Traditional Chinese herbal formula Huo Luo Xiao Ling Dan ameliorates rheumatoid arthritis by suppressing inflammation and oxidative stress via the AGE/RAGE/NF‑κB signaling pathway.

Rheumatoid arthritis (RA) is a chronic autoimmune pathology that arises chiefly from the dysregulated activation of fibroblast-like synoviocytes. The traditional Chinese herbal formula Huo Luo Xiao Ling Dan (HLXL) has unclear mechanisms in RA treatment. This work combined network pharmacology with both cellular and animal-based experiments. Network analysis suggested the advanced glycation end products (AGE)/receptor for advanced glycation end products (RAGE) pathway as a crucial target for HLXL. In vitro experiments showed that HLXL (50, 100 μg/mL) dose‑dependently suppressed TNF‑α‑induced MH7A human fibroblast-like synoviocyte proliferation, migration, invasion, and NF‑κB activation. Additionally, HLXL reduced oxidative stress markers (ROS, MDA) and pro‑inflammatory cytokines (IL‑6, IL‑1β), while enhancing total superoxide dismutase (tSOD) activity. The RAGE agonist D‑Ribose counteracted these effects, confirming the involvement of AGE/RAGE signaling. In collagen‑induced arthritis (CIA) rats, HLXL (7.25, 14.5 g/kg) ameliorated joint swelling, arthritis index, synovial pathology, and cartilage erosion. It also decreased oxidative stress and inflammatory factors in serum and synovial tissues and suppressed AGE/RAGE/NF‑κB signaling in vivo. Collectively, HLXL exerts anti‑RA effects through inhibition of the AGE/RAGE/NF‑κB pathway.