Thymoquinone ameliorates diabetic phenotype in Diet-Induced Obesity mice via activation of SIRT-1-dependent pathways

Abstract

Thymoquinone, a natural occurring quinone and the main bioactive component of plant Nigella sativa, undergoes intracellular redox cycling and re-oxidizes NADH to NAD+. TQ administration (20 mg/kg/bw/day) to the Diet-Induced Obesity (DIO) mice reduced their diabetic phenotype by decreasing fasting blood glucose and fasting insulin levels, and improved glucose tolerance and insulin sensitivity as evaluated by oral glucose and insulin tolerance tests (OGTT and ITT). Furthermore, TQ decreased serum cholesterol levels and liver triglycerides, increased protein expression of phosphorylated Akt, decreased serum levels of inflammatory markers resistin and MCP-1, and decreased NADH/NAD+ ratio. These changes were paralleled by an increase in phosphorylated SIRT-1 and AMPKα in liver and phosphorylated SIRT-1 in skeletal muscle. TQ also increased insulin sensitivity in insulin-resistant HepG2 cells via a SIRT-1-dependent mechanism. These findings are consistent with the TQ-dependent re-oxidation of NADH to NAD+, which stimulates glucose and fatty acid oxidation and activation of SIRT-1-dependent pathways. Taken together, these results demonstrate that TQ ameliorates the diabetic phenotype in the DIO mouse model of type 2 diabetes.

Thymoquinone (2-Isopropyl-5-methyl-1, 4-benzoquinone) as a chemopreventive/anticancer agent: Chemistry and biological effects

“…Thymoquinone is obtained as a result of the oxidation of thymol, which is also a natural product, in the presence of manganese oxide in acidic medium to thymol. The quantity of essential oil in the oil of black seed varies between 0.5 and 1% and approximately one-third of it is TQ which gives yellow color to the black seed oil (Karandrea et al, 2017). TQ is also reported in other plants such as Nepeta Leucophylla, Tetraclinis articulata, Juniperus Cedrus, Callitris quadrivalvis, Monarda fistulosa etc.…”

Thymoquinone Attenuates Myocardial Ischemia/Reperfusion Injury Through Activation of SIRT1 Signaling

“…Furthermore, elevated intracellular NAD+ level activate the SIRT1-dependent metabolic pathways [26]. In addition, SIRT1 was recently found to play an important regulatory role in cardiovascular disease through activation of FOXO to down-regulate the apoptotic molecules and to reduce oxidative stress for cardioprotection [27].…”

<p>GLP-1 mediates the modulating effect of thymoquinone on feeding behaviors in diabetic rats</p>

“…Recent research has indicated that TQ improved islet revascularization and alleviated metabolic and hepatorenal disturbances in STZ-induced diabetic rats 43. In addition, TQ treatment also had a beneficial effect on glucose tolerance and insulin sensitivity in a diet-induced obesity mouse model of type 2 diabetes 5…”

“…TQ exerts ameliorative and therapeutic effects on diabetic animal models,4,5 which could reduce hepatic glucose production 6. In the clinic, the hypoglycemic and hypolipidemic effects of black cumin in patients suffering from diabetes and metabolic syndrome have been reported 3.…”