The Research Of Mono-carbonyl Analogs Of Curcumin And Curcumin With Improved Stability And Pharmacological Activities

AIM1. To research the effect of light, temperature, pH value and biomaterial on stability of curcumin and synthetic compounds.2. To develop the method of HPLC for determination of curcumin and synthetic compound A in rats plasma and the pharmacokinetics in rats and to provide basis of curcumin for clinical application.3. To compare the pharmaco-activity of curcumin with synthetic compounds. Include anti-inflammtory anti-oxidation, anti-tumor andMETHODS1. The stability in vitro:To determine concentration of curcumin and synthetic compounds by HPLC when placed curcumin and synthetic compounds in different conditions, the equation of degradation was established.2. The pharmacokinetics in Rats:The curcumin and the synthetic compound A were lavaged to the rats, and the concentration of curcumin and synthetic compound A in rats blood at different time points were determined by HPLC; The data was analysis by3P97pharmacokinetic software.3.The pharmactivity1) anti-oxidation The anti-oxidation activity were evalute through two levels, one was determined by DPPH method and the anther was the production of MDA and SOD.2)anti-tumor The curcumin and synthetic compounds were dissolved in DMSO and added in cell of HepG2.The anti-oxidation activity were determined by MTT.3) sugar-lowering The curcumin and synthetic compounds were dissolved in DMSO and added in cell of3T3-L1. The sugar-lowering activity were determined by GOD-POD kit.RESULTS1. The curcumin and synthetic compounds was most stable in the environment of low light, low temperature and pH for acid condition. Under the same conditions, the stability of curcumin and synthetic compounds by compound A is best, followed by compound B and then curcumin.2. The plasma concentration-time curves of curcumin and synthetic compound A in rats were fitting to one compartment model respectively; The CL、AUC and t1/2of synthetic compound A were2.47,3.09and2.79times respectively than that of curcumin.3. The pharmactivity of synthetic compounds was differently. The anti-oxidation was not better than Curcumin. The antitumor and sugar-lowering was better than curcumin. The pharmactivity of curcumin and synthetic compounds was closely related with chemical structureCONCLUSIONThe experiment has proved that the synthetic compounds was not only improve the stability in vitro, but also in vivo. it was prolonged half-life, improved the bioavailability and increase the drug concentration and improved the medicine and defects. The pharmacological activity was not reduce compared with curcumin. The activity of antitumor and sugar-lowering was better than curcumin.