Vinpocetine and Lactobacillus improve fatty liver in rats via modulating the oxidative stress, inflammation, adiponectin and gut microbiome.

Therapeutics that interfere with the damage/pathogen-associated molecular patterns (DAMPs/PAMPs) have evolved as promising candidates in the context of hepatic inflammation like that occurring in the non-alcoholic fatty liver disease (NAFLD). Herein, we investigated the therapeutic impact phosphodiesterase-1 inhibitor vinpocetine (Vinpo), alone or when combined with Lactobacillus, on hepatic abnormalities caused by a 13-week high-fat diet (HFD) and diabetes in rats. The results have shown that Vinpo (10 and 20 mg/kg/day) dose-dependently limited HFD-instigated rise of hepatic injury parameters in serum (ALT, AST) and tissue (histological necroinflammation score). These effects were concordant with Vinpo potential to ameliorate HFD-induced fibrosis (Histological fibrosis score, hydroxyproline, TGF-β1 ) and oxidative stress (MDA, NOx) alongside restoring the antioxidants (GSH, SOD, Nrf-2, HO-1) in the liver. Mechanistically, Vinpo attenuated the hepatocellular release of DAMPs like HMGB1 alongside lowering the overactivation of the pattern recognition receptors TLR4 and RAGE. Consequently, there was a less activation and nuclear translocation of the nuclear factor-kappa B that was ensued with a decline in overexpression of the proinflammatory cytokines TNF-α and IL-6 in Vinpo-treated HFD/diabetes-rats. In comparison to Vinpo treatment alone, Lactobacillus probiotics as an adjunctive therapy with Vinpo significantly improved the disease-associated inflammation and oxidative stress injury, as well as the insulin resistance and lipid profile abnormalities via enhancing the restoration of the symbiotic gut microbiota. In conclusion, combining Vinpo and Lactobacillus probiotics may be a successful approach for limiting the NAFLD in humans.