Liver is the most important and functional organ in the body to metabolize and detoxify endogenous compounds and xenobiotics. The major goal of the present narrative review is to assess the hepatoprotective properties of hesperidin against a variety of natural and chemical hepatotoxins via different mechanisms. Scientific databases such as Scopus, Medline, Web of Science and Google scholar were thoroughly searched, based on different keywords. A variety of natural hepatotoxins such as lipopolysaccharide, concanavalin A and microcystins, and chemical hepatotoxins such as ethanol, acrylamide and carbon tetrachloride have been shown to damage hepatocytes as well as other liver cells. In addition to hepatocytes, ethanol can also damage liver hepatic stellate cells, Kupffer cells and sinusoidal endothelial cells. In this regard, the flavanone hesperidin, occur in the rind of citrus fruits, had been demonstrated to possess widespread pharmacological properties. Hesperidin exerts its hepatoprotective properties via different mechanisms including elevation in the activities of nuclear factor-like 2/antioxidant response element and heme oxygenase 1 as well as the levels of enzymatic and non-enzymatic antioxidants. Furthermore, reduction in the levels of high-mobility group box1 protein, inhibitor of kappa B protein-alpha, matrix metalloproteinase-9 and C-reactive protein are some other important hesperidin-derived hepatoprotective mechanisms. Based on several research papers, it could be concluded that hesperidin is able to protect against liver damage from inflammation and/or oxidative stress-mediated natural and chemical toxins.
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