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四味西藏杓兰汤通过调控 JAK2-STAT3 和 NF-κB 信号通路改善 II 型胶原诱导的关节炎大鼠模型。

Siweixizangmaoru Decoction Ameliorated Type II Collagen-Induced Arthritis in Rats via Regulating JAK2-STAT3 and NF-κB Signaling Pathway.

机构信息

Department of Pharmaceutical Engineering and Pharmaceutical Chemistry, School of Chemical Engineering, Qingdao University of Science and Technology.

Department of Pharmacy, College of Medicine, Tibet University.

出版信息

Biol Pharm Bull. 2024;47(9):1511-1524. doi: 10.1248/bpb.b24-00362.

Abstract

Siweixizangmaoru decoction (SXD) is widely used as an anti-rheumatoid arthritis (RA) in Tibet, however, the specific anti-inflammatory mechanism of SXD is still unclear. This research attempts to examine the efficacy and possible mechanisms of SXD in treating RA. The primary chemical components of SXD were identified using UHPLC-Q-Exactive Orbitrap MS. We established a lipopolysaccharide (LPS)-induced RAW264.7 macrophage inflammatory injury model to explore the anti-inflammatory mechanism of SXD and validated it through in vivo experiments. According to our research in vitro as well as in vivo, SXD exhibits anti-inflammatory qualities. SXD can suppress nitric oxide (NO) and pro-inflammatory factor production in RAW264.7 cells activated by LPS. The mechanism underlying this effect might be connected to the janus tyrosine kinase 2-signal transducer and activator of transcription 3 (JAK2/STAT3) and nuclear factor-κB (NF-κB) signaling pathways. In vivo, SXD alleviates joint swelling, decreases the generation of inflammatory factors in the serum, lowers oxidative stress, and improves joint damage. In short, SXD improves joint degeneration and lowers symptoms associated with RA by regulating inflammation via the suppression of NF-κB and JAK2/STAT3 signaling pathway activation.

摘要

四味西藏麻花汤(SXD)在西藏被广泛用作抗类风湿关节炎(RA)的药物,但 SXD 的具体抗炎机制仍不清楚。本研究试图探讨 SXD 治疗 RA 的疗效及其可能的机制。采用 UHPLC-Q-Exactive Orbitrap MS 鉴定 SXD 的主要化学成分。我们建立了脂多糖(LPS)诱导的 RAW264.7 巨噬细胞炎症损伤模型,以探讨 SXD 的抗炎机制,并通过体内实验进行了验证。根据我们的体外和体内研究,SXD 表现出抗炎特性。SXD 可抑制 LPS 激活的 RAW264.7 细胞中一氧化氮(NO)和促炎因子的产生。这种作用的机制可能与 Janus 酪氨酸激酶 2-信号转导和转录激活因子 3(JAK2/STAT3)和核因子-κB(NF-κB)信号通路有关。在体内,SXD 可减轻关节肿胀,降低血清中炎症因子的产生,降低氧化应激,改善关节损伤。总之,SXD 通过抑制 NF-κB 和 JAK2/STAT3 信号通路的激活来调节炎症,从而改善关节退化和降低 RA 相关症状。

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