Abstract:

Rheumatoid arthritis （RA） is a multifactorial chronic autoimmune disease characterized pathologically by synovial inflammation， pannus formation， cartilage destruction， and bone erosion. Although standardized mortality rates for RA have declined， its escalating global prevalence and trend toward earlier onset continue to substantially exacerbate the disease burden. In traditional Chinese medicine （TCM）， RA is primarily categorized under “Bi syndrome.” Within this framework， blood stasis functions not only as a pathological consequence but also as a core pathogenic mechanism that persists throughout the disease course， contributing significantly to its refractory nature. Consequently， therapeutic strategies that activate blood circulation and resolve stasis play a pivotal role in clinical management. Ferroptosis is an iron-dependent form of regulated cell death characterized primarily by intracellular iron accumulation， lipid peroxidation， and redox imbalance. Emerging evidence indicates that ferroptosis exacerbates RA pathology by driving synovial inflammation and joint destruction， highlighting targeted ferroptosis inhibition as a promising therapeutic strategy. Notably， blood stasis and ferroptosis appear to share pathophysiological overlaps in RA progression. Iron accumulation aligns with the clinical manifestations of blood stasis and may critically contribute to its development， while subsequent lipid peroxidation further aggravates stasis formation. Furthermore， pharmacological studies demonstrate that active compounds from blood-activating and stasis-resolving herbs can suppress ferroptosis in RA models by enhancing endogenous antioxidant defenses. Therefore， elucidating RA-related ferroptosis through the lens of “blood stasis” theory may provide novel scientific insights into targeting this cell death pathway， offering a mechanistic rationale for applying blood-activating and stasis-resolving therapies to mitigate RA progression.

Key words: rheumatoid arthritis, stasis, ferroptosis, reactive oxygen species, blood-activating and stasis-transforming