He Qi, Tian Ding, Wang Zhiyuan, Zheng Dan, Zhi Liqiang, Ma Jianbing, An Jing, Zhang Rui
Department of Joint Surgery, Translational Medicine Center, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Department of Medical Technology, Guiyang Healthcare Vocational University, Guiyang, Guizhou, China.
Front Pharmacol. 2024 Jun 21;15:1361561. doi: 10.3389/fphar.2024.1361561. eCollection 2024.
Osteoarthritis (OA) is a chronic degenerative disease mainly characterized by cartilage damage and synovial inflammation. Si Miao Powder, an herbal formula, was recorded in ancient Chinese medicine prescription with excellent anti-inflammatory properties. Based on the classical formula, the modified Si Miao Powder (MSMP) was developed with the addition of two commonly Chinese orthopedic herbs, which had the efficacy of strengthening the therapeutic effect for OA.
In the experiments, thirty-six 8-week-old male C57BL/6 mice were randomly divided into six groups: sham group, OA group, celecoxib group, low-MSMP group, middle-MSMP group, and high-MSMP group. OA mice were constructed by destabilization of medial meniscus (DMM) and treated with MSMP granules or celecoxib by gavage. The effects of MSMP on cartilage, synovitis and inflammatory factor of serum were tested. For experiments, control serum and MSMP-containing serum were prepared from twenty-five C57BL/6 mice. Macrophages (RAW264.7 cells) were induced by lipopolysaccharide (LPS) and then treated with MSMP-containing serum. The expression of inflammatory factors and the change of the NF-κB pathway were tested.
, celecoxib and MSMP alleviated OA progression in the treated groups compared with OA group. The damage was partly recovered in cartilage, the synovial inflammatory were reduced in synovium, and the concentrations of IL-6 and TNF-α were reduced and the expression of IL-10 was increased in serum. The function of the middle MSMP was most effective for OA treatment. The results of experiments showed that compared with the LPS group, the MSMP-containing serum significantly reduced the expression levels of pro-inflammatory (M1-type) factors, such as CD86, iNOS, TNF-α and IL-6, and promoted the expression levels of anti-inflammatory (M2-type) factors, such as Arg1 and IL-10. The MSMP-containing serum further inhibited NF-κB signaling pathway after LPS induction.
The study demonstrated that MSMP alleviated OA progression in mice and MSMP-containing serum modulated macrophage M1/M2 phenotype by inhibiting the NF-κB signaling pathway. Our study provided experimental evidence and therapeutic targets of MSMP for OA treatment.
骨关节炎（OA）是一种慢性退行性疾病，主要特征为软骨损伤和滑膜炎症。四妙散是一种中药方剂，记载于古代中医处方中，具有出色的抗炎特性。在经典方剂的基础上，改良四妙散（MSMP）通过添加两种常用的中医骨科草药研制而成，对OA具有增强治疗效果的功效。
实验中，将36只8周龄雄性C57BL/6小鼠随机分为六组：假手术组、OA组、塞来昔布组、低剂量MSMP组、中剂量MSMP组和高剂量MSMP组。通过内侧半月板不稳定（DMM）构建OA小鼠模型，并用MSMP颗粒或塞来昔布进行灌胃治疗。检测MSMP对软骨、滑膜炎及血清炎症因子的影响。另外，从25只C57BL/6小鼠制备对照血清和含MSMP血清。巨噬细胞（RAW264.7细胞）用脂多糖（LPS）诱导，然后用含MSMP血清处理。检测炎症因子表达及NF-κB信号通路的变化。
与OA组相比，塞来昔布和MSMP减轻了治疗组的OA进展。软骨损伤部分恢复，滑膜炎症减轻，血清中IL-6和TNF-α浓度降低，IL-10表达增加。中剂量MSMP对OA治疗效果最佳。实验结果表明，与LPS组相比，含MSMP血清显著降低了促炎（M1型）因子如CD86、iNOS、TNF-α和IL-6的表达水平，并促进了抗炎（M2型）因子如Arg1和IL-10的表达水平。含MSMP血清在LPS诱导后进一步抑制了NF-κB信号通路。
该研究表明MSMP减轻了小鼠OA进展，含MSMP血清通过抑制NF-κB信号通路调节巨噬细胞M1/M2表型。我们的研究为MSMP治疗OA提供了实验证据和治疗靶点。
