The In Vivo Antidiabetic Activity of Nigella sativa Is Mediatedthrough Activation of the AMPK Pathway and Increased Muscle Glut4Content

Abstract

The antidiabetic effect of N. sativa seed ethanol extract (NSE) was assessed in Meriones shawi after development of diabetes. Meriones shawi were divided randomly into four groups: normal control, diabetic control, diabetic treated with NSE (2 g eq plant/kg) or with metformin (300 mg/kg) positive control, both administered by daily intragastric gavage for 4 weeks. Glycaemia and body weight were evaluated weekly. At study's end, an Oral Glucose Tolerance Test (OGTT) was performed to estimate insulin sensitivity. Upon sacrifice, plasma lipid profile, insulin, leptin, and adiponectin levels were assessed. ACC phosphorylation and Glut4 protein content were determined in liver and skeletal muscle. NSE animals showed a progressive normalization of glycaemia, albeit slower than that of metformin controls. Moreover, NSE increased insulinemia and HDL-cholesterol, compared to diabetic controls. Leptin and adiponectin were unchanged. NSE treatment decreased OGTT and tended to decrease liver and muscle triglyceride content. NSE stimulated muscle and liver ACC phosphorylation and increased muscle Glut4. These results confirm NSE's previously reported hypoglycaemic and hypolipidemic activity. More significantly, our data demonstrate that in vivo treatment with NSE exerts an insulin-sensitizing action by enhancing ACC phosphorylation, a major component of the insulin-independent AMPK signaling pathway, and by enhancing muscle Glut4 expression.

A review on therapeutic potential of Nigella sativa: A miracle herb

“…NSE animals showed a progressive normalization of glycaemia. It was also demonstrate that in vivo treatment with NSE exerts an insulin-sensitizing action by enhancing ACC phosphorylation, a major component of the insulinindependent AMPK signaling pathway, and by enhancing muscle Glut4 content [54] .…”

Dihydromyricetin ameliorates the oxidative stress response induced by methylglyoxal via the AMPK/GLUT4 signaling pathway in PC12 cells

“…In normal mammalian cells, MG is efficiently detoxified via the glutathione-dependent glyoxalase pathway, which involves the enzymes glyoxalase 1(Glo-1) and glyoxalase 2 Xu et al, 2013;Zeng et al, 2013). Under conditions of hyperglycemia and impaired glucose metabolism, MG often accumulates (Benhaddou-Andaloussi et al, 2011). Abundant MG levels induce dysfunction in mitochondrial respiration (Luiken et al, 2008) and increased production of reactive oxygen species (ROS) (Wijesekara et al, 2006).…”

Preclinical and clinical effects of Nigella sativa and its constituent, thymoquinone: A review

“…The N. sativa seed ethanol extract could also inhibit gluconeogenesis by the liver and muscle activation of adenosine monophosphate-activated protein kinase (AMPK)(Benhaddou-Andaloussi et al, 2011). It was demonstrated that TQ (the main constituent of N. sativa) could reduce the expression of gluconeogenic enzymes (glucose-6-phosphatase and fructose 1, 6 bisphosphatase) and hepatic glucose production(Al-Rasheed et al, 2014;Alimohammadi et al, 2013).…”