Vascular complications are the leading cause of morbidity and mortality in patients with diabetes. Quercetin is an important flavonoid with antioxidant and anti-inflammatory activity. Here, the effect of quercetin on diabetes-induced exaggerated vasoconstriction in insulin deficient and insulin resistant rat models was investigated. Insulin deficiency was induced by streptozotocin while, insulin resistance by fructose. Rats were left 8 weeks or 12 weeks after STZ or fructose administration respectively. Quercetin was daily administered in the last 6 weeks. Then, tail blood pressure (BP) was recorded in conscious animals; concentration-response curves for phenylephrine (PE) and KCl were studied in thoracic aorta rings. Non-fasting blood glucose level, serum insulin level, insulin resistance index, serum tumour necrosis factor-α (TNF-α) and serum C-reactive protein (CRP) were determined. Nuclear transcription factor-κB (NF-κB) was assessed by immunofluorescence technique. Histopathological examination was also performed. The results showed that quercetin protected against diabetes-induced exaggerated vasoconstriction and reduced the elevated blood pressure. In addition, quercetin inhibited diabetes associated adventitial leukocyte infiltration, endothelial pyknosis and increased collagen deposition. These effects were accompanied with reduction in serum level of both TNF-α and CRP and inhibition of aortic NF-κB by quercetin in both models of diabetes. On the other hand, quercetin did not affect glucose level in any of the used diabetic models. This suggests that the protective effect of quercetin is mediated by its anti-inflammatory effect rather than its metabolic effects. In summary, quercetin is potential candidate to prevent diabetic vascular complications in both insulin deficiency and resistance via its inhibitory effect on inflammatory pathways especially NF-κB signaling.

Context: Momordica charantia Linn (Cucurbitaceae) (MC) is used in folk medicine to treat various diseases including diabetes mellitus. Objective: This study investigates the antidiabetic activities of Momordica charantia (bitter gourd) on streptozotocin-induced type 2 diabetes mellitus in rats. Materials and methods: Male Wister rats were randomly assigned to 4 groups. Group I, Normal control; Group II, STZ diabetic; Group III and IV, Momordica charantia fruit juice was orally administered to diabetic rats (10 mL/kg/day either as prophylaxis for 14 days before induction of diabetes then 21 days treatment, or as treatment given for 21 days after induction of diabetes). The effects of MC juice were studied both in vivo and in vitro by studying the glucose uptake of isolated rat diaphragm muscles in the presence and absence of insulin. Histopathological examination of pancreas was also performed. Results: This study showed that MC caused a significant reduction of serum glucose (135.99 ± 6.27 and 149.79 ± 1.90 vs. 253.40* ± 8.18) for prophylaxis and treatment respectively, fructosamine (0.99 ± 0.01 and 1.01 ± 0.04 vs. 3.04 ± 0.07), total cholesterol, triglycerides levels, insulin resistance index (1.13 ± 0.08 and 1.19 ± 0.05 vs. 1.48 ± 1.47) and pancreatic malondialdehyde content (p < 0.05). While it induced a significant increase of serum insulin (3.41 ± 0.08 and 3.28 ± 0.08 vs. 2.39 ± 0.27), HDL-cholesterol, total antioxidant capacity levels, β cell function percent, and pancreatic reduced glutathione (GSH) content (p < 0.05) and improved histopathological changes of the pancreas. It also increased glucose uptake by diaphragms of normal (12.17 ± 0.60 vs. 9.07 ± 0.66) and diabetic rats (8.37 ± 0.28 vs. 4.29 ± 0.51) in the absence and presence of insulin (p < 0.05). Conclusions: Momordica charantia presents excellent antidiabetic and antioxidant activities and thus has great potential as a new source for diabetes treatment whether it is used for prophylaxis or treatment.

Insulin resistance (IR) and obesity predispose diseases such as diabetes, cardiovascular and neurodegenerative disorders. Beta-caryophyllene (BCP), a natural sesquiterpene, exerts neuroprotective, anxiolytic and antidepressant effects via its selective agonism to cannabinoid receptor 2 (CB2R). BCP was shown to have an anti-diabetic effect, however, the implication of CB2R is yet to be elucidated. A link between CB2R agonism and PPAR-γ activation has been discussed, but the exact mechanism is not well-defined. This study was designed to examine the role of BCP in improving diet-induced metabolic (insulin resistance), neurobehavioral (anxiety, depression and memory deficit), and neurochemical (oxidative, inflammatory and neurotrophic factor) alterations in the prefrontal cortex of obese rats' brain. The involvement of CB2R and/or PPAR-γ dependent activity was also investigated. Male Wistar rats were fed a high fat/fructose diet (HFFD) for 12 weeks to induce IR and obesity. Rats were treated with BCP for the last 4 weeks. Either CB2R antagonist AM630 or PPAR-γ antagonist BADGE was administered before BCP treatment to study the mechanism of BCP actions. Beta-caryophyllene alleviated HFFD-induced IR, oxidative-stress, neuroinflammation and behavioral changes. The anxiolytic, anti-oxidant and anti-inflammatory effects of BCP were mediated by both PPAR-γ and CB2R. The effects of BCP on glycemic parameters seem to be CB2R-dependent with the non-significant role of PPAR-γ. Furthermore, BCP-evoked antidepressant and memory improvement are likely mediated only via CB2R, mainly by upregulation of PGC-1α and BDNF. This study suggests the potential effect of BCP in treating HFFD-induced metabolic and neurobehavioral alterations. BCP seems to activate PPAR-γ in a ligand-independent manner, via upregulation and activation of PGC-1α. The BCP activation of PPAR--γ seems to be CB2R-dependent.