Lipidomics Analysis of Timosaponin BII in INS-1 Cells Induced by Glycolipid Toxicity and Its Relationship with Inflammation

Chem Biodivers. 2020 Apr;17(4):e1900684. doi: 10.1002/cbdv.201900684. Epub 2020 Apr 3.

Abstract

Anemarrhena asphodeloides Bunge is a traditional Chinese medicine. The timosaponin BII is one of the most abundant and widely studied active ingredients in Anemarrhena asphodeloides Bunge. Related studies have shown that timosaponin BII has potential value for development and further utilization. The protective effect of timosaponin BII on islet β cells under type 2 diabetes was investigated in the glycolipid toxic INS-1 cell model and possible biomarkers were explored by lipidomics analysis. Timosaponin BII was isolated from Anemarrhena asphodeloides Bunge by polyamide resin and Sephadex LH-20. Then, the glycolipid toxicity INS-1 cell model was established to investigate the protective effect of timosaponin BII. The results showed that timosaponin BII could significantly influence the levels of malondialdehyde (MDA) and glutathione (GSH), thereby restoring the insulin secretion ability and cell viability of model cells. Lipidomics analysis was combined with multivariate statistical analysis for marker selection. The four most common pathological and pharmacological lipid markers were phosphatidylserine (PS), suggesting that timosaponin BII had protective effects on model cells related to the reduction oxidative stress and macrophage inflammation. RAW264.7 macrophages were stimulated by LPS to establish a model of inflammation and study the effect of timosaponin BII on the nodes of NOD-like receptor P3 (NLRP3) inflammasome pathway in the model cells. In conclusion, timosaponin BII may have the effect of protecting INS-1 pancreatic β cells through reducing IL-1β (interleukin-1β) production by inhibiting the NLRP3 inflammasome in macrophage and restoring the insulin secretion ability and cell viability by reducing oxidative stress.

Keywords: glycolipid toxicity; inflammation; lipidomics; timosaponin BII; type 2 diabetes.

MeSH terms

  • Anemarrhena / chemistry*
  • Anemarrhena / metabolism
  • Animals
  • Cell Survival / drug effects
  • Discriminant Analysis
  • Glutathione / metabolism
  • Glycolipids / toxicity*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / prevention & control
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Interleukin-1beta / metabolism
  • Lipidomics / methods
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Malondialdehyde / metabolism
  • Mice
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Nitric Oxide / metabolism
  • Oxidative Stress / drug effects
  • Principal Component Analysis
  • Protective Agents / chemistry*
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use
  • RAW 264.7 Cells
  • Saponins / chemistry*
  • Saponins / isolation & purification
  • Saponins / pharmacology
  • Saponins / therapeutic use
  • Steroids / chemistry*
  • Steroids / isolation & purification
  • Steroids / pharmacology
  • Steroids / therapeutic use

Substances

  • Glycolipids
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Protective Agents
  • Saponins
  • Steroids
  • timosaponin B-II
  • Nitric Oxide
  • Malondialdehyde
  • Glutathione