Mechanisms Of 6-gingerol Ameliorates Age-related Fatty Liver In Rats

ObjectiveWe investigated 6-gingerol protected against age-related fatty liver disease of rats and explore its underlying mechanisms.MethodsTwenty seven male SD ageing rats(22-month-old)were assigned into 3 groups: an ageing control group(ageing,n=9 old rats),a 6-gingerol low-dosage(0.05 mg/kg)group(GL,n=9 ageing rats),and a 6-gingerol high dosage(0.2 mg/kg)group(GH,n=9 ageing rats).Six young SD rats(3-month-old)as young control group(young,n=9 young rats).All rats had free access to standard rodent chow and water.Animals in the two 6-gingerol treated groups were administered 6-gingerol at doses of 0.05 or 0.2 mg/kg(suspended in 5% gum arabic solution,once daily gavage)for 7 weeks.At the end of week 6,an oral glucose tolerance test(OGTT)was performed.Animals were weighed and euthanized after being fasted over-night at the end of week 7.The plasma glucose,triglyceride,total cholesterol and nonesterified fatty acid(NEFA),insulin concentrations were measured enzymatically and ELISA,respectively.Hematoxylin-eosin staining(HE)and oil red O staining were used to observe the degree of fat deposition in liver tissue.The liver metabolomics was detected by GC-MS.The mRNA and protein expression revels of fatty liver associated enzymes were analyzed by real-time PCR and Western blot respectively.ResultsThe results showed that 6-gingerol(0.2 mg/kg)dramatically decreased hepatic triglyceride content,plasma insulin concentration and homeostasis model assessment of insulin resistance(HOMA-IR)index of ageing rats.Mechanismly,6-gingerol affected lipid metabolism by increasing β-oxidation and decreasing lipogenesis,as shown by the activation of peroxisome proliferator-activated receptor(PPAR)α,carnitine palmitoyltransferase(CPT)1α and inhibition of acyl-coenzyme A: diacylglycerol acyltransferase(DGAT)-2.The detection of liver antioxidant ability showed that 6-gingerol increased liver glutathione peroxidase(GSH-PX),superoxide dismutase(SOD),and total antioxidant capacity(T-AOC)content,enhanced the antioxidant capacity.Furthermore,6-gingerol reversed the decreased citrate,citrate synthase(Cs)and ATP,up-regulated mitochondrial marker enzyme NADH oxidase(NOX)and succinate dehydrogenase(SDH),and Sirtuin 3(SIRT3)in ageing liver,indicating its ability to strengthen mitochondrial function.ConclusionThe hepatic anti-steatotic effect of 6-gingerol is associated with inhibition of triglyceride biosynthesis,upregulation of fatty acid oxidation(FAO),reduction in oxidative stress and synergistic enhancement of mitochondrial function.