Centella asiatica (L.) extract attenuates inflammation and improve insulin sensitivity in a coculture of lipopolysaccharide (LPS)-induced 3T3-L1 adipocytes and RAW 264.7 macrophages

Drug Discov Ther. 2019;13(5):261-267. doi: 10.5582/ddt.2019.01052.

Abstract

Insulin resistance in obese condition is related to chronic low-grade inflammation which leads to insulin signaling impairment. Centella asiatica (L.) is an herb that exhibits anti-inflammatory and blood sugar-lowering activity (hypoglycemia). The study aims to investigate the molecular mechanism of C. asiatica extract in insulin sensitivity improvement in a coculture of lipopolysaccharide (LPS)-induced 3T3-L1 adipocytes and RAW 264.7 macrophages. A coculture of 3T3-L1 adipocytes and RAW 264.7 macrophages were incubated with LPS to induce insulin resistance in the adipocytes. An extract of C. asiatica was added to coculture cells and after 24 hours, insulin sensitivity and inflammatory response were determined, including glucose consumption, glucose transporter-4 (GLUT-4), insulin receptor substrate-1 (IRS-1), and interleukin-6 (IL-6) mRNA expression. C. asiatica extract at a concentration of 500 µg/mL increased glucose consumption and induced GLUT-4 and IRS-1 mRNA expression significantly in a coculture of LPS-induced 3T3-L1 adipocytes and RAW 264.7 macrophages. The pro-inflammatory cytokines IL-6 mRNA expression was decreased in the coculture cells after treatment with C. asiatica extract at a concentration of 500 µg/mL. This result indicates that C. asiatica has an effect to stimulate glucose consumption in the coculture cells that might be mediated via GLUT-4/IRS-1 pathway as a result of IL-6 inhibition. These findings suggest that the C. asiatica extract inhibits inflammation and improves insulin sensitivity in a coculture of LPS-induced 3T3-L1 adipocytes and RAW 264.7 macrophages.

Keywords: 3T3-L1 adipocytes; Centella asiatica L.; RAW 264.7 macrophages; coculture; insulin sensitivity.

MeSH terms

  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Centella
  • Coculture Techniques
  • Glucose / metabolism
  • Glucose Transporter Type 4 / biosynthesis
  • Inflammation / chemically induced
  • Inflammation / prevention & control*
  • Insulin Receptor Substrate Proteins / biosynthesis
  • Insulin Resistance*
  • Interleukin-6 / biosynthesis
  • Lipopolysaccharides
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Mice
  • Plant Extracts
  • Triterpenes / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Centella asiatica extract
  • Glucose Transporter Type 4
  • Insulin Receptor Substrate Proteins
  • Interleukin-6
  • Lipopolysaccharides
  • Plant Extracts
  • Slc2a4 protein, mouse
  • Triterpenes
  • Glucose