Liver diseases affect millions of people worldwide. In most of the cases, severe hepatic dysfunction and liver cancer stem from mild and common clinical signs including hepatic steatosis, insulin resistance, liver inflammation, and oxidative stress, all together referred to as Nonalcoholic Fatty Liver Disease (NAFLD). Nutraceuticals endowed with antioxidant activity have been shown to reduce NAFLD risk factors and exert hepatoprotective effects. Here, we test the protective effect exerted on liver by the antioxidant Taurisolo, a nutraceutical formulation produced by grape pomace and enriched in Resveratrol and Polyphenols. We analyze the effect of Taurisolo on liver cells by profiling the metabolome of in vitro cultured hepatic HuH7 cells and of C57BL-6J mice fed a High Fat Diet and treated with the nutraceutical. Both in vitro and in vivo, we provide evidence that Taurisolo reduces risk factor markers associated with NAFLD. Taurisolo stimulates glucose uptake and reduces hepatic cholesterol and serum triglycerides. Furthermore, we give new insights into the mechanism of action of Taurisolo. The nutraceutical increases mitochondrial activity and promotes respiration and ATP production, fostering catabolic reactions like fatty acid β-oxidation and amino acid catabolism. On the contrary, Taurisolo reduces anabolic reactions like biosynthesis of cholesterol, bile acids, and plasma membrane lipids.

Grapes and apples are the most cultivated fruits in the Mediterranean basin and their agricultural processing is responsible for the production of a large amount of bio-waste. The reuse of this food biomass would increase the volume of recyclable/renewable biomaterial and lower the environmental impact due to the increasing demand for these biological products. To this purpose, agri-food waste from grape and apple processing have become an important source of phytochemicals, and many pharmaceutical industries are using it as starting material to produce dietary supplements, functional foods, and food additives for human consumption. In virtue of the chemical diversity and complexity of agri-food biowaste, developers and producers of nutraceuticals are advised to assess the safety of their final nutraceutical products, in compliance with European Food Safety Authority regulation. Here, we use the Ames test to assess the mutagenicity of three nutraceuticals obtained from agri-food waste biomasses: Taurisolo^® from grape pomace of Vitis vinifera L. cv ‘Aglianico’, AnnurComplex^® from Malus pumila M. cv ‘Annurca’ and Limoncella Apple Extract from Malus domestica B. cv ‘Limoncella’. The results showed that all three nutraceuticals were non-mutagenic.