Scabiosa Inflorescence and Foliage Alleviate Liver Fibrosis via Suppression of c-Jun and JAK/STAT Signaling Pathways

Liver fibrosis, a major consequence of chronic liver disease, lacks effective antifibrotic therapies. Scabiosa comosa Fisch. ex Roem. et Schult. (Scabiosa), a traditional Mongolian medicinal plant, has demonstrated hepatoprotective properties; however, its underlying mechanisms remain unclear. The antifibrotic effects of Scabiosa inflorescences and foliage were evaluated in a CCl₄-induced murine model of liver fibrosis. Histological staining, serum biomarker analysis, ultra-high-performance liquid chromatography-mass spectrometry profiling, and network pharmacology were employed to assess therapeutic efficacy and to identify bioactive compounds and their potential targets. Key genes and proteins were validated by quantitative reverse transcription polymerase chain reaction and Western blotting. Scabiosa treatment significantly improved liver histopathology, reduced collagen deposition, and decreased the liver-to-body weight ratio. Serum alanine aminotransferase, aspartate aminotransferase, hyaluronic acid, procollagen type III, laminin, and type IV collagen levels were markedly reduced, indicating protection against hepatocellular injury and fibrogenesis. Chemical profiling revealed that multiple bioactive compounds from Scabiosa entered the systemic circulation. Network pharmacology analysis identified core targets, including CD44, c-JUN, OPN, and STAT3, which were downregulated following treatment. Pathway enrichment analysis suggested the involvement of the c-Jun and JAK/STAT signaling pathways in mediating the antifibrotic effects. Scabiosa inflorescences and foliage effectively attenuated liver fibrosis through multicomponent, multitarget actions, primarily by modulating the c-Jun and JAK/STAT pathways. These findings provide mechanistic evidence supporting its traditional use and its potential as a therapeutic candidate for chronic liver disease.