Integrating Silybin and Sirtuin Related Pathways in Steatosis-Related Liver Diseases

Abstract

Silybin represents the most bioactive compound of Silymarin, a flavonoid derived from Silybum marianum species. As a medicinal plant extract, Silybin possesses protective and regenerative action with respect to hepatic parenchyma. Due to its anti-oxidant, anti-inflammatory and anti-fibrotic effects, Silybin has been proposed as an extremely attractive molecule in the prevention and treatment of different hepatic diseases related to steatosis, such as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). However, the full comprehension of the molecular mechanisms by which Silybin acts as hepato-protector is still far from being complete. Silybin-mediated properties usually involve modulation of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor family (PPARs) pathways, which can affect NAD⁺-dependent protein lysine deacetylase Sirtuin (SIRT) family members either directly or indirectly. Starting from a detailed overview of its liver-related features, as well as the underlying molecular mechanisms, this review aimed at collecting evidence that correlates Silybin-mediated outcomes with SIRT pathways. With particular reference to SIRT1 and SIRT2, a theoretical map is designed in an effort to highlight shared molecular interactions. Finally, future perspectives concerning the integration of Silybin and Sirtuin pathways in fatty liver diseases are discussed, along with the major limits for its current therapeutic usage.