Improvement of hyperglycemia in a murine model of insulin resistance and high glucose- and inflammasome-mediated IL-1β expressions in macrophages by silymarin. (25th June 2018)

• Record Type: Journal Article
• Authors: Lu, Chun-Ping; Huang, Chien-Yu; Wang, Szu-Hsuan; Chiu, Chih-Hsien; Li, Lan-Hui; Hua, Kuo-Feng; Wu, Tzu-Hua
• Is Part Of: Chemico-biological interactions. Volume 290(2018)
• Page Start: 12
• Page End: 18
• Publication Date: 2018-06-25
• Subjects: Silymarin -- Hyperglycemia -- Insulin resistance -- High-glucose toxicity -- NLRP3 inflammasome; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2018.05.004
• Languages: English
• ISSNs: 0009-2797

Abstract

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-1α kin/− /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. Highlights: Silymarin reduced hyperglycemia in the mouse model of insulin resistance. Silymarin suppressed high glucose induced IL-1β secretions in LPS-treated macrophages. Silymarin inhibited NLRP3 inflammasome activation by suppressing IL-1β secretions. Silymarin reduced inflammation through pERK 1/2 inhibition in macrophages.