Water Extract of Piper longum Linn Ameliorates Ovariectomy-Induced Bone Loss by Inhibiting Osteoclast Differentiation

Abstract

<i>Piper longum</i> linn has traditionally been used for the treatment of respiratory and gastrointestinal disorders in India. Although various pharmacological effects of <i>P. longum</i> have been studied, its effects on bone have not been clearly elucidated. Therefore, this study examined the inhibitory effect of the water extract of <i>P. longum</i> Linn (WEPL) on osteoclast differentiation. WEPL directly affected the osteoclast precursors and suppressed osteoclast differentiation in vitro. In addition, the expression levels of c-Fos and nuclear factor of activated T cells 1, a critical transcription factor for osteoclastogenesis, were significantly downregulated by WEPL via the suppression of the receptor activator of nuclear factor (NF)-κB ligand-induced mitogen-activated protein kinase and NF-κB signaling pathways. Consistent with the in vitro results, oral administration of WEPL (100 and 300 mpk) to ovariectomized mice for six weeks relieved the OVX-induced bone loss. We also identified phytochemicals in WEPL that are reported to exert inhibitory effects on osteoclastogenesis and/or bone loss. Collectively, the findings of our study indicate that WEPL has an anti-osteoporotic effect on OVX-induced bone loss by diminishing osteoclast differentiation, suggesting that it may be useful to treat several bone diseases caused by excessive bone resorption.