A novel pharmaceutical preparation of Tripterygium wilfordii Hook. f. regulates macrophage polarization to alleviate inflammation in rheumatoid arthritis
A novel pharmaceutical preparation of Tripterygium wilfordii Hook. f. regulates macrophage polarization to alleviate inflammation in rheumatoid arthritis
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DOI：
10.1093/jpp/rgad078
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发表时间：
2023-09-20
影响因子：
3.3
通讯作者：
Li，Fangze
中科院分区：
文献类型：
--
作者：
Wan，Lei;Liu，Jian;Li，Fangze
目的验证雷公藤的增强治疗作用。f. （TWHF）通过恢复M1/M2巨噬细胞的稳态来治疗类风湿性关节炎（RA）。方法采用随机游走模型和网络药理学方法，研究黄芪黄酮在RA中的分子靶点和作用机制。通过临床观察和关节炎动物模型实验，探讨了TWHF对巨噬细胞极化、相关信号通路和靶点的影响。采用雷公藤甲素对关节炎大鼠进行干预。网络药理学分析揭示了与TWHF相关的RA关键靶基因。TWHF与炎症指标的改善有很强的相关性。TWHF抑制M1巨噬细胞分泌IL-1β、IL-6、CXCL8、TNF-α、VEGF-A等因子，促进M2巨噬细胞分泌IL-10。定量液相芯片分析显示，雷公藤甲素降低关节炎模型中TNF-α、CXCL2、VEGF水平，升高IL-4、IL-10水平。同时雷公藤甲素抑制NF-κB、PI3K/AKT、p38 MAPK信号通路，从而改善RA关节炎症，固定免疫失衡。结论striptolide可下调巨噬细胞M1分泌因子的表达，抑制炎症信号通路的过度激活。
ObjectivesTo validate the enhanced therapeutic effect ofTripterygium wilfordiiHook. f. (TWHF) in the treatment of rheumatoid arthritis (RA) by restoring homeostasis of M1/M2 macrophages.MethodsThis study, using random walk models and network pharmacology, examined the molecular targets and mechanism of TWHF in RA. Based on clinical observations and experiments in arthritis animal models, the effects of TWHF on macrophage polarization, related signal pathways, and targets were examined.Triptolide, a component of TWHF, was used to intervene arthritis rats.Key findingsNetwork pharmacological analysis revealed the key RA target genes related to TWHF. TWHF showed a strong correlation with the improvement of inflammatory indicators. TWHF inhibited the factors secreted by M1 macrophages such as IL-1β, IL-6, CXCL8, TNF-α, and VEGF-A, but promoted IL-10 from M2 macrophages. Quantitative liquid-phase chip assay showed thattriptolidereduced the levels of TNF-α, CXCL2, and VEGF, while IL-4 and IL-10 were increased in arthritis model. Meanwhile,triptolideinhibited the NF-κB, PI3K/AKT, and p38 MAPK signaling pathways, which in turn improved the RA joint inflammation and fixed immune imbalance.ConclusionsTriptolidedownregulate the expression of M1 macrophage-secreted factors that inhibit the overactivation of inflammatory signaling pathways.