背景:骨关节炎(OA)的发病率增加,尤其是老年人群,强调需要更有效的治疗,而不仅仅是缓解症状。Tinosporacrispa(L.)钩。f.&汤姆森(TC)拥有丰富的传统遗产,在阿育吠陀广泛使用,中药(TCM),以及东南亚各地不同的本土治疗方法来治疗关节炎,风湿病,发烧,和炎症。
目的:本研究调查了TC茎提取物的抗炎和软骨保护潜力,包括乙醇TC提取物(ETCE)和水性TC提取物(ATCE),通过体外和体内方法调节OA的发病机理。
方法:该研究利用LC-MS/MS鉴定了TC茎提取物中的关键化合物。体外实验评估了ETCE和ATCE在活化巨噬细胞中的抗氧化和抗炎特性,而体内单碘乙酸盐(MIA)诱导的OA大鼠模型评估了ETCE治疗的功效。氧化应激的关键标志物,如超氧化物歧化酶(SOD)和过氧化氢酶(CAT),与促炎细胞因子TNF-α和IL-1β一起评估,和基质降解酶,基质金属蛋白酶(MMP13和MMP3),评价TC茎提取物对OA的治疗作用。
结果:使用LC-MS/MS在正电离中对提取物进行化学分析,鉴定七种化合物,包括假硬脂酸B,苯乙烯,和网状,这是该物种首次报道的。这项研究利用了不同浓度的TC茎提取物,特别是6.25至25μg/mL的体外测定和500mg/kg的体内研究。我们的发现还表明,ETCE和ATCE都表现出剂量依赖性的活性氧(41%至52%)和一氧化氮(NO)水平(50%和72%)的降低,ETCE表现出优异的抗氧化功效和显著的抗炎特性,在浓度高于12.5μg/mL时显著降低TNF-α和IL-6。在MIA诱导的OA大鼠模型中,ETCE治疗明显优于ATCE,显着降低TNF-α(1.9pg/mL)和IL-1β(37.5pg/mL)水平,并有效抑制MMP13和MMP3酶。此外,宏观和组织病理学评估,包括ICRS评分和OARSI评分,表明TC茎提取物可以减少大鼠膝关节软骨的关节损伤和蛋白聚糖的丢失。这些结果表明,TC茎提取物可能在预防软骨降解和潜在缓解与OA相关的炎症和疼痛方面发挥作用。尽管需要进一步的研究来证实这些影响。
结论:这项研究强调了TC茎提取物作为一种新型的,用于OA管理的软骨保护治疗途径。通过靶向氧化应激,促炎细胞因子,和软骨降解酶,TC茎提取物有望防止软骨降解并减轻与OA相关的炎症和疼痛。
BACKGROUND: The increasing incidence of osteoarthritis (OA), especially among the elderly population, highlights the need for more efficacious treatments that go beyond mere symptomatic relief. Tinospora crispa (L.) Hook. f. & Thomson (TC) boasts a rich traditional heritage, widespread use in Ayurveda, traditional Chinese medicine (TCM), and diverse indigenous healing practices throughout Southeast Asia for treating arthritis, rheumatism, fever, and inflammation.
OBJECTIVE: This study investigates the anti-inflammatory and chondroprotective potential of TC stem extracts, including ethanolic TC extract (ETCE) and aqueous TC extract (ATCE), in modulating OA pathogenesis through in vitro and in vivo approaches.
METHODS: The study utilized LC-MS/MS to identify key compounds in TC stem extracts. In vitro experiments assessed the antioxidative and anti-inflammatory properties of ETCE and ATCE in activated macrophages, while an in vivo monoiodoacetate (MIA)-induced OA rat model evaluated the efficacy of ETCE treatment. Key markers of oxidative stress, such as superoxide dismutase (SOD) and catalase (CAT), were assessed alongside pro-inflammatory cytokines TNF-α and IL-1β, and matrix-degrading enzymes, matrix metalloproteinase (MMP 13 and MMP 3), to evaluate the therapeutic effects of TC stem extracts on OA.
RESULTS: Chemical profiling of the extracts was conducted using LC-MS/MS in positive ionization, identifying seven compounds, including pseudolaric acid B, stylopine, and reticuline, which were reported for the first time in this species. The study utilized varying concentrations of TC stem extracts, specifically 6.25-25 μg/mL for in vitro assays and 500 mg/kg for in vivo studies. Our findings also revealed that both ETCE and ATCE exhibit dose-dependent reduction in reactive oxygen species (41%-52%) and nitric oxide (NO) levels (50% and 72%), with ETCE displaying superior antioxidative efficacy and marked anti-inflammatory properties, significantly reducing TNF-α and IL-6 at concentrations above 12.5 μg/mL. In the MIA-induced OA rat model, ETCE treatment notably outperformed ATCE, markedly lowering TNF-α (1.91 ± 0.37 pg/mL) and IL-1β (26.30 ± 3.68 pg/mL) levels and effectively inhibiting MMP 13 and MMP 3 enzymes. Furthermore, macroscopic and histopathological assessments, including ICRS scoring and OARSI grading, indicate that TC stem extracts reduce articular damage and proteoglycan loss in rat knee cartilage. These results suggest that TC stem extracts may play a role in preventing cartilage degradation and potentially alleviating inflammation and pain associated with OA, though further studies are needed to confirm these effects.
CONCLUSIONS: This study highlights the potential of TC stem extracts as a novel, chondroprotective therapeutic avenue for OA management. By targeting oxidative stress, pro-inflammatory cytokines, and cartilage-degrading enzymes, TC stem extracts promise to prevent cartilage degradation and alleviate inflammation and pain associated with OA.