通痹活络汤通过抑制细胞外基质降解减轻膝骨关节炎软骨退变。
Tongbi Huoluo Decoction alleviates cartilage degeneration in knee osteoarthritis by inhibiting degradation of extracellular matrix.
作者信息
Chen Weijian, Liu Weinian, Jiang Tao, Liu Lingyun, He Qi, Lin Tianye, Zhang Jiayuan, Huo Liwei, Xu Xuemeng, Wang Haibin, Liang Du, Liu Wengang
机构信息
The Fifth Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, 510095, China.
Guangdong Second Hospital of Traditional Chinese Medicine (Guangdong Province Engineering Technology Research Institute of Traditional Chinese Medicine), Guangzhou, 510095, China.
出版信息
Chin Med. 2023 Jul 28;18(1):91. doi: 10.1186/s13020-023-00802-z.
BACKGROUND
Knee osteoarthritis (KOA) is an age-related degenerative disease characterized by abrasion of articular cartilage. Tongbi Huoluo Decoction (TBHLD) has been transformed from the famous traditional Chinese medicine Duhuo Jisheng Decoction, which can effectively alleviate pain symptoms in KOA. However, the active components and mechanisms of TBHLD in treating KOA have not yet been elucidated. The purpose of the study was to demonstrate the molecular mechanism of TBHLD in treating KOA.
METHODS
The components and targets of TBHLD and KOA were collected from multiple databases, and the protein to protein interaction (PPI) network was constructed. Next, we performed topological calculation and enrichment analysis. Besides, we performed virtual screening for molecular docking and molecular dynamics simulation (MDS). Furthermore, the vitro and vivo experiments were performed to evaluate the validity and mechanism of TBHLD.
RESULTS
206 active components and 187 potential targets were screened from Tongbi Huoluo Decoction. A total of 50 intersecting genes were identified between TBHLD and KOA, 20 core targets were calculated by network topology analysis. The core targets were enriched in the ECM interaction pathways. The results of virtual screening for molecular docking and MDS showed that the active components of TBHLD had steady binding conformations with core genes. Moreover, we identified 32 differential serum components in TBHLD-containing serum using LC-MS, including 22 upregulated and 10 downregulated serum components. TBHLD improved the proliferation activity of OA chondrocytes, decreased the expression of Col1a1, Col1a2, Mmp2, Mmp13 in OA chondrocytes, ameliorated the cartilage lesions and restored the cartilage abrasion.
CONCLUSION
TBHLD inhibited degradation of cartilage ECM by regulating the expression of type I collagens and Mmps to ameliorate cartilage degeneration in KOA.
背景
膝骨关节炎（KOA）是一种与年龄相关的退行性疾病，其特征为关节软骨磨损。通痹活络汤（TBHLD）由著名的中药独活寄生汤化裁而来，能有效缓解KOA的疼痛症状。然而，TBHLD治疗KOA的活性成分和作用机制尚未阐明。本研究旨在揭示TBHLD治疗KOA的分子机制。
方法
从多个数据库收集TBHLD和KOA的成分及靶点，构建蛋白质-蛋白质相互作用（PPI）网络。接着，进行拓扑计算和富集分析。此外，进行分子对接和分子动力学模拟（MDS）的虚拟筛选。进一步开展体外和体内实验，以评估TBHLD的有效性和作用机制。
结果
从通痹活络汤中筛选出206种活性成分和187个潜在靶点。共鉴定出TBHLD与KOA之间的50个交集基因，通过网络拓扑分析计算出20个核心靶点。核心靶点富集于细胞外基质相互作用通路。分子对接和MDS的虚拟筛选结果表明，TBHLD的活性成分与核心基因具有稳定的结合构象。此外，我们利用液相色谱-质谱联用技术鉴定出含TBHLD血清中的32种差异血清成分，其中22种上调，10种下调。TBHLD提高了OA软骨细胞的增殖活性，降低了OA软骨细胞中Col1a1、Col1a2、Mmp2、Mmp13的表达，改善了软骨损伤并修复了软骨磨损。
结论
TBHLD通过调节I型胶原蛋白和基质金属蛋白酶的表达抑制软骨细胞外基质的降解，从而改善KOA的软骨退变。
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