Network pharmacological analysis and experimental verification of semen cuscutae in treating postmenopausal osteoporosis

Xu Sheng; Zhang Wenwen; Zhang Weiwei; Wang Hongtao; Zhang Jun; Yang Ruisheng; Yuan Yuan; Wang Li; Hao Haihu

doi:10.12307/2026.095

Abstract：BACKGROUND:Semen cuscutae,a traditional Chinese medicine,has gradually shown its potential in anti-postmenopausal osteoporosis because of its relatively small side effects,which provides new ideas and possibilities for the treatment of this disease. OBJECTIVE:To explore the mechanism of anti-postmenopausal osteoporosis of semen cuscutae based on network pharmacological analysis and molecular docking and to validate it with animal experiments. METHODS:The main active components and corresponding targets of semen cuscutae were screened in TCMSP database,and the disease targets of postmenopausal osteoporosis were collected in GeneCards,OMIM and PharmGKB databases.After identification of common targets,a series of analyses were carried out,and core targets were selected.The core targets were analyzed by GO function and their role was verified by molecular docking.The corresponding active components were selected for animal experiments. RESULTS AND CONCLUSION:(1)Eleven main active components of semen cuscutae and 110 common targets of semen cuscutae and postmenopausal osteoporosis were screened out,and 10 core targets were identified.(2)GO function analysis showed that the core targets were closely related to oxidative stress and estrogen.(3)The top two ranked core target proteins,interleukin-6 and activated T-cell nuclear factor 1,were molecularly docked,and the top two ranked affinities,picloram and interleukin-6 as well as picloram and activated T-cell nuclear factor 1,were selected for validation in animal experiments.(4)Animal experimental results showed that matrine could inhibit the levels of interleukin-6 and activated T-cell nuclear factor 1 and improve trabecular bone structure of rats with postmenopausal osteoporosis.To conclude,low-dose matrine may affect the steady state of interleukin-6/soluble interleukin-6 receptor system by decreasing the level of interleukin-6,and inhibit the expression of nuclear factor 1 in downstream transcription factor-activated T cells in combination with nuclear factor-κB and mitogen-activated protein kinase signaling pathway to inhibit osteoclast differentiation,reduce bone resorption,repair trabecular structure and treat postmenopausal osteoporosis.