Berberine Modulates LPA Function to Inhibit the Proliferation and Inflammation of FLS-RA via p38/ERK MAPK Pathway Mediated by LPA1.

Abstract

OBJECTIVE:

This study aimed to investigate whether berberine exerted anti-inflammatory and antiproliferative effects on the fibroblast-like synoviocytes of rheumatoid arthritis (FLS-RA) through regulating the lysophosphatidic acid (LPA) function.

METHODS:

Firstly, the expression levels of LPA and lysophosphatidic acid receptor 1 (LPA1) in RA patients, osteoarthritis (OA) patients, and healthy controls were detected. Moreover, molecular docking was employed to characterize the binding sites of berberine in the predicted protein targets. Later, FLS-RA were stimulated using berberine, LPA, and the specific inhibitor (Ki16425) of LPA1, thereafter, the effects on the proliferation, apoptosis, the release of inflammatory mediators of FLS-RA, and the MAPK pathway were observed.

RESULTS:

Compared with healthy controls (n = 25), the plasma LPA level (n = 28) and synovial fluid (n = 10) were markedly higher in RA patients. LPA1 was highly expressed in RA patients (n = 4) relative to that in OA patients (n = 4). Berberine remarkably inhibited the proliferation and the excessive production of IL-6 and TNF-α in FLS-RA, whereas suppressing the expression of K-ras, c-Raf, and p-38/ERK-phosphorylation. In addition, berberine inhibited the LPA-induced p-38/ERK-phosphorylation through binding to LPA1.

CONCLUSIONS:

LPA plays a certain role in promoting the proliferation and inflammation of FLS-RA. Berberine potentially modulates LPA function to suppress the proliferation and inflammation of FLS-RA through blocking the p38/ERK MAPK pathway mediated by LPA1. These findings suggest that, berberine possesses potential lipid-regulating, antiarthritis, and synovial hyperplasia inhibition activities against RA, which may provide a promising therapeutic target for the clinical drug development for RA patients with dyslipidemia and high CVD risk.

• Authors: Hui Wang, Shenghao Tu, Sisi Yang, Pan Shen, Yao Huang, Xin Ba, Weiji Lin, Ying Huang, Yu Wang, Kai Qin, Zhe Chen
• Journal: Evidence-based complementary and alternative medicine : eCAM (Evid Based Complement Alternat Med) Vol. 2019 Pg. 2580207 ( 2019) ISSN: 1741-427X [Print] United States
• PMID: 31781264 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Hui Wang et al.