Identification of JUN as determinant of osteoarthritis and its inhibition by the Chinese herbal formulae Zhuanggu Huoxue Tang. (September 2022)

• Record Type: Journal Article
• Authors: Zheng, Zhenyu; Guo, Malong; Zhu, Wenxiao; Cheng, Weidong; Kong, Liang; Liu, Yonghui; Qiu, Yongqi; Wang, Xiangyang; Wang, Yidi; Cui, Hongxun
• Is Part Of: Computers in biology and medicine. Volume 148(2022)
• Publication Date: 2022-09
• Subjects: Osteoarthritis -- Synovitis -- Network pharmacology -- Miltirone -- JUN; Medicine -- Data processing -- Periodicals; Biology -- Data processing -- Periodicals; 610.285
• DOI: 10.1016/j.compbiomed.2022.105786
• Languages: English
• ISSNs: 0010-4825

Abstract

Abstract: Synovitis is an essential feature of Osteoarthritis (OA). Increasing evidence demonstrates that synovitis plays a critical role in OA's symptoms and structural progression. However, there is no effective drug for preventing and treating synovitis. Some Chinese herbal formulae have been found to treat clinical OA effectively, however, their mode of action is still unclear. This study investigated the Chinese herbal formulae Zhuanggu Huoxue Tang (ZHT) underlying mechanisms for treating osteoarthritis. Transcriptome data and a network pharmacology analysis were used to investigate the biochemical pathways affected by ZHT during OA treatment with in vitro verification. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were undertaken. The interaction network of the ZHT active constituent targets was determined using Cytoscape 3.7.1 software. Molecular docking of key pathogenic proteins and components of ZHT was performed in silico to confirm the compounds' pharmaceutical activities. The results establish that JUN is a target pathway in the pathogenesis of osteoarthritis. Miltirone, one of the active ingredients of ZHT, demonstrated a suitable binding activity with JUN. Miltirone alleviates the catabolic gene expression induced by IL-1β and IL-6 in synovial fibroblasts (FLS), validating the use of Miltirone as a therapeutic drug for osteoarthritis. Graphical abstract: Image 1 Highlights: JUN was an up-regulated transcription factor in synovitis of osteoarthritis. Miltirone is an active ingredient of Zhuanggu Huoxue Tang in the treatment of OA. Miltirone demonstrated a suitable binding activity with JUN. Miltirone can inhibit il-6 and IL-1β-induced MMP3 and MMP13 expression.