目的:骨关节炎(OA)是一种退行性关节疾病,其特征是关节软骨逐渐退化和局部炎症。本研究旨在探讨黄芩苷(SCU)的抗OA作用,从半枝莲D.Don获得的单一单位类黄酮化合物,在老鼠
方法:用SCU和IL-1β处理提取的大鼠软骨细胞。将软骨细胞分为对照组,IL-1β组,IL-1β+SCU50µmol/L组,IL-1β+SCU100μmol/L组。通过甲苯胺蓝和番红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。ELISA,qRT-PCR,西方印迹,免疫荧光,SAβ-gal染色,流式细胞术,应用生物信息学分析评价SCU对IL-1β干预下大鼠软骨细胞的影响。此外,采用前交叉韧带横断术(ACL-T)建立大鼠OA模型。通过SafraninO/fastgreen检测到组织学变化,苏木精-伊红(HE)染色,和免疫组织化学。
结果:SCU通过多种机制保护软骨并表现出抗炎作用。具体来说,它可以促进软骨细胞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IL-1β诱导的大鼠软骨细胞凋亡和衰老,进一步凸显其在OA治疗中的潜在作用。体内实验表明,SCU(以50mg/kg的剂量)给药2个月可以显着延迟软骨损伤的进展,这反映在较低的骨关节炎研究学会国际(OARSI)评分中,软骨中基质金属蛋白酶13(MMP13)的表达降低。
结论:SCU在OA的治疗管理中是有效的,可以作为未来OA临床药物治疗的潜在候选者。
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: SCU is effective in the therapeutic management of OA and could serve as a potential candidate for future clinical drug therapy for OA.