Antidiarrheal and antispasmodic activities of Vitex negundo are mediated through calcium channel blockade

Munasib Khan, Abdul Jabbar Shah, Anwar Hassan Gilani


Vitex negundo has reputation in the traditional medicine in diarrhea and gut spasm. This study was carried out to provide possible pharmacological basis to its medicinal use in hyperactive gut disorders. In castor oil-induced diarrheal model, the crude extract of V. negundo, caused a dose-dependent protection (53-71%), similar to loperamide. In isolated rabbit jejunum preparation, V. negundo caused inhibition of spontaneous and high K+-induced contractions, with EC50 values of 0.36 (0.22-0.61) and 1.30 mg/mL (0.27-5.89; n=4-5), respectively, suggestive of spasmolytic activity, mediated possibly through calcium channel blockade (CCB). The CCB activity was further confirmed when pre-treatment of the tissue with V. negundo (0.03-0.3 mg/mL) caused a rightward shift in the Ca++ concentration-response curves (CRCs), similar to diltiazem or loperamide.  These data indicate that the antidiarrheal and spasmolytic effects of the crude extract of V. negundo are mediated through the presence of CCB-like constituent(s).


Ca++ antagonist; Diarrhea; Gut spasm; Loperamide; Vitex negundo

Full Text:

PDF Read


Avadhoot Y, Rana AC. Hepatoprotective effect of Vitex negundo against carbon tetrachloride-induced liver damage. Arch Pharm Res. 1991; 14: 96-98.

Awouters F, Niemegeers CJE, Lenaerts FM, Janssen PAJ. Delay of castor oil diarrhea in rats, a new way to evaluate inhibitors of prostaglandin biosynthesis. J Pharm Pharmacol. 1978; 30: 41-45.

Baquar SR. Medicinal and poisonous plants of Pakistan. Karachi, Printas, 1989, pp 472-73.

Bhargava SK. Antiandrogenic effects of a flavonoid-rich fraction of Vitex negundo seeds: A histological and biochemical study in dogs J Ethnopharmacol. 1989; 27: 327-39.

Brading AF. How do drugs initiate contraction in smooth muscles? TIPS. 1981; 2: 261-65.

Bolton TB. Mechanism of action of transmitters and other substances on smooth muscles. Physiol Rev. 1979; 59: 606-718.

Brunton LL. Agents affecting gastrointestinal water flux and motility; emesis and antiemetics; bile acids and pancreatic enzymes. In: Goodman and Gillman's The Pharmacological Basis of Therapeutics. Hardman, JG, Limbird, LE, Molinoff, PB (eds). 9th ed. New York, McGraw Hill, 1996, pp 917-36.

Croci T, Landi M, Elmonds-AltX, Le FurG, Maffrand JP, Manara I. Role of tachykinins in castor oil induced diarrhea in rats. Br J Pharmacol. 1997; 121: 375-80.

Das S, Parveen S, Kundra CP, Pereira BM J. Reproduction in male rats is vulnerable to treatment with the flavonoid-rich seed extracts of Vitex negundo. Phytother Res. 2004; 18: 8-13.

Diaz F, Chavez D, Lee D, Mi Q, Chai HB, Tan, GT, Kardono LB, Riswan S, Fairchild CR, Wild R, Farnsworth NR, Cordell GA, Pezzuto JM, Kinghorn AD. Cytotoxic flavone analogues of vitexicarpin, a constituent of the leaves of Vitex negundo. J Nat Prod. 2003; 66: 865-67.

Evans WC, Trease and Evans Pharmacognosy. 15th ed. London, W B. Saunders, 2006.

Farre AJ, Columbo M, Fort M, Gutierrez B. Differential effects of various Ca++ antagonists. Gen Pharmacol. 1991; 22: 177-81.

Gilani AH, Ghayur MN, Khalid A, Haq Z, Choudhary MI, Rahman A. Presence of antispasmodic, antidiarrheal, antisecretory, calcium antagonist, acetylcholinesterase inhibitory steroidal alkaloids in Sarcococca saligna. Planta Med. 2005; 71: 1-6.

Gilani AH, Shah AJ, Manzoor A, Shaheen F. Antispasmodic effect of Acorus calamus Linn., is mediated through calcium channel blockade. Phytother Res. 2006; 20: 1080-84.

Godfraind T, Miller R, Wibo M. Calcium antagonism and calcium entry blockade. Pharmacol Rev. 1986; 38: 321-416.

Gupta M, Mazumder UK, Bhawal SR. CNS activity of Vitex negundo Linn. in mice Indian J Exp Biol. 1999; 37: 143-46.

Huang J, Wang GC, Wang CH, Huang XJ, Ye WC. Two new glycosides from Vitex negundo. Nat Prod Res. 2013 Jan 29 (in press).

Iwao I, Terada Y. On the mechanism of diarrhea due to castor oil. Jpn J Pharmacol. 1962; 12: 137-45.

Karaki H, Weiss, G. Mini-review: Calcium release in smooth muscles. Life Sci. 1983; 42: 111-22.

Jebunnessa, Uddin SB, Mahabub-Uz-Zaman M, Akter R, Ahmed NU. Antidiarrheal activity of ethanolic bark extract of Mitragyna diversifolia. Bangladesh J Pharmacol. 2009; 2: 144-46.

Khan A, Gilani AH. Antidiarrheal and bronchodilator potential of olive extract. Lat Am J Pharm. 2011; 30: 5-9.

Munasinghe JTC, Seneviratne CK, Thabrew MI, Abeysekera AM. Antiradical and anti-lipoperoxidative effects of some plant extracts used by Sri Lankan traditional medical practitioners for cardioprotection. Phytother Res. 2001; 15: 519-23.

National Research Council, Guide for the care and use of laboratory animals. National Academy Press, Washington DC, 1996.

Perumal-Samy R, Ignacimuthu S, Sen A. Screening of 34 Indian medicinal plants for antibacterial properties. J Ethnopharmacol. 1998; 62: 173-82.

Reynolds IJ, Gould RJ, Synder SH. Loperamide blockade of calcium channel as mechanism for antidiarrheal effects. J Exp Pharmacol Ther. 1984; 231: 628-32.

Shah AJ, Sabira B, Syed IH, Syed NA, Bina SS, Gilani AH. Pharmacological basis for the medicinal use of Psidium guajava leaves in hyperactive gut disorders. Bangladesh J Pharmacol. 2011a; 6: 100-05.

Shah AJ, Mudassar A, Zaidi, Hassan S, Hamidullah, Gilani AH. Antidiarrheal and antispasmodic activities of Vincetoxicum stocksii are mediated through calcium channel blockade. Bangladesh J Pharmacol. 2011b; 6: 46-50.

Shinwari ZA, Khan AA, NakaikaT. Medicinal and other useful plant of District Swat Pakistan. 2003, p 106.

Tandon VR, Gupta RK. Vitex negundo Linn (Vn) leaf extract as an adjuvant therapy to standard anti-inflammatory drugs. Indian J Med Res. 2006; 124: 447-50.

Usmanghani K, Saeed A, Alam MT. Indusyunic medicine. Karachi, University Of Karachi Press, 1997, pp 441-42.

van-Rossum JM. Cumulative dose-response curves. II. Techniques for the making of dose-response curves in isolated organs and the evaluation of drug parameters. Arch Int Pharmacodyn. 1963; 143: 299-330.

Wall ME, Eddy CR, McClenna ML, Klump ME. Detection and estimation of steroid and sapogenins in plant tissue. Anal Chem. 1952; 24: 1337-42.

Zhu M, Phillipson JD, Greengrass PM, Bowery NE, Cai Y. Plant polyphenols: Biologically active compounds or non-selective binders to proteins?. Phytochemistry 1997; 44: 441-47.

Zhu F, Huang B, Hu CY, Jiang QY, Lu ZG, Lu M, Wang MH, Gong M, Qiao CP, Chen W, Huang PH. Effects of total flavonoids of Hippophae rhamnoides L. on intracellular free calcium in cultured vascular smooth muscle cells of spontaneously hypertensive rats and Wistar-Kyoto rats. Chin J Integr Med. 2005; 11: 287-92.


Article Metrics

Metrics Loading ...

Metrics powered by PLOS ALM

Copyright (c) 2013 Munasib Khan, Abdul Jabbar Shah, Anwar Hassan Gilani

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Bangladesh Journal of Pharmacology (Bangladesh J Pharmacol) is a single-blinded peer-reviewed, video component, open access official publication of the Bangladesh Pharmacological Society (BDPS). eISSN: 1991-0088. For contact: Editor-In-Chief