit’s ethanolic extract (500 mg/kg) against perchloromethane-induced toxic hepatitis in New Zealand albino rats, indicating the hepatoprotective action of F. benghalensis fruit. The elevated liver biomarkers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), total serum bilirubin, and malondialdehyde) were reduced upon administration of the fruit extract [ 95 ]. The study suggested that the diminution of lipid peroxides potentially by the antioxidant compounds in the fruit may have contributed to lipid-protective action. The fruit is known to be rich in coumarins, that reportedly possess hepatoprotective activity.

Oral administration of F. religiosa leaves’ extracts to CCl 4 -induced hepatotoxicity in albino rats and paracetamol-induced hepatic damage in rats displayed a significant reduction in the serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), which will be elevated in a liver-damaging phenomenon. The F. religiosa leaves’ extract was found to reduce those biochemical markers, thus improving liver function [ 96 ].

5.10. Anti-Aging

Wound healing is the skin repair process that occurs naturally after damage, which is important in restoring the tissue’s normal function [ 97 ]. F. bengalensis and F. religiosa are traditionally used in wound healing [ 98 ]. The ethanolic extract of the F. benghalensis root has significantly improved collagen synthesis. It showed high content of hydroxyproline that probably stimulates collagen synthesis [ 97 ]. Meanwhile, the aqueous extracts of F. religiosa bark and leaves were found to have a significant skin-tightening effect [ 46 ].

5.11. Anticoagulant Activity

Anticoagulant activity is the process of hindering thrombus formation or blood clotting, thus preventing coagulation or reducing the formation of new blood clots, especially in patients with a high risk of having a stroke. Anticoagulant agents can lead to gastrointestinal problems in the long run [ 99 ]. Therefore, the findings on the potential anticoagulant agents from medicinal plants are encouraged. Evaluation of F. benghalensis and F. religiosa leaves’ methanolic extract in human plasma showed significant activity, with prothrombin time (PT) ranging from 17.7 to 26.7 s and activated partial thromboplastin time (APTT) varying from 47.7 to 72.3 s. F. religiosa extract showed better activity than the other species [ 99 ].

5.12. Immunomodulatory Activity

Modulation of the immune system or immunomodulatory activity is an important mechanism that regulates the activity of the immune system by stimulating or suppressing its functions [ 100 ]. F. benghalensis leaves’ hydroethanolic extract has displayed a potential immunomodulatory activity by stimulating the neutrophils to phagocytic action significantly, by 45%. The butanol fraction obtained from the crude hydroethanolic extract showed the highest results, with 89% stimulation of the phagocytic activity. Furthermore, the crude extract stimulated the phagocytosis of the killed Candida albicans at 1000 mg/mL, which is comparable to the pooled serum activity [ 42 ]. The F. benghalensis aerial root’s methanolic extract showed an elevated response for the plaque-forming response and quantitative hemolysis assay. The extract also stimulated the production of a circulating antibody titer in response to sheep red blood cells. The extract was found to increase the delayed-type hypersensitivity response by facilitation of the footpad thickness response and improved lymphocytes and rosettes formation. The results are comparable to that of the standard, Levamisole, and the extract exhibited potential immunomodulatory effects via a specific and non-specific immune response [ 101 ].

5.13. Antistress

Stress is an emotional and physical tension that causes psychological and physiological disturbance when ones’ emotions are challenged or when a certain demand in life is not fulfilled. In this era of a demanding world, life has been stressful for many individuals, which has led to increased cases of depression in current times. Humans are dwelling in stress and intolerance on a daily basis. The psychological and physiological effects from natural sources will be of help, rather than medicines. F. benghalensis has scientifically shown potential antistress activity [ 102 , 103 ]. The fruits’ methanolic extract were investigated using the anoxia stress tolerance test, swimming endurance test, and immobilization stress animal models, exhibiting significant antistress results at the minimal dosage tested (125, 250, and 500 mg/kg) [ 102 ]. The bark (methanol extract) was tested using acetylcholinesterase inhibitory activity against SHSY5Y cell lines, measuring a 228.3 µg/mL IC 50 value. Acetylcholine is one of the neurotransmitters released by brain cells upon stress [ 103 ]. The fruit and bark extract could be a stress-relieving remedy that may help the affected person combat stress.

5.14. Miscellaneous

Apart from the pharmacological activities discussed above, F. religiosa has been reported for its use as a remedy for polycystic ovary syndrome (PCOS) using an animal model. The female rats were induced with PCOS using letrozole in 0.5% carboxymethyl cellulose (CMC) and orally administered the F. religiosa leaves’ (dry and fresh leaves) water extract at the dosage of 1 mg/kg BW for 21 days, consecutively. The findings indicated that treatment using fresh leaf extracts was found to upregulate the PPAR-γ and Cyp19a1 pathways in the ovary to significant levels, similar to the positive control, pioglitazone [ 104 ]. These two genes are involved in the insulin-resistance action and the stimulation of androgen production via synthesizing aromatase, respectively. These pathways are involved in the mechanisms of PCOS. The study stated that the water extract also inhibited the synthesis of androgen by reducing the levels of steroidogenic enzymes. The dry leaves’ extract has overall alleviated the steroid imbalances, thus regulate the estrous cycle. The reduction of the multiple ovarian cysts measured by the weight of the ovary was found to be improved by the leaf-treated rats. The study also suggested that the presence of propionic acid and its derivatives, mainly 3-acetoxy 3-hydroxy propionic acid, may have potentially exhibited the activity observed. The compound has previously been reported to improve the PPAR-γ expression, through which PCOS and associated complications are ameliorated [ 104 ].

All the pharmacological activities discussed above are summarized in Table 3 below.

Note: * IC 50 = half maximal inhibition constant; ** BW = body weight.

6. Toxicity Studies

One of the important parts of drug development is toxicological screening, be it for new drugs or for the extension of the existing ones. According to the US Food and Drug Administration (FDA), it is essential to screen any new molecules for their potential therapeutic activity and toxicity potential using animal models. Plants may contain metabolites with synergistic or antagonistic nature, and some may cause serious intoxication or hypersensitivity reactions and, in some cases, may result in anaphylactic shock. Therefore, it is crucial to evaluate the adverse and toxic effects of plant extracts and phytochemical compounds isolated which are intended to be used for human therapy [ 105 ].

F. benghalensis aerial roots exhibited no signs of toxicity and were considered safe up to 5000 mg/kg in an acute toxicity study. Its crude ethanol root extract was found to be safe up to 3000 mg/kg body weight of Wister albino rats [ 105 ]. Meanwhile, the 50% ethanolic leaves’ extract did not cause mortality or any apparent effect on motor activity, feeding behavior, fecal output, or muscular weakness in adult albino mice up to 2000 mg/kg [ 106 ]. The albino mice did not exhibit any lethal effect or abnormalities or mortality upon treatment with 2000 mg/kg of the methanolic extract of F. benghalensis fruit.

F. religiosa leaves’ petroleum ether extract was found to be safe with the absence of mortality up to the dose of 4000 mg/kg when orally administered to adult male Wistar rats [ 107 ]. Generally, in toxicity assessment, the median lethal dose (LD 50 ) determined is considered poorly toxic when the value is measured to be 2000–5000 mg/kg body weight of the animal model used, and practically non-toxic when it is above 5000 mg/kg. The extracts studied are poorly toxic and are considered for further analyses and application in the pharmaceutical and nutraceutical industry [ 105 ].

7. Recent Applications

Nanotechnology has recently piqued the interest of researchers due to its effective mechanism. Cellular level penetration and effects of nanoparticles may be beneficial to the pharmacological, nutraceutical, and cosmeceutical industries [ 108 ]. The use of plant extracts for the synthesis of nanoparticles is actively performed in recent times. This method is considerably more environmentally friendly and produces more biodegradable waste compared to the routine techniques, which have the opposite effect.

Sulfur nanoparticles have been reported for their wide uses, especially in agriculture (pesticides and fungicides), medicine (cancer therapy), and catalytic applications (batteries). Synthesis of sulfur nanoparticles using F. benghalensis leaves’ extract has been demonstrated by Tripathi et al. [ 109 ]. During the procedure, stable nanoparticles’ formation was observed, in which the proteins and phytoconstituents in the leaves act as stabilizing agents, thus enhancing the disproportionation reaction that took place.

The roots of F. benghalensis are also utilized in the green synthesis process as the reducing agent. The water extract of F. benghalensis prop root was mixed with silver nitrate solution to obtain silver (Ag 2 O) nanoparticles. The resulting Ag 2 O nanoparticles were examined for their anti-leishmaniasis activity against Leishmania donovani [ 110 ]. Similarly, another study investigated the antibacterial activity of the Ag 2 O nanoparticles against dental pathogens ( Streptococcus mutans and Lactobacilli sp.) [ 111 ]. The nanoparticles analyzed exhibited excellent activity in both studies.

F. religiosa leaves’ aqueous extract was used to synthesize zinc oxide nanoparticles (ZnO) and titanium dioxide nanoparticles (TiO 2 ). These nanoparticles showed potential larvicidal activity. The highest mortality rate was observed in the ZnO nanoparticle treatment against fourth-instar A. stephensi larvae [ 112 ].

Besides the medicinal and nanotechnology applications discussed above, Ficus species are also utilized as insecticides and repellent agents. Various medicinal plants are studied for their vector control properties, and these plants have the potential to be developed as environmentally safe vector and pest managing agents. One of the recent studies demonstrated larvicidal effects of F. religiosa leaves’ methanolic extract. The extract caused an almost 70% mortality rate in the early third-instar larvae of Aedes aegypti [ 113 ].

Apart from that, F. religiosa leaves’ extracts (ethanol, acetone, benzene, and hexane) displayed significant repellent activity against C. quinquefasciatus , A. stephensi , and A. aegypti , with ethanol extract showing the highest activity at 4.0 mg/cm 2 . These activities are probably due to the presence of terpenoids in the extracts analyzed [ 114 , 115 ]. Both the plant parts were effectively repurposed as insect repellents, thus indicating the vast potential of these species.

8. Conclusions and Future Research Prospective

Both the Ficus species plant parts have attracted much attention for their various pharmacological potentials contributed by the phytochemicals present in the plant matrix. The species contain a range of flavonoids, phenolics, terpenes and terpenoids, fatty acids, sterols, organic acids, proteins, and some long-chained hydrocarbon compounds. Some of the distinct compounds present in Ficus species plant parts include bengalenoside, leucodelphinidin, leucoanthocyanin, leucocyanidin, and derivatives. Besides that, the presence of flavonoids and terpenoids is potentially responsible for their pharmacological activities.

The studies reviewed confirmed the antimicrobial, antidiabetic, anti-inflammatory, and anticancer activity, which provides a scientific basis for the use of the species in traditional medicines. Moreover, the plants’ constituents are found to be effective mosquito repellents and mosquitocidal agents. However, the effectiveness of the plant parts in urinary and urinogenital disorders of its traditional claim are yet to be discovered scientifically. Comparably, F. benghalensis has been investigated more extensively for various pharmacological functions than F. religiosa . Some of the potential medicinal actions of F. religiosa that need to be explored include anti-stress, antitumor, antiproliferative, antimutagenic, and immunomodulatory actions. The plant may exhibit tremendous activity for its potential phytoconstituents, that mainly consist of flavonoids, phenolics, terpenes, and terpenoids.

Apart from that, bioactivity-based fractionation and bioactive compound isolation should be validated for their abundance, accuracy, reproducibility, and cost-effectiveness. Further analyses should be carried out using animal models to measure the compounds’ potential in the bioactivity observed. These could increase the probability of the optimal use of the phytoconstituents of interest. Overall, the present compilation of chemical constituents with their pharmacological properties will provide prospective information on the existing studies and the research gap or pharmacological aspects that may require further attention and experimental values to be added to this genus. The Ficus species can be utilized as functional foods and pharmaceutical ingredients with respect to its pharmacological potentials and its availability in nature.

Acknowledgments

The authors would like to thank the Institute of Tropical Agriculture and Food Security (ITAFoS), Universiti Putra Malaysia (UPM), and the Faculty of Food Science and Technology, UPM, for their support and resources. The authors also would like to thank MOHE, Malaysia, for the HICoE rendered to ITAFoS, UPM. The authors would like to thank Zoya Akulova, a botanist from LSA Associates, Inc., for allowing us to cite her amazing photo collections (© 2021 Zoya Akulova) in our publication.

Author Contributions

Conceptualization, S.M. and V.P.; resources, V.P. and J.S.; writing—original draft preparation, S.M.; writing—review and editing, S.M., V.P. and J.S.; supervision, J.S.; funding acquisition, J.S. All authors have read and agreed to the published version of the manuscript.

This research was funded by the Ministry of Higher Education (MOHE), Malaysia, grant number FRGS/1/2020/STG04/UPM/01/1.

Conflicts of Interest

The authors declare no conflict of interest.

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

International Journal of Phytomedicine and Phytotherapy

• Open access
• Published: 09 April 2021

Phytochemistry and pharmacological studies of Plumbago zeylanica L.: a medicinal plant review

• Babita Shukla 1 ,
• Sumedha Saxena 1 ,
• Shazia Usmani 1 &
• Poonam Kushwaha 1  

Clinical Phytoscience volume  7 , Article number:  34 ( 2021 ) Cite this article

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Plumbago zeylanica L. (Plumbaginaceae) commonly known, as chitrak is pharmacologically important plant. Various studies have been undertaken to assess the pharmacological potential of different parts of the plant namely like roots, stem, flower, and leaves as antimicrobial, hepatoprotective, anticancer, antifertility, antiulcer, antifungal and wound healing. The intention of the present review is to deliver a concise account on its ethnobotanical uses, phytochemistry with an in-depth study of its phytoconstituents, facts and prospects of its potential pharmacological activities of this golden plant. An extensive literature survey was undertaken through different online platforms viz. Google Scholar and online databases namely PubMed, Science Direct and Springer. All papers based on traditional medicinal uses and pharmacological properties were included. Sixty three research articles and review articles were found to be apt for inclusion into the review. About 150 articles were retrieved for the purpose. The elaborative results vindicated that Plumbago zeylanica L. holds significant prospects in major health conditions such as diabetes, cardiovascular disorders, ulcer, liver problems, obesity, wound healing, cancer etc.

Introduction

Plants have been extensively exploited for varied pharmacological activities since prehistoric times and gaining thrust in the current scenario. Many of the presently available drugs have been obtained from some or other natural resources [ 1 ]. They have been the basis of many traditional medicinal systems for thousands of years and continue to provide humankind with new remedies for each disease. Most practitioners formulate and dispense their own recipes, which necessitates proper documentation and utmost attention to research oriented services [ 2 ]. This attempts to prove scientific insight behind the traditional adaption. Less toxicity and increased therapeutic effect leading to better patient compliance are the few main reasons for adhering to drugs from natural origin [ 3 ]. Although, there lies a prevalent use of herbs in traditional systems of medicines, despite the fact that written documentation is missing from historic times. Therefore, it is of utmost importance to document all such data for systematic regulation and appropriate application. This may lead to development of significant number of synthetic drugs having sound background of literature with actual origin from plant/isolated ingredient through derivatization [ 4 ]. An intensive study of the naturally occurring molecules known as ‘therapeutically active’ is need of the hour to come up with novel therapeutic moieties [ 5 ]. Active constituents present in many plants species are isolated for direct use as drugs, lead compounds, or as pharmacological agents.

The ethnopharmacological and chemotaxonomic importance of the genus Plumbago became the driving force, which led us to investigate the infochemicals present in its species.

The genus Plumbago belonging to the family Plumbaginaceae, comprises 10 genera and 280 species [ 5 , 6 ]. Three main species included in genus Plumbago namely, Plumbago indica L., Plumbago auriculata L. and Plumbago zeylinica L. (Fig.  1 ). Among these species, Plumbago zeylanica L. is more popular due to its therapeutic properties. Plumbago zeylanica L. usually referred to as Ceylon leadwort, doctor bush and wild leadwort, is one of the well-known herbal plant. It also named as chitramula and chitrak in Ayurveda. Chitrak is a perennial herb cultivated in shady places in the garden for its brilliant inflorescence [ 6 , 8 , 9 ]. It is widely distributed throughout India and Sri Lanka [ 6 ].

Genus Plumbago Species [ 7 ]

The present compilation aimed to highlight the phytochemicals present in Plumbago zeylanica L. and provide a comprehensive data regarding its pharmacological potentials.

Morphological studies

Plumbago zeylanica L. , is an abundantly branched perennial herb with alternate leaves (Fig.  2 ) [ 9 ]. It an annual plant. The plant grows up to height of 3–4 ft. Leaves are thick, fleshy, sessile, oval and lance-elliptic in shape. Flowers of this plant are 10–25 cm long and arranged in terminal and axillary elongated spikes [ 6 ].

Morphological description of the Plumbago zeylanica L. [ 7 ]

Taxonomic classification and common names [ 10 ]

Traditional perspective.

Plant parts of Plumbago zeylanica L. have been utilized since centuries for its wide variety of medicinal properties. It is a very potent medicinal herb. In Ayurveda, it is considered as rasayan. Root and root bark of this herb utilized in preparation of varied ayurvedic medicines. In traditional system of medicine, it has been indicated for its significant protective role in enlarged liver and spleen. It is a bitter tonic and suggested as a rejuvenator, well known for its use in chronic colds and cough. It also finds its use in correcting chronic menstrual disorders, viral warts and chronic diseases of nervous system. Extract of chitramula are reported as anticancer drugs. Root bark additionally considered beneficial in obesity [ 6 , 9 ]. It has been described for its potential use in digestive disorders such as loss of appetite and indigestion. Also recommended in piles, worms, colitis, ascites and liver diseases. Flowers of this plant are used as digestant [ 11 ]. Leaves possess aphrodisiac property. They are used in treatment of scabies, in sore and swelling. Leaves have shown their effective role in treatment of infections and digestive problems such as dysentery. They are also used as stimulant. Paste of leaves are topically applied in painful rheumatic areas or in chronic and itchy skin conditions [ 12 ]. Roots of this plant are demonstrated as laxative, expectorant, tonic, abortifacient, good appetizer. Roots are also reported to be beneficial in treatment of rheumatism, laryngitis, scabies and disease of spleen. Decoction of seeds are used for reducing muscular pain [ 13 , 14 ].

Methodology adopted

Literature search.

Substantial literature survey was undertaken to abridge the traditional medicinal uses of Plumbago zeylanica L. and its therapeutic properties comprising information from previous couple of decades. The information retrieval was carried out through various online platforms viz. Google scholar and other online databases such as PubMed, Springer and Science Direct, using keywords Plumbago zeylanica L . , its traditional Medicine uses and pharmacological activities. The acceptability criteria of the included studies and execution of study design was based on PICOS model (Population, Intervention, Comparison, Outcome, Study design), to report the retrieved relevant articles, and to explain data collection process comprehensively.

Study design

Well-explained and most suitable research articles based on in-vitro and in-vivo studies on pharmacological properties and clinical studies were covered in study design. If articles were, unpublished works or communications, letters, case reports or if they were unavailable as full-length papers, they were excluded. The study outcomes were assessed if there was outcome information on the nutritional composition of the plant and its application or clinical benefits and harms. An extensive literature survey was undertaken by screening sources with title and abstract. Eligible studies with full text were selected. Unrelated and identical articles were eliminated during sorting. The exploration of articles was concluded through a reference list sorting and assessed considering the criteria articulated above. The included articles were heterogeneous considering both the outcomes and the quality, which made the comparison quite difficult. The quality of the retrieved papers was analyzed and evaluated based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach.

As per GRADE system, reviews on the single studies relevant to the topic were sorted and covered in the review. The incorporated studies were evaluated and the results were explicated based on the nature of evidence such as in-vitro studies, animal activities, patents and investigation. Total 150 articles were identified. The literature review was completed through 63 full-length research articles (reference lists which include research articles on traditional and medicinal properties, studies on pharmacological activities both in-vitro and in-vivo. No randomized controlled trials investigated on the human population were identified.

Phytochemical profiling

Plumbago zeylanica L. is a most substantially used plant in the traditional medicine due to the variety of pharmacological activities obtained by its active constituents.

Several researches have made various investigations to reveal the presence of phytoconstituents in its plant parts. Ganesan and Gani reported the presence of four macroelements (Na, K, Ca and Mg) in adequate proportion, five critical microelements (Zn, Fe, Mn, Cr, and Co) and eight other elements (Mo, Sb, Bi, Cd, Sr, Pb, Cd, and As) in leaves, stems and roots of Plumbago zeylanica L. Many anticancer and antioxidant compounds normally have these elements [ 11 ]. Ravikumar and Sudha investigated the presence of various constituents in ethanol, petroleum ether and aqueous extract of Plumbago zeylanica L. From the investigation, they confirmed the presence of alkaloids, carbohydrates, triterpenoids, flavonoids, gums, mucilage, protein, fatty acids and saponins [ 15 ]. Jijhotiya and team carried a study to evaluate scientific data for presence of various phytochemicals in the leaves extract of methanol, aqueous and petroleum benzene. All the three different extracts of leaves were found to contain triterpenoids, flavonoids, phenolic tannins, saponins & carbohydrate. Study suggested the importance of these reported secondary metabolites for the pharmacological properties of the plant [ 11 ]. Recently Roy et.al, studied fatty acid methyl ester profile of five different accession of Plumbago zeylanica L. The fatty acid methyl ester analysis revealed the presence of several types of fatty acids in the plant. They found that these accessions are affluent in octadecadienoic acid (8–22%), octadecatrienoic acid (7–24%), pentadecanoic acid (11–22%) fatty acids [ 16 ].

Phytoconstituents present in various plant parts

Different researchers report phytochemicals from different parts of the plant (Table  1 ). Large range of therapeutic activities possessed by this plant are due to presence of this valuable constituent. Number of secondary metabolites such as naphthoquinones flavonoids, alkaloids, glycosides, saponins, steroids, tannins, triterpenoids, coumarins, carbohydrates, phenolic compounds, fixed oils, fats and proteins reported to be present in Plumbago zeylanica L. [ 12 , 13 ]. Major naphthoquinones present in the plant are plumbagin, chitranone, 3-biplumbagin, chloroplumbagin, elliptone, coumarins includes seselin, 5-methoxy seselin, xanthyletin, suberosin. Other phytoconstituents present in the plant includes plumbagic acid, β sitosterol, 2-dimethyl-5-hydroxy-6-acetylchromene, saponaretin, and isoaffinetin [ 14 ]. Several other naphthoquinones, difuranonaphthoquinones binaphthoquinones, coumarins, di-phenyl sulfone, carboxylic acids and esters, monoterpenes, tri-terpenoids, amino acids, anthraquinones, steroids, steroid glucosides, sugars and other compounds are also reported to be present [ 17 , 18 , 19 , 20 , 21 ].

The roots of the plant contains plumbagin, and other constituents such as 3-chloroplumbagin, binaphthoquinone named as 3′, 6′-biplumbagin, 3,3′-biplumbagin and four other pigments reported as isozeylanone, zeylanone, elliptone, and droserone. Isoshinanolone and a new napthalenone i.e., 1, 2(3)-tetrahydro-3, 3′-biplumbagin isolated from the phenolic fraction of the light petrol extract of the roots has also been identified. Two plumbagic acid glucosides; 3′-O-beta-glucopyranosyl plumbagic acid and 3′-o-beta-glucopyranosyl plumbagic acid methylester along with five naphthoquinones (plumbagin, chitranone, maritinone, elliptone and isoshinanolone), and five coumarins (seselin, methoxyseselin, suberosine, xanthyletin and xanthoxyletin) are reported to be isolated from the roots [ 21 , 22 , 23 ].

Stem contains plumbagin, campesterol, sitosterol, stigmasterol, isozeylanone and zeylanone. The leaves of Plumbago zeylanica L. reported to contain chitanone, plumbagic acid and plumbagin. The presence of alkaloids, glycoside, reducing sugars, simple phenolics, tannins, lignin, saponins and flavonoids are reported from the qualitative phytochemicals analysis of leaves [ 17 , 18 ]. Seeds mainly contain plumbagin. Stem revealed the presence of plumbagin, zeylanone, isozeylanone, sitosterol, stigmasterol, campesterol, and dihydroflavonol. Plumbagin, zeylanone and sitosterol identified in the flowers of the plant. Fruit confirmed the presence of plumbagin, glucopyranoside and sitosterol [ 22 , 23 , 24 ].

Since plumbagin is one of the pharmaceutically important phytoconstituent of P. zeylanica . However, the productivity of this constituent is very low, which is insufficient to meet the demand. Keeping this view, in a recent study Andhale and his coworkers attempted an investigation to study the effect of fungal endophytes on increment of plumbagin content in the plant. They assume fungal endophytes have the potential to synthesize various secondary metabolites and influence the synthesis of the secondary metabolites in plants [ 25 ].

Pharmacological and therapeutic activities

Plumbago zeylanica L., is a pharmaceutically important plant. It exhibits broad range of pharmacological activities, which includes antibacterial, antifungal, anti-inflammatory, antidiabetic, anticancer, antioxidant, hepatoprotective, cytotoxic and wound healing.

The reported pharmacological activities of various parts of Plumbago zeylanica L. are detailed below:

Antimicrobial activity

Shweta and Dubey studied antimicrobial properties of the leaves extracts of the plant against some known drugs. The in-vitro antimicrobial activity and the minimum inhibitory concentration (MIC) of the crude extract and the standard antibiotics were studied. Maximum inhibition was reported with leaves extracts as compared to the standard antibiotics [ 26 ]. In another study, Singh and colleagues investigated methanolic extracts of the stem and the leaves against six bacterial species and nine fungal species for antimicrobial studies. Both the extracts showed antimicrobial activity in a dose-dependent manner. Moreover, the antimicrobial activities assayed from the zones of inhibition. Leaves extract indicated maximum antimicrobial activity against both Staphylococcus aureus and Fusarium oxysporum whereas the stem extract was noted to be more antimicrobial against the Pseudomonas aeruginosa and the Penicillium expansum species. Study suggests that the methanolic extract of Plumbago zeylanica L. stem possess significant antibacterial activity [ 27 ]. In another study, Ogunleye and coworkers carried an investigation to evaluate the antibacterial activity of the ethanolic extract of Plumbago zeylanica L. root bark against seven bacteria extracted from two dumpsites within the city of Akure. Study revealed, antibacterial activity of the extract enhances with increasing concentration [ 28 ].

In a recent experiment Jain et al., investigated Plumbago zeylanica L. for its antifungal activity. Antifungal potential was studied against four pathogenic fungal species Fusarium oxysporum, Rhizoctonia solanii, Alternaria sp. and Sclerotium rolfsii . Study suggested excellent inhibitory activities against Alternaria spp. whereas least against S. rolfsii at 62.5 μg/ml [ 29 ].

Anti-inflammatory activity

Sheeja et al., investigated anti-inflammatory activities of acetone and petroleum ether extracts of Plumbago zeylanica L. leaves using in vivo experimental models at two dose levels (200 and 400 mg/kg, p.o.). The acetone extract significantly decreased inflammation in rats induced by carrageenan compared to the control group. Study revealed anti-inflammatory activity of the extract may be linked to reduction in prostaglandin synthesis and release, rather than preformed inflammatory agents [ 30 , 31 , 32 ]. In another study Thanigavelan et al., investigated the anti-inflammatory activity of hydroalcoholic extract of Plumbago zeylanica L. root bark through in-vitro human red blood cell membrane protective activity, and in-vivo through carrageenan induced rat paw oedema and complete freund’s adjuvant induced chronic inflammatory model in rat. In both acute and chronic model of inflammation, hydroalcoholic extract of root bark of Plumbago zeylanica L. showed moderate anti-inflammatory response at the dosage of 250 mg/kg b.w comparable with standard indomethacin. Carrageenan injection is the biphasic occurrence that contributes to the development of paw oedema in the rat. Study indicated, the mechanism of anti-inflammatory activity might be due to prostaglandins inhibition [ 33 ]. Further Nile et al., studied anti-inflammatory activity of root and shoot extracts of Plumbago zeylanica L. at a concentration of 25, 50, 75, and 100 mg/mL using diene-conjugate and β-glucuronidase assays [ 34 ]. Later on, Subramaniyan et al., investigated dichloromethane extract of Plumbago zeylanica L. against carrageenan-induced paw oedema at the doses of 250 mg/kg and 500 mg/kg. Study showed inhibition effect of oedema was comparable to diclofenac (standard drug). Study suggested that the inhibition effect may be attributed to its free radical scavenger activity and protection of apoptosis [ 35 ]. In another research Poosarla et al., investigated a freeze-dried ethyl acetate fraction (PZE-6) of Plumbago zeylanica L., roots for the management of joint inflammation. Study showed PZE-6 substantially suppressed arthritis by reducing paw volume, clinical score and delayed-type hypersensitivity reaction. In addition, PZE-6 was found to inhibit the development of inflammation in adjuvant-induced arthritis rats [ 36 ]. As reported by Zaki et al., plumbagin prominently hampered high mobility group box 1 expression and subsequently quelled inflammatory cascades, as nuclear factor κB (NF-κB), tumour necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO) activity [ 37 ].

Antioxidant activity

Plumbago zeylanica L. has been widely investigated for its anti-oxidant properties. Tilak and coworkers studied anti-oxidant activity of the aqueous and alcoholic root extracts against known medicinal preparations and the active constituent, plumbagin. Ferric reducing/anti-oxidant power (FRAP), radical scavenging of 1,1-diphenyl-2-picryl hydrazyl (DPPH) and 2,2′-azobis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS), lipid peroxidation, phenolic and flavonoid content was assessed for evaluation of its anti-oxidant potential. In FRAP/DPPH assays, ethanolic extracts were shown to be most efficient, whereas in the ABTS assay aqueous extracts were reported to be the more effective. These extracts also demonstrated significant lipid peroxidation inhibition and augmented proportion of polyphenols and flavonoids. Antioxidant and pulse radiolysis studies were performed to examine the detailed mechanisms of action [ 38 ].

In a recent study, Gabriel and colleagues investigated free radical scavenging activity of methanolic root extract (ME) and ethylacetate extract (EA) by using 1,1-diphenyl-2-picrylhydrazyl (DPPH). Study showed ME extract possess highest antioxidant activity in comparison to EA extract [ 39 ].

Hair growth promoter and regulation

Androgenetic alopecia (AGA) is a common type of baldness characterized by progressive hair loss. Yamada et.al, investigated the potential of Plumbago zeylanica L. roots extract in the prevention AGA. Study examined the inferences of cellular senescence of DP cells in prevention of AGA. Quantitative RT-PCR and Western blotting analysis in DP cells examined the expression of the 5α-reductase type II (SRD5A2) gene. In addition, DP cells were cultured with the herbal extract of P zeylanica roots. Study demonstrated up-regulation in the expression of the SRD5A2 in senescent DP cells whereas, the herbal extract of Plumbago zeylanica L. root enhanced the growth of DP cells and showed down-regulation in expression of SRD5A2 in DP cells. Observations confirmed the role of senescent DP cells in the development of AGA through up-regulating SRD5A2 expression, and suggested the potential of Plumbago zeylanica L. extract and role of plumbagin in suppressing its development through enhancing the growth of DP cells and down-regulating SRD5A2 expression in DP cells [ 40 ].

Antidiabetic activity

Plumbago zeylanica L. account for its sweet inactivation property to the presence of its chief active constituent plumbagin. Experimental trials confirmed the antidiabetic effect of Plumbago zeylanica L. in various studies. Zarmouh et al., reported antidiabetic activity of ethanolic extract of Plumbago zeylanica L. roots. The study was conducted in streptozotocin induced diabetic rats at the doses of 100–200 mg/kg for six weeks. Results showed marked increase in hepatic hexokinase activity and reduction in hepatic glucose-6- phosphatse, serum acid phosphatase (ACP), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) levels [ 41 ]. Furthermore, an investigation to determine the antidiabetic activity of plumbagin derived from the root of Plumbago zeylanica L. and its implication on GLUT4 translocation in STZ-induced diabetic rats was performed by Christudas et al. Plumbagin orally administered to STZ-induced diabetic rats for 28 days in the dose concentration of 15 and 30 mg/kg body weight. On 21st day, oral glucose tolerance test was performed. Plumbagin showed remarkable reduction in the blood glucose. All the other biochemical parameters were observed to near normal. In addition, increased activity of hexokinase and reduction in glucose-6-phosphatase and fructose-1,6-bisphosphatase was indicated in treated diabetic rats. The GLUT4 mRNA and protein expressions found raised in diabetic rats after treatment with plumbagin. The obtained results concludes that plumbagin exhibit remarkable antidiabetic activity [ 42 ].

In another research Khatwani et al., investigated potential synergistic activity of aqueous extracts of leaves of Murraya koenigii (MK), Annona squamosa (AS), and roots of Plumbago zeylanica L. (PZ) using STZ induced diabetic rat model. All the ingredients of the capsules were mixed together in required proportion with suitable excipients and filled into the capsules . Study results with the polyherbal formulation was noted to be more significant as compared to Glibenclamide [ 43 ].

Antiulcer activity

Falang and coworkers investigated aqueous extract of Plumbago zeylanica L. root against aspirin and indomethacin induced acute gastric ulceration in albino rats. They determined and compared ulcer score, ulcer index and percentage protection of the extract with negative and positive control groups. The extract showed significant dose dependent inhibition of aspirin induced gastric mucosal damage at the doses of 25, 50 and 100 ml/kg whereas in case of indomethacin-induced ulcer, extract showed inhibition at doses of 50 and 100 mg/kg respectively [ 44 ].

Antiobesity

Kotecha and Rao investigated anti-obesity activity of Plumbago zeylanica L . A clinical study was conducted on obese patients taken from I.P.G.T & R. Hospital at Jamnagar, Gujarat. During the investigation, an intervention of Plumbago zeylanica L. and haridra powder within the dose of 500 mg and 1 g (4 times a day) respectively administered in a capsule form to the patients for 45 days with restricted diet schedule of low calorie diet. Proposed intervention of Plumbago zeylanica L. and haridra powder showed potential reduction in the weight of the patient as compared to the haridra alone [ 45 ].

Antihyperlipidemic activity

Pendurkar and Mengi evaluated the antihyperlipidemic activity of aqueous extract of Plumbago zeylanica L. roots in diet-induced hyperlipidemic rats. Ameliorated effect in hyperlipidemic condition was displayed by lowering of cholesterol and triglyceride levels on oral administration of the extract at the doses of 20, 40, and 80 mg kg − 1 . Similar effects were also obtained with standards fenofibrate (20 mg kg − 1 ) and atorvastatin (8 mg kg − 1 ). In addition, significant reduction in the total lipid content in the liver was also noted with the extract. Results obtained demonstrated the beneficial role of aqueous extract of Plumbago zeylanica L. roots in hyperlipidemic condition [ 46 ].

Hepatoprotective activity

Kanchana et.al, reported hepatoprotective activity of petroleum ether extract of Plumbago zeylanica L. roots against paracetamol induced liver damage. Various biochemical parameters were studied to evaluate the hepatoprotective activity. Elevated levels of markers in the animals treated with paracetamol confirmed the severe hepatic damage by paracetamol. Following the administration of extract, significant reduction was noted in the serum markers indicating the effect of the extract in restoring the normal functional ability of the hepatocytes. The study concludes the petroleum ether extract of Plumbago zeylanica L. root could provide a significant protection against paracetamol-induced hepatocellular injury [ 47 ].

Wound healing activity

Plumbago zeylanica L. has been widely recommended for its wound healing potential in the traditional system of medicine. Kodati et al., reported significant wound healing activity of methanolic extract of Plumbago zeylanica L. roots in wistar rats. For the evaluation of wound healing activity, 10% (w/w) extract ointment was applied on the wound surface. It was found that the wound contracting ability of the extract treated rats displayed significant wound healing from the sixth day onwards. The wound closure time was lesser, as well as the percentage of wound contraction was more with the extract. Moreover, the extract treated groups demonstrated complete healing of wound in 16 days whereas the control group showed epithelization in more than 20 days [ 48 ].

Furthermore, in another study Jyothi and collegues investigated wound healing potential of the ethanolic root extract of Plumbago zeylanica L. Study indicated the increased wound healing activity of the ethanolic root extract might be attributed to the presence of phytoconstituents (alkaloids, terpenoids, flavonoids etc.) which may act individually or have additive effect [ 49 ].

Nephroprotective activity

Rajakrishnan and coworkers studied the nephroprotective effect of hydroalcoholic extract of Plumbago zeylanica L. ( HAPZ) roots in cisplatin-induced nephrotoxicity in Swiss albino mice. Study revealed that, high dose (400 mg/kg) administration of HAPZ significantly reversed the adverse effect of cisplatin on kidney weight, serum urea and creatinine, and displayed the renoprotective effect of HAPZ. The results of the study supports nephroprotective effect of hydroalcoholic extract of Plumbago zeylanica L. [ 50 ] .

Antifertility activity

Edwin and co-workers assessed antifertility potential of extracts of Plumbago zeylanica L. leaves. They studied the effect of petroleum ether, chloroform, acetone, ethanol and aqueous extracts on the estrous cycle of rats at the doses of 200 and 400 mg/kg. The acetone and ethanol extracts were found to be more promising in interrupting the estrous cycle of the rats. It was observed that, the anti-ovulatory activity reversed on discontinuation of treatment. Therefore, the study suggests the antifertility potential of acetone and ethanolic extracts of Plumbago zeylanica L. leaves [ 51 ].

In another study, Vishnukanta and Rana evaluated antiimplantation activity of hydroalcoholic extract of Plumbago zeylanica L. leaves. The estrogenic/antiestrogenic activity of the extract was studied on immature ovariectomized female wistar rats for 1–7 days of post-coitum. Significant antiimplantation activity was noted at the dose of 200 mg/kg. Extract showed antiestrogenic activity and caused overall structural and functional changes in uterus [ 52 ].

Anticancer and cytotoxic activity

Plumbago zeylanica L. reported to possess number of phytoconstituents that have cytotoxic activity. Plumbagin is one of the major bioactive widely investigated for anticancer and cytotoxic potential. Eldhose et.al, studied the potential of plumbagin against colon cancer cells. Study examined the proliferation and survival of colon cancer cells in attached culture conditions i.e. experimental conditions resembling the environment in primary tumors and in unattached conditions i.e. circulating tumor cells. Observations showed the exposure of HCT116 cells to plumbagin in the low micromolar concentrations in both the experimental conditions resulted in cell cycle arrest at the G1 phase, apoptosis via the mitochondrial cell death pathway, and enhanced production of reactive oxygen species. The cell cycle effects were more significant in attached cells, whereas the induction of cell death was more noticeable in unattached cells. Study findings displayed that plumbagin lacks toxicity on normal colon cells and showed its striking anti-survival effect on colon cancer cells [ 53 ].

Many researchers have also reported in-vitro anticancer activities of extracts derived from Plumbago zeylanica L . In an experimental study, Mani and Jayachitra investigated anticancer effect of ethanolic extract of Plumbago zeylanica L. (EEPZ) leaves against the standard 5-Fluorouracil (20 mg/kg). The EEPZ was administered orally to the tumor-bearing group at doses of 200 mg/kg and 400 mg/kg body weight for 14 consecutive days. It was found that both doses of EEPZ evidentially reduced average body weight, decreased viable tumor cell count for packed cell volume (PCV), and increased mice’s lifetime for DAL treatment, with a reduction in blood flows, serum enzymes and lipid profile close to normal values [ 54 ]. Furthermore, Kumar et.al evaluated cytotoxicity activity and compared the toxicity potential of the Plumbago zeylanica L. roots petroleum ether (PZPE), acetone (PZAC) and hydroalcoholic (PZHA) extracts in rodents. According to OECD guidelines 425 and 407, acute and sub-acute toxicities of the extracts in female rats was evaluated. Study revealed PZPE was more toxic than PZAC and PZHA, based on LD 50 values. The observed difference was attributed to the plumbagin content of extracts. Sub-acute toxicity study displayed significant increase in organ weights (liver, adrenal glands, and/or heart) in PZPE and PZAC treated groups. Whereas all the extracts showed significant rise in serum aspartate aminotransferase and urea. PZAC produced a remarkable increase in serum creatinine as compared to control. Moreover, reduction in hematocrit was observed in the highest dose PZPE group, and a decrease in leukocytes was observed in all PZAC groups. Hepatic and renal changes were also noticed in all extract treated groups. Study suggests liver and kidney are the primary organs being adversely affected following sub-acute administration of Plumbago zeylanica L. root extract [ 55 ]. In a recent study, Tokarz et.al, investigated survival strategy of Plumbago zeylanica L. to the lead toxicity via photosynthetic apparatus acclimatization. Study revealed the plants acclimate to lead toxicity by Pb accumulation in roots [ 56 ].

Anthelmintic activity

Desai and associates evaluated anthelminitic effects of aqueous and methanolic extract of Plumbago zeylanica L. roots at the concentrations of 5, 10, 15 and 20 mg/ml against the standard Piperazine citrate. Results were assessed in respect of time for paralysis and time for death of worms. Significant effect was recorded with methanolic extract as compared to aqueous extract [ 57 ]. Furthermore, in another study Weldemariam et.al, investigated anthelmintic potential of chloroform and ethanolic extracts of Plumbago zeylanica L. roots in both crude and fractions . Both crude and fractions paralyses and killed the worms in lesser time than that of the positive control. Chloroform extracts demonstrated significant results as compared to ethanolic extract. These significant findings suggests the long lasting use of this plant for helminthes [ 58 ].

Plumbago zeylanica L. contain a wide range of phytoconstituents like flavonoids, alkaloids, glycosides, saponins, steroids, tannins, triterpenoids, coumarins and phenolic compounds which have been found to be beneficial in the prevention and treatment of various diseases, including cancer, and also to have antimicrobial [ 26 ], antihyperlipidemic [ 46 ], antiulcer [ 44 ], hepatoprotective [ 47 ], antioxidant [ 38 ], anti-inflammatory [ 36 ], antihyperglycemic [ 42 ] and wound healing properties [ 48 ]. Encouragingly, current review discusses several promising pharmacological activities, which are intrigued by extensive variety of potential phytoconstituents of Plumbago zeylanica L .

Plumbago zeylanica L. was reported to possess protective effects against hepatotoxicity [ 47 ]. Treatment with paracetamol is potentially ascribe to hepatic injury inducing necrosis and inflammatory reactions due to the disruption of hepatocyte [ 59 ]. Plumbago zeylanica L. was found to maintain membrane integrity and limit the leakage of hepatic enzymes [ 41 ]. Scientists discovered that flavonoids, among the plant metabolites have an effect on cancer cells and inhibit their proliferation [ 60 ]. Assuredly, having ample flavonoids would possibly lead Plumbago zeylanica L. to exhibit antiproliferative activity.

Phytoconstituent showing toxicity may be a major concern of researchers and our reviewed plant was found to indicate cytotoxicity that is most frequently associated with chemoprevention. The cytotoxic activity of this plant may be mainly attributed to the plumbagin, which was previously reported as anticancer agent [ 55 ]. Some of the phytoconstituents, viz. tannins, flavonoids, terpenoids, and alkaloids, are indicated for antimicrobial activity [ 26 , 27 ]. Noteworthy, the reviewed plant contains plumbagin, which is a pharmacologically active naphthoquinones that has displayed antimicrobial property earlier [ 28 , 61 ]. Besides, it is profoundly enriched with terpenoids and henceforth may be leading to a remarkable antibacterial activity.

Several investigations disclosed hypoglycemic potentials of Plumbago zeylanica L. Moreover, stem bark of this plant contains two promising phytoconstituents; specifically, β-sitosterol and stigmasterol, which could be the contributive to hypoglycemic potential [ 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. Presence of these two constituents, β-sitosterol and stigmasterol, which play a significant role in glucose metabolism, might be accountable for the degradation of incretins like glucagon-like peptide. Earlier reports recommend that the reviewed plant exhibit potent anti-oxidant activity. It is well established that oxidative damage to biomolecules, due to the overproduction of free radical plays a vital role in the etiology of various diseases such as atherosclerosis, cancer, diabetes, rheumatoid arthritis etc. [ 62 ]. Scavenging of a large range of free radicals including the most active hydroxyl radicals, which initiate lipid peroxidation process also displayed by the Plumbago zeylanica L. [ 63 ].

Admittedly, Plumbago zeylanica L. can be considered as a versatile plant having a plethora of medicinal activities. This plant is distinctive source of a large range of compounds having diverse therapeutic properties. The current information relating to this medicinal plant could serve as the baseline knowledge to enforce to do in depth studies for the discovery of new potent compounds and more investigations for their biological activities.

Conclusion and future perspectives

The present review investigated the traditional medicinal uses, phytochemical profile and pharmacological properties of Plumbago zeylanica L. The retrieved data documented that Plumbago zeylanica L is a good source of diverse phytoconstituents and has tremendous therapeutic properties. Major constituents reported in the plant were flavonoids, alkaloids, glycosides, saponins, steroids, tannins, triterpenoids, coumarins and phenolic compounds. Literature indicates its huge utility towards numerous diseases including cardiovascular disorders, ulcer, liver problems, diabetes, obesity, wound healing, cancer etc. The work reviewed substantiated most of the traditional claims on its health benefits. But as seen during literature search it was found that major work has been done on extracts therefore, there is need for future investigations to isolate and characterize pharmacologically active agents that confer medicinal properties on Plumbago zeylanica L., as well as elucidate the structures of these agents, their pathways by which they exert their healing properties and to scientifically validate the prevailing ancient practices regarding its health benefits. Besides, the isolation studies can help to leverage the pharmacological attributes while reducing the side effects.

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Shukla, B., Saxena, S., Usmani, S. et al. Phytochemistry and pharmacological studies of Plumbago zeylanica L.: a medicinal plant review. Clin Phytosci 7 , 34 (2021). https://doi.org/10.1186/s40816-021-00271-7

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Article Contents

Introduction, antioxidant compounds in banana fruits, carotenoids, phenolic compounds, health benefits of bioactive components in banana fruits.

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Bioactive compounds in banana fruits and their health benefits

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Jiwan S Sidhu, Tasleem A Zafar, Bioactive compounds in banana fruits and their health benefits, Food Quality and Safety , Volume 2, Issue 4, December 2018, Pages 183–188, https://doi.org/10.1093/fqsafe/fyy019

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Banana is an edible fruit and is herbaceous flowering plant belonging to the genus Musa and the family Musaceae . Banana is also eaten as cooked vegetable (and is then called plantains). All the edible banana fruits are seedless (parthenocarpic) and belong to two main species, Musa acuminata Colla and Musa balbisiana Colla. The hybrid from these two species Musa x paradisiaca L. is also available nowadays. Although banana is native to Indomalaya and Australia, Papua New Guinea was the first to domesticate this fruit. Banana has now spread to almost 135 countries around the world. As per 2016 data, nearly 28 per cent of the total world’s banana production comes from India and China. Cavendish group banana, being the main export item from the banana-exporting countries, usually refers to soft, sweet, and dessert banana in the Western countries, but the plantain bananas have firm, starchy fruit which is suitable for cooking as a vegetable. Banana is known to be rich not only in carbohydrates, dietary fibres, certain vitamins and minerals, but is also rich in many health-promoting bioactive phytochemicals. General composition including various bioactives and their health contributions has been reviewed in this paper.

The consumption of fruits and fruit products is known not only to promote general good health but also lower the risk of various chronic diseases, such as heart diseases, stroke, gastrointestinal disorders, certain types of cancer, hypertension, age-related macular degeneration, cataract of the eye, skin conditions, lowering of low-density lipoprotein (LDL) cholesterol, and improved immune function. To promote healthy eating lifestyle, the USDA recommends filling up half the plate with fruits and vegetables, because these provide a good amount of dietary fibres, certain vitamins ( e.g . ascorbic acid, folic acid, and vitamin A precursors), many minerals ( e.g . potassium, magnesium, iron, and calcium), and many other important phytochemicals having strong antioxidative properties. Fruits make an important part of the balanced diet adopted by the humans. USDA recommends daily five servings of fruits to obtain most of the health benefits. Depending upon their origin and production area temperature, fruits are classified into temperate fruits, sub-tropical fruits, and tropical fruits. Banana belongs to the tropical fruits as it grows more profusely in tropical rain forest areas. Interestingly, banana fruit has flesh not only rich in starch which changes into sugars on ripening but is also a good source of resistant starch. Banana is known to be rich in carbohydrates, dietary fibres, certain vitamins, and minerals ( Table 1 ). The presence of various bioactive phytochemicals and their nutritional significance has been discussed in this review paper ( Figure 1 ).

Chemical composition of banana fruit (as is basis per 100 g)

Adopted from: Wikipedia, Internet, USDA databases.

Banana tree and banana fruits of various maturities. (Source: Internet Wikipedia.)

The reactive oxygen species (ROS) and reactive nitrogen species (RON), such as hydroxyl radicals, superoxide ions, nitric oxide radicals, and singlet oxygen and hydrogen peroxide, have now been implicated in the causation of many disorders like arthritis, diabetes, arteriosclerosis, age-related macular degeneration, certain types of cancer, inflammation, genotoxicity, and Alzheimer disease. The exact mechanism is not known but the reaction of these ROS and RNS species with biomolecules such as lipids, proteins, and DNA may be the cause of these disease conditions ( Shukla et al ., 2009 ; Septembre-Malaterre et al ., 2016 ). Kandaswamy and Aradhya (2014) have shown the banana rhizome to be a rich source of many polyphenolic compounds having antioxidant activities. Pazmino-Duran et al. (2001) have suggested the use of anthocyanins from banana bracts (florets) as natural colourants. They identified various anthocyanins such as cyanidin-3-rutinoside (main one as 80 per cent of total pigments, being 32.3 mg/100 g) and 3-rutinoside derivatives of delphinidin, pelargonidin, peonidin, and malvidin. Interestingly, the addition of heat-treated onion extract was found to inhibit the polyphenol oxidase (PPO) during ripening of banana fruit at room temperature ( Lee, 2007 ). Even the Maillard reaction products (MRP) significantly affected the banana PPO activity. The phytochemistry and pharmacology of wild banana ( Musa acuminata Colla) have been reviewed by Mathew and Negi (2017) and they suggested the use of banana pulp and peel for the development of drugs and use in functional foods.

Not only banana pulp, but pseudo stem and banana fruit peel have been found to be the good sources of antioxidants ( Table 2 ). Aziz et al . (2011) have analysed the native banana pseudo-stem flour (NBPF) and tender core of pseudo-stem flour (TCBPF) for chemical and functional properties. They found higher content of polyphenols, flavonoids, total dietary fibre, insoluble dietary fibre, lignin, hemicellulose, cellulose, antioxidant capacity, and free-radical scavenging capacity in NBPF than TCBPF. In exhaustive reviews, Pereira and Maraschin (2015) and Singh et al . (2016) have reported that banana is rich in many bioactive compounds, such as carotenoids, flavonoids, phenolics, amines, vitamin C, and vitamin E having antioxidant activities to provide many human health benefits. Recently, Vu et al . (2018) have also reviewed the phenolic compounds and their potential health benefits coming from banana peel. They have suggested the use of this valuable by-product from banana fruit processing industry in food and pharmaceutical industry. Anyasi et al . (2018) have analysed the essential macro and trace minerals as well as phenolic compounds in unripe banana flour obtained from the pulp of four cultivars treated with ascorbic, citric, and lactic acids before drying in a forced air dryer at 70°C. Results of their liquid chromatography-mass spectrometry-electrospray ionization (LC-MS-ESI) assay of phenolics revealed the presence of two flavonoids, epicatechin and 3-O-rhmnosyl-glucoside in varying concentrations. Among the essential minerals, zinc had the lowest concentration of 3.55 mg/kg, but the potassium was the highest, 14746.73 mg/kg in these cultivars.

Antioxidant activity, total polyphenol, and individual polyphenolic compounds present in organic acid treated (20 g/l) unripe banana flour

Means with different letters across rows are significantly different at P < 0.05. Values are Means ± SE of triplicate measurements. DPPH, 1,1-diphenyl-2-picrylhydrazyl. (Adopted and modified from Anyasi et al ., 2018 .)

Carotenoids is a class of compounds having some 600 members in this family. Some of these are precursors for vitamin A, and others are known to have strong antioxidant capacity to scavenge ROS. Among the carotenoids present in banana fruit, α-carotene, β-carotene, and β-cryptoxanthin have provitamin A activity, but others like lycopene and lutein have a strong antioxidant capacity ( Erdman et al ., 1993 ). Lycopene is known to provide protection against prostate cancer among men, and lutein offers human health benefits to serve as an inhibitor of age-related macular degeneration ( Davey et al ., 2006 ). Later, Davey et al . (2009) have analysed 171 different genotypes of Musa spp. for provitamin A carotenoids and 47 genotypes for two minerals (iron and zinc). They found a great variability in provitamin A among the various cultivars, but a low variability in iron and zinc, irrespective of the soil type and growing environmental conditions. They suggested the use of high provitamin A and trace mineral cultivars as development strategies to improve the nutritional health and alleviation of micronutrient deficiencies among the Musa -consuming populations.

Yellow- and orange-fleshed banana cultivars are known to be richer in trans-β-carotene content ( Englberger et al ., 2006 ). Carotenoid content of some of the banana cultivars is presented in Table 3 . Consumption of fruits rich in carotenoids is reported to boost immunity and reduce the risk of various diseases, such as cancer, type II diabetes, and cardiovascular problems ( Krinsky and Johnson, 2005 ). Certain banana cultivars rich in provitamin A carotenoids can be grown and consumed by the poor population of the world that is having serious vitamin A deficiency, and the consumption of such banana fruit would alleviate vitamin A deficiency ( Fungo and Pillay, 2013 ).

Carotenoid content of different banana cultivars (µg/100 g)

Source: Adopted and modified from: Singh et al ., 2016 .

Phenolics present in banana fruit are the major bioactive compounds having antioxidant properties and are known for providing health benefits ( Table 4 ). Various phenolics present in banana have been identified as follows: gallic acid, catechin, epicatechin, tannins, and anthocyanins. Banana rhizome is used as food and for medicinal properties as well in South India as it is very rich in phenolics ( Kandasamy and Aradhya, 2014 ). Russel et al . (2009) have detected many phenolics in banana, such as ferulic, sinapic, salicylic, gallic, p-hydroxybenzoic, vanillic, syringic, gentisic, and p-coumaric acids as major components. However, ferulic acid content was the highest (69 per cent of cinnamic acids) among these phenolics. Banana peel is also a rich source of phenolic compounds. Tsamo et al . (2015) analysed banana pulp and peel from nine plantain cultivars and two dessert banana cultivars. According to their results, hydroxycinnamic derivatives, such as ferulic acid-hexoside, were the major ones (4.4–85.1 µg/g DW) in plantain pulp. They observed large variations in the phenolic contents among the cultivars tested. In the peel from plantain cultivars, rutin was the most abundant flavonol glycoside (242.2–618.7 µg/g DW). Thus, the banana peel and pulp both are good sources of health-promoting phenolic compounds. Among the flavonoids detected in banana are as follows: quercetin, myricetin, kaempferol, and cyanidin which provide health benefits mainly because they act as free radicals, ROS, and RNS scavengers ( Kevers et al ., 2007 ). Most of these phenolics are known to also exhibit antibacterial, antiviral, anti-inflammatory, antiallergenic, antithrombotic, and vasodilatory activities ( Cook and Sammon, 1996 ). Sulaiman et al . (2011) have determined the total phenolic and mineral contents in pulp and peel from eight banana ( Musa spp.) cultivars grown in Malaysia. With a few exceptions, the peel extracts had the higher total phenolics and total antioxidant activities than the pulp. Among minerals, potassium was the major element found in both the peel and pulp followed by phosphorus, magnesium, and sodium.

Uses and health benefits of bioactive compounds in banana

Health benefits of phenolics

A flavonoid, leucocyanidin, has been identified as a predominant component of aqueous extract of unripe banana pulp that showed significant anti-ulcerogenic activity ( Lewis et al ., 1999 ). Thus, many flavonoids, especially leucocyanidin analogues, may offer immense therapeutic potential in the treatment of gastric disease conditions.

The structure–activity relationship of flavonoids indicates that their antioxidant capacity, scavenging free radicals, and chelating action are related to the presence of functional groups in their nuclear structure ( Heim et al ., 2002 ). They also attributed most of the health benefits from the consumption of flavonoids to their antioxidant and chelating properties. Because of these properties, flavonoids are also shown to exhibit antimutagenic and antitumoral activities ( Rice-Evans et al ., 1996 ). The flavonoids can also inhibit many enzymes, such as oxygenases (prostaglandin synthase), required in the synthesis of eicosanoids. Thus, the flavonoids inhibit hyaluronidase activity and help in maintaining the proteoglycans of connective tissues. This would prevent the spread of bacterial or tumour metastases ( Havsteen, 2002 ). As the flavonoids get preferentially oxidized, they are reported to prevent the oxidation of body’s natural water-soluble antioxidants like ascorbic acid ( Korkina and Afanas’ev, 1997 ). Generally, after the consumption of banana fruit, the peel ends up as a feed for the animals only. The disposal of peel (pomace) and other by-products from banana-processing industry causes a serious environmental problem ( Zhang et al ., 2005 ). Banana peel is reported to be rich in many high-value health-promoting antioxidant phytochemicals, such as anthocyanins, delphinidin, and cyanidins ( Seymour, 1993 ). In a recent study, Rebello et al . (2014) have also shown the banana peel extract to be a rich source of total phenolics (29 mg/g as GAE), which are responsible for the very high antioxidant activity. They also determined various other antioxidant compounds, namely, highly polymerized prodelphinidins (~3952 mg/kg), flavonol glycosides (mainly 3-rutinosides and predominantly quercetin-based compounds, ~129 mg/kg), B-type procyanidin dimers, and monomeric flavan-3-ols (~126 mg/kg).

Health benefits of biogenic amines

Banana peel and pulp are known to be good sources of certain biogenic amines (catecholamines) which are produced by the decarboxylation of amino acids or by the amination of aldehydes and ketones. Catecholamines include dopamine, serotonin, epinephrine, and norepinephrine and are reported to occur in many plants in considerable amounts ( Ponchet et al ., 1982 ). In animals, these biogenic amines are reported to work as neurotransmitters for the hormonal regulation of glycogen metabolism ( Kimura, 1968 ). When banana is consumed by humans, serotonin present in the pulp (ranging from 8 to 50 µg/g) creates a feeling of well-being and happiness. Banana contains a large amount of dopamine and norepinephrine ( Buckley, 1961 ). Waalkes et al . (1958) were the first to report the amount of various catecholamines in banana pulp as follows: serotonin, 28 µg/g; norepinephrine, 1.9 µg/g; and dopamine, 7.9 µg/g. The concentrations of dopamine in the pulp of yellow banana ( M. acuminata ), red banana ( Musa sapientum ), and plantain has been reported to be 42, 54, and 5.5 µg/g, respectively ( Feldman et al ., 1987 ). They highlighted the role of dopamine in human brain and body as a neurotransmitter having a strong influence on mood and emotional stability. Dopamine in the peel and pulp of commercially ripened Musa Cavendish is reported to range from 80 to 560 mg/100 g, and 2.5 to 10 mg/100 g, respectively ( Kanazawa and Sakakhibara, 2000 ). Tryptophan being one of the precursors for the synthesis of dopamine, the presence of this amino acid in banana peel increases the interest in possibilities of preventing neurodegenerative diseases like Parkinson’s using this by-product of food-processing industry by developing pharmaceutical formulations. However, the increase in dopamine content from unripe to the ripened stage in both the peel and pulp has been reported by many workers ( Romphophak et al ., 2005 ; Gonzalez-Montelongo et al ., 2010 ). They also suggested that the decline in dopamine concentration during over-ripening stage may be due to its oxidation to quinones which may further polymerize to melanin pigments.

Using peroxide value and thiobarbituric activity determination, the antioxidant compounds present in water extract of banana peel have shown to suppress the autooxidation of linoleic acid by 65 to 70 per cent after 5 days of incubation ( Kanazawa and Sakakhibara, 2000 ). When they compared dopamine with other natural antioxidants, such as ascorbic acid, reduced glutathione, and phenolic acids ( e.g. gallocatechin gallate), the dopamine showed higher antioxidant activity in vitro (DPPH assay). Gonzalez-Montelongo et al . (2010) have reported the banana peel extracts to be rich in dopamine, L-dopa, and catecholamines with a significant antioxidant capacity. They found no significant difference in the antioxidant activity in the banana peel extracts from different cultivars. The biogenic amines are also shown to play an important role in offering plants’ resistance to various invading pathogens through their interaction with phytohormones ( via auxin oxidation), thus affecting the growth and development of plants ( Newman et al ., 2001 ; Roepenack-Lahaye et al ., 2003 ).

Health benefits of phytosterols

These naturally occurring plant sterols have attracted the attention of food manufacturers to produce functional foods having higher health benefits. Because of their structural similarity with cholesterol, they compete with cholesterol for absorption in the gut, thus lowering the blood cholesterol levels ( Marangoni and Poli, 2010 ). They reported that a daily intake of 3 g of phytosterols results in marked reduction of LDL cholesterol levels. Various phytosterols reported in the banana peel are stigmasterol, -sitosterol, campesterol, 24-methylene cycloartenol, cycloeucalenol, and cycloartenol ( Knapp and Nicholas, 1969 ). Now the health professionals recommend the consumption of plant sterols–rich diet to lower the LDL cholesterol in patients who do not tolerate cholesterol-lowering statin drugs ( Ostlund et al ., 2003 ). Banana fruit has been shown to contain a good amount of phytosterols both in the peel and pulp ( Akihisa et al ., 1986 ). The phytosterols content in unripe banana in the range of 2.8 to 12.4 g·kg DW has been reported by Vilaverde et al. (2013) . According to their results, the Musa balbisiana cultivars, such as ‘Dwarf Red’ and ‘Silver’, had higher amounts of phytosterols than the M. acuminata cultivars. The lipophilic extract of ripe banana pulp from several cultivars of the M. acuminata and M. balbisiana species has been found to be a source of ω-3 and ω-6 fatty acids, phytosterols, long-chain aliphatic alcohols, and α-tocopherol, thus offering well-established nutritional and health benefits ( Vilela et al ., 2014 ).

The above discussion brings out the importance of consuming banana fruits for obtaining various health benefits. It is not only the banana fruit pulp, but also the peel of this fruit is known to contain many important phytochemicals and offers many health benefits. More research is needed to be carried out to find ways of using banana fruit peel in the development of many new functional foods.

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Investigation of the interaction of promethazine hydrochloride drug with tetradecyltrimethylammonium bromide: Impacts of hydrotropes composition and temperature

• Original Paper
• Published: 05 June 2024

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• Afzal Hosaain Shah 1 ,
• Md. Tuhinur R. Joy 2 ,
• Sharifur Rahman 1 ,
• Md. Ruhul Amin 1 ,
• Javed Masood Khan 3 ,
• Dileep Kumar   ORCID: orcid.org/0000-0003-2913-5032 4 , 5 ,
• Md Abdul Goni 6 ,
• Md. Anamul Hoque 1 &
• Mahbub Kabir 1  

Herein, the micellization characteristics of tetradecyltrimethylammonium bromide (TTAB) and promethazine hydrochloride (PMH) mixtures have been explored in the presence of various hydrotropes (HyTs) (sodium salicylate (NaS), sodium benzoate (NaB), and p-amino benzoic acids (4-AmBA)) by applying the conductivity measurement method. The investigation was carried out by varying the composition of HyTs at definite temperature as well as variable temperatures while the composition of HyTs remained unchanged. The influences of hydrotropes and temperatures on the micellization of TTAB and PMH mixture have been examined from the changes in physico-chemical parameters of the respective system with the variation in composition/nature of HyTs and temperatures. A single critical micelle concentration (CMC) was noted for the employed drug + surfactant mixture in the appearance of HyTs. The introduction of NaS disrupted the micelle development whereas the presence of NaB and 4-AmBA promoted micelle formation in TTAB and PMH mixtures. At 6 mmol kg −1 concentration of HyTs, the magnitudes of CMC demonstrated the order of CMC as (aq. NaS) \(> \text{CMC }\left(\text{aq}.\text{ NaB}\right)>\text{ CMC }\left(\text{aq}. 4-\text{AmBA}\right).\) The CMC values of PMH + TTAB mixtures showed significant changes with the augmentation of temperatures. The appearance of negative \({\Delta G}_{m}^{0}\) apparently indicating the spontaneous nature of aggregation of surfactant species. Other thermodynamic parameters such as enthalpy change ( \({\Delta H}_{m}^{0}\) ), entropy change ( \({\Delta S}_{m}^{0}\) ), molar heat capacity ( \({\Delta C}_{m,P}^{0}\) )), thermodynamics of transfer and enthalpy-entropy compensation quantities have also been determined and the results were described in detail. The interaction forces among the components within the studied system were found to be electrostatic and hydrophobic in nature.

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Authors are grateful to the Researchers Supporting Project number (RSP2024R360), King Saud University, Riyadh, Saudi Arabia.

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Shah, A.H., Joy, M.T.R., Rahman, S. et al. Investigation of the interaction of promethazine hydrochloride drug with tetradecyltrimethylammonium bromide: Impacts of hydrotropes composition and temperature. Chem. Pap. (2024). https://doi.org/10.1007/s11696-024-03523-1

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June 4, 2024

Winning papers announced for 2024 Population Health Library Research Awards

This award was created in 2017 in partnership with the University of Washington Libraries and is open to undergraduates from all three UW campuses. The projects submitted were completed for either UW course credit or for the Undergraduate Research Program.

The key factors for choosing awardees included the innovativeness of their research hypothesis, the quality of their writing and how well they connected their work to the theme of population health. The following section describes the four awardees, their majors, the titles of their projects and summaries of their projects.

Lindsay Lucenko (Law, Societies, and Justice), "Gender Dynamics in King County Drug Diversion Court: Exploring Experiences and Perspectives"

This research explores the experiences of men and women in the King County Drug Diversion Court, a rehabilitative program for drug-related offenses. Participants undergo a five-phase program with the potential for charge dismissal, but concerns about coercion persist. Participants must maintain sobriety, undergo frequent tests, attend support meetings, communicate with case managers, find employment, and fulfill familial duties.

The study investigates how gender influences these obligations’ fulfillment, especially considering the court’s predominantly male population. Through nine semi-structured interviews, I examined participants’ experiences with the criminal justice system, focusing on gender impacts. Findings reveal nuanced gendered experiences, informing justice system reform. By combining qualitative interviews and existing research, this study sheds light on gender dynamics within the court, contributing to policy and practice for a fairer criminal justice system.

Evelyn Erickson (Chemical Engineering), "Tandem dechlorination and hydrogenolysis of waste PVC plastic into value added chemicals "

Plastic waste is a serious problem with detrimental environmental impacts, within this mixed plastics pose a significant challenge in depolymerization. My project focuses on polyvinyl chloride (PVC), a particularly difficult plastic to break down due to the chlorine atom. Chlorine can poison catalysts and release harmful by products like hydrochloric acid or chlorine gas.

I have been working to dechlorinate PVC and then further break down this waste plastic to form value added products. Once dechlorinated PVC becomes a hydrocarbon and can be treated similar to other waste plastics like polyethylene and polypropylene. This tandem dechlorination and depolymerization occur in a single step through a strong amine base and ruthenium catalyst helping to activate the reaction.

Nede Ovbiebo (Pre-science - Biochemistry), "What are the health outcomes of phytochemical supplements versus fruits and vegetables?"

This research stems from concerns about the efficiency of modern diets, which increasingly rely on supplements rather than natural food sources. I analyzed data and reviewed information to compare the effectiveness of phytochemical supplements and whole fruits and vegetables. The study emphasized that while phytochemicals are used in various therapies, their individual effects cannot be compared to the combined benefits of whole foods based on current scientific developments. I have placed the results in a booklet to be printed and disseminated in the future to enable more people to plan their diets wisely and incorporate phytochemicals flexibly into their daily routines.

Hayden Goldberg (Public Health-Global Health, Biochemistry), "An Evaluation of Agricultural Safety and Health in Pesticide Application Technology"

The use of pesticides in the Pacific Northwest is essential in the process of safeguarding public health, most notably by mitigating pests, protecting our food supply, and aiding in produce distribution. However, long-term exposure to pesticides can result in illness for those handling the substances as well as their families. Newer methods, such as aerial drone spraying involve the use of emerging technologies that are poised to change the landscape of the agricultural industry and health outcomes of farmworkers.

This project will be assessing thoughts regarding adoption of these technologies. Through the creation of an electronic survey, I will be obtaining a variety of responses from individuals involved in the application of pesticides on farms. I will then analyze responses both quantitatively and qualitatively. The main objective of my research project is to capture the attitudes of the pesticide application technologies to inform policy, regulations, and decision-making regarding their uses.

Please visit our funding page to learn more about these awards.

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