Integrated pharmacology reveals the mechanism of action of Bu-Shen-Tong-Du prescription against collagen-induced arthritis.

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. Bu-Shen-Tong-Du prescription (BSP) has traditionally been used in to treat RA but its underlying mechanisms remain unclear. In this study, we explored the potential mechanisms of BSP in collagen-induced arthritis (CIA) rats, a classic animal model of RA. We employed an integrated pharmacology approach in combination with network pharmacology, 1H-nuclear magnetic resonance (NMR) metabolomics, and biochemical analyses to determine the mechanisms of BSP for treating RA. We found that BSP can regulate immunity and inflammation by decreasing the spleen index; inhibiting hyperplasia of the white pulp; reducing the levels of IL-1β, IL-6, IL-17A, and IFN-γ; and increasing the levels of IL-10 in the serum. Network pharmacology was utilized to predict related signal transduction pathways of BSP in RA treatment. 1H NMR metabolomics of the serum confirmed that BSP regulated energy metabolism and amino acid metabolism. Finally, we validated the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling pathway using immunohistochemical methods, which demonstrated that BSP controlled RA-induced inflammation by inhibiting the TLR4/NF-κB signaling pathway. These results confirm the therapeutic effect of BSP in a CIA rat model, which is exerted via the inhibition of the inflammation and the improvement of the immune function, balancing energy metabolism and amino acid metabolism, and inhibiting the TLR4/NF-κB signaling pathway. This study provides an experimental basis for using BSP as a combinatorial drug to inhibit inflammation and regulate immunity in the treatment of RA.

• Authors: Xiaolu Wei, Mingming Peng, Danbing Liu, Lijuan Zhao, Xinru Gu, Linna Wang, Yanyan Zhou, Haiyu Zhao, Nan Si, Hongjie Wang, Liping Hou, Zunpeng Shu, Baolin Bian
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 143 Pg. 112160 (Nov 2021) ISSN: 1950-6007 [Electronic] France
• PMID: 34560546 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Antirheumatic Agents
• Collagen Type II
• Cytokines
• Drugs, Chinese Herbal
• NF-kappa B
• Tlr4 protein, rat
• Toll-Like Receptor 4

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antirheumatic Agents (pharmacology)
• Arthritis, Experimental (chemically induced, drug therapy, immunology, metabolism)
• Collagen Type II
• Cytokines (metabolism)
• Drugs, Chinese Herbal (pharmacology)
• Energy Metabolism (drug effects)
• Joints (drug effects, immunology, metabolism, pathology)
• Male
• Medicine, Chinese Traditional
• NF-kappa B (metabolism)
• Network Pharmacology
• Rats, Sprague-Dawley
• Signal Transduction
• Toll-Like Receptor 4 (metabolism)