Chen Guang-Yao, Wang Yi-Fei, Yu Xin-Bo, Liu Xiao-Yu, Chen Jia-Qi, Luo Jing, Tao Qing-Wen
Beijing University of Chinese Medicine, Beijing 100029, China.
Department of TCM Rheumatology, China-Japan Friendship Hospital, Beijing 100029, China.
Evid Based Complement Alternat Med. 2022 Jul 14;2022:1826299. doi: 10.1155/2022/1826299. eCollection 2022.
is a representative tonifying kidney drug and is widely used for osteoarthritis (OA) in traditional Chinese medicine. However, its regulatory mechanisms in treating OA remain to be sufficiently investigated. The main chemical components of were screened through the TCMID database and the corresponding targets were acquired through SwissTargetPrediction. The OA-related targets were obtained from the OMIM, Genecards, Genebank, TTD, and DisGeNET databases. The prediction of key targets and pathways of in the treatment of OA was achieved by constructing a compounds-targets network and performing KEGG enrichment analysis. The OA model rats were established by the Hulth method and used to explore the protective effect of via cartilage pathological assessment. In vitro models of OA were built by the proinflammatory factor interleukin-1 (IL-1) induced SW1353 cells and used to validate the mechanisms predicted by network pharmacology. Network pharmacology results suggested that the therapeutic effects of were closely related to matrix metalloproteinase (MMP)-1, 3, 13 and inflammation-related gene COX2, which are regulated by the NFB pathway. In vivo experiments revealed that could effectively restrain cartilage from degeneration and inhibit the mRNA expression of MMP-1, MMP-3, MMP-13, and COX2 in cartilage. In vitro experiments indicated that water extract (CBWE) could significantly inhibit the expression of MMP-1, MMP-3, MMP-13, and PGE in IL-1-induced SW1353 cells and markedly prevent the translocation of NFB p65 from the cytoplasm to the nuclei and decrease its phosphorylation level. After small-interfering RNA (siRNA) was used to suppress the synthesis of NFB p65 to block NFB signaling pathway, the ability of CBWE to inhibit MMP-1, MMP-3, MMP-13, and PGE was greatly reduced. has a chondroprotective effect on OA by inhibiting the response to inflammation and substrate degradation, and the related mechanism is associated with the inhibition of the NFB pathway.
是一种典型的补肾药物，在传统中医中广泛用于治疗骨关节炎（OA）。然而，其治疗OA的调节机制仍有待充分研究。通过中药综合数据库（TCMID）筛选出的主要化学成分，并通过瑞士药物靶点预测（SwissTargetPrediction）获取相应靶点。OA相关靶点从在线孟德尔人类遗传数据库（OMIM）、基因卡片（Genecards）、基因银行（Genebank）、治疗靶点数据库（TTD）和疾病基因数据库（DisGeNET）中获取。通过构建化合物-靶点网络并进行京都基因与基因组百科全书（KEGG）富集分析，预测在治疗OA中的关键靶点和通路。采用 Hulth 法建立OA模型大鼠，通过软骨病理评估探讨的保护作用。通过促炎因子白细胞介素-1（IL-1）诱导SW1353细胞建立OA体外模型，用于验证网络药理学预测的机制。网络药理学结果表明，的治疗作用与基质金属蛋白酶（MMP）-1、3、13和炎症相关基因COX2密切相关，这些基因受核因子κB（NF-κB）通路调控。体内实验表明，可有效抑制软骨退变，抑制软骨中MMP-1、MMP-3、MMP-13和COX2的mRNA表达。体外实验表明，水提取物（CBWE）可显著抑制IL-1诱导的SW1353细胞中MMP-1、MMP-3、MMP-13和前列腺素E（PGE）的表达，并明显阻止NF-κB p65从细胞质向细胞核的转位并降低其磷酸化水平。使用小干扰RNA（siRNA）抑制NF-κB p65的合成以阻断NF-κB信号通路后，CBWE抑制MMP-1、MMP-3、MMP-13和PGE的能力大大降低。通过抑制炎症反应和底物降解对OA具有软骨保护作用，其相关机制与抑制NF-κB通路有关。
