Preliminary Toxicological Evaluations of Polypeptide-K Isolated from Momordica Charantia in Laboratory Rats

This study examined the toxicological effects and safety of polypeptide k isolated from the seeds of Momordica charantia in laboratory rats. 30 male Sprague Dawley rats (12 weeks old, bodyweight 180-200 g) were randomly divided into 3 groups (1000 mg/kg, 500 mg and 0 mg/kg). Rats were acclimatized to laboratory conditions for 7 days and at day 8 rats were dosed orally with polypeptide k (in 2% DMSO/normal saline) and the controls received the dosed vehicle only. Rats were then observed for 72 hours before sacrificed. Rats were anaesthetized by pentobarbital (50 mg/kg ip) and 2-3.0 mL of blood was taken by cardiac puncture and rats were scarified by anaesthetic overdose. Immediately, organs (heart, lungs, liver, kidneys) were weigh and taken for histology. Organ sections were then evaluated by a histopathologist. Serum samples were assayed for liver functions (ALT and γ-GT) and kidney functions (BUN and creatinine). All rats showed normal behavior after the dosing and no statistical changes were observed in all blood parameters and organ weight. Histological examinations revealed normal organ structures. In conclusion, dosing of rats up to 1000 mg/kg did not have any effects on the rat behavior, liver or kidney functions nor histology of the selected organs.

Authors:

• M Nazrul-Hakim
• A Yaacob
• Y Adam
• A Zuraini

Keywords:

• Polypeptide k
• safety
• histology
• toxicology
• Momordica charantia

References:

[1] O. Ahmed, I., Adeghate, E., Sharma, A.K., Pallot, D.J., Singh, J., 1998.
Effects of Momordica charantia fruit juice on islet morphology in the
pancreas of the streptozotocin-diabetic rat. Diabetes Research Clinical
Practices 40, 145-151.
[2] Modak, M., Dixit, P., Londhe, J., Ghaskadbi, S., Devasagayam, T. 2007.
Indian Herbs and Herbal Drugs Used for the Treatment of Diabetes.
Journal of Clinical Biochemistry & Nutrition 40: 163-173.
[3] Basch, E., Gabardi, S., Ulbricht, C., 2003. Bitter melon (Momordica
charantia): a review of efficacy and safety. American Journal of Health
and Systemic Pharmacology 65, 356-359.
[4] Grover, J.K., Yadav, S.P. 2004. Pharmacological actions and potential
uses of Momordica Charantia: A Review. Journal of
Ethnopharmacology 93: 123-124.
[5] Akhtar, M.S., 1982. Trial of Momordica charantia Linn (karela) powder
in patients with maturity-onset diabetes. Journal of Pakistan Med
Association 32, 106-107.
[6] Jayasooriya, A.P., Sakono, M., Yukizaki, C., Kawano, M., Yamamoto,
K., Fukuda, N., 2000. Effects of Momordica charantia powder on serum
glucose levels and various lipid parameters in rats fed with cholesterol
free and cholesterol-enriched diets. Journal of Ethnopharmacology 72,
331-336.
[7] Grover, J.K., Vats, V., Rathi, S.S., Dawar, R., 2001. Traditional Indian
antidiabetic plants attenuate progression of renal damage in
streptozotocin induced diabetic mice. Journal of Ethnopharmacology 76,
233-238.
[8] Pari, L., Ramakrishnan, R., Venkateswaran, S., 2001.
Antihyperglycaemic effect of Diamed, a herbal formulation, in
experimental diabetes in rats. Journal of Pharmacy Pharmacology 53,
1139-1143.
[9] Virdi, J., Sivakami, S., Shahani, S., Suthar, A.C., Banavalikar, M.M.,
Biyani, M.K., 2003. Antihyperglycemic effects of three extracts from
Momordica charantia. Journal of Ethnopharmacology 88, 107-111.
[10] Khanna, P., Jain, S.C., Panagariya, A. 1981. Hypoglycemic activity of
polypeptide-p from a plant source. Journal of Natural Products 44: 648-
655.
[11] Matsuda, H., Li, Y., Murakami, T., Matsumura, N., Yamahara, J.,
Yoshikawa, M., 1998. Antidiabetic principles of natural medicines. Part
III. Structure-related inhibitory activity and action mode of oleanolic
acid glycosides on hypoglycemic activity. Chemical and Pharmaceutical
Bulletin (Tokyo) 46, 1399-1403.
[12] Kanna, P. 2004. Protein/polypeptide-k obtained from Momordica
charantia. United States Patent 6831162.
[13] Kusamran, W.R., Ratanavila, A., Tepsuwan, A., 1998. Effects of neem
flowers, Thai and Chinese bitter gourd fruits and sweet basil leaves on
hepatic monooxygenases and glutathione S-transferase activities, and in
vitro metabolic activation of chemical carcinogens in rats. Food and
Chemical Toxicology 36, 475-484.
[14] Somchit, N., Norshahida, A. R., Hasiah, A. H., Zuraini, A., Sulaiman,
M. R., Noordin, M. M., Hepatotoxicity induced by antifungal drugs
itraconazole and fluconazole in rats: a comparative in vivo study,
Human and Experimental Toxicology, vol. 23, no. 11, pp. 519-525,
2004.
[15] Tennekoon KH, Jeevathayaparan S, Angunawala P et al. Effect of
Momordica charantia on key hepatic enzymes. J Ethnopharmacol. 1994;
44:93-7.
[16] Yuan, X., Gu, X., Tang, J. 2008. Purification and characterisation of a
hypoglycemic peptide from Momordica Charantia L. Var. abbreviate
Ser. Food Chemistry 111: 415-420.
[17] Baldwa, V.S., Goyal, R.K., Bhandari, C.M., Pangariya, A., 1976. A
clinical trial of insulin obtained from the vegetable source (plant insulin)
in patients with diabetes mellitus. Rajasthan Medical Journal 16, 54.
[18] Lee-Huang, S., Huang, P.L., Chen, H.C., Huang, P.L., Bourinbaiar, A.,
Huang, H.I., Kung, H.F., 1995a. Anti-HIV and anti-tumor activities of
recombinant MAP30 from bitter melon. Gene 61, 151-156.