Isosakuranetin inhibits subchondral osteoclastogenesis for attenuating osteoarthritis via suppressing NF-κB/CXCL2 axis

作者：Shuai Lu, Chao Fang · 发表于：International Immunopharmacology · 年份：2024 · DOI：10.1016/j.intimp.2024.113321 · 被引用次数：11 · 研究领域：Osteoarthritis Treatment and Mechanisms、Bone Metabolism and Diseases、Inflammatory mediators and NSAID effects

• CMC/TOFMS method, a biological affinity chromatographic system, was utilized to screen potential constituents from a natural plant. • We for the first time identified Isosakuranetin (ISN) from Rhizoma anemarrhenae (Zhimu) via the CMC/TOFMS method. • ISN inhibits subchondral osteoclastogenesis in osteoarthritis (OA) mice model, thereby ameliorating articular cartilage deterioration. • ISN ameliorated abnormal angiogenesis in the subchondral bone marrow and alleviated osteoclast-associated pain in OA mice model. • NF-κB/CXCL2 axis was required for ISN targeting of osteoclastogenesis. As the most predominant form of arthritis, osteoarthritis (OA) is featured with irreversible progress and involvement of the whole joint. Since OA onset, abnormal mechanical load initiates excessive osteoclastogenesis, evolving a rapid turnover of subchondral bone, cyst creation, synovitis, cartilage degradation, and ultimately resulting in joint failure. Additionally, aberrant vascularization and nociceptive pain are invoked by osteoclast-induced angiogenesis and sensory innervation in the subchondral bone. Rhizoma anemarrhenae (Zhimu) has been extensively demonstrated to show multiple pharmacological effects including anti-inflammation, anti-aging, and immunomodulation. Herein, Broussonin a (BRA), Markogein (MAN), and Isosakuranetin (ISN) derived from Rhizoma anemarrhenae, were initially discovered for their affinity with Bone marrow mononuclear cell (BMMC) membranes using the Cell membrane chr...