Zingiber officinaleextract and omega‐3 fatty acids ameliorate endoplasmic reticulum stress in a nonalcoholic fatty liver rat model

Abstract

Endoplasmic reticulum (ER) stress was reported to play a major role in non‐alcoholic fatty liver disease (NAFLD) induction and progression. Here, we study the effect of Zingiber officinale and omega‐3 fatty acids on ER stress for treating NAFLD. Male Wistar rats were fed on a normal diet (control group) or high‐fat diet (HFD) for 8 weeks. The HFD rats were later treated with vehicle, omega‐3 or with Z. officinale extract. HFD group demonstrated significantly more body weight gain and higher plasma lipid profile, glucose, and hepatic enzymes. The expressions of lipogenic ChREBP and ER stress genes CHOP, XBP1, and GRP78 were increased. This was accompanied by intrahepatic fat accumulation visualized by hepatic morphology and H&E‐stained sections. Treatment with Z. officinale and omega‐3 fatty acids reverted these changes into a normal healthy state. From these results, we prove that both therapeutic approaches can be potential drugs for treating NAFLD besides other ER stress‐associated diseases. Practical applications The effect of Zingiber officinale extract and omega‐3 fatty acid on ER stress associated with NAFLD was investigated. The results revealed that Z. officinale extract and omega‐3 fatty acids significantly inhibited ER stress and intrahepatic fat accumulation with the upper hand for Z. officinale extract. Both can be used as future promising therapies for the treatment of NAFLD patients and also treating different diseases that involve ER stress as a pathological modulator like diabetes mellitus, Alzheimer's disease, Parkinson's disease, and cancer.

Effects of Long-Term DHA Supplementation and Physical Exercise on Non-Alcoholic Fatty Liver Development in Obese Aged Female Mice

“…Interestingly, our data show that DHA-fed mice exhibited a marked reduction in the mRNA expression of both Xbp1 and Ern1, the gene that encodes for IRE1α, which could also account for the anti-lipogenic properties of this fatty acid in liver and thus the prevention of NAFLD in old obese mice. These data are in agreement with those observed by Kandeil et al [89] evidencing a marked reduction of Xbp1 mRNA levels and other ER stress biomarkers (CHREBP, CHOP, GRP78) in liver of young rats supplemented with n-3 PUFA, in parallel with the reduction of hepatic lipid content. The study of Gonçalves et al [90] has also found reduced expression of hepatic Xbp1 after dietary supplementation with the n-3 PUFA α-linolenic acid (ALA).…”

Protective Effect of α-Linolenic Acid on Non-Alcoholic Hepatic Steatosis and Interleukin-6 and -10 in Wistar Rats

“…The capacity of n-3 to reduce IL-6 is linked to lower expression of associated apoptosis protein, transcription factor C/EBP homologous protein (CHOP), and modulation of the expression of XBP1, with the consequent blockage of the activation of the JNK inflammatory pathways and inhibiting nuclear factor-κB (IκB) kinase (IKK) and regulation of the mediators of inflammation [49]. This PUFA can inhibit the production of sterol regulatory element-binding protein (SREBP)-1c, which leads to reduced de novo lipogenesis and accumulation of TG in the liver, resulting in lower organ weight and less liberation of very-low-density lipoprotein (VLDL) and TG in the blood, vital factors for reducing risks related to cardiovascular diseases and metabolic inflammation [18,19,31].…”

Perindopril ameliorates experimental Alzheimer’s disease progression: role of amyloid β degradation, central estrogen receptor and hyperlipidemic-lipid raft signaling

“…Normal chow diet (ATMID Co., Egypt) contained corn, soybean, soybean oil, sodium chloride, lecithin, methionine, dicalcium phosphate, calcium carbonate and mineral/ vitamins mixture, consisting of 23% protein, 60-70% carbohydrates, 6% fat, 3% fibers and 1-4% mineral/vitamins mixture. HFFD was prepared according to earlier studies with slight modification, where it contained 40% normal chow, 30% fat of beef tallow, 10% corn starch, 20% sucrose, 2% cholesterol and 0.2% bile salt in addition to 10% fructose and 10% sucrose in drinking water (Kandeil et al 2019;Niu et al 2016;Sato et al 2010). Weight of each rat was recorded at the end of each week for 4 weeks and growth pattern of rats was evaluated.…”