Safety Evaluation of a Standardized Dalbergia sissoo Leaf Extract (DSLE)

Background: Dalbergia sissoo, also known as Indian Rosewood, is a plant known for its medicinal value with the leaves used traditionally for its effect on joint inflammation and joint pain. Recently, Dalbergia sissoo leaves and its derived novel compound Caviunin glycoside (CAFG) was shown to alleviate symptoms and signs of osteoarthritis in a rat model. Objectives: The objective of the study was to investigate potential adverse effects, if any, of a standardized Dalbergia sissoo leaf extract (DSLE) in rats following sub-chronic administration. Materials and Methods: DSLE was standardized to a composition of not less than 2% w/w CAFG and not less than 6% w/w total flavonoids. In the sub-chronic study, Wistar rats (10/sex/group) were administered via gavage 0 (control), 310, 620, 1240 mg/kg body weight/day of DSLE for 90 days. Two additional groups received 0 and 1240mg/kg /day of the extract for 90 days, followed by a 28-day reversal phase. Results: The study revealed that administration of the DSLE did not result in any toxicologically significant treatment related changes in clinical observation, ophthalmic examination, body weight, body weight gain, feed consumption, clinical pathology and organ weight. The haematology and serum chemistry parameters compared to the control group were also within the normal laboratory limits. Terminal necroscopy did not indicate any treatment related gross or histopathological findings. The results of genotoxicity studies as evaluated by gene mutations in Salmonella typhimurium, and in vitro chromosome aberration assay did not reveal any genotoxicity of the extract. Conclusion: Based on the results of this study, the no observed-adverse-effect level (NOAEL) for this standardized Dalbergia sissoo leaf extract was determined as 1240 mg/kg body weight/day, the highest dose tested.