Baicalein has been shown to have chondroprotective potential in vitro. However, its effect on disease modification in osteoarthritis (OA) is largely unknown. The present study is aimed at determining whether baicalein could slow the progression of OA and inhibit OA-related inflammation in a rat model of destabilization of the medial meniscus (DMM) and the underlying mechanisms. The rats subjected to DMM surgery were treated with baicalein (0.8, 1.6, and 3.2 μg/L, 50 μL, once a week) by intra-articular injection for 6 weeks. Dexamethasone (0.4 mg/mL, 50 μL, once a week) was used as a positive control. Histologic grading of cartilage degeneration was performed using the Osteoarthritis Research Society International (OARSI) recommended grading system (on a scale of 0-6). The expression levels of molecules associated with cartilage homeostasis and inflammatory cytokines were analyzed; moreover, the NLRP3 inflammasome activation and cartilage oxidative stress-associated molecules were determined. Baicalein treatment reduced the OARSI score and slowed OA disease progression in a dose-dependent manner within a certain range. Compared with DMM rats, intra-articular injection of baicalein led to (1) reduced levels of inflammatory mediates such as IL-1β and TNF-α, (2) reduced immunochemical staining of MMP-13 and ADAMTS-5, (3) suppressed immunochemical staining loss of type II collagen, (4) reduced expression of cartilage degradation markers including CTX-II and COMP in urine, and (5) inhibited NLRP3 inflammasome activation rather than regulated expression of SOD, GSH, and MDA. In contrast to the administration of baicalein, dexamethasone injection showed similar effects to slow OA progression, while dexamethasone inhibited NLRP3 inflammasome partly through decreasing levels of SOD, GSH, and MDA. This study indicated that baicalein may have the potential for OA prevention and exerts anti-inflammatory effects partly via suppressing NLRP3 inflammasome activation without affecting oxidative stress-associated molecules, and inhibition of cartilage catabolism enzymes in an OA rat model.

中文翻译：

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关节内注射黄芩素抑制创伤后 OA 模型中的软骨分解代谢和 NLRP3 炎性体信号传导

黄芩素已被证明在体外具有软骨保护潜力。然而，它对骨关节炎 (OA) 疾病改变的影响在很大程度上是未知的。本研究旨在确定在内侧半月板 (DMM) 不稳定的大鼠模型中，黄芩素是否可以减缓 OA 的进展并抑制 OA 相关炎症及其潜在机制。接受DMM手术的大鼠通过关节内注射黄芩素（0.8、1.6和 3.2μg /L，  50μL ，每周一次）治疗6周。地塞米松（0.4 mg/mL，50  μL，每周一次）用作阳性对照。使用国际骨关节炎研究协会 (OARSI) 推荐的分级系统（0-6 级）对软骨退化进行组织学分级。分析了与软骨稳态和炎性细胞因子相关的分子的表达水平；此外，还测定了 NLRP3 炎性体激活和软骨氧化应激相关分子。黄芩素治疗在一定范围内以剂量依赖性方式降低 OARSI 评分并减缓 OA 疾病进展。与 DMM 大鼠相比，关节内注射黄芩素导致 (1) 炎症介质水平降低，例如 IL-1 β和 TNF - α(2) 减少 MMP-13 和 ADAMTS-5 的免疫化学染色，(3) 抑制 II 型胶原蛋白的免疫化学染色损失，(4) 减少尿液中包括 CTX-II 和 COMP 在内的软骨降解标志物的表达，以及 (5)抑制 NLRP3 炎症小体的激活，而不是调节 SOD、GSH 和 MDA 的表达。与黄芩素相比，地塞米松注射液对减缓 OA 进展表现出相似的效果，而地塞米松通过降低 SOD、GSH 和 MDA 水平部分抑制 NLRP3 炎性体。本研究表明，黄芩素可能具有预防 OA 的潜力，并部分通过抑制 NLRP3 炎性体激活而不影响氧化应激相关分子，以及抑制 OA 大鼠模型中的软骨分解代谢酶来发挥抗炎作用。