Effect And Mechanism Of Coffee Peel Polyphenols On Non-Alcoholic Fatty Liver Disease

Coffee peel(CP),a major by-product of coffee processing,is rich in plant compounds,such as polyphenols.However,the phytochemical compositions and health effects of CP have remained unclear.In this study,CP and its polyphenol were considered as the research object.High performance liquid chromatography-tandem mass spectrometry(HPLCMS/MS)was used to identify the main components of CP crude extract and coffee peel polyphenol(CPP)extract.A mouse model of non-alcoholic fatty liver disease(NAFLD)was established with a high-fat diet to investigate the preventive and therapeutic effects of CP crude extract and CPP extract on NAFLD,and to clarify the possible molecular mechanism.(1)The plant compounds in CP crude extract were identified by using HPLC-MS/MS.The results showed that the major plant compounds in CP crude extract were mainly polyphenols,mainly containing caffeine and seven flavonoid monomers,namely catechin,cyanidin-3-O-glucoside,cyanidin-3-Orutinoside,delphinidin-3-rhamnoside,rutin,quercetin,and quercetin-3β-D-glucoside.After 8 weeks of intervention,compared with the model group,the body weight,liver weight,hepatic lipid deposition and steatosis were significantly decreased in CP crude extract intervention groups.Analysis of biochemical parameters showed that the concentrations of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),fibroblast growth factor 21(FGF21),triglyceride(TAG),cholesterol(TC)and insulin in CP rude extract groups were lower than those in the model group,while serum adiponectin concentrations were higher(P < 0.05).In addition,compared with the model group,the concentrations of hepatic tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and IL-1β were significantly lower in CP rude extract groups(P < 0.05).(2)The mixture of ethanol/water/acetic acid(60:40:0.3,v/v/v)and an ion exchange resin column were employed to extracted and purified polyphenols from CP,and the main components of CPP extract were identified with HPLC-MS/MS.In addition,the high-fat diet model was established to investigate the improvement effects of CPP extract on NAFLD.Our results showed that a total of 35 phenolic compounds were identified from CPP extracts,mainly including chlorogenic acid(51.75%),D-(-)-quinic acid(13.37%);3-O-feruloylquinic acid(11.37%),rutin(5.11%),and the content was 638.47 ± 46.41 μg EGCG/mg.After 8 weeks of intervention,compared with the high-fat diet group,CPP extract treatment significantly reduced body weight gains,liver weights,food intakes,fat weights,and hepatic lipid accumulation and steatosis,as well as serum FGF21,ALT,AST,TAG,TC,insulin,glucose and LDL-C showed lower concentrations in CPP extract intervention groups(P < 0.05).In addition,serum adiponectin concentrations and the protein expression levels of adiponectin in adipose tissues in CPP extract groups were higher than those in the model group(P < 0.05).(3)Based on non-targeted lipidomics analysis,the volcano plot showed the largest increase in C18:0-ceramide in the liver of mice induced by a high-fat diet.Therefore,serum and hepatic ceramide concentrations were further targeted detection in this study.The results showed that C16:0-and C18:0-ceramide concentrations in serum and liver of mice in the CPP extract groups were significantly lower,and the protein expression levels of acid ceramidase in liver were higher than those in the model group(P < 0.05).Compared with the model group,the expression levels of proteins related to fatty acid synthesis(ACC1,FASN,SREBP-1c)were significantly lower in the liver of mice fed with CPP extract,while the expression levels of proteins related to fatty acid β-oxidation(ACOX1,CPT1 A,PPAR-α)were significantly higher.In conclusion,polyphenols were the bioactive substances of CP,CPP extract might regulate FGF21-adiponectin-acid ceramidase pathway to promote ceramide catabolism,and then to reduce fatty acid synthesis and stimulate fatty acid β-oxidation,which contributed to inhibiting TAG deposition and steatosis,finally preventing and improving NAFLD induced by a high-fat diet.These results provided a theoretical basis that coffee peel was a new raw material to explore plant compounds.