Phytochemistry and Biological activity of Vitex rotundifolia L.

 

Gul-e-Saba Chaudhry¹*, Muhammad Naveed Zafar², Yeong Yik Sung¹

 Tengku Sifzizul Tengku Muhammad¹

¹Institute of Marine Biotechnology, Universiti Malaysia Terengganu, 21030, Malaysia.

²Department of Chemistry, Quaid-i-Azam University, Islamabad, 45320, Pakistan.

 

ABSTRACT:

Natural products play an important role in the treatment of a variety of diseases. Several medicinal plants were screened to study phytochemistry and biological activity against various diseases.  Amongst the coastal medicinal plants, Vitex rotundifolia (beach vitex) possessed potential phytochemical constituents. Chemical constituents of Vitex rotundifolia include phenolics, flavonoids, and terpenoids as major compounds present. Various flavonoids such as Vitexicarpin, 4-hydroxybenzoic acid methyl ester, vanillic acid methyl ester, 4-hydroxy benzaldehyde, luteolin, and artemetin were isolated from the leaves of Vitex rotundifolia. Similarly, different types of terpenoids that have been isolated from Vitex rotundifolia include Eurostoside, Iridolactone, Viteoid I, Viteoid II, Iridoid compounds such as 10-O-vanilloylaucubin, 10-O-p hydroxybenzoylaucubin and aucubin, Vitexifolin A, Vitexifolin B, Viterotulin A, and Viterotulin B have been isolated from Vitex rotundifolia. The pharmacological importance of Vitex rotundifolia is due to various biological activities such as anti-cancer, anti-inflammatory, anti-proliferative, anti-bacterial and anti-oxidant activities. Therefore, plant species Vitex rotundifolia, from genus Vitex was selected to discuss the phytochemicals present and its biological activity. However, remarkable anticancer activities of several compounds isolated from Vitex rotundifolia enriches its cancer therapeutics potential and demands for further exploration of mode and mechanism of cell death as part of preclinical trials.

 

 

 

INTRODUCTION:

Natural products and their derivatives play a vital role in the development of a variety of drugs.¹ Around 80% of the world's population still relies on natural products derived medicines for the treatment of a variety of ailments and 50% of all the drugs in use are derived from plant origin.^2,3 Over the past several decades, interest in the role of plant extracts as a source of therapeutic agents has increased all over the world. Several medicinal plants have been identified and show great potential in the field of pharmacology.

 

Marine organisms and terrestrial plants contain several chemically diverse compounds, which are beneficial to human health.^4-15 Due to the presence of secondary metabolites, natural products are considered important in screening potential compounds and drug discovery. Natural products active components, regardless of source (from marine organism or terrestrial plants) play a vital role in cancer therapy as they possess antitumor properties.^16-19 Various traditional healers and herbalists have been using several medicinal plant species for the treatment of cancer.²⁰  About 114,000 extracts from 35,000 plant species have been screened against several tumor systems by the National Cancer Institute (NCI), USA³.  Cancer is complex deadly disease and amongst the major causes of death.^21-22 There is an estimate of about 50% of the anticancer therapeutic agents are obtained from plants includes Taxol and Vinca alkaloids which are known to prevent the rapid proliferation of cancer cells.^4-5,23

 

Figure 1: Vitex rotundifolia, phytochemicals, and biological properties

 

Along with various carriers, natural product derived anticancer agents like paclitaxel shows effective cytotoxicity against various cancer cells.^24-25 It is now becoming clear that several natural products and their derivatives are potential therapeutic agents having the ability to target various molecular biomarkers,⁸ the same as a drug functions. 

 

Genus Vitex:

The genus Vitex includes about 270 known species distributed around the world.  This genus species are usually present in tropical and sub-tropical regions while a few species are also found in temperate zones⁵. Various species of Vitex have been studied for their pharmaceutical properties and biological activities, these include, V. agnus-castus, V. negundo, V. trifolia V. rotundifolia, V. gardneriana, V. ferrugenia, V. cannabifolia, V. doniana, V. polygama, V. leucoxylon, V. pinnata etc. The available literature reveals that V. agnus-castus Linn. and V. negundo Linn are used in medicine.²⁷ The studies conducted to date reveal that various potential biologically active compounds are present in species of genus Vitex, which possess analgesic, anti-inflammatory, anti-cancer, anti-microbial, anti-oxidant, anti-bacterial, anti-fungal, anti-histamine, and anti-asthmatic properties.^5,28

Table 1: Taxonomy of Vitex rotundifolia

 

Vitex rotundifolia:

The present study will primarily focus on Vitex rotundifolia from genus Vitex to provide an overview of chemical constituents isolated from the species and enlighten potential biological effects. Figure 1 shows the photochemistry and biological properties of Vitex rotundifolia.

 

Phytochemistry:

Various studies performed to investigate the presence of chemical constituents in Vitex rotundifolia suggest that phenolics, flavonoids, and terpenoid compounds are major compounds present in leaves and fruits Vitex rotundifolia. Table 2 summarizes the isolated compounds from Vitex rotundfolia.

 

 

Table 2: Compounds isolated from plant species Vitex rotundfolia

Phenolics and flavonoids:

Nine different phenolics and flavonoid compounds were isolated from leaves and fruits of Vitex rotundifolia.³² Vitexicarpin (flavonoid) was isolated from both leaves and fruits while 4-hydroxybenzoic acid methyl ester, vanillic acid methyl ester, 4-hydroxy benzaldehyde, 4-hydroxybenzoic acid, 5, 5’-dihydroxy-4’,6,7-trimethoxyflavanone and luteolin were isolated from fruits. Ferulic acid and artemetin were isolated from the leaves of Vitex rotundifolia.³²

 

Casticin (vitexicarpin), a flavonoid compound is considered as the major biologically active compound to be found in fruits of Vitex rotundifolia.³³ In another study from Japan, flavonoids compounds were isolated from leaves of Vitex rotundifolia and it was reported that 96.4–97.1% of total flavonoids generally found in V. rotundifolia plant species are luteolin type.³⁴ Two flavonoid compounds have been isolated from quercetagetin and penduletin have also been isolated from fruits of Vitex rotundifolia.^35-36

 

Terpenoids:

Different types of monoterpenoids that have been isolated from Vitex rotundifolia include 10-O-Vanilloyl aucubin, Eurostoside, Iridolactone, Viteoid I, Viteoid II, Pedicularis lactone, Eucommiol, and 1-Oxoeucommiol.^37-39 Iridoid compounds/ monoterpenoids such as 10-O-vanilloylaucubin, 10-O-p hydroxybenzoylaucubin and aucubin have been isolated from Vitex rotundifolia.⁴⁰ Diterpenes that have been isolated from the fruits of Vitex rotundifolia comprises of Vitexifolin A, Vitexifolin B, Vitexifolin C, Vitexifolin D, and Vitexifolin E.⁴¹ Rotundifuran, diterpene is also present in the leaves of Vitex rotundifolia.³⁸ Viterotulin A and Viterotulin B have been isolated from Vitex rotundifolia.⁴²

 

Other compounds:

Two C-glycoside flavones have been isolated from Vitex rotundifolia and are identified as vitexin and orientin.⁴⁰ Several iridoid glucoside, phenylbutanone glucoside, and agnuside are reported to be present in Vitex rotundifolia.³⁸ Several lignin compounds have been isolated from vitex rotundifolia which are identified as, Vitrofolal A, Vitrofolal B, Vitrofolal C, Vitrofolal D, Vitrofolal E, Vitrofolal F, Vitex lignin 7 and Vitex lignin 8.^43-44

 

Biological activities of Vitex rotundifolia:

Vitex rotundifolia has long been utilized for the treatment of a variety of diseases. Effective biological properties of Vitex rotundifolia include anti-cancer,^45-46 anti-inflammatory, anti-proliferative, anti-bacterial and anti-oxidant activities. 

 

Anti-inflammatory, anti-proliferative and anti-cancer activities:

Various studies were conducted to explore the potential activity of Vitex rotundifolia suggested the presence of biologically active compounds and among them, few compounds are reported to possess potential anti-cancerous activity. Polymethoxyflavonoids extracted from the fruit of V. rotundifolia, inhibits proliferation in human myeloid leukemia HL-60 cells in a dose-dependent manner.⁴⁷ In another study six polymethoxy flavonoids for test for cytotoxicity activity and out of them, four polymethoxy flavonoids (Oroxylin A, casticin, artemetin and 5,3′-dihydroxy-6,7,4′-trimethoxyflavanone) inhibit the proliferation of HepG2 cell line.⁴⁸ Vitexicarpin (Casticin), a flavonoid compound extracted from Vitex rotundifolia fruit exhibits anti-inflammatory, anti-proliferative and anti-cancer activity by inducing apoptosis in human prostate and gallbladder cancer cell lines.^35,49-50 Casticin is also a potent agent in decreasing the growth of human NSCLC cells, leukemia K562 cells and cervical cancer HeLa cells.^51-53 Moreover, growth inhibitory activity of casticin was also reported against human lung cancer cells and human colon cancer cells.⁴¹ Furthermore, casticin significantly inhibited cell proliferation in esophageal squamous cell carcinoma cell lines via inducing apoptosis.⁵⁴ Luteolin, flavonoid compound from Vitex rotundifolia (fruit), has been reported to induce apoptosis in human myeloid leukemia HL-60 cells.⁵⁵ Rotundifuran (diterpene) isolated from fruit extract showed anti-proliferative activity on human myeloid leukemia cells.⁵⁶ The essential oil obtained from the fruits of Vitex rotundifolia exhibited strong estrogenic activity on the proliferation of MCF-7 cells by proliferation assay method.²⁷  Acetone extract from Vitex rotundifolia exhibited the cytotoxic activity on the HT-29 cells in a dose-dependent manner with an IC₅₀ value of 10µg/ml.⁵⁷ Apoptosis is the fundamental mechanism of cell death.²¹ Vitex rotundifolia fruit extract has been reported to suppress the cell viability and induce apoptosis in human colorectal cancer cells, HCT116 and SW480 through the downregulation of ATF3-mediated Bcl-2 expression and by decreasing cyclin D1 and CDK4 via proteasomal-dependent degradation and transcriptional inhibition.^58-59 Vitexicarpin isolated from fruits of Vitex rotundifolia showed both anti-angiogenic and antitumor activities against hepatocellular carcinoma.⁶⁰ Our previous studies have shown that Vitex rotundifolia fractions induce apoptosis in the human breast cancer cell line, MCF-7 and T47D via extrinsic and intrinsic pathways.^45-46

 

 

Antibacterial, antioxidant activity, and other activities:

Various studies have been done to determine the biological activity of Vitex rotundifolia.  Phenylnaphthalene compounds isolated from Vitex rotundifolia possess antibacterial activity against Staphylococcus aureus.⁴⁴ Vitex rotundifolia has also shown antibacterial activity against Helicobacter pylori.⁶¹ Diterpenoid (ferruginol), isolated from fruit exhibit strong antioxidant activity. Also, extract prepared from twig and fruit of Vitex rotundifolia exhibit strong antioxidant activity.^27,32,40 VR-I (10-o-vanilloyl aucubin) a constituent of Vitex rotundifolia fruit was found to possess strong antioxidant activity.³² Vitex rotundifolia has long been used as a source of traditional medicine to treat migraine, night blindness, neuralgia, asthma, gastrointestinal infections, and bacterial dysentery.^40,41,43 Polyphenol, trans-resveratrol obtained from Vitex rotundifolia showed highly potent tyrosinase inhibition effect, so it can play an important role as anti-aging and skin-whitening agent.^44,61 Rotundial, a cyclopentene dialdehyde obtained from leaves of Vitex rotundifolia exhibits potent mosquito repellent activity against Aedes aegypti.⁶²  Vitex rotundifolia ethanol extract and other constituents possess the estrogenic activity and can be useful for the treatment of premenstrual syndrome.³³ Polyalthic acid isolated from the fruit of Vitex rotundifolia possesses antimutagenic activity.⁶³ Further screening and isolation of active compounds need to be done to explore the vast secondary metabolites that have the potential to be as future therapeutics. 

 

CONCLUSION:

The review enlisted the enormous potential for the Vitex rotundifolia to be developed as a potent therapeutic agent for a variety of diseases. Potent secondary metabolites such as phenolics, flavonoids, and terpenes have been identified as the major chemical constituents of Vitex rotundifolia. The various biological activities including anti-cancer, anti-inflammatory, anti-bacterial and anti-oxidant activities makes Vitex rotundifolia an excellent candidate with potential bioactivity. Therefore, plant species Vitex rotundifolia was selected to discuss the phytochemicals present and its biological activity. The phytochemicals play important role in development of drug therapeutics. Interestingly, due to presence of some compounds with potential anticancer activities empathize its anticancer potential and therefore effective need for further exploration of the underlying mechanism of anti-cancer drug therapeutic effect. 

 

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Received on 25.02.2020           Modified on 13.04.2020

Accepted on 29.05.2020         © RJPT All right reserved