Hepatoprotective Effect of Camel Thorn Polyphenols in Concanavalin A-Induced Hepatitis in Mice

Objective:To explore the prophylactic and therapeutic effects of Alhagi maurorum ethanolic extract(AME)in concanavalin A(Con A)-induced hepatitis(CIH)as well as possible underlying mechanisms.Methods:Polyphenols in AME were characterized using high performance liquid chromatography(HPLC).Swiss albino mice were divided into 4 groups.Normal group received intravenous phosphate-buffered saline(PBS);Con A group received 40 mg/kg intravenous Con A.Prophylaxis group administered 300 mg/(kg·d)AME orally for 5 days before Con A intervention.Treatment group received intravenous Con A then administered300 mg/kg AME at 30 min and 3 h after Con A intervention.After 24 h of Con A injection,hepatic injury,oxidative stress,and inflammatory mediators were assessed.Histopathological examination and markers of apoptosis,inflammation,and CD4^(+)cell infiltration were also investigated.Results:HPLC analysis revealed that AME contains abundant polyphenols with pharmacological constituents,such as ellagic acid,gallic acid,ferulic acid,methylgallate,and naringenin.AME alleviated Con A-induced hepatic injury,as manifested by a significant reduction in alanine aminotransferase,aspartate aminotransferase and alkaline phosphatase(P<0.01).Additionally,the antioxidant effect of AME was revealed by a significant reduction in oxidative stress markers(nitric oxide and malondialdehyde)and restored glutathione(P<0.01).The levels of proinflammatory cytokines(tumor necrosis factor-α,interferon-γ,and interleukin-6)and c-Jun N-terminal kinase(JNK)activity were reduced(P<0.01).Histopathological examination of liver tissue showed that AME significantly ameliorated necrotic and inflammatory lesions induced by Con A(P<0.01).Moreover,AME reduced the expression of nuclear factor kappa B,pro-apoptotic protein(Bax),caspase-3,and CD4^(+)T cell hepatic infiltration(P<0.01).The expression of anti-apoptotic protein Bcl-2 was increased(P<0.01).Conclusions:AME has hepatoprotective and ameliorative effects in CIH mice.These beneficial effects are likely due to the anti-inflammatory,antioxidant,and anti-apoptotic effects of the clinically important polyphenolic content.AME could be a novel and promising hepatoprotective agent for managing immune-mediated hepatitis.