Hepatoprotective effect of fisetin loaded silk nanofibrils on acetaminophen induced acute liver injury

Fisetin is a flavonoid polyphenol widely found in vegetables and fruits, which has been proved to own protective effects for the liver. However, fisetin shows poor water solubility and stability, leading to low bioavailability and critically restricts its in vivo administration. In this work, Fisetin was physically adsorbed onto SF to construct the fisetin loaded silk nanofibrils/fisetin complex (SF/fisetin). The hepatoprotective ability of fisetin on acetaminophen (APAP)-induced acute liver injury was enhanced by loading fisetin onto SF. The SF/fisetin combined the dispersion stability and biocompatibility of SF, as well as the antioxidant and anti-inflammatory property of fisetin, in this way to show a synergetic enhanced hepatoprotective effect. SF/fisetin exhibited strong in vitro antioxidant ability, the in vivo analysis showed that SF/fisetin normalized the activities of serum aspartate/alanine aminotransferase (AST/ALT) and inhibited pathological hepatic injury. SF/fisetin relieved the APAP-induced oxidative stress and inflammatory response through restraining the generation of malondialdehyde (MDA) and reducing proinflammatory cytokines (e.g., TNF-α, IL-1β). The SF/fisetin should be a potential effective therapeutic agent for alleviating APAP-induced acute liver injury.