Curcumin improves prostanoid ratio in diabetic mesenteric arteries associated with cyclooxygenase-2 and NF-κB suppression

Abstract

BackgroundCurcumin, the active ingredient from turmeric rhizomes, has been shown to have a wide range of pharmacological properties including antioxidant and anti-inflammatory effects. Curcumin has been reviewed for its multiple molecular action on inhibiting tumor angiogenesis via its mechanisms of cyclooxygenase (COX)-2, and vascular endothelial growth factor (VEGF) inhibition. In this present study, we aimed to assess the effects of curcumin on preventing diabetes-induced vascular dysfunction in association with COX-2, nuclear factor-κB (NF-κB) expression, and prostanoid production.MethodsTwelve-week-old male Wistar rats were separated into five groups: 1) diabetes with 0.9% normal saline (DM-NSS; n =10), 2) diabetes treated with curcumin 30 mg/kg (n =10), 3) diabetes treated with curcumin 300 mg/kg (n =10), 4) the control with 0.9% normal saline (n =10), and 5) the control treated with 300 mg/kg (n =10). Daily oral feeding of curcumin was started at 6 weeks after the streptozotocin injection. Levels of 6-keto prostaglandin (PG) F1αand thromboxane (TX) B2 were determined from mesenteric perfusates using enzyme immunoassay kits. Protein kinase C (PKC)-β II and COX-2 with NF-κB levels were analyzed in the mesenteric arteries by immunofluorescent staining and immunohistochemistry, respectively.ResultsThe ratio of 6-keto-PGF1αand TXB2 was significantly decreased in DM-NSS compared with the control (P < 0.05). Double-immunofluorescent staining with specific antibodies for PKC-βII and α-smooth muscle actins showed that the diabetic mesenteric arteries contained increased of PKC-βII within the vascular wall. Also, COX-2 expression and activated NF-κB in the small mesenteric artery of diabetes mellitus rats were markedly increased when compared with the control. Interestingly, curcumin could inhibit the upregulation of all of these biomarkers.ConclusionThese findings show that curcumin can attenuate diabetes-induced vascular dysfunction in association with its potential for COX-2 and NF-κB suppression, PKC inhibition, and improving the ratio of prostanoid products PGI2/TXA2.