Aqueous leaf extract of Clinacanthus nutans improved metabolic indices and sorbitol‐related complications in type II diabetic rats (T2D)

Abstract

Clinacanthus nutans (Burm. f.) Lindau ( C. nutans ) has been reported to lower blood glucose level; however, evidence on its efficacy in lowering diabetic complications is limited. The antidiabetic properties of C. nutans aqueous leaf extract on serum metabolic indices, sorbitol production, and aldose reductase enzyme activities in the kidneys, lens, and sciatic nerve of type II diabetic (T2D) rats were evaluated. All rats except normal control rats were fed with a high‐fat diet for 8 weeks to induce obesity and subsequently injected with 35 mg/kg streptozotocin to induce type II diabetes. Aqueous leaf extract of C. nutans (100 and 200 mg kg −1 day −1 ) and quercetin (10 mg kg −1 day −1 ) were fed orally for 4 weeks. Diabetic rats administered with C. nutans at 100, 200 mg kg −1 day −1 and quercetin had significantly ( p < 0.05) lower fasting blood glucose levels post‐intervention: 14.2, 14.0, and 19.9 m m , respectively, compared with the untreated group (22.1 m m ). Total cholesterol was significantly ( p < 0.05) lower in the C. nutans groups in comparison with the diabetic control group. Levels of F2‐isoprostane, a marker of oxidative stress, were attenuated in the presence of the extract. Aldose reductase enzyme activity increased by 64, 99, and 0% and total antioxidant activities by 22, 29, and 126%, respectively. Sorbitol levels in the kidney, lens, and nerve were reduced in diabetic rats administered with C. nutans and quercetin group (by 8, 16, and 3%, respectively). The protective effect of the extract to the liver and kidney was confirmed through liver and kidney enzyme markers and histological analyses. The C. nutans has the potential to attenuate T2D‐induced metabolic perturbations and complications related to sorbitol accumulation.

Clinacanthus nutans Leaves Extract Reverts Endothelial Dysfunction in Type 2 Diabetes Rats by Improving Protein Expression of eNOS

“…The inhibition of this enzyme reduces intestinal carbohydrate metabolism by retarding the cleavage of polysaccharide to glucose; this will reduce glucose intestinal absorption [ 7 ]. This effect was supported by a recent study that demonstrated lowering of blood glucose concentrations in a type 2 diabetic (T2DM) rat model treated with C. nutans [ 8 ]. As mentioned above, chronic hyperglycemia can impair NO bioavailability causing ED.…”

“…The process of gluconeogenesis can be potentiated in diabetes to provide glucose, as the cells of the body do not uptake enough for their metabolism. The substrates for gluconeogenesis are often derived from protein and fat sources, through the processes of glycogenolysis and lipolysis, resulting in loss of tissue protein, muscle wasting, and weight loss [ 8 , 25 ]. In this study, both diabetic groups treated with CNME or metformin had higher body weight compared to untreated diabetic rats.…”

“…Cinnamic acid and caffeic acid, phenolic compounds detected in C. nutans extract, have been shown to inhibit the process of gluconeogenesis [ 26 ]. Attenuation of gluconeogenesis could slow down the breakdown of body fat and proteins thus reducing weight loss associated with diabetes [ 8 ].…”

“…Prior in vitro studies [ 6 , 7 ] have reported that C. nutans extracts inhibit α -glucosidase enzyme. A more recent study [ 8 ] observed that the aqueous extract of C. nutans significantly reduced blood glucose concentrations in diabetic rats. Inhibition of α -glucosidase enzyme at the small intestine reduces hydrolysing of carbohydrate into glucose, thus reducing its absorption [ 6 , 28 ].…”

“…Ox-LDL-C increases synthesis of caveolin-1, which inactivates eNOS [ 12 ]; ox-LDL-C also reduces the expression of eNOS protein, resulting in impairment of NO-mediated vasodilatory response [ 13 , 14 ]. C. nutans extracts have been reported to reduce serum LDL-C levels in high-fat diet- (HFD-) induced T2DM rat model [ 8 ], and the hypercholesterolemic rat model [ 4 ].…”