Figure 1: Vitex negundo

Table 1: Scientific classification.

Kingdom	Plantae
Subkingdom	Tracheobionata
Superdivision	Spermatophyta
Division	Magnoliophyta
Class	Magnoliopsida
Subclass	Asteridae
Order	Lamiales
Family	Verbenaceae
Genus	Vitex
Species	negundo

Table 2: Vernacular names of Vitex negundo.

Names	Languages
Sambhalu	Hindi
Nirgundi	Indian Trade name
Nisinda	Bengali
Lakkaginda	Kannad
Kari-nocchi	Malyalam
Indian Privet	English
Huangjing	Chinese
Marwan	Punjabi
Nagorha	Gujarati

Table 3: Common species of Vitex.

S. No.	Common Species	Common Name	Habitat
1	Vitex angus-castus	Chaste tree	Western Asia
2	Vitex altissima	Nemaliadugu	Srilanka, Malaysia
3	Vitex glabrata	Nevalendi	India, China
4	Vitex leucoxylon	Nirochi	Srilanka
5	Vitex longisepala	Halban	Malaysia
6	Vitex mollis	Cuayotomate	Mexico
7	Vitex negundo	Nirgundi	India, China, Japan
8	Vitex penduncularis	Nevalendi	Bihar, Assam
9	Vitex pubescens	Malandi	Malay Island
10	Vitex trifolia	Nirnochi	Ceylon, Japan

Leaves: Petiolate, 3-5 foliate, opposite, leaflets are narrow lanceolate, mostly entire, glabrous above and pale whitish green covered with a white tomentum beneath.

Flowers: Small, bluish-purple, peducled cymes, group into large terminal, pyramidal panicles.

Fruit: Globulous drupe, black when ripe, 5-6 mm in diameter.

Roots: Fairly thick, woody brownish and up to 1.2 mm in length and 8-10 cm in diameter.

Bark: 3-5 mm thick, outer surface dark brown, inner surface light brown and fibrous^{1, 4, 6, 7}.

Habitat:

Vitex negundo Linn. is used as medicine fairly throughout the greater part of India and found mostly at warmer zones and ascending to an altitude of 1500 metres in outer Western Himalayas⁵. It is cultivated as a hedge plant. It prefers a loose, well-drained soil that is moist or on the dry side, not wet, but tolerates drained clay or sandy soil. The tree often suffers from die back inorganic, mucky, or other soil which is kept too moist⁸.

Distribution and Propagation:

The plant is distributed throughout India, Ceylon, Afghanistan, Tropical Africa, Madagascar, China, Philippines, Nepal, Bhutan, and Pakistan. The plant is propagated by soft wood cutting in early summer or by seeds.

Traditional Uses:

The plant has a pungent, bitter, acrid taste, possesses anthelminthic activity; it promotes hair growth, useful in disease of the eye, inflammation, leucoderma, enlargement of spleen, bronchitis, and killing pain⁴.The root of the plant is considered tonic, febrifuge, and expectorant. The root also acts as an anti-dote to snake-venom. Bark is useful in the treatment of odontalgia, verminosis and in various eye disorders⁷. The leaves are aromatic, tonic, and vermifuge. Dried leaves are smoked for relief of headache and catarrh; these are useful in treatment of acute rheumatism. Decoction of the leaves is used in fever, dullness of hearing, and for removing foetid discharges and worms⁵.

Chemical Constituents:

A diverse category of phytoconstituents are reported in the various species of Vitex. Different parts of the plant such as leaves, seeds, fruit, bark, root and flowers posses various constituents. A number of constituents that are present in the plants are terpenoids, irridoids, steroids, phenolic compounds, lignane derivatives, amino acids, fatty acids and aliphatic alcohol.

Terpenoids:

Monoterpenes:

Pinene (1), cineol (2), limonene (3), linalool (4), camphene (5), have been isolated from the leaves of Vitex angus-castus⁹ and sabinine (6) from the leaf of Vitex angus-castus¹⁰.

Sesquiterpenoids:

Sesquiterpenoids isolated by steam distillation of leaves of Vitex negundo are β-carryophylene (7) and farnesene (8) from essential oil of fruit and leaves of Vitex negundo^{9, 10}.

Triterpenoids:

Betulic acid (9), urosolic acid (10) and pentacyclic triterpenoids have been isolated from the leaves of Vitex negundo, and have shown pesticidal activity¹¹. 3-β-acetoxyolean-12-en-27-oic acid (11) and its derivative extracted from chloroform extract of defatted seeds of Vitex negundo have shown anti-inflammatory activity¹².

Flavonoids:

A cytotoxic flavone vitexicarpine (12) isolated from chloroform extract has exhibited broad cytotoxicity in human cancer cell^{3, 13}. Vitexin (13) and isovitexin (14) have been isolated from the root of Vitex negundo¹⁰. 3’,5-dihydroxy-4’,7,8-trimethoxyflavanone (15), 3’,5-dihydroxy-4’,6,7-trimethoxyflavanone (16), have been isolated from the leaves¹⁴. A number of other flavonoids isolated from the Vitex negundo have been identified as luteoline (17), orientin (18), iso-orientin (19) and casticin (20)¹⁰.

Iridoids:

Negundoside (21), an iridoid has been isolated from the methanolic root extract of Vitex negundo³ and aucubin (22) from leaf extract of Vitex angus-castus¹⁰.

Steroids:

Progesterone (23) and testosterone (24) were identified in the flowers of Vitex angus-castus¹⁰. β-sitosterol (25) and stigmasterol (26) have been reported in the methanol extract of the roots of Vitex negundo³.

Phenolic compounds

p-hydroxybenzoic acid (27), 3,4 dihydroxybenzoic acid (28) and 5-hydroxyisophthalic acid (29) have been isolated from leaves of Vitex negundo¹⁴.

Alkaloid (Lignan derivatives):

Vitedoin A1 (30), a phenyldihydronapthalene-type and vitedoamine A2 (31) a phenylnapthelene type lignan alkaloid have been isolated from the seeds of Vitex negundo and have showed strong anti-oxidant property¹⁵.

Amino acids:

Glycine (32), alanine (33), valine (34), and leucine (35) have been reported in seed extract of Vitex negundo.

Fatty acids:

Oleic acid (36), linolic acid (37), and palmitic acid (38) have been isolated from the seeds of Vitex negundo¹⁴.

Aliphatic alcohol:

An alcohol named n-hentriacontanol (39) has been isolated for the first time from the leaves of Vitex negundo¹¹.

Pharmacological Activities:

Anti-inflammatory activity:

The chloroformextract of the defatted seeds of Vitex negundo Linn. exhibited anti-inflammatory activity¹². Extract obtained from leaf of Vitex negundo Linn. showed anti-inflammatory activity in Carrageenan induced hind paw edema and cotton pellet granuloma test in albino rats¹⁴.

Anti-androgenic effect:

The flavonoid rich fraction from the seeds of Vitex negundo has shown to antagonize the androgen action of exogenous testosterone propionate on the male reproductive system¹⁶. It also produced pregnancy interceptory effect in mice¹⁷. It has shown to affect the reproductive system of male rats by producing adverse toxicity in other vital organs. Sperm derived from the epidydmis of treated animals showed only a marginal change in sperm number, vitality and motility¹⁸.

Biopesticidal and Anti-feedant activity:

Callosobruchus maculates Fab. was effected by solvent residue of Vitex negundo and Cassia fistula leaves. Different concentration, i.e., 0.5 and 1% significantly reduced the number of eggs. Vitex leaf and Cassia seed extracts significantly protected stored paddy seeds from Sitrotroga cerealella¹⁹. Two compounds, betulinic acid and urosolic acid, isolated from the leaves of Vitex negundo showed anti-feedant activity against the larvae of an agricultural pest, Castor semilooper¹¹.

Mosquito repellent activity:

The oil obtained from the leaves by steam distillation showed mosquito repellent activity, as evaluated against Aedes aegypti. This activity was shown by polar fraction, chloroform: benzene (25:75). The chloroform fraction showed the highest protection period of 3 hrs²⁰.

Analgesic activity:

The ethanolic leaf extract of Vitex negundo possessed both central and peripheral analgesic activity at the doses of 100, 250, and 500 mg/kg body weight. The central analgesic action was not through the opioid receptors. Hence it might be useful in relieving both the visceral and integument pain²¹. Aqueous extract of the fruit of Vitex negundo suppressed the thermal pain stimulus at the dose of 3 g/rat and 2 g/rat. This difference was not antagonized by nalorphine whereas the effect produced by pethidine was completely reversed⁵. Nirgundi possess good analgesic property which closely resembled to anti-pyretic analgesic like aspirin²².

Anti-snake venom activity:

The methanolic extracts of Vitex negundo roots have shown to antagonize the Vipra russellii and Naja kaouthia venom and have induced lethal activity in both in, in vitro and in vivo studies. V. russellii venom-induced haemorrhage, coagulant, defibrinogenating and inflammatory was significantly reduced by the plant²³.

CNS depressant activity:

The methanolic extract of Vitex negundo leaves potentiated significantly the sleeping time induced by pentobarbitone sodium, diazepam and chlorpromazine in mice. Methanolic extract at the dose of 0.15, 0.20 and 0.30 g/kg body weight showed significant CNS depressant action in a dose dependant manner. Methanolic extracts decreased the touch response, pain response, righting reflex and grip strength of mice in comparison with control groups²⁴.

Anti-convulsant activity:

The ethanolic extract of Vitex negundo leaf at the dose of 1000 mg/kg showed 50% protection against colonic convulsion and 24 h mortality²⁵.

Enzyme inhibiting activity:

The methanolic extract of roots of Vitex negundo showed the potent inhibitory activity against lipoxygenase enzyme and showed moderate activity against butyryl-cholinestrase²⁶.

Anti-cancer activity:

Vitexicarpine, a flavone isolated from the fractionation of the chloroform soluble extract of the leaves of Vitex negundo exhibited broad cytotoxicity in a human cancer cell line panel¹³.

Anti-bacterial activity:

Urosolic acid and betulic acid from the leaves of Vitex negundo showed anti-bacterial activity against Bacillus subtilis and Escherichia coli¹¹.

CONCLUSION:

In developing countries, providing modern healthcare facilities is still in infancy. Due to economic constraint, it is prudent to look for options in herbal medicines. The extensive literature survey revealed that Vitex negundo Linn. is an important source of many pharmacologically and medicinally important chemicals such as pinene, cineol, camphene, limonene, vitexin, luteoline, orientin, casticin, negundoside, aucubin, progesterone, testosterone, β-sitosterol, stigmasterol, glycine, alanine, valine and leucine. The plant has also been widely studied for its various pharmacological activities like anti-inflammatory, analgesic, anti-androgenic, biopesticidal, mosquito repellent, anti-snake venom activity, CNS depressant, anti-convulsant, enzyme inhibiting, anti-bacterial, anti-cancer. While the drug is described in Ayurveda, Charaka Samhitaa, Sushruta Samhitaa, and in Bhavaprakasha, more clinical trials should be conducted to support its therapeutic uses. This review aims to highlight the medicinal importance of Vitex negundo Linn. so that it’s potential can be fully utilized.

ACKNOWLEDGEMENT:

The authors wish to thank Dr. Neeru Vasudeva, Guru Jambheshwar University, for her moral support.

REFERENCES:

1. Sharma R. Medicinal plants of India- An encyclopedia. Daya Publishing House, New Delhi. 2003; pp. 260.

2. Jarald EE. Medicinal plants. CBS Publishers and Distributor, New Delhi. 2006; pp. 257.

3. Dev S. A selection of prime ayurvedic plant drugs. Anamaya Publisher, New Delhi. 2008; 2^nd ed: pp. 438-440.

4. Kitikar KR and Basu BD. Indian medicinal plants. Sri Satguru Publication, New Delhi. 1981; 3^rd ed: pp. 2665-2677.

5. Chopra RN, Nayar SL and Chopra IC. Glossary of Indian medicinal plants. Publication and Information Directorate, Council of Scientific and Industrial Research, New Delhi. 1956; pp. 256-257.

6. Bhattacharjee SK. Handbook of aromatic plants. Pointers Publishers, Jaipur. 2000; pp. 469-470.

7. Tandon VR. Medicinal uses and biological activities of Vitex negundo. Natural Product Radiance. 4(3); 2005: 162-165.

8. Gilmen EF and Watson DG. Vitex negundo ‘Hetrophylla’ Cut-Leaf Chastetree. Fact Sheet ST. 668; 1994: 1-3.

9. Kustrak D, Kuftinec J and Blazevic N. The composition of essential oils of Vitex angus- castus. Planta Medica. 58(supp. 7); 1992: 681.

10. McKenna D, Jones K and Hughes K. Botanical medicines. Vinod Vasishtha, New Delhi. 2005; 2^nd ed: pp. 1039-1077.

11. Chandramu C, Manohar RD, Krupadunam DG and Dashavantha RV. Isolation, characterization and biological activity of betulinic acid and urosolic acid from Vitex negundo L. Phytotherapy Research. 17(2); 2003: 129-134.

12. Chawla AS, Sharma AK, Handa SS and Dhar KL. Chemical investigation and anti-inflammatory activity of Vitex negundo seeds. Journal of Natural Products. 55(2); 1992: 163-167.

13. Diaz F, Chavez D, Lee D, Mi Q, Chai HB, Tan GT, Kardono B.S, Riswan S, Fairchild CR, Cordell GA, Pezzuto JM and Kinghorn AD. Cytotoxic flavone analogues of Vitexicarpin, a constituent of leaves of Vitex negundo. Journal of Natural Products. 66(6); 2003: 865-867.

14. Zaware BB and Nirmal SA. An overview of Vitex negundo Linn. chemistry and pharmacological profile. Research Journal of Pharmaceutical, Biological and Chemical Sciences. 1(1); 2010: 104-114.

15. Ono M, Nishida Y, Masuoka C, Li JC, Okawa M, Ikeda T and Nohra T. Lignan derivatives and a norditerpene from the seeds of Vitex negundo. Journal of Natural Products. 67(12); 2004: 2073-2075.

16. Bhargava SK. Antiandrogenic effects of a flavonoid-rich fraction of Vitex negundo seeds: A histological and biochemical study in dogs. Journal of Ethnopharmacology. 27(3); 1989: 327-339.

17. Bhargava SK. Effect of plumbagin on reproductive function of male dog. Indian Journal of Experimental Biology. 22(3); 1984: 153-156.

18. Das S, Parveen S, Kundra CP and Pereira BMJ. Reproduction in male rats is vulnerable to treat with flavonoid-rich seeds extract of Vitex negundo. Phytotherapeutic Research. 18(1); 2004: 8-13.

19. Raja N, Albert S and Ignacimuthu S. Effect of solvent residues of Vitex negundo Linn. and Cassia fistula Linn. on pulse beetle, Callosobruchus maculatus Fab. and its larval parasitoid, Dinarmus vagabundus (Timberlake). Indian Journal of Experimental Biology. 38(3); 2000: 290-292.

20. Hebbalkar DS, Hebbalkar GD, Sharma RN, Joshi VS and Bhatt VS. Mosquito repellent activity of oils from Vitex negundo Linn. leaves. The Indian Journal of Medical Research. 95; 1992: 200-203.

21. Gupta RK and Tandon VR. Anti-nociceptive activity of Vitex negundo Linn. leaf extract. Indian Journal of Physiology and Pharmacology. 49(2); 2005: 163-170.

22. Shrivastava SC and Sisodia CS. Analgesic studies on Vitex negundo and Valeriana wallichii. Indian Veterinary Journal. 47(2); 1970: 170-175.

23. Alam MI and Gomes A. Snake venom neutralization by Indian medicinal plants (Vitex negundo and Emblica officinalis Linn. root extract. Journal of Ethnopharmacology. 86(1); 2003: 75-80.

24. Gupta M, Mazumder UK and Bhawal SR. CNS activity of Vitex negundo Linn. in mice. Indian Journal of Experimental Biology. 37(2); 1999: 143-146.

25. Tandon VR and Gupta RK. An experimental evaluation of anticonvulsant activity of Vitex negundo. Indian Journal of Physiology and Pharmacology. 49(2); 2005: 199-205.

26. Haq-ul A, Malik A, Anis I, Khan SB, Ahmed E, Ahmad Z, Nawaz SA and Choudhary Ml. Enzyme inhibiting lignans from Vitex negundo. Chemical Pharmaceutical Bulletin. 52(11); 2004: 1269-1272

Received on 19.08.2011

Accepted on 11.09.2011

Research Journal of Pharmacognosy and Phytochemistry. 3(6): Nov. - Dec. 2011, 249-255