Chen Xiaolu, Liu Jian, Wang Guizhen, Sun Yanqiu, Ding Xiang, Zhang Xianheng
Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui Province, 230038, People's Republic of China.
Institute of Rheumatology, Anhui University of Chinese Medicine, Hefei, Anhui Province, 230012, People's Republic of China.
Int J Gen Med. 2024 Jul 26;17:3293-3318. doi: 10.2147/IJGM.S466148. eCollection 2024.
Jianpi Qingre Tongluo Recipe (JQP) has been widely used in clinical practice, and its anti-Osteoarthritis (OA) effectiveness and specific mechanism have been concerned. This study aims to explore the clinical effect of JQP in reducing inflammation and dyslipidemia in OA and the molecular mechanism.
The clinical efficacy of JQP in OA treatment was assessed through data mining. Through the network pharmacology technology, the interactive network of "active component-target-disease" was developed, the interaction relationship of the related proteins was analyzed, and enrichment analysis of gene pathway biological process was conducted. Molecular docking was carried out with PyMOL and AutodockTools-1.5.7. Finally, cell experiments were used to verify JQP's delay of immune inflammation in OA.
We found that JQP could ameliorate the immune inflammatory and lipid metabolism indicators; reduce VAS and SAS score in OA. A total of 98 genes overlapped between target genes of JQP and OA. TNF, IL-6, IL-1β, and AKT1 shared the highest centrality among all target genes. KEGG analysis unveiled that 98 intersection genes were predominantly enriched in PI3K/AKT pathway in the anti-OA system. In vitro, after peripheral blood mononuclear cell (PBMC) stimulation, inflammatory cytokines imbalances and the expressions of adiponectin (APN) were decreased in osteoarthritis-chondrocytes (OA-CH). Furthermore, JQP-containing serum protected OA-CHs through down-regulating HOTAIR levels, thereby up-regulating APN and depressing PI3K/AKT pathway.
This study suggests that JQP might reduce inflammation and improve lipid metabolism of OA by regulating HOTAIR/APN/PI3K/AKT. Our results bring a new solution for OA.
健脾清热通络方（JQP）已在临床实践中广泛应用，其抗骨关节炎（OA）的有效性及具体机制备受关注。本研究旨在探讨JQP减轻OA炎症和血脂异常的临床疗效及分子机制。
通过数据挖掘评估JQP治疗OA的临床疗效。利用网络药理学技术构建“活性成分-靶点-疾病”相互作用网络，分析相关蛋白的相互作用关系，并进行基因通路生物学过程的富集分析。使用PyMOL和AutodockTools-1.5.7进行分子对接。最后，通过细胞实验验证JQP对OA免疫炎症的延缓作用。
我们发现JQP可改善免疫炎症和脂质代谢指标；降低OA患者的视觉模拟评分（VAS）和西安大略和麦克马斯特大学骨关节炎指数（WOMAC）评分。JQP的靶点基因与OA共有98个重叠基因。肿瘤坏死因子（TNF）、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）和蛋白激酶B1（AKT1）在所有靶点基因中具有最高的中心性。京都基因与基因组百科全书（KEGG）分析显示，98个交集基因在抗OA系统中主要富集于磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/AKT）通路。体外实验中，外周血单个核细胞（PBMC）刺激后，骨关节炎软骨细胞（OA-CH）中炎性细胞因子失衡，脂联素（APN）表达降低。此外，含JQP血清通过下调HOTAIR水平保护OA-CH，从而上调APN并抑制PI3K/AKT通路。
本研究表明JQP可能通过调节HOTAIR/APN/PI3K/AKT减轻OA炎症并改善脂质代谢。我们的研究结果为OA带来了新的解决方案。
