Cinnamaldehyde Ameliorates Vascular Dysfunction in Diabetic Mice by Activating Nrf2.

BACKGROUND: Oxidative stress is known to be associated with the development of diabetes. Cinnamaldehyde (CA) is a spice compound in cinnamon that enhances the antioxidant defense against reactive oxygen species (ROS) by activating nuclear factor erythroid-related factor 2 (Nrf2), which has been shown to have a cardioprotection effect. However, the relationship between CA and Nrf2 in diabetic vascular complications remains unclear. METHODS: Leptin receptor-deficient (db/db) mice were fed normal chow or diet containing 0.02% CA for 12 weeks. The vascular tone, blood pressure, superoxide level, nitric oxide (NO) production, renal morphology, and function were measured in each group. RESULTS: CA remarkably inhibited ROS generation, preserved NO production, increased phosphorylated endothelial nitric oxide synthase (p-eNOS), attenuated the upregulation of nitrotyrosine, P22 and P47 in aortas of db/db mice, and apparently ameliorated the elevation of type IV collagen, TGF-ß1, P22, and P47 in kidney of db/db mice. Feeding with CA improved endothelium-dependent relaxation of aortas and mesenteric arteries, and alleviated the remodeling of mesenteric arteries in db/db mice. Additionally, dietary CA ameliorated glomerular fibrosis and renal dysfunction in diabetic mice. Nrf2 and its targeted genes heme oxygenase-1 (HO-1) and quinone oxidoreductase-1 (NQO-1) were slightly increased in db/db mice and further upregulated by CA. However, these protective effects of CA were reversed in Nrf2 downregulation mice. CONCLUSIONS: A prolonged diet of CA protects against diabetic vascular dysfunction by inhibiting oxidative stress through activating of Nrf2 signaling pathway in db/db mice.

Tiaopi huxin recipe improved endothelial dysfunction and attenuated atherosclerosis by decreasing the expression of caveolin-1 in ApoE-deficient mice.

The Tiaopi Huxin recipe (TPHXR) is widely used in traditional Chinese medicine for the clinical treatment of coronary heart disease. However, the mechanism of TPHXR treatment of atherosclerosis (AS) has not been fully elucidated. In this study, we have aimed to explore the potential antiatherosclerotic effect of TPHXR and its underlying mechanisms. Male ApoE knockout (ApoE-/- ) mice were fed a high-fat diet for 12 weeks and were randomly divided into four groups: the control group, and the low-dose, medium-dose, and high-dose TPHXR groups. The nitric oxide (NO) levels in arterial tissue and human umbilical vein endothelial cells (HUVECs) were measured by diaminofluorescein-2 diacetate staining. Vasorelaxation of mice aorta was performed by wire myograph. Inflammatory cytokines, including tumor necrosis factor-α (TNF-α), hs-CRP, IL-6, and IL-1ß, in mice plasma were analyzed by enzyme-linked immunosorbent assay. Western blot analysis was applied to observe protein expression. Oil Red O staining was utilized for the quantification of atherosclerotic plaques. Results showed that 4 weeks of high- and medium-dose TPHXR treatment by oral gavage reduced atheromatous lesions in ApoE -/- mice. The high- and medium-dose TPHXR treatment, but not the low-dose treatment, promoted eNOS phosphorylation, increased NO levels and improved endothelium-dependent vasorelaxation in ApoE -/- mice. High- and medium-dose TPHXR, but not low-dose TPHXR, decreased the expression of cav-1, NF-κB p50, NF-κB p65, ICAM1, VCAM-1, TNF-α, IL-6, and IL-1ß in the vasculature of ApoE -/- mice. Enzyme-linked immunosorbent assay analysis indicated that high- and medium-dose TPHXR decreased the levels of TNF-α, IL-6, hs-CRP, and IL-1ß. In conclusion, our findings show that TPHXR improved the endothelial function and reduced atheromatous lesions in ApoE -/- mice. This result may be due to the decreased expression of caveolin-1 and NF-κB and, hence, the attenuated inflammatory response in AS mice vasculature. TPHXR may represent a promising intervention in patients with AS.