RESUMO
AIM:To investigate the ameliorative effect of salvianolic acid B on vasodilatory function in diabetic rats and the possible mechanisms.METHODS:SD rats(n=40)were fed on high-sugar and high-fat diet for 4 weeks, followed by a single intraperitoneal injection of streptozotocin(40 mg/kg).The rats with random blood glucose level over 16.7 mmol/L were considered diabetic and randomly allocated to 3 groups, namely model group, low dose(80 mg· kg-1· d-1)of salvianolic acid B group and high dose(160 mg· kg-1· d-1)of salvianolic acid B group.The rats in salvianolic acid B groups were intragastrically administered with corresponding doses of salvianolic acid B for 6 weeks. Vasodilatory function was measured as endothelium-dependent and-independent vasodilation of the aortic rings.The primary histopathological changes of aorta were observed by HE staining.Serum levels of interleukin-6(IL-6),tumor necrosis fac-tor-α(TNF-α)and C-reactive protein(CRP)were measured by ELISA.The levels of total antioxidant capacity,malondi-aldehyde(MDA)and nitric oxide(NO)in aortic tissues were evaluated by colorimetric assays.The protein levels of inter-cellular adhesion molecule-1(ICAM-1)and monocyte chemotactic protein-1(MCP-1), and the activation of nuclear fac-tor-κB(NF-κB)were determined by Western blot.RESULTS: Treatment with salvianolic acid B evidently ameliorated endothelium-dependent diastolic function and pathological changes of aorta in diabetic rats(P<0.05 or P<0.01).Sup-plementation with salvianolic acid B resulted in significant increases in NO content and total antioxidant capacity in aortic tissues,accompanied by marked decreases in the level of MDA in aorta tissues and the serum levels of IL -6, TNF-αand CRP(P<0.05 or P<0.01).Salvianolic acid B markedly down-regulated NF-κB p65 nuclear translocation and protein expression of ICAM-1 and MCP-1 in aorta tissues(P<0.05 or P<0.01).CONCLUSION:Salvianolic acid B effectively ameliorates endothelium-dependent diastolic function of aorta in diabetic rats, which might be attributed to suppression of NF-κB activation and subsequent expression of inflammatory cytokines.The beneficial effect of salvianolic acid B on vascu-lar endothelium might be derived from its antioxidant capacity.
RESUMO
Crocetin, a naturally occurring carotenoid, possesses antioxidant and antiatherosclerotic properties, of which the underlying mechanism remains unclear. In the present study, we examined the effects of crocetin (0.1, 1, 10 μmol·L(-1)) on angiotensin II (Ang II, 0.1 μmol·L(-1)) induced expression of vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) and monocyte-endothelial cell adhesion. The effects of crocetin on the activation of nuclear factor kappa B (NF-κB) and intracellular reactive oxygen species (ROS) were also observed. The results demonstrated that crocetin notably suppressed Ang II induced NF-κB activation (P<0.01) and VCAM-1 expression (P<0.05, P<0.01) in HUVECs, accompanied by a markedly reduced monocyte-endothelial cell adhesion (P<0.05, P<0.01). In addition, preincubation with crocetin resulted in a significant enhancement of cellular antioxidant capacity (P<0.05, P<0.01), while Ang II induced intracellular ROS decreased markedly (P<0.05, P<0.01). These results indicated that crocetin was capable of suppressing Ang II induced VCAM-1 expression and monocyte-endothelial cell adhesion by suppression of NF-κB activation, which might be derived from the enhancement of antioxidant capacity and subsequent reduction of intracellular ROS.