Network Pharmacology and Experimental Verification of Si Shen Decoction Regulating FABP4/PPARγ/NFκB Pathway in the Treatment of Collagen-induced Arthritis

Rui Guan; Jiashu Yao; Qing Qi; Jing Yu; Ruoshi Liu; Mingli Gao

doi:10.2174/0113862073296957240312090935

Network Pharmacology and Experimental Verification of Si Shen Decoction Regulating FABP4/PPARγ/NFκB Pathway in the Treatment of Collagen-induced Arthritis

Comb Chem High Throughput Screen. 2024 Apr 3. doi: 10.2174/0113862073296957240312090935. Online ahead of print.

Authors

Rui Guan¹, Jiashu Yao², Qing Qi³, Jing Yu⁴, Ruoshi Liu⁵, Mingli Gao³

Affiliations

¹ Liaoning University of Traditional Chinese Medicine, Shenyang, China.
² Rheumatology Department, The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, China.
³ The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine Rheumatology Department shenyang China.
⁴ The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine Rheumatology Department Shenyang China.
⁵ Traditional Chinese Medicine Department, The First Affiliated Hospital of China Medical University, Shenyang, China.

PMID: 38584563
DOI: 10.2174/0113862073296957240312090935

Abstract

Aim: This study aimed to investigate the mechanism of SSD in rats with Collagen- Induced Arthritis (CIA).

Background: Rheumatoid arthritis (RA) is a complex immune disease characterized by bilateral symmetrical multi-joint pain and swelling. Si Shen Decoction (SSD) has shown good results in treating RA in clinical applications, but its mechanism of action remains unclear.

Objective: To investigate the mechanism of SSD in rats with Collagen-Induced Arthritis (CIA).

Methods: Bioinformatics and network pharmacology analyses were used to predict the possible treatment targets and signaling pathways. Elisa, Western blotting, and quantitative real-time polymerase chain reaction were used to verify the mechanism of SSD in the treatment of RA.

Results: FABP4, MMP9, and PTGS2 were the most common predicted therapeutic targets. SSD treatment significantly reduced synovitis, ankle swelling and bone erosion in CIA rats. The SSD group also significantly reduced the serum secretion of CRP, TNFα, and IL1β, decreased mRNA levels of FABP4, IKKα, and p65 in the synovial membrane, but increased PPARγ. Western blot showed that SSD treatment could significantly reduce the expression of FABP4, IKKα, and phosphorylated p65 (p-p65) proteins in the synovium. SSD was found to inhibit the FABP4/PPARγ/NFκB signaling pathway and reduce the inflammatory response in CIA rats. The therapeutic effect of SSD was significant with the increase of dose.

Conclusion: SSD can relieve joint symptoms in CIA rats and alleviate inflammation by inhibiting the FABP4/PPARγ/NFκB signaling pathway. The effect of high-dose SSD was more prominent.

Keywords: FABP4; NF&B signaling pathway; Network pharmacology.; Rheumatoid Arthritis; Si Shen Decoction.