Pharmacological Study On Endogenous Opioid Peptide (Endomorphins) And Natural Polyphenol Compound (Caffeic Acid Phenethyl Ester)

It has been reported the impaired endothelium-dependent relaxation was observed in diabetic rabbit aorta and in normal aorta exposed to elevated concentrations of D-glucose in vitro. In this paper, we investigated if endomorphins------potent, selectiveμ-opioid receptor agonists, which have significant, naloxone-sensitive cardiovascular activity------had protective effect on the endothelium of diabetes mellitus in vitro, and we explored the potent mechanisms. Rings of aorta incubated in elevated D-glucose, contracted submaximally by phenylephrine, showed significantly decreased endothelium-dependent relaxations induced by acetylcholine, compared with the aorta incubated in control D-glucose. And the cGMP content of aortic rings were reduced by high D-glucose. Treatment with endomorphins (1-1000nmol/L) restored acetylcholine relaxations of aorta rings incubated in elevated glucose to normal (P<0.01) and increase the cGMP content (P<0.05). Moreover, the protective effect of endomorphins on endothelial cells was inhibited by naloxone (1μmol/L) (P<0.05). And the increase of the cGMP content was also blocked by naloxone (P<0.05). These findings suggested that endomorphins had protective effect on endothelial cells exposed to high D-glucose condition and endomorphins exerted this effect through specific activation of opioid receptor, and probably via the NO-cGMP pathwany.Caffeic acid phenethyl ester (CAPE) together with caffeic acid, ferulic acid and ethyl ferulate are constituents of propolis and structurally related, which allowed us to gather important information regarding the structure-activity relationships underlying the biological activity of such compounds. In this work, we have investigated the direct scavenging effects of the antioxidants on 1, 1-diphenyl-2picrylhydrazyl (DPPH) radicals, galvinoxyl radicals and superoxide anions (O₂^·-), as well as the anti-lipoperoxidative capacity on human erythrocytes hemolysis and rat liver microsomal membranes peroxidation induced in vitro by two different sources of free radicals: 2,2'-azobis (2-amidinopropane) (AAPH) and Fe²⁺/ascorbate (OH·). The results established that the radical scavenging activity of the compounds increased with increasing numbers of hydroxyl groups or catechol moieties in the molecule, while in the biomembrane systems, the antioxidative activity of the test compounds depends not only on the hydroxyl groups or catechol rings but also on the polarity and hydrophobicity of the antioxidants. In addition, CAPE is the most effective antioxidant of the compounds we tested in our in vitro systems.