Isolation of Cowanol from the Garcinia oblongifolia Plant and Evaluation of its in vivo Toxicity and Bone-protective Activity in Medaka Fish (Oryzias latipes)

Garcinia oblongifolia Champ. ex Benth is a plant species widely distributed in Vietnam. It contains xanthones - bioactive compounds known for their potent antioxidant, anti-inflammatory, and anticancer properties. Xanthones have also emerged as potential bone-protective agents. Here, cowanol, a common xanthone, was isolated from the branches of G. oblongifolia in Binh Dinh Province, with 98.4% purity. The in vivo toxicity and bone-protective activity of cowanol were assessed using medaka (Oryzias latipes), a standardized fish model in toxicity and disease research. Acute toxicity was evaluated over a 96-hour exposure period, assessing wild-type embryos (24-120 hours post-fertilization) to concentrations ranging from 2 to 50 µM and larvae (7-11 days post-fertilization) to the doses of 2 to 30 µM. Results showed that cowanol was non-toxic to embryos but exhibited dose- and time-dependent toxicity to larvae, with the lethal concentration 50 (LC50) of 11.4 µM. At the doses of 2 µM or lower, cowanol was safe for medaka larvae. The bone-protective effect of cowanol was investigated using rankl:HSE:CFP transgenic larvae model for osteoporosis. Our findings revealed that cowanol significantly reduced bone damage in the Rankl-induced osteoporosis fish at three tested doses of 0.5, 1.5, or 2 µM with bone protection indexes reaching up to 29.38%. This study highlights the potential exploration of xanthones from Vietnamese plants for therapeutic applications.