Zhang Yi-Li, Tang Bin, Jiang Jun-Jie, Shen Hao, Xie Yan-Ming, Wei Xu
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Beijing University of Chinese Medicine, Beijing 100029, China.
Zhongguo Zhong Yao Za Zhi. 2018 Oct;43(20):4125-4131. doi: 10.19540/j.cnki.cjcmm.20180508.002.
Drynariae Rhizoma has great significance in the clinical practice of osteoporosis treatment. Based on the perspective of integrative pharmacology, the study explored the mechanism of action of Drynariae Rhizoma in the treatment of osteoporosis. Six active components in Drynariae Rhizoma were obtained, mainly including glycosides and sterols. Taking the median of 2 times of "node connectivity" as the card value, the core node of the Chinese medicine target disease gene interaction network was selected. Based on this, three topological structural eigenvalues, such as "node connectivity" "node tightness" and "node connectivity" were calculated, thereby screening out four core targets of Drynariae Rhizoma treatment for osteoporosis, including thyroid parathyroid hormone 1 receptor (PTH1R), parathyroid hormone 2 receptor (PTH2R), calcitonin receptor gene (CALCR), and SPTBN1 gene (SPTBN1). Based on the gene ontology database GO and KEGG pathway database, the molecular function, intracellular localization, and biological reactions and pathways of proteins encoded by drug target genes were determined. Combined with enrichment calculation, it is predicted that osteoporosis may play a role in biosynthetic processes, such as circulatory system, nervous system, energy metabolism, prolactin signal pathway, GnRH signaling pathway, neurotrophic factor signaling pathway and other pathway. The conclusion of this study is certain with the existing research results, and the new target and new pathway could also be used as a theoretical basis for the further verification of osteoporosis.
骨碎补在骨质疏松症治疗的临床实践中具有重要意义。基于整合药理学的视角,该研究探讨了骨碎补治疗骨质疏松症的作用机制。获得了骨碎补中的6种活性成分,主要包括糖苷和甾醇。以“节点连通性”2倍的中位数作为卡值,选取中药靶点疾病基因相互作用网络的核心节点。在此基础上,计算“节点连通性”“节点紧密性”“节点介数”等3个拓扑结构特征值,从而筛选出骨碎补治疗骨质疏松症的4个核心靶点,包括甲状腺甲状旁腺激素1受体(PTH1R)、甲状旁腺激素2受体(PTH2R)、降钙素受体基因(CALCR)和SPTBN1基因(SPTBN1)。基于基因本体数据库GO和KEGG通路数据库,确定了药物靶点基因编码蛋白的分子功能、细胞内定位以及生物学反应和通路。结合富集计算,预测骨质疏松症可能在生物合成过程中发挥作用,如循环系统、神经系统、能量代谢、催乳素信号通路、GnRH信号通路、神经营养因子信号通路等通路。本研究结论与现有研究结果具有一定的契合性,新靶点和新通路也可为进一步验证骨质疏松症提供理论依据。