Leaf paste of Telfairia occidentalis favourably modulates deleterious effects associated with exposure to diethylnitrosamine in male Wistar rats.

OBJECTIVES: Diethylnitrosamine (DEN) is found in workplaces, processed meats, tobacco smoke, whiskey, etc. It is capable of forming DNA-adducts. Fluted pumpkin (Telfairia occidentalis [To]) is a medicinal plant, and its herbal preparations have been employed variously in ethnomedicine. Furthermore, it has been reported to possess anti-oxidant, anti-cancer, anti-inflammatory properties. We investigated the possible mitigating effect of the leaf paste of To on DEN-induced deleterious effects in male Wistar rats. METHODS: Forty-five rats weighing between 100 and 150 g were equally divided into nine groups and treated thus: Group 1 (negative control), Group 2 (0.05 mg/kg carboxymethyl cellulose [CMC] daily), Group 3 (positive control, 25 mg/kg bw DEN administered intraperitoneally thrice per week), Group 4 (25 mg/kg bw quercetin [QUE] daily alone), Groups 5 and 6 (100 and 200 mg/kg bw To daily, respectively), Group 7 (25 mg/kg bw DEN and QUE), Groups 8 and 9 (25 mg/kg bw DEN with 100 and 200 mg/kg bw To, respectively). Blood glucose levels, liver damage biomarkers (aspartate aminotransferase [AST], alanine aminotransferase [ALT] and gamma-glutamyltransferase [γ-GT]), frequency of micronucleated polychromatic erythrocyte (mPCEs), and liver histology were assessed. RESULTS: DEN significantly (p<0.05) increased blood glucose levels, activities of ALT, AST and γ-GT, and frequency of mPCEs. Histologically, DEN caused a severe architectural anarchy. However, the intervention groups demonstrated the remarkable protective properties of To by ameliorating the adverse effects caused by DEN. CONCLUSIONS: Taken together, the leaf paste of To is capable of mitigating DEN-induced hepatotoxicity and clastogenicity in male Wistar rats.

In vivo and in vitro safety evaluation of fermented Citrus sunki peel extract: acute and 90-day repeated oral toxicity studies with genotoxicity assessment.

BACKGROUND: Citrus sunki Hort. ex Tanaka peel has been traditionally used as an ingredient in folk medicine due to its therapeutic effects on promotion of splenic health and diuresis as well as relief of gastrointestinal symptoms. Although a growing interest in health-promoting natural products and the development of highly concentrated products have facilitated consumption of C. sunki peel, its safety assessment has not been explored, posing a potential health risk. In this study, we carried out a series of systemic and genetic toxicity tests on fermented C. sunki peel extract (FCPE) to provide the essential information required for safe use in human. METHODS: We conducted acute and 90-day repeated oral toxicity studies in Sprague-Dawley rats to evaluate systemic toxicity, and three genotoxicity assays to measure bacterial mutation reversion, cellular chromosome aberration and in vivo micronucleus formation. RESULTS: Single oral administration of FCPE did not cause any clinical signs and lethality in all animals, establishing LD50 to be over 2000 mg/kg BW. Repeated administration of up to 2000 mg/kg BW FCPE for 90 days revealed no test substance-related toxicity as demonstrated in analysis of body weight gain, food/water intake, blood, serum biochemistry, organ weight and histopathology, collectively determining that the no-observable-adverse-effect-level of FCPE is over 2000 mg/kg BW. In addition, we detected no mutagenicity and clastogenicity in FCPE at 5000 µg/plate for the in vitro assays and 2000 mg/kg BW for the in vivo micronucleus test. CONCLUSION: FCPE did not cause systemic and genetic toxicity in our model systems at the tested dose levels. These results suggest a guideline for safe consumption of C. sunki peel in human.

Preclinical study of safety of Dendropanax morbifera Leveille leaf extract: General and genetic toxicology.

ETHNOPHARMACOLOGY RELEVANCE: Dendropanax morbifera Leveille (DM) has been used in traditional medicines for infectious and skin diseases, and dysmenorrhea. It exhibits a diverse therapeutic potential including anti-cancer, anti-thrombotic, anti-diabetic, anti-oxidant, and anti-inflammatory activities. AIM OF THE STUDY: Despite promising health benefits of DM, knowledge of its potential adverse effects is very limited. The current study focused on the investigation of subchronic toxicity and genotoxicity of extract obtained from DM according to the test guidelines published by the Organization for Economic Cooperation and Development. MATERIALS AND METHODS: We conducted a toxicological evaluation of DM extracts using 14-day repeated-dose toxicity study and 13-week repeated-dose toxicity study in Sprague-Dawley rats administered orally at doses of 500, 1000, or 2000 mg/kg/day. The clastogenicity of DM extract was also evaluated by in vitro chromosome aberration assay and in vivo micronucleus assay. RESULTS: Assessment of subchronic toxicity of DM extract by oral administration in rats revealed unremarkable treatment-related findings with respect to food/water consumption, body weight, mortality, urinalysis, hematology, serum biochemistry, necropsy, organ weight and histopathology at doses of 500, 1000, and 2000 mg/kg. Accordingly, the level of no-observed-adverse-effect for DM extract in 13-week subchronic toxicity study was considered to be 2000 mg/kg/day in rats. The data observed from in vitro chromosome aberration assay and in vivo micronucleus assay exclude any clastogenicity of DM extract. CONCLUSION: The results suggest that the oral consumption of DM extract has no adverse effects in humans and represents a safe traditional medicine.

50% Ethanol extract of Orthosiphon stamineus modulates genotoxicity and clastogenicity induced by mitomycin C.

Herbal products contain a variety of compounds which may be useful in protecting against cellular damage caused by mutagens. Orthosiphon stamineus (O.s) also known as Cat whiskers. The herb has been shown anti-oxidative properties and can modulate key cellular proteins that have cytoprotective effect. The study aimed to evaluate the effects of different doses (250, 500 and 1000 mg kg-1) of 50% ethanol extract of O.s (Et. O.s) on micro-nucleated polychromatic erythrocytes (MNPCE), Polychromatic to normachromatic erythrocytes ratio (PCE/NCE), Mitotic index (MI), and Chromosomal aberration (CA) in Bab/c mice. Moreover, these parameters were used to evaluate the anti-genotoxic and clastogenic potencies of (Et. O.s) against mitomycin c (MMC) that interact with biological molecules and induce genotoxic and clastogenic disorders in non-tumor cells. MMC (4 mg kg-1) was injected intraperitoneally (i.p.) to the mice before and after treatment with three different doses of (Et. O.s). The results indicated that the extract at different doses did not show significant (p ≥ 0.05) differences in (MNPCE), (PCE/NCE) ratios, and (CA) values. The higher doses sowed high (MI) values compared with untreated control group. MMC showed significant increase (p ≤ 0.001) in (MNPCE), (CA) and reduce (PCE/NCE) and (MI) values compared with untreated control group. Treatment with (Et. O.s) at different doses before and after MMC injection showed to modulate MNPCE, PCE/NCE ratios, CA and MI values in mice bone marrow cells suggesting genoprotective potential of this plant extract.

Mutagenicity and clastogenicity of some Philippine medicinal plants

The mutagenic potential of some medicinal plants for fertility control was determined using four different tests. The plants studied were makahiya, ampalaya, malunggay and kamias. Results of the Rec assay showed that the plants studied did not possess direct DNA-damaging capacity. This was confirmed by the Ames test which indicated that these plants were not mutagenic per se. Mutagenic activity following metabolism in a host animal and chromosome-breaking effects were likewise not observed. (Auth)