Jiangu formula modulates the gut microbiota structure and the NF-κB/NLRP3 signaling pathway to alleviate synovitis

Shuying Li; Aoyu Zhang; Jie Qiao; Jingjing Yang; Haozhu Chen; Shiyan Shang; Tingshuai Fu; Beier Zhang; Kemin Xu; Gongxu Yang; Qing Zhang

doi:10.1016/j.phymed.2025.156995

Jiangu formula modulates the gut microbiota structure and the NF-κB/NLRP3 signaling pathway to alleviate synovitis

Phytomedicine. 2025 Jun 16:145:156995. doi: 10.1016/j.phymed.2025.156995. Online ahead of print.

Authors

Shuying Li¹, Aoyu Zhang¹, Jie Qiao², Jingjing Yang³, Haozhu Chen¹, Shiyan Shang¹, Tingshuai Fu³, Beier Zhang⁴, Kemin Xu⁵, Gongxu Yang², Qing Zhang⁶

Affiliations

¹ College of Acupuncture and Orthopedics, Hubei University of Chinese Medicine, Wuhan 430061, China.
² Department of Orthopedics, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430061, China.
³ Hubei University of Chinese Medicine, Wuhan 430061, China.
⁴ Department of First Clinical Medical College, Hubei University of Chinese Medicine, Wuhan 430065, China.
⁵ School of Laboratory Medicine, Hubei University of Chinese Medicine, Hubei Shizhen Laboratory, Wuhan 430065, China.
⁶ Hubei Sizhen Laboratory, Wuhan 430061, Hubei, China; Affiliated Hospital of Hubei University of Traditional Chinese Medicine, Wuhan 430061, Hubei. China. Electronic address: 15121210@qq.com.

PMID: 40578037
DOI: 10.1016/j.phymed.2025.156995

Abstract

Background: Synovitis is a pivotal pathological hallmark of arthritis, and timely intervention is essential for mitigating joint degeneration. Jiangu formula (JGF) can reduce inflammation in joint synovial fluid. However, its mechanism in treating synovial inflammation remains unclear.

Method: Chemical characterization of JGF's principal constituents was achieved through liquid chromatography-tandem mass spectrometry analysis. This study established a CFA -induced adjuvant arthritis model and investigated both the joint synovium and gut ecology. Through methodologies including 16S rRNA gene sequencing, it elucidated the mechanism by which JGF influences joint inflammation by modulating the NF-κB/NLRP3 signaling pathway and regulating gut microbiota structure.

Results: JGF significantly improved behavioral and histopathological alterations in the CFA-induced mouse, enhanced locomotor function, reduced serum inflammatory factor levels, downregulated NF-κB/NLRP3 pathway in joint and gut tissues, and modulated the structure of gut microbiota. It may reduce inflammation by promoting arginine and proline metabolism, inhibiting amino sugar and nucleotide sugar metabolism, aiding in the repair of the intestinal mucosa.

Conclusion: JGF ameliorates synovial inflammatory response in mice model through modulation of gut microbiota structure and intervention in the NF-κB/NLRP3 signaling pathway, with the beneficial effects demonstrating gut microbiota dependency.

Keywords: Gut microbiota; Inflammation; NF-κB/NLRP3 signaling pathway; Synovitis.