Ethanol Extract of Cyclea barbata Miers Exhibited A Favorable Safety Profile at Moderate Doses in Wistar Rats

Abstract

BACKGROUND: Cyclea barbata Miers has been identified as a phytoestrogenic candidate with comparable estrogen receptors (ER)α binding activity with 17β estradiol. Though phytoestrogens are reported to modulate reproductive and hormonal physiology, but no systematic in vivo toxicological evaluation of C. barbata extract has been reported. Therefore, this study was conducted to evaluate the acute and subacute oral toxicity of the ethanol extract of C. barbata (EECB) in Wistar rats.

METHODS: For acute toxicity, rats received single oral doses of 2,000 or 5,000 mg/kg BW and were observed for 14 days. For subacute toxicity, EECB was administered orally at doses of 100–500 mg/kg BW/day for 28 consecutive days. Body weight, relative organ weights, haematological and biochemical parameters, and histopathological changes in major organs were evaluated.

RESULTS: No mortality occurred at 2,000 mg/kg BW in either sex, whereas mortality was observed only in female rats at 5,000 mg/kg BW (20%). EECB was therefore classified as GHS Category 5 or unclassified (LD50 >2,000 mg/kg BW), indicating low acute oral toxicity. Repeated administration for 28 days caused no significant changes in body weight, organ weights, serum biochemical markers, or histopathological findings. However, a significant reduction in white blood cell counts was observed at doses ≥400 mg/kg BW/day (p<0.05). The subacute no-observed-adverse-effect-level (NOAEL) and lowest-observed-adverse-effect-level (LOAEL) were established at 300 and 400 mg/kg BW/day, respectively.

CONCLUSION: Based on the parameters assessed, the acute NOAEL for EECB was 2,000 mg/kg BW, while the subacute NOAEL and LOAEL for EECB were 300 and 400 mg/kg BW/day, respectively. These findings indicate that EECB might be safe at moderate doses, providing in vivo evidence supporting its further development as a phytoestrogenic agent.

KEYWORDS: Cyclea barbata Miers, ethanol extract, acute toxicity, subacute toxicity, haematological parameters