Caffeic Acid Phenylethyl Amide Protects against the Metabolic Consequences in Diabetes Mellitus Induced by Diet and Streptozocin

Abstract

Caffeic acid phenyl ester is distributed wildly in nature and has antidiabetic and cardiovascular protective effects. However, rapid decomposition by esterase leads to its low bioavailability in vivo. In this study, chronic metabolic and cardiovascular effects of oral caffeic acid phenylethyl amide, whose structure is similar to caffeic acid phenyl ester and resveratrol, were investigated in ICR mice. We found that caffeic acid phenylethyl amide protected against diet or streptozocin-induced metabolic changes increased coronary flow and decreased infarct size after global ischemia-reperfusion in Langendorff perfused heart. Further study indicated that at least two pathways might be involved in such beneficial effects: the induction of the antioxidant protein MnSOD and the decrease of the proinflammatory cytokine TNFα and NFκB in the liver. However, the detailed mechanisms of caffeic acid phenylethyl amide need further studies. In summary, this study demonstrated the protective potential of chronic treatment of caffeic acid phenylethyl amide against the metabolic consequences in diabetes mellitus.

Caffeic acid phenethyl amide improves glucose homeostasis and attenuates the progression of vascular dysfunction in Streptozotocin-induced diabetic rats

“…In STZ-induced type 1 diabetic rats, CAPA lowered plasma glucose levels even though this diabetic rat model has low insulin secretion activity, suggesting that insulin-independent mechanisms may be involved. Our findings were concordant with those studies that reported plasma glucose lowering activity of CAPA in STZ-induced type 1 diabetic mice [35] and increased glucose transporter 4 protein expression along with insulin-induced glycogen synthesis in diet-induced type 2 diabetic mice [10]. The detailed mechanism responsible for the antidiabetic activity in type 1 diabetic rats remains to be investigated.…”

“…Streptozotocin (STZ) is the most frequently used drug to induce diabetes and has been useful for the study of multiple aspects of the disease [9]. In the cardiovascular system, studies have shown decreased basal coronary arterial flow in STZ-induced diabetic mice [10], decreased aortic blood flow in STZ-induced diabetic rats [11], and decreased sensitivity to phenylephrine of vascular tissues in type 1 diabetic rats [12]. In addition, nitric oxide (NO) production is reduced in STZ-induced diabetes, and the decrease in NO may be related to the pathogenesis of diabetic endothelial damage [13].…”

“…In addition, CAPA has shown α-glucosidase inhibitory effects in yeast [33], adiponectin productive activity in 3T3-L1 cells [34], as well as antihyperglycemic activity and cardioprotection effects in diabetic mice [10,35]. It also attenuates cardiac dysfunction in abdominal aortic banding-induced cardiac hypertrophy [36], indicating that CAPA may be beneficial to treat diabetes and cardiovascular complications.…”

KS370G, a caffeamide derivative, attenuates unilateral ureteral obstruction-induced renal fibrosis by the reduction of inflammation and oxidative stress in mice

“…1) was synthesized using the amide-binding coupling method as previously described (Chuang et al, 2014;Weng et al, 2012aWeng et al, , 2012b. …”

“…Caffeic acid phenethyl ester (CAPE) is also a polyphenolic compound with anti-oxidant, anti-inflammation and anti-fibrosis effects. However, rapid decomposition by esterases reduces its bioavailability in vivo (Chuang et al, 2014;Wang et al, 2007;Weng et al, 2012a). Caffeic acid phenylethyl amide (KS370G) is a synthetic caffeamide derivative and has been reported to exert hypoglycemic effects in diet and streptozocin-induced diabetic mice (Weng et al, 2012a) and cardiovascular protection in pressure-overloaded mouse hearts (Weng et al, 2012b).…”