Exploration of Hepatoprotective Potential and Phytochemicals of Ziziphus oxyphylla Edgew

Abstract

Ziziphus oxyphylla Edgew (ZO) has been traditionally used for the treatment of hepatic diseases in Pakistan. The current study was carried out to investigate the effectiveness and mechanism underlying hepatoprotective effect of ZO. Hepatoprotective potential of root extracts (crude methanolic extract and subsequent fractions) was investigated against carbon tetrachloride (CCl4) induced hepatotoxicity in BALB/c mice via determination of serum biomarkers, antioxidant enzymes (catalase, superoxide dismutase), lipid peroxidation and histopathology. Membrane stabilizing activity was determined via inhibition of hypotonic solution and heat-induced hemolysis. Crude methanolic extract and chloroform fraction ameliorated CCl4 induced elevated levels of alanine transaminase (ALT), alkaline phosphatase (ALP), total proteins (TP), total bilirubin (TB) and reversed the antioxidants imbalance in terms of catalase (CAT), superoxide dismutase (SOD) and reduced malondialdehyde (MDA) level. Crude methanol extract inhibited hemolysis induced by hypotonic solution and heat. Histopathological examination of liver specimens of extracts administered mice exhibited recovery from CCl4 induced pathological changes. Moreover, CCl4 induced alteration in body and liver weight was countered by the administration of ZO. Compounds betulinic acid (AZO1), ceanothic acid (AZO2) and zizybrenalic acid (AZO3) were isolated from chloroform fraction of the plant. The structures of compounds were deduced using 1D-and 2D-NMR spectroscopy techniques. The results show that Ziziphus oxyphylla roots extract possess antihepatotoxic activity mediated by the protection of anti-oxidant defense system and membrane-stabilizing activity, probably due to the presence of pentacyclic triterpenes