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

Abstract

Sirada Rungseesantivanon1, Naris Thengchaisri4, Preecha Ruangvejvorachai2, Suthiluk Patumraj31Interdepartment of Physiology, Graduate School, 2Department of Pathology, 3Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 4Department of Companion Animal Clinical Sciences, Faculty of Veterinary Medicine, Kasetsart University, Bangkok, ThailandBackground: Curcumin, 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.Methods: Twelve-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) F1α and thromboxane (TX) B2 were determined from mesenteric perfusates using enzyme immunoassay kits. Protein kinase C (PKC)-ßII and COX-2 with NF-κB levels were analyzed in the mesenteric arteries by immunofluorescent staining and immunohistochemistry, respectively.Results: The ratio of 6-keto-PGF1α and TXB2 was significantly decreased in DM-NSS compared with the control (P < 0.05). Double-immunofluorescent staining with specific antibodies for PKC-βII and a-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.Conclusion: These 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.Keywords: diabetes, endothelial dysfunction, COX-2, prostanoids