Hepatoprotective effect of gentiopicroside in combination with leflunomide and/or methotrexate in arthritic rats

Aims: This study aimed to examine whether gentiopicroside (GPS) could exert hepatopmtective effects on leflunomide (LEF)- and/or methotrexate (MTX)-treated arthritic rats through anti-inflammatory and antioxidant pathways. Main methods: We observed the external symptoms of joints, analysed serum indicators, measured haematological parameters and mRNA levels, and performed HE staining. Key findings: LEF and/or MTX combined with GPS ameliorated oxidative stress by increasing the mRNA levels of the antioxidant gene Nrf2, GCLC, HO-1, and NQO1, increasing the antioxidant enzymes superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT), reducing the oxidant substance malondialdehyde (MDA), reducing the inflammatory response by decreasing the mRNA levels of NF-kappa B, tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6), and inhibiting the secretion of the pro-inflammatory cytokines TNF alpha, IL-6, IL-1 beta and reducing C-reactive protein (CRP), as well as alleviating the external symptoms of arthritis. Significance: These results show that GPS plays an antioxidant and anti-inflammatory role in LEF- and/or MTX-treated arthritic rats by affecting the Nrf2 and NF-kappa B signalling pathways, thus exerting hepatopmtective effects.