Aqueous extract of Saposhnikovia divaricata root alleviates rheumatoid arthritis by acting on TNF-α and RAGE signaling pathways

Anjing Xu; Yuanyuan Wen; Bao Hou; Shijie Zhang; Tsedien Nhamdriel; Xiaoyue Ma; Liyuan Cui; Xuexue Zhu; Weiwei Cai; Liying Qiu; Haijian Sun

doi:10.1016/j.bbrep.2025.102153

Biochemistry and Biophysics Reports (Sep 2025)

Aqueous extract of Saposhnikovia divaricata root alleviates rheumatoid arthritis by acting on TNF-α and RAGE signaling pathways

Anjing Xu,
Yuanyuan Wen,
Bao Hou,
Shijie Zhang,
Tsedien Nhamdriel,
Xiaoyue Ma,
Liyuan Cui,
Xuexue Zhu,
Weiwei Cai,
Liying Qiu,
Haijian Sun

Affiliations

Anjing Xu: MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of Medicine, Jiangnan University, Wuxi, 214122, China; Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China
Yuanyuan Wen: MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of Medicine, Jiangnan University, Wuxi, 214122, China; Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China
Bao Hou: MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of Medicine, Jiangnan University, Wuxi, 214122, China; Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China
Shijie Zhang: MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of Medicine, Jiangnan University, Wuxi, 214122, China; Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China
Tsedien Nhamdriel: Department of Basic Medicine, Tibet University of Medicine, 850000, Lhasa, China
Xiaoyue Ma: MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of Medicine, Jiangnan University, Wuxi, 214122, China; Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China
Liyuan Cui: MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of Medicine, Jiangnan University, Wuxi, 214122, China; Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China
Xuexue Zhu: MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of Medicine, Jiangnan University, Wuxi, 214122, China; Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China
Weiwei Cai: MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of Medicine, Jiangnan University, Wuxi, 214122, China; Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China
Liying Qiu: MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of Medicine, Jiangnan University, Wuxi, 214122, China; Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China; Corresponding author. Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University. Wuxi, 214122, China.
Haijian Sun: MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of Medicine, Jiangnan University, Wuxi, 214122, China; Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing, 210009, China; Corresponding author. State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing 210009, China.

DOI: https://doi.org/10.1016/j.bbrep.2025.102153
Journal volume & issue: Vol. 43
p. 102153

Abstract

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Saposhnikovia divaricata (Turcz.) Schisch (SADS) is classified as a special-grade traditional Chinese medicine in Shennong's Materia Medical due to its immune-protective effects, including dispelling cold, relieving edema and pain, and its potential in treating rheumatoid arthritis (RA). Over 130 traditional Chinese medicine formulations containing SADS are used for RA treatment. However, the active ingredients and serum metabolites of SADS remain underexplored, and its precise mechanism of action in RA is not fully understood. Therefore, the study aims to explore the active ingredients and serum metabolites of SADS by UPLC-Q-TOF-MS and investigate its therapeutic mechanisms in the context of RA. A total of 5536 compounds were identified in SADS, and 19 active components were finally selected. In serum metabolites following SADS administration, 4945 compounds were identified, of which 17 showed anti-inflammatory activity. Network pharmacology analysis showed that SADS may play a role in the treatment of RA through the TNF and Receptor for Advanced Glycation End-products (RAGE) signaling pathway. SADS alleviated RA symptoms in IL-1RA deficient RA mice. In cellular models, SADS inhibited the abnormal proliferation of fibroblast-like synoviocytes through regulating the TNF-α and RAGE pathways. In addition, SADS promoted the polarization of M2 macrophages but inhibited the polarization of M1 macrophages. SADS alleviated the progression of experimental arthritis in a RA mouse model by modulating the TNF-α and RAGE signaling pathways, supporting its potential as a therapeutic agent for RA.

Published in Biochemistry and Biophysics Reports

ISSN: 2405-5808 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General); Science: Chemistry: Organic chemistry: Biochemistry
Website: https://www.sciencedirect.com/journal/biochemistry-and-biophysics-reports

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