Xu Mengdai, Chen Xi, Du Shasha, Xu Huanhuan, Liu Changyu
Department of Clinical Nutrition, Traditional Chinese and Western Medicine Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People's Republic of China.
Department of Clinical Nutrition, Wuhan No.1 Hospital, Wuhan, Hubei, 430022, People's Republic of China.
Mol Med. 2025 Jun 22;31(1):246. doi: 10.1186/s10020-025-01302-6.
Osteoarthritis (OA) is the most prevalent chronic articular disease in adults. The degree of cartilage degradation and matrix depletion in OA have been substantially connected with chondrocyte inflammatory response. Consequently, pharmacological anti-inflammatory agents provide OA patients a new therapeutic option. Isoginkgetin (IGK), a bioactive bioflavonoid derived from the medicinal herb Ginkgo Biloba, defends against obesity-induced heart diastolic dysfunction and harmful remodeling. Whether IGK has a regulatory effect on OA remains unknown. This study investigated whether IGK could attenuate the progression of OA both in vivo and in vitro.
Cell Counting Kit-8 (CCK8) was used to measure the vitality of chondrocytes. Mediators of inflammation, anabolism and catabolism were tested by Western blot and RT-PCR. Safranin-O staining, Hematoxylin-Eosin (H&E) staining, immunofluorescence, and Osteoarthritis Research Society International (OARSI) standards were used to assess the severity of OA and the degradation of articular cartilage. The phenotype of cartilage, NF-κB and P21 signaling pathway were measured by Western Blot. The mRNA sequencing was selected to find the differentially expressed genes and potential pathway. Pain of mice was measured by Von Frey hair mechanosensitivity. The senescence level of chondrocyte was SA-β-Gal staining.
IGK inhibited catabolism and promoted anabolism after stimulating by IL-1β in vitro. Following destabilization of the medial meniscus (DMM) surgery, administration of IGK significantly reduced OARSI scores and attenuated AGGRECAN and COLLAGEN2 loss, overexpression of MMP3 and articular cartilage deterioration. IGK relieved pain of mice after DMM. Besides, PI3K/AKT/NF-κB, P53, Autophagy, Ferroptosis pathway and reactive oxygen species (ROS), senescence of cartilage were changed after IGK treatment.
IGK protects articular cartilage and reduces the progression of OA in a mouse model and shows promise as a potential therapeutic strategy for OA.
骨关节炎（OA）是成人中最常见的慢性关节疾病。OA中软骨降解和基质消耗的程度与软骨细胞炎症反应密切相关。因此，药理抗炎剂为OA患者提供了一种新的治疗选择。异银杏双黄酮（IGK）是一种从药用植物银杏中提取的生物活性生物黄酮，可预防肥胖引起的心脏舒张功能障碍和有害重塑。IGK对OA是否具有调节作用尚不清楚。本研究调查了IGK在体内和体外是否能减缓OA的进展。
使用细胞计数试剂盒-8（CCK8）测量软骨细胞活力。通过蛋白质免疫印迹法（Western blot）和逆转录-聚合酶链反应（RT-PCR）检测炎症、合成代谢和分解代谢介质。采用番红O染色、苏木精-伊红（H&E）染色、免疫荧光和国际骨关节炎研究学会（OARSI）标准评估OA的严重程度和关节软骨的降解。通过蛋白质免疫印迹法检测软骨表型、核因子κB（NF-κB）和P21信号通路。选择mRNA测序以发现差异表达基因和潜在途径。通过von Frey毛发机械敏感性测量小鼠疼痛。通过衰老相关β-半乳糖苷酶（SA-β-Gal）染色检测软骨细胞的衰老水平。
体外IL-1β刺激后，IGK抑制分解代谢并促进合成代谢。内侧半月板不稳定（DMM）手术后，给予IGK可显著降低OARSI评分，减轻聚集蛋白聚糖（AGGRECAN）和胶原蛋白2（COLLAGEN2）损失、基质金属蛋白酶3（MMP3）过表达和关节软骨退变。IGK减轻了DMM后小鼠的疼痛。此外，IGK处理后PI3K/AKT/NF-κB、P53、自噬、铁死亡途径和活性氧（ROS）、软骨衰老发生改变。
IGK在小鼠模型中保护关节软骨并减缓OA的进展，有望成为OA的潜在治疗策略。
