Department of Orthopedics, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China.
Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Curr Med Sci. 2024 Apr;44(2):355-368. doi: 10.1007/s11596-024-2854-6. Epub 2024 Apr 4.
Osteoarthritis (OA) is a degenerative joint disorder characterized by the gradual degradation of joint cartilage and local inflammation. This study aimed to investigate the anti-OA effect of scutellarein (SCU), a single-unit flavonoid compound obtained from Scutellaria barbata D. Don, in rats.
The extracted rat chondrocytes were treated with SCU and IL-1β. The chondrocytes were divided into control group, IL-1β group, IL-1β+SCU 50 µmol/L group, and IL-1β+SCU 100 µmol/L group. Morphology of rat chondrocytes was observed by toluidine blue and safranin O staining. CCK-8 method was used to detect the cytotoxicity of SCU. ELISA, qRT-PCR, Western blotting, immunofluorescence, SAβ-gal staining, flow cytometry, and bioinformatics analysis were applied to evaluate the effect of SCU on rat chondrocytes under IL-1β intervention. Additionally, anterior cruciate ligament transection (ACL-T) was used to establish a rat OA model. Histological changes were detected by safranin O/fast green, hematoxylin-eosin (HE) staining, and immunohistochemistry.
SCU protected cartilage and exhibited anti-inflammatory effects via multiple mechanisms. Specifically, it could enhance the synthesis of extracellular matrix in cartilage cells and inhibit its degradation. In addition, SCU partially inhibited the nuclear factor kappa-B/mitogen-activated protein kinase (NF-κB/MAPK) pathway, thereby reducing inflammatory cytokine production in the joint cartilage. Furthermore, SCU significantly reduced IL-1β-induced apoptosis and senescence in rat chondrocytes, further highlighting its potential role in OA treatment. In vivo experiments revealed that SCU (at a dose of 50 mg/kg) administered for 2 months could significantly delay the progression of cartilage damage, which was reflected in a lower Osteoarthritis Research Society International (OARSI) score, and reduced expression of matrix metalloproteinase 13 (MMP13) in cartilage.
SCU is effective in the therapeutic management of OA and could serve as a potential candidate for future clinical drug therapy for OA.
骨关节炎（OA）是一种退行性关节疾病，其特征为关节软骨逐渐降解和局部炎症。本研究旨在探讨从黄芩中提取的单体黄酮化合物野黄芩苷（SCU）对大鼠 OA 的治疗作用。
提取大鼠软骨细胞，用 SCU 和白细胞介素-1β（IL-1β）处理。将软骨细胞分为对照组、IL-1β 组、IL-1β+SCU50µmol/L 组和 IL-1β+SCU100µmol/L 组。用甲苯胺蓝和番红 O 染色观察大鼠软骨细胞的形态。CCK-8 法检测 SCU 的细胞毒性。应用 ELISA、qRT-PCR、Western blot、免疫荧光、SAβ-半乳糖苷染色、流式细胞术和生物信息学分析评估 IL-1β 干预下 SCU 对大鼠软骨细胞的作用。此外，采用前交叉韧带切断（ACL-T）建立大鼠 OA 模型。用番红 O/快绿、苏木精-伊红（HE）染色和免疫组织化学检测组织学变化。
SCU 通过多种机制保护软骨并发挥抗炎作用。具体而言，它可以增强软骨细胞外基质的合成并抑制其降解。此外，SCU 部分抑制核因子κB/丝裂原活化蛋白激酶（NF-κB/MAPK）通路，从而减少关节软骨中炎性细胞因子的产生。此外，SCU 显著降低了 IL-1β 诱导的大鼠软骨细胞凋亡和衰老，进一步凸显了其在 OA 治疗中的作用。体内实验表明，SCU（剂量为 50mg/kg）连续给药 2 个月可显著延缓软骨损伤的进展，表现为 OARSI 评分较低，软骨中基质金属蛋白酶 13（MMP13）表达减少。
SCU 对 OA 的治疗管理有效，可能成为未来 OA 临床药物治疗的潜在候选药物。
