Bioinformatic and biochemical findings disclosed anti-hepatic steatosis mechanism of calycosin

Bioorg Chem. 2020 Jul:100:103914. doi: 10.1016/j.bioorg.2020.103914. Epub 2020 May 11.

Abstract

As revealed in previous reports, calycosin is a functional flavonoid characterized with identified pharmacological activities. Most of evidences are used to demonstrate the anti-cancer benefits of calycosin, however, the existing study of anti-fatty liver medicated by calycosin is limitedly reported. Recently, an emerging avenue based on network pharmacology may contribute to excavate the biological targets and molecular mechanisms of calycosin for anti-fatty liver. In confirmatory experiments, the human and animal studies were subjected to verify some of bioinformatic results. Accordingly, bioinformatic data based on network pharmacology suggested that discoverable biotargets of calycosin for anti-fatty liver were aldehyde dehydrogenase (ALDH2), Niemann pick C1 (NPC1), high mobility group protein 1 (HMGB1), bilirubin UDP glucuronosyltransferase 1 (UGT1A1), mitogen-activated protein kinase 3 (MAPK3), epidermal growth factor receptor (EGFR), hydroxytryptamine receptor 2 (HTR2), migration inhibitory factor (MIF), cytochrome P450, family 19A1 (CYP19A1). Furthermore, all significant biological characteristics and mechanisms of to treat fatty liver were revealed in several. In human findings, the blood tests showed changed glucose and lipid contents, elevated insulin resistance and inflammatory stress. And fatty liver sections from patients resulted in negative expressions of ALDH2, NPC1, and positive HMGB1 expression. In a study in vivo, calycosin-treated high fat diet (HFD)-fed mice exhibited reduced liver weights, decreased fasting serum glucose and insulin, liver functional transaminases, blood lipids, metabolic enzymes, and inflammatory cytokines. And the data in gene tests displayed up-regulations of ALDH2, NPC1 mRNAs, and down-regulation of HMGB1 mRNA in calycosin-treated liver samples. Together, the current bioinformatic data demonstrate biological targets, functions and mechanisms of calycosin for anti-fatty liver. Interestingly, these bioinformatic findings can be partially verified with clinical and animal samples.

Keywords: Bioinformatic data; Biomarkers; Calycosin; Hepatic steatosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Computational Biology
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Fatty Liver / drug therapy*
  • Fatty Liver / genetics
  • Fatty Liver / metabolism
  • Fatty Liver / pathology
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Isoflavones / pharmacology
  • Isoflavones / therapeutic use*
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice, Inbred ICR
  • Protein Interaction Maps / drug effects
  • Signal Transduction / drug effects

Substances

  • Drugs, Chinese Herbal
  • Isoflavones
  • 7,3'-dihydroxy-4'-methoxyisoflavone