Inhibition of hepatic stellate cell activation by nutraceuticals: an emphasis on mechanisms of action.

Liver diseases emerge as a serious threat to humans worldwide due to increasing morbidity and mortality. Liver disease related deaths accounts for one third of all disease related death globally. A simple fatty liver if unattended advances further to liver fibrosis, cirrhosis and hepatocellular carcinoma. During liver fibrogenesis, hepatic stellate cells gets activated into myofibroblast like cells and exhibit proliferative and fibrogenic features. Targeting these activated hepatic stellate cells offer promising therapeutic approach towards liver fibrosis management. To date there is no Food and Drug Administration approved treatments for liver fibrosis. However, a large number of clinical trials are being conducted employing monoclonal antibodies, drugs, dietary supplements and herbal medicines. A vast number of research findings demonstrated nutraceuticals to be effective against experimental liver fibrosis both in vitro and in vivo. Nutraceuticals typically regulate key signaling pathways in activated hepatic stellate cells and exhibit anti-fibrotic effect. In this review, the mechanistic action of nutraceuticals targeting activated hepatic stellate cells were summarized to establish them as a possible therapeutic candidate for liver fibrosis.

Role of adipocyte-derived extracellular vesicles during the progression of liver inflammation to hepatocellular carcinoma.

Extracellular vesicles are membrane-bound cargos that vary in size and are stably transported through various bodily fluids. Extracellular vesicles communicate information between the cells and organs. Extracellular vesicles from the diseased cells alter cellular responses of the recipient cells contributing to disease progression. In obesity, adipocytes become hypertrophic and the extracellular vesicles from these dysfunctional adipocytes showed altered cargo contents instigating pathophysiological response leading to chronic liver diseases. In this review, the role of adipocyte-derived extracellular vesicles on the progression of liver inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma are extensively discussed. Newer approaches are crucial to take advantage of extracellular vesicles and their content as biomarkers to diagnose initial liver inflammation before reaching to an irreversible liver failure stage.