The Lipid-lowering And Anti-inflammation Effects And The Potential Molecular Mechanism Of Myricitrin

Bayberry(Myrica rubra Sieb.et Zucc.)is a popular fruit with moderately sweet and sour tastes.It is eaten raw or dried processed,made into sauce,preserved,etc.Its juice can also be made into wine.In juice or wine form,it is used for thirst quenching,hydration(body fluid),and helps food digestion.Bayberry contains many functional or bioactive ingredients that elicits a variety of biological functions.Myricitrin is one of the main active components from bayberry fruits,with records of a variety of biological effects,but its mechanism of action is still unclear.In this paper,mouse model with high-fat diet induced obesity and liver cancer HepG2 cell lines induced by oleic acid were used to evaluate the potential lipid-lowering effect of myricitrin and explore its mechanism of action.Secondly,inflammatory lipopolysaccharide-induced RAW264.7 macrophages cell lines were used to evaluate the potential anti-inflammatory effect of myricitrin,explore its mechanism of action,provide a theoretical basis for the research and basis for the development of bayberry as a functional food to ameliorate hyperlipidemia and chronic inflammation.1.Myricitrin's lipid-lowering effect and its molecular mechanismThirty C57BL/6 male mice were randomly divided into three groups:control;high-fat diet fed;and a myricitrin protected group.The myricitrin mice protected group had 100 mg/kg.bw/day myricitrin solutions by gavage.The solution was a supplement to the high fat diet throughout the experiment.Results showed that weight measurements for mice body;liver;spleen;and fat tissue were significantly reduced with myricitrin protection.Likewise,serum total triglyceride(TG),total cholesterol(TC)and low-density lipoprotein(LDL-C)content was reduced,while the serum high-density lipoprotein(HDL-C)content increased.The HE staining analysis of the mice liver and adipose tissues revealed many fatty vacuoles and larger lipid droplets in hepatocytes and adipose tissues of the high-fat diet fed group,however myricitrin supplementation slowed down these liver diseases,inhibited the development of lipid droplets,and reduced the hypertrophy of fat cells.Analysis of mice liver mRNA(through qRT-PCR)and protein(through Western blot)showed that myricitrin regulated genes related to lipid metabolism such as peroxisome proliferators-activated receptors(PPARs);silence information regulation factor 1(SIRT1);sterol harmonic element binding protein-1c(SREBP-lc);cluster of differentiation 36(CD36);acetyl coenzyme A carboxylase(ACC);and fatty acid synthetase(FASN).Myricitrin also down-regulated obesity induced liver inflammation.Expressions of inflammatory factors such as interleukin 1?(IL-1?),interleukin 6(IL-6),and inducible nitric oxide synthase(iNOS)were suppressed in liver tissues with myricitrin supplementation.These results showed that myricitrin relieved hyperlipidemia caused by high-fat diet,may play a lipid-lowering effect by activating AMP-activated protein kinase(AMPK)and PPAR pathways,and inhibited high-fat diet induced inflammation.2.Myricitrin anti-inflammatory effect and its molecular mechanismIn an experimentally stimulated inflammatory cell model by lipopolysaccharide,myricitrin inhibited the expressions of inflammatory factors such as IL-6,IL-1?,iNOS,tumor necrosis factor-?(TNF-?)and cyclooxygenase-2(COX-2)mRNA,these protein levels increased in a dose-dependent manner.Western blot,qRT-PCR and luciferase reporter gene techniques showed that myricitrin inhibited the increase in levels of transcription factors in cells induced by lipopolysaccharide.Activator protein 1(AP-1)and luciferase activity of nuclear factor kappa-B(NF-?B)were significantly lower in myricitrin groups than that in the lipopolysaccharide group.Therefore,myricitrin relieved inflammation by inhibiting the activities of AP-1 and NF-?B,which in turn downregulated the expression of inflammatory downstream gene/proteins.