| Background Cyclocarya paliurus(Batal)Iljinskaja is a medicinal and edible homology plant of the Cyclocarya genus of Juglandaceae with the functions of dispelling wind and relieving pruritus,generating water and relieving thirst,and prolonging life in traditional Chinese medicine.In modern pharmacological studies,it has been found to have pharmacodynamic activities such as Hypoglycemic effect,Lipid-lowering effect,Antihypertensive action,and anti-inflammatory effects.The main active components include polysaccharides,flavonoids,triterpenoids and phenolic acids.In recent years,the incidence of non-alcoholic steatohepatitis(NASH)has increased.Long-term use of NASH drugs include statins,fibrates,etc in clinical practice has side effects of liver and kidney damage and risks of inducing cardiovascular diseases.Therefore,the treatment of NASH should focus on prevention and give preventive drugs to potential patients to avoid the occurrence and aggravation of the disease.Due to its good effect on improving lipid metabolism disorder,Cyclocarya paliurus has gradually become a research hotspot.In this paper,we will systematically study the lipid-lowering and liver-protecting pharmacological activity and pharmacodynamic substance basis of Cyclocarya Cyclocarya in NASH.Objective To study the pharmacologically active substances and chemical components of Cyclocarya paliurus in regulating lipid metabolism.Using Cyclocarya paliurus leaves as the research object,the mechanism of Lipid-lowering effect and liver protection effect of ethanol extract from Cyclocarya paliurus leaves on mice non-alcoholic steatohepatitis(NASH)caused by methionine-choline deficiency diet(MCD)was systematically carried out,and the chemical components of n-butanol extract from Cyclocarya paliurus leaves were separated and identified.Methods(1)Sixty male SPF-grade C57BL/6J mice were randomly divided into the blank control group(MCS),the model control group(MCD),the dosage of simvastatin positive group(SV)was 4mg/kg/day,the dosage of low dose group of Cyclocarya paliurus alcohol extract(CCE-L,0.5g/kg/day),the dosage of medium dose group of Cyclocarya paliurus alcohol extract(CCE-L,1.0g/kg/day),the dosage of high dose group of Cyclocarya paliurus alcohol extract(CCE-H,2.0g/kg/day),with 10 mice in each group.Blank control group was fed with normal MCS diet,all other groups were fed with MCD diet.Feeding at the same time,the positive group was given simvastatin once a day,and the low,medium and high doses of Cyclocarya paliurus alcohol extract were given extract from Cyclocarya paliurus leaves once a day for 6 weeks,while the blank control group and model control group were given the same dose of 0.5% carboxymethyl cellulose sodium.After 6 weeks,mouse blood and liver tissue samples were collected for biochemical index detection,pathological histology observation,and related gene expression detection.(2)The n-butanol extract of Cyclocarya paliurus leaves was separated and purified using various column chromatography techniques and semi-preparative high performance liquid chromatography.After compound enrichment and purification,the isolated compounds were structurally analyzed and identified using one-dimensional and two-dimensional nuclear magnetic resonance spectroscopy,mass spectrometry,and other techniques.Results(1)The extract of Cyclocarya paliurus has lipid-reducing and liver-protecting ac tivity on NASH mice.The liver index of the Cyclocarya paliurus alcohol extract treated group increased,while the activity of alanine aminotransferase(ALT)and aspartate aminotransferas e(AST)in serum decreased,cholinesterase(CHE)level increased,and high-density lipoprote in cholesterol(HDL-C)concentration increased.The triglycerides(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)in the liver decreased,and the concentration of HDL-C increased.The sections stained with hematoxylin-eosin(H&E)showed that the tre atment group effectively reduced hepatic steatosis and inflammatory infiltration in mice.q PC R results showed that the expression of inflammatory factors IL-6 and TNF-ɑ was down-regul ated,the expression of lipogenesis-related genes Srebp-1c,Fas and Lxr was down-regulated,a nd the expression of cholesterol transporter genes Abcg5 and Abcg8 was up-regulated in the C yclocarya paliurus treated group.(2)Nineteen compounds were isolated from the n-butanol fr action of Cyclocarya paliurus,including kaempferol(1),quercetin(2),chlorogenic acid(3),methyl chlorogenate(4),Pyridoxine(5),kaempferol-3-O-β-D-glucopyranoside(6),quercetin-3-O-β-D-glucuronide(7),kaempferol-3-O-β-D-glucuronide(8),isoquercitrin(9),Kaempferol-3-O-α-L-rhamnoside(10),mururin A(11),hyperoside(12),citroside A(13),benzyl-6-O-α-Larabinofuranosyl-β-D-glucopyranoside(14),(+)-(6S,9R)-9-O-β-D-glucopyranosyl-6-hydroxy-3-O-α-ionol(15),myricetin-3-O-β-D-glucopyranoside(16),(4R)-4-(3-Oxo-1-buten-1-ylidene)-3α,5,5-trimethyl-cyclohexane-1α,3β-diol(17),quercetin-3-O-α-L-rhamnopyranosyl(18),3,5-O-dicaffeoylquinic acid(19).Among them,compounds(11),(13),(14),(15),(17),and(19)were isolated from Cyclocarya paliurus for the first time.Conclusion(1)This study preliminarily suggests that Cyclocarya paliurus can reduce lipid and protect liver by regulating lipid metabolism in NASH mice,and the underlying mechanism may be related to the cholesterol transporter Abcg5 and Abcg8 pathway.(2)Flavonoids are the main components of the n-butanol fraction of Cyclocarya paliurus,and the six compounds isolated for the first time enriched the chemical composition library of Cyclocarya paliurus laying the foundation for further research on the efficacy substances of Cyclocarya paliurus. |
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