Vitex negundo Linn; a Review on Its Ethnobotany, Phytochemical and Pharmacological Profile

AK Meena¹, Uttam S Niranjan²*, AK Yadav², Brijendra Singh², AK Nagaria², A Gaurav² and MM Rao¹

¹National Institute of Ayurvedic Pharmaceutical Research, Patiala – 147001, Punjab, (India).

²School of Pharmaceutical Sciences, Shobhit University, Meerut, UP, (India).

ABSTRACT:

Vitex negundo Linn. is an large shrubs or small trees which is used in several traditional medicines to cure various diseases. This shrub has been known to posses hepatoprotective, antioxidant, anti-inflammatory, analgesic and antifungal activity. A wide range of chemical compounds including polyphenolic, terpenoids , glycosidic iridoids and alkaloids are present in this shrubs. Vitegnoside, negundoside, agunside, 5,3-dihydroxy-7,8,4-trimethoxy flavanone, 7,8-dimethyl herbacetin 3-rhamnoside etc. have been isolated from this plant. The presented review summarizes the information concerning the botany, ethnopharmacology, phytpchemistry, biological activity and toxicity of the Vitex negundo shrubs.

KEYWORDS: Vitex negundo Linn, antioxidant, phytpchemistry, anti-inflammatory, toxicity.

INTRODUCTION:

1. Occurrence, botanical description and ethnopharmacology

Vitex negundo Linn., Verbenaceae, known as Nirgundi in Hindi, grows gregariously in wastelands and is also planted as a hedge-plant. It is an erect, 2–5 m in height, slender tree with quadrangular branchlets distributed throughout India. The leaves have five leaflets in a palmately arrangement, which are lanceolate, 4–10 cm long, hairy beneath and pointed at both ends. The bluish purple flowers are numerous. The fruit is succulent, black when ripe, rounded and about 4 mm in diameter^1,2. It is known by various names e.g. Nirgundi, Sugandhika, Sinduka, Indranika, Sinduvara. Various vernacular names, Five Laved chest tree in English, Samhalu, Nirgand, Shivari in Hindi, Nishinda in Bengali, Banna, Marwan in Punjabi, Pasutia, Aggla-chita in Assami, Indrani in Oriya. The shurb grow throughout the India, ascending to 1500m in the outer Himalaya, fairly common in waste lands, on roadsides, the bank of streams or in the most places near deciduous forests³.

The large shrubs or small trees up to 4.5m high. Leaves petiolate, digitately compound; leaflets 3-5,lanceolate or elliptic-lanceolate, unequal, entire or coarsely crenate-serrate,acute to acuminate ,nearly glabrous above, tomentose beneath. Flowers blue –purple , crowded in short cymes ,forming erect, narrow, tapering, terminal or axillary panicles. Fruits subglobose, drupaceous, 2-3mm across, Seeds 2-4, in bony endocarp³.

The roots are woody, fairly thick ,8-10cm in diameter; external surface brownish ,rough due to presence of longitudinal fissures and a small rootlets³. The roots contain a furanoeremophilane. They are used as an antidote to snake venom. The Boxa tribe of Uttar Pradesh give the powdered root with boiled water for piles.

Leaf paste is also applied on piles .Alcoholic extract of root when administered orally to rats, showed 40-60% anti-implantation activity with no anti-ovulatory effect. The dried powder of roots contains hentriacontane, β-stiosterol and its acetate,and stigmasterol 4-6. The stem barks occurs in channeled pieces,0.3-0.5 cm thick; outer surface yellowish grey, rough, lenticellular, longitudinally channeled³. It contains β-sitosterol, vanillic and p-hydroxybenzoic acid, luteolin, methyl ester of leucodelphinidin. The bark is used for toothache eye disease and rheumatism^4,5. The leaves are palmetely compound , 3-5 foliate; the middle leaflets is petiolulate. The leaves contains the iridioid glycosides,2-p-hydroxybenzoyl mussaenosidic acid negundoside. The extract of leaves was found to possess anti inflammatory and antibacterial properties. It also showed antifungal activity against ring worm causing fungi^6-9. It is used for treatment of eye-disease, toothache, inflammation, leucoderma, enlargement of the spleen, skin-ulcers, in catarrhal fever, rheumatoid arthritis, gonorrhoea, and bronchitis. They are also used as tonics, vermifuge, lactagogue, emmenagogue, antibacterial, antipyreticand antihistaminic agents^10-12.

2. Phytochemistry:

Phytochemical studies on V. negundo have afforded several types of compounds,such as volatile oils^13-16, lignans^17-18, Flavonoids^19-24, iridoids^25-27, terpenes (triterpenes, diterpenes, sesquiterpenes)^28-30, and steroids³¹.

2.1.Leaves:

The most flavonoid glycoside fom Vitex negundo of Ethanolic extract is 5-hydroxy-3,6,7-trimethoxy-2-(3,4-dimtoxypheny)-4H-chrome-4-on,5,7-dihydroxy-2-(3,4-dihydroxyphenyl) -4H-chromen-4-one³³. methanolic extract also contains, Negundoside, Agnuside, Vitegnoside³⁴.( Fig. 1)

2.2. Bark:

Phytochemical Constituents of the Bark of Vitex negundo Linn. p-Hydroxybenzoic acid (1) and β-sitosterol (2) (fig.2)were isolated, and identified from the methanol and hexane extracts of Vitex negundo. The structure of the compounds were established on the basis of spectral analysis⁴⁹. Studies on the steam barks of Vitex negundo have resulted in the isolation of many terpenes, sterols, phenolic compounds, flavanoids, alkaloids, organic acids, glucosides, and anthocyanines^50-60.

2.3. Seeds:

From the acetoacetatefraction, twophenylnaphtha- lene-typelignans (were obtained and identified as 6-hydroxy-4-(4-hydroxy-3-methoxy-phenyl)-3-hydroxy- methyl-7-methoxy-3,4-dihydro-2-naphthaldehyde and vitedoamine A (fig.3),both of which have been previously reported and isolated from the seeds of Vitex negund The structures were elucidated unambiguously by spectroscopic methods including 1Dand 2DNMR analysis and also by comparing experimental data with literature data.

2.4. Roots:

Powdered roots is used for piles as a demulcent for dysentery. It also used in dyspepsia, colic, rheumatism, worms, boils and leprosy⁶⁸. The roots contain a furanoeremophilane. They are used as an antidote to snake venom⁶⁹. Tyrosinase inhibitory lignin’s from the methanol extract of the roots of Vitex negundo Linn⁷².

3. Bioactivity:

Vitex negundo has been found to possess significant hepatoprotective, antioxidant, anti-inflammatory, analgesic, antifungal, leucoderma, enlargement of spleen, skin ulcers and fever².

3.1. Hepatoprotective:

Hepatoprotective activity of Vitex negundo leaf ethanolic extract was investigated against hepatotoxicity produced by administering a combination of three anti-tubercular drugs isoniazid -7.5 mg/kg, rifampin-10 mg/kg and pyrazinamide-35 mg/kg for 35 35 days by oral route in rats. Vitex negundo leaf ethanolic extract was administered in three graded doses of 100, 250 and 500 mg/kg orally, 45 min prior to anti-tubercular challenge for 35 days. Hepatoprotective effect of Vitex negundo leaf ethanolic extract was evident in the doses of 250 and 500 mg/kg as there was a significant decrease in Tuberculosis, aspartate aminotransferase, alanine aminotransferase and alkaline phosphates levels in comparison to control. Histology of the liver section of the animals treated with the Vitex negundo leaf ethanolic extract in the doses of 250 and 500 mg/kg further confirms the Hepatoprotective activity³⁵.

3.2. Antioxidant:

Vitex negundo Linn. contains many polyphenolic compounds, terpenoids, glycosidic iridoids and alkaloids. Since polyphenolic compounds have high antioxidant potential, the antioxidant potency of Vitex negundo was investigated by employing various established in vitro systems, such as 2,20-azino-bis 3-ethyl benzothiazoline- 6-sulfuric acid /Lipid Peroxide /Superoxide/Hydroxyl radical scavenging and iron ion chelation. Total antioxidant capacity was determined by the assay based on the preformed radical monocation. Lipid peroxidation was assessed in terms of thiobarbituric acid reactive substances by using egg yolk homogenates as lipid rich media. Superoxide radical scavenging assay was based on the riboflavin-light-Nitro blue tetrazolium system. Hydroxyl radical trapping potential was determined by evaluating hydroxyl radical induced deoxyribose degradation using the thiobarbituric acid method. In order to assess the metal chelation properties, hydroxyl radical induced deoxyribose degradation was evaluated in the absence of Ethylenediamine tetra acetic acid. All the polar fractions significantly showed trapping of free radicals, and thereby inhibition of lipid peroxidation, and also chelated the iron ion. Interestingly, the hexane fraction did not show any activity against superoxides radicals and it had minimum trapping potential for other free radical species also. Thus, it may be concluded that the polar fractions of VN possess potent antioxidant properties, which may be mediated through direct trapping of the free radicals and also through metal chelation. Therefore its reported anti-inflammatory properties, could be through the down regulation of the free radical mediated pathway of inflammation³⁶.

3.3. anti-inflammatory:

The oral anti-inflammatory, analgesic and antihistamine properties of mature fresh leaves of Vitex negundo Linn. claimed in the Ayurvedic medicine by orally treating a water extract of the leaves to rats. The carrageenan-induced rat paw oedema was significantly suppressed in an inversely does-dependent manner. In the formaldehyde-induced rat paw oedema test, the 2.5 and 5 g/kg leaves significantly. In the hot plate test, 2.5 and 5 g/kg showed a significant and directly dose-dependent analgesic activity at 1 h of treatment while the activity was absent in the tail flick test in rats. The leaves showed an inversely dose-dependent in vivo antihistamine and in vitro prostaglandin synthesis inhibition, membrane stabilizing and antioxidant activities. Naloxone did not abolish the analgesic activity in the hot plate test. Flowering of the tree did not abolish the analgesic and anti-inflammatory activities of the leaves. These observations revealed that the fresh leaves of Vitex negundo have anti-inflammatory and pain suppressing activities possibly mediated via PG synthesis inhibition, antihistamine, membrane stabilizing and antioxidant activities. The antihistamine activity can produce the anti-itching effect claimed in Ayurvedic medicine³⁷. Activity in past including its mechanism of action. However, nobody has evaluated its potential role as an adjuvant with standard anti-inflammatory therapy. Therefore, the present study was undertaken to investigate interaction of ethanolic leaf extract of Vitex negundo Linn with standard anti-inflammatory drugs in sub-effective doses per orally to evaluate its potential role as an adjuvant therapy⁴³.Leaves of Vitex negundo have been investigated for its anti-inflammatory activity in past, including its mechanism of action^44-47.

3.4. Antifungal activity:

Flavonoids are ubiquitous in photosynthesizing cells and are common part of human diet. For centuries, preparations containing these compounds as the principal physiologically active constituents have been used to treat human diseases. Increasingly, this class of natural products is becoming the subject of anti-infective research. Our bioactivity guided fractionation of ethanolic extract of leaves of Vitex negundo resulted in the isolation of new flavones glycoside. All the isolated compounds were evaluated for their antimicrobial activities. The new flavones glycoside 4, 5, 7-trihydroxy-3,-O-β-D-glucuronic acid-6-methyl ester and compound negundoside were found to have significant antifungal activity against Trichophyton mentagrophytes and Cryptococcus neoformans at MIC 6.25 lg/ml³⁸.

3.5 Other activity:

3.5.1 Anti-hyperglycemic potentials:

Leaves of Vitex negundo exhibited anti-hyperglycemic activities when fed simultaneously with glucose³⁹.

3.5.2 Antibacterial:

Vitex negundo exhibited significant activity against E. coli, K. aerogenes, P. vulgaris and P. aerogenes at all dosages. extract of leaves of V. negundo showed activity against all bacteria at all dosages. A standard disc containing chloramphenicol antibiotic drug (30 mg:disc) was used as a positive control⁴⁰.

3.5.3 Antiasthmatic activity

Ethanolic extract and various fractions like petroleum ether, aqueous leaves of Vitex negundo were prepared. The antiasthmatic activity evaluated by various experimental models like mast cell degranulation by compound 48/80, passive cutaneous anaphylaxis, and egg-albumin induced asthma. Dexamethasone was used as a reference standard. Ethanolic extract, and aqueous of leaves of Vitex negundo are found to be effective in various experimental models of asthma. Stabilization of mast cells, inhibitory effects on immediate hypersensitivity reactions and antieosinophilic activity appear to be involved in its mode of action⁴¹. Vitex negundo seems to be a promising plant for treatment of bronchial asthma because of its reported immunomodulatory and anti-inflammatory activity⁴².

3.5.4 Effects on diabetic rats:

Diabetic rats were given idopyranose isolated from the plant, Vitex negundo showed significant reduction in blood glucose, alanine aminotransaminase and aspirate aminotransaminase activities. Serum urea, creatinine and cholesterol were also significantly reduced when compared to diabetic control. Apart from these parameters, idopyranose showed improvement in parameters like body weight, lipid profile such as triglyceride, high density lipoprotein and low density lipoprotein. In diabetic rats changes like coarsening of acinar cells of endoplasmic reticulation, destruction of beta cells and alternation in their secretary function were observed in the histomorphology of the pancreas. The changes like dilation of vein, loss of unusual concentric arrangement of hepatocytes and liver fibrosis were observed in the liver. Thickening of tubules and expansion of glomerulus were observed in kidneys. All these altered parameters were reversed close to normal condition by the treatment of idopyranose. According to biochemical and histological results obtained, it can be concluded that the idopyranose helps in regeneration of damaged pancreas and protects pancreatic ß cells and hyperglycemic nature against streptozotocin-induced diabetes⁶¹.

3.5.5 Anti-implantation activity /Antinociceptive Activity:

Anti-implantation activity of the methanolic extract of leaves of Vitex negundo Linn. Pregnant female mice were dosed with the extract from Days 1 to 6 of pregnancy. No implantation sites were observed in treated animals when they were surgically opened on Day 15 of pregnancy. Biophysical alterations were observed in the endometrium in treated animals. A sharp increase in superoxide anion radicals that was seen in the endometrium from control animals was altered in treated animals. Thus, the physiological alterations induced by extract of Vitex negundo Linn. during the process of implantation may serve as a good lead for further research on natural contraceptive targets stigated implantation⁶². The antinociceptive activity of ethanolic leaf extract of Vitex-negundo. Is alsio present⁷⁴.

3.5.6 In vitro Trypanocidal:

Vitex negundo leaves extract exhibited in vitro antitrypanosomal activity ranged from immobilization to the actual killing of the parasites. The modified Vero cell confluent monolayer although supported the survival of trypanosomes for more than 12 h, no apparent multiplication of the flagellates was seen. Parasites counts decreased in concentration and time-dependent manner with significant difference. At concentration 250 μg/ml give significant reduction in parasites counts resulting from immobilization to killing of parasites as denoted by mean parasites counts Nevertheless, at 500 μg/ml, complete killing of the parasites were observed at 8 h of incubation⁶⁵.

3.5.7 Xanthine oxidase inhibitory activity:

Xanthine oxidase inhibitory activity was assayed from Vitex negundo. Traditionally used for the treatment of gout and related symptoms by indigenous people of India. The aqueous, methanol–water mixture and methanolic extract of these plants were used for the experiment. showed more than 50% inhibition, hence, they were screened for their in vivo hypouricaemic activity against potassium oxonate-induced hyperuricaemia in mice⁶⁶.

3.5.8 Snake venom neutralization:

The methanolic root extracts of Vitex negundo Linn. and Emblica officinalis Gaertn. were explored for the first time for antisnake venom activity. The plant (Vitex negundo and Emblica officinalis) extracts significantly antagonized the Vipera russellii and Naja kaouthia venom induced lethal activity both in vitro and in vivo studies. V. russellii venom-induced haemorrhage, coagulant, defibrinogenating and inflammatory activity was significantly neutralized by both plant extracts. No precipitating bands were observed between the plant extract and snake venom. The above observations confirmed that the plant extracts possess potent snake venom neutralizing capacity and need further investigation⁷⁰.

3.5.9 Larvicidal activity:

Petroleum ether extracts of the leaves of Vitex negundo were evaluated for larvicidal activity against larval stages of Culex tritaeniorhynchus in the laboratory. The V. negundo leaf extract served as a potential larvicidal agent against Japanese encephalitis vector C. tritaeniorhynchus and additionally acted as a promising repellent against various adult vector mosquitoes⁷¹.

3.5.10 Laxative Activity:

Crude aqueous extract of Vitex negundo Linn. leaves at investigated for laxative activity. in albino rats that were compared with standard drug agar-agar in normal saline. The rats were fasted for 12 hours before the experiment. After 8 hours of drug administration the faeces were collected and weighed. The extract was found to produce significant laxative activity in dose dependant manner. The activity may be contributed to the phytoconstituents present⁷³.

3.5.11 Anthelmintic Activity:

Ethanolic extracts of Vitex negundo were taken for anthelmintic activity against Indian earthworm Pheritima posthuma. Various concentrations of both extracts were tested and results were expressed in terms of time for paralysis and time for death of worms. Piperazine citrate was used as a reference standard and distilled water as a control group. Dose dependent activity was observed in the plant extracts⁷⁵.

4. Toxicological study:

Pharmacokinetic-interaction of Vitex negundo Linn. & paracetamol Currently, herbal preparations are clinically used as functional food, food supplements or as add on therapy, which affects the bioavailability and also the net therapeutic potential of co-administered allopathic drugs. Therefore, it is important to assess the interaction among these two classes of drugs. Here we studied the interaction between orally-administered ethanolic extract of leaves of Vitex negundo extract and paracetamol in albino rats. Vitex negundo extract or its ayurvedic formulation if co-administered with allopathic drug like paracetamol, the dose of allopathic drug needs to be adjusted in order to achieve desired therapeutic response of paracetamol⁴⁸.

5. CONCLUSION:

The scientific research on Vitex negundo Linn. suggests a huge biological potential of this plant. It is strongly believed that detailed information as presented in this review on the phytochemical and various biological properties of the extracts might provide detailed evidence for the use of this plant in different medicines.The phytochemical variations and efficacy of the medicinal values of Vitex negundo Linn is dependent on geographical locations and seasons. Leves of this plant are very commonly used by local people of Uttar Prades as a reduction of pain and inflammation and in curing several diseases. However, ethanolic extract of leaves of Vitex negundo extract and paracetamol some toxicological side effects. There is a demand to standardize the toxic properties of Vitex negundo and their detailed clinical trials. After proper processing, identification and removal of the harmful interaction with paracetamol, they may be utilized to a good for patient compliance.

ACKNOWLEDGEMENT:

The authors are very grateful to Dr. G. S. Lavekar, Director CCRAS, New Delhi and for providing encouragement and facilities for carrying out this work. Authors are thankful to Ms. Rekha her assistance for the paper.

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Received on 28.01.2010

Accepted on 11.03.2010

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Research Journal of Pharmacognosy and Phytochemistry. 2(2): March -April 2010, 122-128