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Investigating the medicinal potential,material basis and mechanism of Polygoni Orientalis Fructus based on multi-technology integrated network pharmacology
Affiliation:1. Department of Pharmacy, The Hospital Affiliated to Medical School of Yangzhou University (Taizhou People''s Hospital), Taizhou, China;2. State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, China;3. Jiangsu Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, College of Health Sciences, School of Life Science, Jiangsu Normal University, Xuzhou, China;1. State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, Guangdong, China;2. The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China;3. Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
Abstract:BackgroundPolygoni Orientalis Fructus (POF) refers to the dried ripe fruit of Polygonum orientale L. which has a long historical application in clinic for treatment of various conditions in China. However, its chemical constituents, pharmacological effects and their coupled correlation have not been intensively investigated.PurposeIn present work, we aimed to elucidate the medicinal material basis, optimum indication and corresponding therapeutic mechanism of POF.MethodsThe main phytochemical ingredients in POF were characterized by liquid chromatography-mass spectrometry (LC-MS) analysis. The optimum medicinal potential and corresponding molecular mechanism of POF were deduced based on integrated statistic pattern recognition and network pharmacology. The deduced pharmacologic efficacy and mechanism of POF were further validated through in vitro study in free-fatty acid (FFA)-induced LO2 cells.ResultsTotal 30 main phytochemical ingredients were identified in POF in which 18 ingredients were screened to yield 277 potential targets. Based on analyzing the quantitative data matrix of drug-disease targets by statistic pattern recognition, non-alcoholic fatty liver disease (NAFLD) was screened as the optimum indication of POF from 23 candidate diseases. Promising action targets (PPARG, IL6, TNF, IL1B, IKBKB, RELA, etc.) and signaling pathways (AMPK signaling pathway, NF-κB signaling pathway, etc.) were screened and refined to elucidate the therapeutic mechanism of POF against NAFLD based on network pharmacology. In vitro study demonstrated that POF effectively alleviated FFA-induced steatosis, oxidative stress, mitochondrial dysfunction and inflammation, and these beneficial effects were attributed to the activation of AMPK signaling pathway and suppression of NF-κB signaling pathway.ConclusionPOF could be exploited as a promising phytotherapy in the treatment of NAFLD.
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