Natural products in rheumatoid arthritis: Cell type-specific mechanisms and therapeutic implications

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-06-13 DOI:10.1016/j.phymed.2025.156980

Yang Liao , Xian Xiao , Wen Cheng , Yiyuan Wang , Jiayan Lu , Jingtao Zhang , Jiaqi Zhang , Peiyu Liu , Liang Liu , Hudan Pan

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引用次数: 0

Abstract

Background

The pathogenesis of rheumatoid arthritis (RA) involves abnormal activation and interactions among various cell types. Traditional Chinese medicine (TCM) natural products show therapeutic potential with multi-target anti-inflammatory effects, but their specific impacts on RA-related cell types remain unclear.

Purpose

This review aims to provide a comprehensive overview of the effects of natural products on key cell types in RA.

Methods

We extensively searched PubMed, Web of Science, and Scopus until April 2025, using keywords like "natural products," "rheumatoid arthritis," "cellular mechanisms," and specific cell types. Studies on natural products' effects on RA-related cells were included and analyzed.

Results

This review marks the first attempt to integrate cellular resolution in evaluating therapeutic mechanisms of natural products in RA. The key findings highlight the cell-type-specific effects and mechanistic underpinnings of natural products. Sinomenine preferentially inhibits fibroblast-like synoviocytes (FLS) proliferation via toll-like receptor 4 (TLR4) /MyD88/NF-κB blockade, whereas icariin reprograms macrophage polarization through ERK/HIF-1α/GLUT1 signaling pathway. Besides, natural products exhibit shared mechanisms across different cell types, such as oxidative stress and inflammatory pathway regulation. Importantly, certain natural products exhibit pan-cellular effects, targeting multiple cell types involved in RA pathogenesis. For example, resveratrol acts on a wide range of cell types including FLS, human umbilical vein endothelial cells (HUVECs), T cells, osteoclasts, chondrocytes, macrophages, monocytes, osteoblasts, and neutrophils.

Conclusions

Through an in-depth analysis of cellular mechanisms, this work highlights the specific regulatory effects of natural products on key cell types and their extensive influence across cellular networks. By examining these effects at the cellular level, this review establishes a new framework for developing novel RA therapeutics with increased cell selectivity, thus advancing precision phytomedicine and translational research.

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类风湿性关节炎的天然产物：细胞类型特异性机制和治疗意义

背景类风湿性关节炎（RA）的发病机制涉及多种细胞类型的异常激活和相互作用。中药天然产物具有多靶点抗炎作用，但其对ra相关细胞类型的具体影响尚不清楚。目的综述天然产物对类风湿关节炎中关键细胞类型的影响。方法到2025年4月，我们广泛检索PubMed、Web of Science和Scopus，使用“天然产物”、“类风湿关节炎”、“细胞机制”和特定细胞类型等关键词。包括并分析了天然产物对ra相关细胞的影响。结果本综述首次尝试整合细胞分辨率来评估天然产物在RA中的治疗机制。关键发现强调了细胞类型特异性效应和天然产物的机制基础。青叶碱通过toll样受体4 (TLR4) /MyD88/NF-κB阻断优先抑制成纤维细胞样滑膜细胞（FLS）的增殖，而淫羊苷通过ERK/HIF-1α/GLUT1信号通路重编程巨噬细胞极化。此外，天然产物在不同细胞类型中表现出共同的机制，如氧化应激和炎症通路调节。重要的是，某些天然产物表现出泛细胞效应，针对参与RA发病的多种细胞类型。例如，白藜芦醇作用于多种细胞类型，包括FLS、人脐静脉内皮细胞（HUVECs）、T细胞、破骨细胞、软骨细胞、巨噬细胞、单核细胞、成骨细胞和中性粒细胞。通过对细胞机制的深入分析，这项工作强调了天然产物对关键细胞类型的特定调节作用及其在细胞网络中的广泛影响。通过在细胞水平上研究这些作用，本综述为开发具有更高细胞选择性的新型RA治疗方法建立了一个新的框架，从而推进精确植物医学和转化研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.