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土木香中的 chromone 成分通过抑制炎症反应来减轻类风湿性关节炎的发展。

Chromone components of Saposhnikovia divaricate attenuate rheumatoid arthritis development by inhibiting the inflammatory response.

机构信息

Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Harbin, 150040, China; Traditional Chinese medicine (TCM), biological Genetics (Heilongjiang Province Double First-class Construction Interdiscipline), China.

Heilongjiang Zbd Pharmaceutical Co., Ltd. Harbin, 150046, China.

出版信息

J Ethnopharmacol. 2025 Jan 30;337(Pt 2):118912. doi: 10.1016/j.jep.2024.118912. Epub 2024 Oct 5.

DOI:10.1016/j.jep.2024.118912
PMID:39369926
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Saposhnikovia divaricata (Turcz.) Schisck., a traditional Chinese medicine (TCM), has historically been utilized in the clinical treatment of RA. It was initially documented in the 'Shennong Ben Cao Jing' as a superior quality, with the text stating: 'The herb is widely renowned for its efficacy in alleviating whole-body discomfort, bone pain, malaise, and promoting long-lasting vitality. Chromones (CHR) were identified as the primary active components in Saposhnikovia divaricata. However, the specific molecular mechanisms by which CHR impacts RA remain incompletely understood.

AIM OF THE STUDY

To explore the therapeutic efficacy of CHR, a class of compound derived from Saposhnikovia divaricata, in alleviating arthropathy and immune hyperactivity in a collagen-induced arthritis (CIA) mouse model.

MATERIAL AND METHODS

Surface plasmon resonance (SPR) molecular fishing and UHPLC-QTOF/MS technology were used to identify CHR in Saposhnikovia divaricata as an active ingredient for treating RA. A CIA mouse model was used to verify the anti-RA effect of CHR in vivo. The anti-RA efficacy of CHR in vivo was evaluated by body weight change, joint swelling, arthritis index, immune organ index, ankle joint disease, and immunoglobulin G (IgG) content. The mechanism of improving RA was further analyzed by a protein chip assay and verified by Western blotting.

RESULTS

CHR treatment reduced swelling, arthritis index, and IgG, IgG1, IgG2a, and IgG2b levels in CIA mice. Protein microarray indicated that CHR mitigated CIA-induced joint inflammation by inhibiting immune cell activation, reducing the expression of inflammatory factors and chemokines, potentially by modulating the rheumatoid arthritis pathway involving tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), and chemokines. This hypothesis was supported by the upregulation of bone morphogenetic proteins 3 (BMP3) and phospho-Smad2 (p-Smad2) proteins, coupled with the downregulation of interleukin-6 (IL-6), interleukin-1β (IL-1β), TNF-α, and IL-17A proteins in the joints of CHR-treated mice.

CONCLUSION

CHR shows promise as a potential therapeutic agent for RA, exerting its effects through anti-inflammatory mechanisms.

摘要

民族药理学相关性

防风(Turcz.)Schisck.,一种传统的中药(TCM),在临床上曾被用于治疗类风湿关节炎。它最初被记录在《神农本草经》中,被描述为一种高质量的草药,其文本说明:“该草药广泛用于缓解全身不适、骨痛、不适和促进持久活力。在防风中,已鉴定出查耳酮(CHR)为主要活性成分。然而,CHR 影响类风湿关节炎的具体分子机制尚不完全清楚。

研究目的

探讨从防风中提取的一类化合物 CHR 对胶原诱导性关节炎(CIA)小鼠模型中关节炎和免疫过度活跃的治疗效果。

材料和方法

利用表面等离子体共振(SPR)分子钓捕和 UHPLC-QTOF/MS 技术鉴定防风中的 CHR 作为治疗 RA 的活性成分。利用 CIA 小鼠模型在体内验证 CHR 的抗 RA 作用。通过体重变化、关节肿胀、关节炎指数、免疫器官指数、踝关节疾病和免疫球蛋白 G(IgG)含量来评估 CHR 体内的抗 RA 疗效。通过蛋白质芯片分析进一步分析改善 RA 的机制,并通过 Western blot 进行验证。

结果

CHR 治疗降低了 CIA 小鼠的肿胀、关节炎指数和 IgG、IgG1、IgG2a 和 IgG2b 水平。蛋白质微阵列表明,CHR 通过抑制免疫细胞激活、降低炎症因子和趋化因子的表达,减轻 CIA 诱导的关节炎症,可能通过调节肿瘤坏死因子-α(TNF-α)、白细胞介素-17(IL-17)和趋化因子涉及的类风湿关节炎途径。这一假设得到了 CHR 治疗小鼠关节中骨形态发生蛋白 3(BMP3)和磷酸化 Smad2(p-Smad2)蛋白上调,以及白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、TNF-α和 IL-17A 蛋白下调的支持。

结论

CHR 有望成为一种治疗类风湿关节炎的潜在治疗药物,通过抗炎机制发挥作用。

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