Xiaolu Chen,1– 3 Jian Liu,1,2 Guizhen Wang,1,2 Yanqiu Sun,1,2 Xiang Ding,1– 3 Xianheng Zhang1– 3 

1Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui Province, 230038, People’s Republic of China; 2Institute of Rheumatology, Anhui University of Chinese Medicine, Hefei, Anhui Province, 230012, People’s Republic of China; 3Anhui University of Traditional Chinese Medicine, Hefei, People’s Republic of China

Correspondence: Jian Liu, Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui Province, 230038, People’s Republic of China, Tel +86 551 62838582, Fax +86 551 62821605, Email liujianahzy@126.com

Objective: 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.
Methods: 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.
Results: 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.
Conclusion: 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.

Keywords: osteoarthritis, chondrocytes, inflammation, LncRNA HOTAIR/APN/PI3K/AKT