Proanthocyanidins biotransformed by Saccharomyces cerevisiae prevent the pathogenesis of steatosis and progression to steatohepatitis in vitro

Oligomeric and polymeric proanthocyanidins (PAC) were biotransformed with Saccharomyces cerevisiae to improve bioavailability and bioactivity. Biotransformation significantly increased the bioavailability of PAC in vitro and generated many metabolites, most notably, 3-aminophenol, pyrogallol, phloroglucinol, 4-hydroxyphenylacetamide, 2,4-dihydroxy-6-methylbenzaldehyde, 2,4,6-trihydroxyacetophenone, and 2-hydroxyphenylacetic, 3-aminosalicylic, dihydroxybenzoic, 2-hydroxycinnamic, 3-phenyllactic, and gallic acids. The bioactivity of biotransformed (BT)-PAC and non-BT-PAC was compared using palmitic acid (PA)-induced steatosis/nonalcoholic fatty liver disease (NAFLD) and PA + bacterial lipopolysaccharide-induced nonalcoholic steatohepatitis (NASH) models of AML12 hepatocytes. BT-PAC reduced the PA-induced cellular oxidative stress and lipid accumulation by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway and modulating key regulators of cellular lipid metabolism. BT-PAC reduced the progression of steatosis to NASH in vitro by suppressing toll-like receptor 4-mediated cellular inflammation. Non-BT-PAC was less potent in the reduction of cellular lipotoxicity and inflammation. S. cerevisiae-mediated biotransformation significantly enhances the bioavailability of PAC and the bioactivity against steatosis and NASH.