Phenolic Constituents from Black Quinoa Alleviate Insulin Resistance in HepG2 Cells via Regulating IRS1/PI3K/Akt/GLUTs Signaling Pathways

J Agric Food Chem. 2023 Dec 6;71(48):18780-18791. doi: 10.1021/acs.jafc.3c05900. Epub 2023 Nov 22.

Abstract

Quinoa is a nutrient-rich pseudocereal with a lower glycemic index and glycemic load. However, its therapeutic potency and underlying mechanism against insulin resistance (IR) have not been fully elucidated. In this work, network pharmacology was applied to screen IR targets and their related pathways. The efficacy and mechanism of black quinoa polyphenols (BQP) on IR improvement were evaluated and uncovered based on the IR model in vitro combined with molecular docking. Ten phenolic constituents of BQP were detected, and the network pharmacology results show that PI3K/Akt pathways are the main pathways in BQP against IR. The in vitro assay proved that BQP increases the glucose consumption and glycogen synthesis via upregulating insulin receptor substrate 1 (IRS1)/PI3K/Akt/glucose transporters (GLUTs) signaling pathways to alleviate IR. Rutin, resveratrol, and catechin show lower binding energy docking with IRS1, PI3K, Akt, and GLUT4 proteins, indicating better interactions. It might be an effective constituent against IR. Hence, BQP could become a potential functional food source for blood glucose management among insulin-resistant people.

Keywords: PI3K/Akt; insulin resistance; molecular docking; network pharmacology; polyphenols; quinoa.

MeSH terms

  • Chenopodium quinoa* / metabolism
  • Glucose / metabolism
  • Hep G2 Cells
  • Humans
  • Insulin / metabolism
  • Insulin Receptor Substrate Proteins / genetics
  • Insulin Receptor Substrate Proteins / metabolism
  • Insulin Resistance* / physiology
  • Molecular Docking Simulation
  • Phenols / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction

Substances

  • Glucose
  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • Insulin Receptor Substrate Proteins
  • Insulin
  • Phenols
  • IRS1 protein, human