Improvement of hyperglycemia in a murine model of insulin resistance and high glucose- and inflammasome-mediated IL-1β expressions in macrophages by silymarin

Chun Ping Lu, Chien Yu Huang, Szu Hsuan Wang, Chih Hsien Chiu, Lan Hui Li, Kuo Feng Hua, Tzu Hua Wu

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Macrophages and inflammasome pathway are involved in high-glucose toxicity and development of insulin resistance. Silymarin (SMR) was known to modulate glucose homeostasis and reduce inflammation. However, it is still unknown whether SMR possess anti-hyperglycemic effects in diabetic-like knockout mice (Hnf-1αkin/−/Ins.cre mice) with insulin resistance and also unclear how SMR regulates LPS induced stress markers and pro-inflammatory cytokines under stresses of high glucose (HG) or NLRP3 inflammasome activation. Current results show that oral administration of SMR (100 mg/kg) reduced hyperglycemia in the mouse model of maturity-onset diabetes of the young type 3-like mice. In cultured macrophages, SMR (5–20 μg/ml) reduces high glucose (HG)-enhanced expressions of inducible nitric oxide synthase, nitric oxide generation stimulated by LPS; however, no effects on COX-2 expressions. The enhanced interleukin-1β (ΙL-1β) secretions in the presence of HG or palmitate were also significantly down regulated by SMR in dose-dependent manner in LPS-treated macrophages. Such observations may result from the decreased extracellular signal-regulated kinase 1/2 phosphorylation, while without affecting protein kinase C-α phosphorylation and nuclear factor-κB activation. These findings together show that SMR acts as a protector against HG-related stresses not only by lowering hyperglycemia but also suppressing HG- and inflammasome-mediated IL-1β expressions to improve insulin resistance.

Original languageEnglish
Pages (from-to)12-18
Number of pages7
JournalChemico-Biological Interactions
Volume290
DOIs
Publication statusPublished - Jun 25 2018

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Keywords

  • High-glucose toxicity
  • Hyperglycemia
  • Insulin resistance
  • NLRP3 inflammasome
  • Silymarin

ASJC Scopus subject areas

  • Toxicology

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