Synthesis And Anti-diabetic Activity Of Chromium (Ⅲ) Carnosinate

Chromium is an essential trace element for mammals and is required for maintenance of proper carbohydrate, lipid and protein metabolism. Chromium deficiency leads to signs and symptoms of 2 diabetes mellitus and cardiovascular disease.The chromium (â…¢) tricarnosinate, chromium (â…¢) bicarnosinate and chromium (â…¢) bicarnosinate dimer were first synthesized and separated by size exclusion chromatography. The prepared chromium carnosinate complexes were characterized by elemental analysis, UV-Visible, Infrared, Nuclear Magnetic Resonance, Circular Dichroism and Mass Spectra. The results indicate that carnosine (Hcar) functions as bidentate ligand in [Cr(car)3] (HC-I), [Cr2(car)4(H2O)(OMe)]+ (AC-I) and [Cr2(car)4(OH)2] (PC-I) with carboxyl O and imidazole N, and acts as tridentate ligend in [Cr(car)2]+ (PC-II) with carboxyl O, imidazole N and amino N, or quadridentate ligand in [Cr2(H-1car)2(OH)(OMe)] (RC) with carboxyl O, imidazole N, amino N, and peptide N respectively.Secondly, the stability of chromium carnosinate complexes was also studied by electronic spectra. The chromium monocarnosinate dimer (RC) and chromium bicarnosinate dimer (PC-I, AC-I) was stable at pH above 5, it could be decomposed in acidic condition; But chromium tricarnosinate (HC-I) was stable at pH from 1 to 9, and it could be hydrolyzed in high pH after a period of time. Besides, the effects of chromium (â…¢) tricarnosinate (CarnCr) on glucose and lipid metabolism in alloxan-induced diabetic model rats and normal rats were investigated. The levels of serum glucose, total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) cholesterol were significantly decreased (P < 0.05, or P < 0.01) in 800μg·kg^-1 body weight of Cr (â…¢) as chromium tricarnosinate after 6 weeks of treatment. Moreover, the high-density lipoprotein (HDL) cholesterol was obviously increased (P < 0.05). And the area under the curve in oral glucose tolerance test (OGTT) was dramatically reduced. The effects of chromium tricarnosinate appear to be dose-dependent. However, it had no significantly different on the normal rats.The chromium tricarnosinate is water-soluble compound, and its absorption is better than that of chromium (â…¢) picolinate (CrPic). The effects on glucose and lipid metabolism of CarnCr to diabetic rats were more significant than that of the CrPic. Moreover, synergism and antagonism of cinnamon and chromium tricarnosinate on the lowering blood glucose and lipid were studied. The results indicate that it has no significantly effects comparing with the chromium supplementation alone. But the cinnamon has some beneficial effects to the level glucose tolerance and HDL cholesterol.Finally, DNA Cleavage Reactions by chromium tricarnosinate complexes was pilot studied for the first time. We discovered that Chromium tricarnosinate (9 mmol·L^-1) didn't nick supercoiled DNA in the presence of 215μmol·L^-1 H₂O₂, 5 mmol·L^-1 DTT or 5 mmol·L^-1 ascorbate. So did chromium (â…¢) histidinate (9 mmol·L^-1) and chromium picolinate (120μmol·L^-1). However, when the concentration of chromium picolinate rose to 1.20 mmol·L^-1, it could cleave DNA to a significant degree. The safety of chromium (â…¢) is largely dependent on the structure of ligand, and it is dose-dependent.