Study On Andrographolide's Therapeutic Effect And Hepatoprotective Effect On Freund's Complete Adjuvant Arthritis Rats

Objective:Methotrexate is one of the most widely used disease-modifying anti-rheumatic drugs.The hepatotoxicity of methotrexate resulted in poor compliance with therapy.The protective effect of andrographolide against hepatotoxicity and inflammation has been published in previous studies.The current study was designed to analyse the combination therapy of andrographolide(AD)and methotrexate(MTX)for complete Freund's adjuvant(CFA)-induced arthritis,focusing on hepatoprotective effects,oxidative stress and arthritic-related cytokines.Method:Wistar rats were injected with CFA into the right hind paw.Ten days post-CFA injection,the Wistar rats were administered with 1%CMC-Na,methotrexate(2 mg/kg/week),AD(50 mg/kg/d)and combined therapy for 35 days.The anti-arthritic effect was assessed by paw volume,X-ray and serum TNF-?,IL-6 and IL-1? levels.Serum samples were also analysed for glutamic oxaloacetic transaminases(GOT),serum glutamic pyruvic transaminase(GPT),alkaline phosphatase(AKP)and lactate dehydrogenase(LDH).Liver tissue samples were used to examine the cellular antioxidant defence activities using CAT and GSH as well as GSH-Px and MDA.Histopathology and immunohistochemistry were conducted to evaluate liver damage.Results:AD treatment strengthened the anti-arthritic capacity of MTX.AD and MTX-combined therapy additively reduced the inflammatory symptoms in complete Freund's adjuvant rats.The combination therapy showed a significantly hepatoprotective effect indicated by an improvement in the serum marker,possibly due to antioxidant action and confirmed by liver histopathological changes.Furthermore,the combined therapy significantly reduced serum TNF-?,IL-6 and IL-1? levels.Conclusions:According to our results,we have shown that AD can be a useful auxiliary drug for arthritis by strengthening the anti-arthritic effect of MTX.A combined therapy of AD and methotrexate significantly alleviated MTX-induced hepatocellular injury.Further clinical studies should be done to further verify the possibility of combined its clinical usage.