Glucose Metabolism Reprogramming in Rheumatoid Arthritis: Pathogenic Mechanisms and Therapeutic Interventions With Traditional Chinese Medicine

Abstract

Rheumatoid arthritis (RA) is a prevalent autoimmune disease characterized primarily by chronic inflammation of the synovial membrane and destruction of articular cartilage and bone. Previous research has predominantly focused on the abnormal activation of immune cells and the cascade of inflammatory cytokines. However, recent studies have reported that energy metabolism disorders, particularly glucose metabolism reprogramming, are closely associated with the pathogenesis of RA. Hypoxia, lactate production, and lactate modification within the synovial microenvironment are closely associated with glucose metabolism reprogramming. This reprogramming supports the elevated energy and nutrient requirement for abnormal immune cell activation and effector cell proliferation, thereby serving as a core event in RA pathogenesis. Traditional Chinese medicine (TCM) that modulates regulatory factors or pathological products related to glucose metabolism reprogramming in RA represents a promising therapeutic strategy for regulating immune responses and delaying disease progression. This review innovatively summarizes the distinct characteristics of glucose metabolism reprogramming in multiple immune and stromal cells (including fibroblast-like synoviocytes, macrophages, B cells, vascular endothelial cells and T cells) during RA progression, and systematically elucidates the regulatory mechanisms by which hypoxic microenvironments, lactate metabolism, and lactylation trigger glucose metabolic dysregulation. Furthermore, we provide a comprehensive and cutting-edge overview of the targeted modulatory effects of TCM monomers, active ingredients, and compound formulas on glucose metabolism reprogramming and lactylation in RA. Graphical Abstract