Apocynum venetum leaf extract ameliorates postmenopausal osteoporosis by inhibiting RANKL-induced osteoclastogenesis

Identification of the novel therapeutic efficacies of traditional Chinese medicine (TCM) and the underlying mechanisms of the efficacies is essential for TCM modernization and development. Apocynum venetum leaf (AVL) is used both as an antihypertensive medicine and as a food. Whether AVL extract is of other therapeutic efficacy is still waiting for investigation. Here, we investigated the potential effect of AVL extract on ameliorating postmenopausal osteoporosis (PMO), and identified the effective fractions of the AVL extract and the underlying mechanisms of the efficacy. We found that the total extract of AVL substantially relieves the osteoporosis symptoms both in a mouse and a rat ovariectomized model. Moreover, the AVL-95% fraction, only accounting for ~ 2% of the total extract, exhibits a comparable therapeutic effect on osteoporosis to the total extract of AVL. To be noted, AVL-95% fraction improves both cancellous and cortical bones. In addition, it exhibits beneficial effect on both femurs and vertebrae in the OVX mice. Mechanistic study showed that AVL-95% inhibits osteoclastogenesis through inhibiting RANKL signaling. Importantly, AVL-95% does not show apparent toxicity in the acute and chronic toxicity evaluations. Together, our work discloses a previously unknown efficacy of AVL in PMO intervention and an underlying mechanism of the efficacy, highlighting the anti-PMO application potential of AVL.