Nigella sativa stimulates insulin secretion from isolated rat islets and inhibits the digestion and absorption of (CH2O)n in the gut

Abstract

Nigella sativa seeds are traditionally reputed as possessing anti-diabetic properties. As a result, we aim to explore the mechanism of its anti-hyperglycemic activity. The present study uses various experimental designs including gastrointestinal (GI) motility, intestinal disaccharidase activity and inhibition of carbohydrate digestion and absorption in the gut. The animals used as type 2 diabetic models were induced with streptozotocin to make them as such. Oral glucose tolerance test was performed to confirm that the animals were indeed diabetic. The extract reduced postprandial glucose, suggesting it interfered with glucose absorption in the gut. It also improved glucose (2.5g/kg, b/w) tolerance in rats. Furthermore, treatment with N. sativa produced a significant improvement in GI motility, while reduced disaccharidase enzyme activity in fasted rats. The extract produced a similar effect within an acute oral sucrose (2.5g/kg, b/w) load assay. Following sucrose administration, a substantial amount of unabsorbed sucrose was found in six different parts of the GI tract. This indicates that N. sativa has the potentiality to liberate GI content and reduce or delay glucose absorption. A potential hypoglycemic activity of the extract found in insulin release assay, where the extract significantly improved insulin secretion from isolated rat islets. These concluded present findings give rise to the implication that N. sativa seeds are generating postprandial anti-hyperglycemic activity within type 2 diabetic animal models via reducing or delaying carbohydrate digestion and absorption in the gut as well as improving insulin secretion in response to the plasma glucose.

Keywords: Disaccharidase enzyme activity; GI motility; Glucose tolerance; Gut perfusion; Nigella sativa; Sucrose malabsorption.

Figure 1. Effects of methanol extract of N. sativa on (A,B) glucose tolerance (GTT), (C,D) serum glucose after sucrose load (SGASL) in type 2 diabetic rats and (E) glucose adsorption capacity (GAC) in vitro

Rats were fasted for 12 and 24 h and administered glucose or sucrose solution (2.5 g/kg, body weight) by oral gavage in presence or absence of methanol extract of N. sativa (500 mg/kg, body weight). Values are means and standard deviations represented by vertical bars (n=6, for GTT and SGASL and n=4 for GAC. The mean values that are marked with an asterisk (*) were substantially different from those of respective type 2 diabetic control rats (*P<0.05 and **P<0.01) alone (this was derived from repeated-measures ANOVA and adjusted using Bonferroni correction).

Figure 2. Effects of methanol extract of N. sativa on (A–F) GI sucrose content after oral sucrose loading in type 2 diabetic rats

Type 2 diabetic rats were fasted for 24 h prior to the oral administration of sucrose solution (2.5 g/kg body weight) in the presence (treated group) or absence of (control group) methanol extract of N. sativa (500 mg/kg body weight). The values are means and standard deviations represented by vertical bars (n=6). The mean values that are marked with an asterisk (*) were substantially different from those of respective type 2 diabetic control rats (*P<0.05 and **P<0.01) (this was derived from repeated-measures ANOVA and adjusted using Bonferroni correction).

Figure 3. Effects of methanol extract of N. sativa on (A,B) intestinal glucose absorption, (C) disaccharidase enzyme activity, and (D) GI motility (by BaSO4 traversed) in non-diabetic rats

Rats were fasted for 36 h (gut perfusion) and 20 h (enzyme activity and gut motility), and intestine was perfused with glucose (54 g/l) in the presence (treated group) or absence of (control group) methanol extract of N. sativa (10 mg/ml; with every individual obtaining 15 ml of perfusion). Enzyme activity was determined and BaSO₄ administered at 60 min. Motility was measured over the following 15 min. Acarbose (ACB) (200 mg/kg) and bisacodyl (10 mg/kg) were used as standard drugs for disaccharidase activity and GI motility test correspondingly. The values are means and standard deviations represented by vertical bars (n=8). The mean values that are marked with an asterisk (*) were substantially different from those of respective control rats (*P<0.05 and **P<0.01) (this was derived from repeated-measures ANOVA and adjusted using Bonferroni correction).