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乌头汤:关于分子机制、临床研究、质量控制、药代动力学研究、药理作用、毒性及靶点预测的最新综述

Wutou decoction: A latest review on molecular mechanisms, clinical studies, quality control, pharmacokinetic studies, pharmacological effects, toxicity, and target prediction.

作者信息

Liu Peiyu, Chen Zhengmin, Huang Jiayi, Wang Xuezhen, Chen Yuqing, He Xizi, Lu Jiayan, Ke Qingming, Liu Yishen, Zhu Haiqiong, Pi Yani, Sun Qidi, Yao Zhenming, Kong Xiao, Pan Hudan

机构信息

State Key Laboratory of Traditional Chinese Medicine Syndrome /The Second Clinical College, Guangzhou University of Chinese Medicine, Guangdong Province, 510405, China.

School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.

出版信息

J Ethnopharmacol. 2025 Feb 11;341:119307. doi: 10.1016/j.jep.2024.119307. Epub 2024 Dec 30.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Traditional Chinese Medicine (TCM) has great potential and advantages in the treatment of rheumatoid arthritis (RA). Wutou decoction (WTD) was first recorded as a pill in the TCM classical book Synopsis of Prescriptions of the Golden Chamber written by Zhang Zhongjing in the Eastern Han Dynasty (25-220 CE). It has significant therapeutic effects in delaying and reversing RA while improving patients' clinical symptoms, making it the best example of TCM treatment for RA.

AIM OF THE REVIEW

This article reviews the clinical research, molecular mechanisms, pharmacological effects, synergistic reduction and enhancement, quality control, pharmacokinetics, chemical composition, toxicity, and core targets of WTD and its components in the treatment of RA in recent years, in order to provide a reference for future research.

MATERIALS AND METHODS

Use multiple internationally recognized databases (including PubMed Embase, Springer, Web of science, SciVerse ScienceDirect, Clinical Trails, CNKI and Wanfang) conducted a comprehensive literature search on keywords such as WTD, rheumatoid arthritis, TCM, clinical research, molecular biology, pharmacokinetics, etc. Use molecular docking technology to perform molecular docking on the screened core targets and active ingredients. Use databases such as TCMSP, PubMed, NCBI Gene, GenCards to screen the active ingredients and core targets for WTD treatment of RA. Use software such as AutodockTools 1.5.6 for format conversion and determination of docking pockets.

RESULTS

WTD is widely used in the clinical treatment of RA. In randomized controlled trials and clinical cohort studies, WTD can significantly reduce the pathological degree of RA patients, effectively reduce their visual analog scale (VAS), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) levels, and has a high clinical cure efficiency. In terms of molecular mechanisms, WTD can alleviate RA by regulating cell apoptosis, inhibiting the formation of vascular opacities, regulating M1 and M2 macrophages and T lymphocytes, reducing inflammatory factors, and regulating antioxidant and protein modifications. Based on the theory of "Jun Chen Zuo Shi" in traditional Chinese medicine, we have summarized the core principles of traditional Chinese medicine compatibility in WTD and its unique role in reducing toxicity and improving efficacy. Subsequently, the testing system for WTD quality control was summarized, and the accuracy and efficiency of quality control for each active ingredient under each system were analyzed. The pharmacokinetic results showed that WTD exhibits differences in the absorption and tissue distribution of its active ingredients in pathological conditions compared to healthy conditions, and has a better ability to reduce toxicity compared to a single herb. Finally, the core effective chemical components and targets of WTD for treating RA were screened and validated by molecular docking.

CONCLUSION

WTD is a safe and effective drug for treating RA, with high clinical and evidence-based value in the treatment of RA. However, there are also some issues that need to be addressed, and future work should focus on strengthening quality control, elucidating pharmacological and pharmacokinetic processes, and reconfirming clinical safety.

摘要

民族药理学相关性

传统中医(TCM)在类风湿关节炎(RA)的治疗中具有巨大潜力和优势。乌头汤(WTD)最早在东汉(公元25 - 220年)张仲景所著的中医经典《金匮要略》中被记载为丸剂。它在延缓和逆转RA方面具有显著治疗效果,同时改善患者临床症状,是中医治疗RA的最佳范例。

综述目的

本文综述近年来乌头汤及其成分在治疗RA方面的临床研究、分子机制、药理作用、减毒增效、质量控制、药代动力学、化学成分、毒性及核心靶点,以便为未来研究提供参考。

材料与方法

使用多个国际认可的数据库(包括PubMed、Embase、Springer、Web of science、SciVerse ScienceDirect、Clinical Trails、CNKI和万方),以乌头汤、类风湿关节炎、中医、临床研究、分子生物学、药代动力学等关键词进行全面文献检索。使用分子对接技术对筛选出的核心靶点和活性成分进行分子对接。利用TCMSP、PubMed、NCBI Gene、GenCards等数据库筛选乌头汤治疗RA的活性成分和核心靶点。使用AutodockTools 1.5.6等软件进行格式转换和对接口袋的确定。

结果

乌头汤广泛应用于RA的临床治疗。在随机对照试验和临床队列研究中,乌头汤可显著降低RA患者的病理程度,有效降低其视觉模拟评分(VAS)、C反应蛋白(CRP)和红细胞沉降率(ESR)水平,且临床治愈率高。在分子机制方面,乌头汤可通过调节细胞凋亡、抑制血管翳形成、调节M1和M2巨噬细胞及T淋巴细胞、减少炎症因子以及调节抗氧化和蛋白质修饰来缓解RA。基于中医“君臣佐使”理论,总结了乌头汤中中药配伍的核心原则及其在减毒增效方面的独特作用。随后,总结了乌头汤质量控制检测体系,并分析了各体系下各活性成分质量控制的准确性和效率。药代动力学结果表明,与健康状态相比,乌头汤活性成分在病理状态下的吸收和组织分布存在差异,且与单味药相比具有更好的减毒能力。最后,通过分子对接筛选并验证了乌头汤治疗RA的核心有效化学成分和靶点。

结论

乌头汤是治疗RA的安全有效药物,在RA治疗中具有较高的临床和循证价值。然而,也存在一些问题需要解决,未来工作应集中在加强质量控制、阐明药理和药代动力学过程以及重新确认临床安全性方面。

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