Hawthorn fruit extract protect against MC-LR-induced hepatotoxicity by attenuating oxidative stress and apoptosis

Microcystins (MCs) is a class of cyclic heptapeptide compounds with biological activity. There is no effective treatment for liver injury caused by MCs. Hawthorn is a medicinal and edible plant traditional Chinese medicine with hypolipidemic, reducing inflammation and oxidative stress in the liver. This study discussed the protective effect of hawthorn fruit extract (HFE) on liver damage caused by MC-LR and the underlying molecular mechanism. After MC-LR exposure, pathological changes were observed and hepatic activity of ALT, AST and ALP were increased obviously, but they were remarkably restored with HFE administration. In addition, MC-LR could significantly reduce SOD activity and increase MDA content. Importantly, MC-LR treatment resulted in mitochondrial membrane potential decreased, and Cytochrome C release, eventually leading to cell apoptosis rate increase. HFE pretreatment could significantly alleviate the above abnormal phenomena. To examine the mechanism of protection, the expression of critical molecules in the mitochondrial apoptosis pathway was examined. The levels of Bcl-2 was inhibited, and the levels of Bax, Caspase-9, Cleaved Caspase-9, and Cleaved caspase-3 were upregulated after MC-LR treatment. HFE reduced MC-LR-induced apoptosis via reversing the expression of key proteins and genes in the mitochondrial apoptotic pathway. Hence, HFE could alleviate MC-LR induced hepatotoxicity by reducing oxidative stress and apoptosis.