Pioneering rheumatoid arthritis treatment:Magnesium ionmediated natural multi-component hydrogel synergistically regulates macrophage polarization,pannus formation,and bone regeneration  

作　　者：Luping Yang Xiang Zhang Yihang Zhao Zhijia Wang Xinru Tan Yuxin Zhang Zhiwei Wang Jihui Lu Shuchang Yao Jingyi Jiao Xuemei Huang Penglong Wang 

机构地区：[1]School of Chinese Pharmacy,Beijing University of Chinese Medicine,Beijing 102488,China [2]Institute of Metabolic Diseases,Guang'anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China

出　　处：《Nano Research》2025年第4期346-363,共18页纳米研究(英文版)

基　　金：funded by the National Natural Science Foundation of China(Nos.82274072 and 82474059);the Beijing Municipal Natural Science Foundation(Nos.7242221 and 7254503);Beijing Nova Programme Interdisciplinary Cooperation Project(No.20240484578);the Fundamental Research Funds for the Central Universities(China,Nos.2023-JYB-JBZD-049,2022-XJKYQD-008,and 2024-JYB-XJSJJ004);Beijing Key Laboratory for Basic and Development Research on Chinese Medicine(Beijing,No.100102).

摘　　要：Rheumatoid arthritis(RA)is a chronic inflammatory autoimmune disease that affects millions of people worldwide.Current therapeutic drugs for RA are often limited by poor solubility,unresponsive to monotherapy,low bioavailability,and severe side effects.To address these challenges,we developed a pH-responsive,biodegradable,and multifunctional oral hydrogel delivery system(GTPM Gel)based on the major active ingredients(glycyrrhizic acid(GA),total alkaloids of FZ(TAC),pseudoephedrine(PE),Mg^(2+))from Mahuang Fuzi decoction for the treatment of RA in clinic.In this system,all four components synergistically contributed to gel formation and pharmacodynamics,making each component indispensable.Notably,Mg2+in GTPM Gel promoted the gelation of GA via coordination bonds while exhibiting anti-inflammatory properties and facilitating osteochondral regeneration.Moreover,GTPM Gel enhanced the solubility of TAC and reduced its toxicity,leading to improved anti-RA effects.In vitro and In vivo studies demonstrated that GTPM Gel effectively inhibited the polarization of inflammatory macrophages,reduced pannus formation,and inhibited bone and cartilage erosion by downregulating the PI3K/AKT/NF-κB signaling pathway.This study suggested that the magnesium ion-mediated natural multi-component hydrogel,with its remarkable efficacy and biocompatibility,holds promise as a potential therapeutic candidate for RA treatment.

关 键 词：magnesium ion-mediated natural multi-component hydrogel rheumatoid arthritis macrophages polarization PI3K/AKT/NF-κB signaling pathway 

分 类 号：R285[医药卫生—中药学]