Genetically modified Scutellaria Radix alleviates rheumatoid arthritis and is associated with suppression of interleukin 1 beta-related signaling.

Scutellaria Radix (SR), the dried root of Scutellaria baicalensis Georgi, has been traditionally used as an antipyretic and analgesic agent. Genetically modified SR (GS), engineered to enhance the active constituents baicalin (BA), baicalein (BE), and wogonin (WG), was hypothesized to exhibit enhanced efficacy at equal or lower doses. Although the pharmacological properties of SR have been reported previously, its therapeutic potential in rheumatoid arthritis (RA) remains unclear. This study aimed to evaluate the therapeutic potential of GS compared with SR in a mouse model of RA. The efficacy of GS was assessed in collagen-induced arthritis mice by monitoring clinical arthritis scores and histopathological features. Serum cytokine levels were measured to determine systemic inflammatory responses. In vitro experiments were conducted using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and tumor necrosis factor (TNF)-α-stimulated C20A4 chondrocytes. A single-dose oral toxicity study was performed to assess safety. GS treatment resulted in dose-dependent amelioration in arthritis severity and histopathological features, despite being administered at the same dosages as SR. Serum cytokine analysis showed significant reductions in interleukin (IL)-1β, a key pro-inflammatory mediator in RA. In vitro, GS significantly suppressed IL-1β expression in macrophages, with BE and WG showed greater potency than BA. GS showed limited direct effects on TNF-α-stimulated C20A4 chondrocytes. However, the GS-treated macrophages markedly reduced MMP-9 expression in co-cultured chondrocytes. The single-dose oral toxicity test revealed no death, clinical symptoms, or organ abnormalities. GS demonstrates enhanced anti-inflammatory efficacy by modulating IL-1β signaling and exhibits superior therapeutic outcomes compared with SR, while showing favorable safety in preclinical studies. These findings suggest GS as a promising candidate for RA treatment.