A Molecular Insight into the Role of Antioxidants in Nonalcoholic Fatty Liver Diseases

Abstract

Nonalcoholic fatty liver disease (NAFLD) defines fat accumulation in the liver, and it is commonly associated with metabolic syndromes like diabetes and obesity. Progressive NAFLD leads to nonalcoholic steatohepatitis (NASH) and ultimately causes cirrhosis and hepatocellular carcinoma, and NASH is currently a frequent cause of liver transplantation. Oxidative stress is often contributed to the progression of NAFLD, and hence, antioxidants such as silymarin, silybin, or silibinin, pentoxifylline, resveratrol, and vitamins A, C, and E are used in clinical trials against NAFLD. Silymarin induces the peroxisome proliferator-activated receptor α (PPARα), a fatty acid sensor, which promotes the transcription of genes that are required for the enzymes involved in lipid oxidation in hepatocytes. Silybin inhibits sterol regulatory element-binding protein 1 and carbohydrate response element-binding protein to downregulate the expression of genes responsible for de novo lipogenesis by activating AMP-activated protein kinase phosphorylation. Pentoxifylline inhibits TNF-α expression and endoplasmic reticulum stress-mediated inflammatory nuclear factor kappa B (NF-κB) activation. Thus, it prevents NAFLD to NASH progression. Resveratrol inhibits methylation at Nrf-2 promoters and NF-κB activity via SIRT1 activation in NAFLD conditions. However, clinically, resveratrol has not shown promising beneficial effects. Vitamin C is beneficial in NAFLD patients. Vitamin E is not effectively regressing hepatic fibrosis. Hence, its combination with antifibrotic agents is used as an adjuvant to produce a synergistic antifibrotic effect. However, to date, none of these antioxidants have been used as a definite therapeutic agent in NAFLD patients. Further, these antioxidants should be studied in NAFLD patients with larger populations and multiple endpoints in the future.

Bioactive Compounds Formulated in Phytosomes Administered as Complementary Therapy for Metabolic Disorders

“…Therefore, the health of the liver is very important for the health of the whole body. NAFLD or the metabolic-associated fatty liver disease (MAFLD) affects over 30% of the world population [157]. It arises from lipid accumulation in hepatocytes, a process that alters the liver's normal function.…”

Roles of peroxisome proliferator‐activated receptors in hepatocellular carcinoma

“…PPARα, the first identified member of the PPAR family, is mainly expressed in tissues with high levels of fatty acid catabolism, such as the liver, skeletal muscle and heart. PPARα is closely associated with energy homeostasis and lipid metabolism 25,26 . Abnormal expression of PPARα may be related to a variety of metabolic disorders including fatty liver, alcoholic cardiomyopathy, atherosclerosis, etc.…”

Role of macrophage scavenger receptor MSR1 in the progression of non-alcoholic steatohepatitis

“…Damaged cells release DAMPs, which bind to TLR4 or TLR9 on KCs to activate the NF-κB signaling pathway, thereby generating more ROS to amplify the inflammatory response ( 64 ) ( Figure 3 ) . Accordingly, antioxidants such as silymarin or silybin, resveratrol, hexoketococine, and vitamins A, C, and E, are potential agents against NASH ( 79 ).…”