The Protective Effect of Myristica fragrans Houtt. Extracts Against Obesity and Inflammation by Regulating Free Fatty Acids Metabolism in Nonalcoholic Fatty Liver Disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a disorder characterized by the excess accumulation of fat in the hepatocytes. It is commonly associated with severe obesity and inflammation. Free fatty acids (FFAs) are the key to regulate lipid metabolism and immune response in hepatocyte cells. This study examined the effects of AEN (alcohol extract of nutmeg, the seed of Myristica fragrans Houtt.) on the inhibition of lipid synthesis and inflammation in vitro and in vivo and on high-fat diet-induced obesity in NAFLD mice. Our results showed that AEN treatment could downregulate the expression of lipid synthesis-related genes fatty acid synthase (FASN) and sterol regulatory element-binding protein 1c (SREBP-1c) and lower the lipid content of cells. AEN also inhibited FFAs-mediated inflammation-related cytokines interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) expression in cells. In a mouse model, AEN reduced the bodyweight of obese mice and improved NAFLD without affecting food intake. Further analysis revealed that AEN significantly reduced inflammation level, cholesterol and lipid accumulation, blood glucose, and other liver function indexes in mice fed with a high-fat diet. In conclusion, AEN inhibited the aggravation of obesity and inflammation by downregulating lipid-gene expression in the liver to ameliorate NAFLD.

Polyphenol-Rich Extracts of Xylopia and Aframomum Species Show Metabolic Benefits by Lowering Hepatic Lipid Accumulation in Diet-Induced Obese Mice

“… 32 In addition, treatment may downregulate the activity of numerous enzymes involved in TAG synthesis, such as acyl-CoA synthetases, acyltransferases glycerol-3-phosphate 4 (GPAT4), and diacylglycerol acyltransferase 2 (DGAT2), which allow for the expansion of preexisting lipid droplets. 29 Similar results were reported earlier, 33 , 34 where both have shown that downregulation of lipogenic-gene expression in the liver by Myristica fragrans Houtt. and Morus alba L. extracts inhibit the progression and development of NAFLD.…”

Myristica fragrans (Jaiphal): A Significant Medicinal Herbal Plant

“…Models were fed with high-fat-diet. It was revealed from the study, alcohol extract of nutmeg significantly reduced the body weight and levels of inflammation, cholesterol and lipid accumulation, blood glucose which supports its use as an hepatoprotective agent [143]. Dkhil et al, also studied hepatoprotective activity of Myristica fragrans.…”

Hydrogen Sulfide Attenuates High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease by Inhibiting Apoptosis and Promoting Autophagy via Reactive Oxygen Species/Phosphatidylinositol 3-Kinase/AKT/Mammalian Target of Rapamycin Signaling Pathway

“…Administration of H 2 S reduced NEFA level in the liver of mice fed with HFD. It has been reported that pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) play important roles in the development of NAFLD ( Ji et al, 2018 ; Liu et al, 2020b ; Zhao et al, 2020 ). Our results indicated that H 2 S reduced the levels of TNF-α, IL-1β, and IL-6 in the liver of HFD-fed mice, suggesting that H 2 S may relieve NAFLD partly by decreasing inflammation in the liver.…”

“…For ORO staining, the frozen tissues were cut into 10 μm thick sections, stained with ORO, and then counterstained with hematoxylin. The sections were observed using an Olympus BX51 microscope (Olympus, Tokyo, Japan) and analyzed by Image J software (National Institutes of Health, Bethesda, MD, United States), and the area of hepatic steatosis was determined using optical density values ( Zhao et al, 2020 ).…”