Naringenin and its Nano-formulations for Fatty Liver: Cellular Modes of Action and Clinical Perspective

Abstract

Naringenin exerts diverse biological actions including the decrease of biomarkers of lipid peroxidation and protein carbonylation, increase of antioxidant defenses, scavenging of reactive oxygen species and modulation of signaling pathways related to fatty acid metabolism which can favor the oxidation of fatty acid, lower lipid accumulation in the liver and thereby prevent fatty liver.

Calcium supplementation shows a hepatoprotective effect against high-fat diet by regulating oxidative-induced inflammatory response and lipogenesis activity in male rats

“…In addition, we further examine the involvement of hepatic AMP-activated protein kinase (AMPK) activity after considering its potential role in hepatic lipid metabolism and could be a possible target for the treatment of fatty liver. 14 The down-regulation AMPK activity during HFD consumption in our study may be associated with the pathological consequences of obesity-induced fatty liver as seen in earlier reports. 50 AMPK, is a crucial metabolic sensor whole activation through phosphorylation down-regulates the hepatic lipogenesis activity and glucose production during the development of NAFLD.…”

“…These receptors are regulated by hepatic lipid accumulation which in turn alters the expression of several genes involved in fatty acid metabolism. 14 We observed a decline in PPAR-γ activity in animals of the calcium-supplemented group which might, in turn, suppressed the lipogenic activity as shown by inhibition of hepatic FAS activity and triglyceride accumulation . The entry of fatty acid through blood circulation into the liver from obese adipose tissue in the HFD group might have up-regulated the PPAR-γ activity as fatty acids within the liver act as a ligand for its activation.…”

“… 46 Thus, the low level of circulating FFA in our calcium supplemented rats might further prevent the activation of the inflammatory response by downregulating the production of TNF-α which are produced by FFA induced activated Kupffer cells. 14 …”

“… 49 Dietary effect of calcium supplementation seemed to prevent the progression of NAFLD towards NASH as seen by an effective dietary supplement like Naringenin, through several cellular mechanism involving the inhibition of pro-inflammatory reactions mediated by TNF-α, IL-6, TLR-4, inducible nitric oxide synthase (iNOs), cyclooxygenase-2 and NADPH oxidase-2 and also prevent the metabolic dysregulation by activating AMP-activated protein kinase (AMPK). 14 …”

“…Its activation by phosphorylation stimulates the hepatic fatty acid oxidation and inhibits the hepatic lipogenesis pathway and prevents the development of NAFLD. 14 Calcium and VitD are found to activate AMPK through phosphorylation in different tissues. Post weaning low calcium diet decreases the AMPK activation in skeletal muscle.…”