EVALUATION OF ACUTE AND SUB-ACUTE TOXICITY OF A STANDARDIZED POLYHERBAL FORMULATION (HC9): AN IN VIVO STUDY
Keywords:Acute and sub-acute oral toxicity, HC9, Swiss albino mice
Objective: In the present study, we have performed the acute and sub-acute toxicity of a standardized polyherbal formulation (HC9) in Swiss albino mice.
Methods: In acute toxicity study, the mice were orally administered with different doses (1750 and 2000 mg/kg) of HC9 and monitored for 14 d. In the sub-acute toxicity study, animals received HC9 extract by oral gavage at the doses of 250, 500 and 1000 mg/kg/day (????=5/group/sex) for 28 d. At the end of the study, the animals were sacrificed and evaluated for effect of HC9 on biochemical, hematological and histopathological parameters.
Results: HC9 did not produce any adverse effects in biochemical, hematological, urine and histopathological parameters in mice. HC9 did not induce any adverse effects in terms of mortality and clinical signs in the acute toxicity study. It was well-tolerated by mice up to 2000 mg/kg/body weight. In sub-acute toxicity study, no treatment-related adverse effects were found in the mice upto 1000 mg/kg/day dose. No significant changes were observed in biochemical and hematological parameters as well as histopathology of tissues (liver, kidney, spleen, heart, lung, thymus, adrenal gland, epididymis and testis/ovary) among mice of either sex.
Conclusion: Our results showed that HC9 did not induce any acute and sub-acute toxicity in male and female mice, thereby, suggesting its safety for future clinical application.
Pathak K, Das RJ. Herbal medicine-a rational approach in health care system. Int J Ayurvedic Herbal Med 2013;1:86.
Sharma R. Recommendations on herbs and herbal formula in cancer prevention. Open Nutraceuticals J 2010;3:129-40.
Vaidya ADB, Devasagayam TPA. Current status of herbal drugs in india: an overview. J Clin Biochem Nutr 2007;41:1-11.
Kuruvilla A. Herbal formulations as phamacotherapeutic agents. Indian J Exp Biol 2002;40:7-11.
Gatkal S, Punde A, Balap A, Chaudhari P. Safety of herbal medicine: a review. Int J Chem Pharm Sci 2012;1:1624-39.
Osemene KP, Elujoba AA, Ilori MO. A comparative assessment of herbal and orthodox medicines in nigeria. Res J Med Sci 2011;5:280-5.
Bent S. Herbal medicine in the united states: review of efficacy, Safety, and regulation: grand rounds at university of california, San francisco medical center. J General Int Med 2008;23:854-9.
Suryavanshi S, Choudhari A, Deshpande R, Kulkarni O, Kaul-Ghanekar R. Analyzing the antioxidant potential of aqueous and ethanolic preparations of a herbal composition (HC9) and evaluating their cytotoxic activity in breast cancer cell lines. J Biotechnol Bioinf Bioeng 2011;1:513-22.
Chanda S, Bhayani D, Desai D. Polyphenols and flavonoids of twelve Indian medicinal plants. Bioscan 2013;8:595-601.
Choudhari AS, Suryavanshi SA, Ingle H, Kaul-Ghanekar R. The antioxidant potential of aqueous and alcoholic extracts of Ficus religiosa using ORAC assay and assessing their cytotoxic activity in cervical cancer cell lines. Biotechnol Bioinf Bioeng 2011;1:443-50.
Choudhari AS, Suryavanshi SA, Kaul-Ghanekar R. The Aqueous extract of ficus religiosa induces cell cycle arrest in human cervical cancer cell lines siha (HPV-16 Positive) and apoptosis in hela (HPV-18 Positive). PloS One 2013;8:e70127.
Koppikar SJ, Choudhari AS, Suryavanshi SA, Kumari S, Chattopadhyay S, Kaul-Ghanekar R. Aqueous cinnamon extract (CE-c) from the bark of Cinnamomum cassia causes apoptosis in human cervical cancer cell line (SiHa) through loss of mitochondria membrane potential. BMC Cancer 2010;10:210.
Choudhari SA, Raina P, Deshpande MM, Wali AG, Zanwar A, Bodhankar SL, et al. Evaluating the anti-inflammatory potential of Tectaria cicutaria L. rhizome extract in vitro as well as in vivo. J Ethnopharmacol 2013;150:215-22.
Wani K, Ahmed A, Kitture R, Koppikar S, Choudhari A, Kale S, et al. Synthesis, characterization and in vitro study of curcumin-functionalized citric acid-capped magnetic (CCF) nanoparticles as drug delivery agents in cancer. Bionanosci 2011;5:59-65.
Aggarwal BB, Prasad S, Reuter S, Kannappan R, Yadev VR, Park B, et al. Identification of novel anti-inflammatory agents from Ayurvedic medicine for prevention of chronic diseases: “reverse pharmacology” and “bedside to bench” approach. Curr Drug Targets 2011;12:1595-653.
Kennedy DO, Wightman EL. Herbal extracts and phytochemicals: plant secondary metabolites and the enhancement of human brain function. Int Review 2011;2:32-50.
Kumar S, Malhotra R, Kumar D. Euphorbia hirta: Its chemistry, traditional and medicinal uses, and pharmacological activities. Pharmacogn Rev 2011;4:58-61.
Efferth T, Kaina B. Toxicities by herbal medicines with emphasis to traditional Chinese medicine. Curr Drug Metab 2011;12:989-96.
Hussin AH. Adverse effects of herbs and drug-herbal interactions. Malaysian J Pharm 2001;1:39-44.
Suryavanshi S, Zanwar A, Hegde M, Kaul-Ghanekar R. Standardization of a polyherbal formulation (HC9) and comparative analysis of its cytotoxic activity with the individual herbs present in the composition in breast cancer cell lines. J Pharmacogn 2014;2:8.
Chandra P, Sachan N, Kishore K, Ghosh AK. Acute, sub-chronic oral toxicity studies and evaluation of antiulcer activity of Sooktyn in experimental animals. J Adv Pharm Technol Res 2012;3:117.
Rashid A, Ali R, Jaimini A, Nishad D, Mittal G, Chaurasia O, et al. Acute and sub acute toxicity and efficacy studies of Hippophae rhamnoides based herbal antioxidant supplement. Indian J Pharmacol 2012;44:504.
Jothy SL, Zakaria Z, Chen Y, Lau YL, Latha LY, Sasidharan S. Acute oral toxicity of methanolic seed extract of cassia fistula in mice. Molecules 2011;16:5268-82.
Neergheen-Bhujun VS. Underestimating the toxicological challenges associated with the use of herbal medicinal products in developing countries. BioMed Res Int 2013;2013:1-9.
Singh T, Sinha N, Singh A. Biochemical and histopathological effects on liver due to acute oral toxicity of aqueous leaf extract of ecliptaalba on female swiss albino mice. Indian J Pharmacol 2013;45:61.
Gautam MK, Singh A, Rao CV, Goel RK. Toxicological evaluation of Murraya Paniculata (L.) leaves extract on rodents. Am J Pharmacol Toxicol 2012;7:62-7.
Adeneye AA, Ajagbonna OP, Adeleke TI, Bello SO. Preliminary toxicity and phytochemical studies of the stem bark aqueous extract of Musanga cecropioides in rats. J Ethnopharmacol 2006;105:374-9.
Ping KY, Darah I, Chen Y, Sreeramanan S, Sasidharan S. Acute and subchronic toxicity study of euphorbia hirta L. methanol extract in rats. BioMed Res Int 2013;2013:1-14.
Agbaje EO, Adeneye AA, Daramola AO. Biochemical and toxicological studies of aqueous extract of Syzigium aromaticum (L.) Merr. and amp; Perry (Myrtaceae) in rodents. Afr J Tradit Complementary Altern Med 2009;6:241.
Singh A, Bhat TK, Sharma OP. Clinical biochemistry of hepatotoxicity. J Clin Toxicol 2011;S4:001.
Pillai PG, Suresha P, Mishrab G, Annapurna M. Evaluation of the acute and sub acute toxicity of the methanolic leaf extract of Plectranthus amboinicus (Lour) Spreng in Balb C mice. Eur J Exp Biol 2011;1:236-45.
Fuchs TC, Frick K, Emde B, Czasch S, Von Landenberg F, Hewitt P. Evaluation of novel acute urinary rat kidney toxicity biomarker for subacute toxicity studies in preclinical trials. Toxicol Pathol 2012;40:1031-48.
Abotsi WK, Ainooson GK, Gyasi EB. Acute and sub-acute toxicity studies of the ethanolic extract of the aerial parts of Hilleria Latifolia (Lam.) H. Walt.(Phytolaccaceae) in rodents. Afr J Pharm Pharmacol 2011;22:27-35.
Gowda S, Desai PB, Kulkarni SS, Hull VV, Math AAK, Vernekar SN. Markers of renal function tests. N Am J Med Sci 2010;2:170.