Thymoquinone, a bioactive component of Nigella sativa, normalizes insulin secretion from pancreatic β-cells under glucose overload via regulation of malonyl-CoA

Am J Physiol Endocrinol Metab. 2016 Mar 15;310(6):E394-404. doi: 10.1152/ajpendo.00250.2015. Epub 2016 Jan 19.


Thymoquinone (2-isopropyl-5-methylbenzo-1,4-quinone) is a major bioactive component of Nigella sativa, a plant used in traditional medicine to treat a variety of symptoms, including elevated blood glucose levels in type 2 diabetic patients. Normalization of elevated blood glucose depends on both glucose disposal by peripheral tissues and glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. We employed clonal β-cells and rodent islets to investigate the effects of thymoquinone (TQ) and Nigella sativa extracts (NSEs) on GSIS and cataplerotic metabolic pathways implicated in the regulation of GSIS. TQ and NSE regulated NAD(P)H/NAD(P)(+) ratios via a quinone-dependent redox cycling mechanism. TQ content was positively correlated with the degree of redox cycling activity of NSE extracts, suggesting that TQ is a major component engaged in mediating NSE-dependent redox cycling. Both acute and chronic exposure to TQ and NSE enhanced GSIS and were associated with the ability of TQ and NSE to increase the ATP/ADP ratio. Furthermore, TQ ameliorated the impairment of GSIS following chronic exposure of β-cells to glucose overload. This protective action was associated with the TQ-dependent normalization of chronic accumulation of malonyl-CoA, elevation of acetyl-CoA carboxylase (ACC), fatty acid synthase, and fatty acid-binding proteins following chronic glucose overload. Together, these data suggest that TQ modulates the β-cell redox circuitry and enhances the sensitivity of β-cell metabolic pathways to glucose and GSIS under normal conditions as well as under hyperglycemia. This action is associated with the ability of TQ to regulate carbohydrate-to-lipid flux via downregulation of ACC and malonyl-CoA.

Keywords: acetyl-CoA carboxylase; insulin secretion; malonyl-CoA; thymoquinone; β-cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyl-CoA Carboxylase / drug effects*
  • Acetyl-CoA Carboxylase / metabolism
  • Animals
  • Benzoquinones / pharmacology*
  • Cell Line
  • Down-Regulation
  • Fatty Acid Synthase, Type I / drug effects
  • Fatty Acid Synthase, Type I / metabolism
  • Fatty Acid-Binding Proteins / drug effects
  • Fatty Acid-Binding Proteins / metabolism
  • Glucose / pharmacology*
  • Hydrogen Peroxide / metabolism
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism
  • Malonyl Coenzyme A / metabolism*
  • Mice
  • Nigella sativa / chemistry*
  • Oxidation-Reduction / drug effects
  • Plant Extracts / pharmacology*
  • Rats


  • Benzoquinones
  • Fatty Acid-Binding Proteins
  • Insulin
  • Plant Extracts
  • Malonyl Coenzyme A
  • Hydrogen Peroxide
  • Fatty Acid Synthase, Type I
  • Acetyl-CoA Carboxylase
  • Glucose
  • thymoquinone