Therapeutic Potential of Phellodendrine/ Atractylenolide-I Combination in Rheumatoid Arthritis: Targeting Neutrophil Apoptosis through LTB4/BLT1 Pathway Suppression.

INTRODUCTION

To investigate the therapeutic effects of rheumatoid arthritis (RA) Phellodendrine and Atractylenolide-I (PHE/ATL-1) on RA and their mechanisms.

METHODS

In this study, first clinical experiments were conducted to investigate whether the delayed neutrophil apoptosis in the course of RA was related to the Leukotriene B4 (LTB4)/ Leukotriene B4 receptor 1 (BLT1) pathway, and then the effects of PHE/ATL-1 inhibition of the LTB4/BLT1 pathway to promote neutrophil apoptosis to inhibit inflammation were evaluated in vitro, as well as the in vivo effects of PHE/ATL-1 on the collagen-induced arthritis (CIA) model.

RESULTS

Clinical studies revealed elevated BLT1 expression in RA neutrophils, impairing apoptosis and exacerbating inflammation. In vitro, PHE/ATL-1 restored neutrophil apoptosis and reduced inflammation by inhibiting the LTB4/BLT1 pathway. The CIA mouse model further confirmed PHE/ATL-1's therapeutic potential in alleviating arthritis symptoms.

DISCUSSION: PHE/ATL-1 ameliorates RA through LTB4/BLT1 pathway inhibition, reversing neutrophil apoptosis delay and attenuating inflammation. Clinical evidence of upregulated BLT1 in RA neutrophils and therapeutic efficacy in both in vitro and CIA models establishes PHE/ATL-1 as a compelling RA treatment candidate requiring clinical validation.

CONCLUSION

These findings suggest that PHE/ATL-1 may serve as a potential therapeutic agent for RA treatment.