滇黄精(polygonatum kingianum coll。et Hemsl。，PK)是我国传世经典食药两用食物，营养物质丰富，具有护肝等功效。九蒸九制是炮制滇黄精的经典方法，但其对滇黄精护肝作用及机制的影响尚无报道。基于LO2细胞酒精性损伤模型，探究九蒸九制滇黄精水提物(Nine Steaming Nine Drying processed PK extracts，PPK)对酒精性肝损伤的改善作用，采用代谢组学和生物信息数据库联合分析以及分子对接揭示其物质基础及潜在的调控机制。结果表明:PPK可以显著提升酒精诱导损伤的LO2细胞活性，改善氧化应激和炎症指标，提高乙醇脱氢酶和乙醛脱氢酶活性;代谢组学分析联合生物数据库检索发现PPK显著富集芦丁、呋喃酮、咖啡酸、没食子儿茶素等23种代谢物，通过PI3K-Akt、AMPK、NF-κB信号通路调控肝脏氧化应激与炎症;分子对接结果证实PPK的核心代谢物与酒精代谢酶之间具有良好的结合能力。研究结果初步揭示PPK能够通过调控氧化应激、减轻肝脏炎症、增强乙醇代谢功能来缓解酒精性肝损伤，为P P K营养功能的定位提供了科学依据。
Protective effects of Polygonatum kingianum Coll.et Hemsl.on alcoholic liver injury
Polygonatum kingianum Coll.et Hemsl.(PK),a well-known Food and Medicine homology in China,riches in various bioactive ingredients and has been consumed for thousands of years with a wide range of applications.PK has shown great tonic effects.Previous studies have consistently shown nutritional functions of PK including liver protection.The Nine Steaming Nine Drying is a traditional processing technique that has been considered as an effective method in enriching tonic properties,but its impacts on improving efficacy of PK on liver protection remain largely unexplored.This study herein applied integrative analysis of metabolomics and bioinformatics,as well as molecular docking,to reveal the core bioactive compounds responsible for the improved effects of Nine Steaming Nine Drying processed PK extracts(PPK)on the prevention and treatment of alcoholic liver injury and its underlying mechanisms.Through constructing an alcohol induced injury model using LO2 cells,the regulatory effects of PPK on cell activity,oxidative stress,and alcohol metabolism enzymes(ethanol dehydrogenase and acetaldehyde dehydrogenase)were investigated.A total of 204 metabolites in the PPK were compared with crude PK extracts(CPK).Alcohol induced liver injury related targets were obtained by searching for DisGeNET,TTD,GeneCard,and OMIM databases,and a compound-target network was established.Results from protein-protein interaction networks and enrichment analysis identified 23 functional metabolites(including rutin,furanone,caffeic acid,gallic acid,etc.)that may be responsible for the protective effects of PPK on alcoholic liver injury via regulating 15 action targets involved in PI3K-Akt,AMPK,NF-kB signaling pathways.High affinity between the identified key constituents of PPK and their predicted acting targets was confirmed using molecular docking.Results indicate that PPK can alleviate alcoholic liver injury by regulating oxidative stress,inflammation,and ethanol metabolisms.It provides novel insights in nutritional functions of PPK,and an effective strategy for systematically elucidating the mechanisms of functional foods.
Food and Medicine homologyPolygonatum kingianum Coll.et Hemsl.alcohol induced injury of LO2 cellsmetabolomicsbioinformation databasemolecular docking
万方数据
维普
