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

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.

Keywords: Clinical study; Molecular docking; Molecular mechanism; Pharmacology; Rheumatoid arthritis; Wutou decoction.