The relationship between the chemistry characteristic and the hepatoprotective effects of (1E,6E)-1,7-diphenylhepta-1,6-diene-3,5-dione (DDD), a curcumin analogue, in operative liver injury rats was investigated to reveal the mechanism of hepatic protection effects of DDD. DDD (1.2–4.8 mmol/kg) was administrated 10 min before reperfusion phase in hepatic ischemia-reperfusion injury (IRI) rats. DDD (4.8 mmol/kg) administrated 10 min before ischemia and N-acetylcysteine (NAC) (4.8 mmol/kg) administrated 10 min before reperfusion were included for comparative studies. The plasma liver enzyme activities, histopathological indices and markers of lipid peroxide were determined to evaluate the hepatic protection effects. Effects of DDD on succinate dehydrogenase (SDH) activity were also investigated. DDD showed dose-dependent hepatocyte protections when administrated 10 min before reperfusion stages in hepatic IRI rats. DDD showed almost equivalent hepatoprotective effects when administrated 10 min before ischemia phase demonstrating that DDD acted on the reperfusion stages selectively against the hepatic IRI, instead of ischemia phase. NAC was not effective against hepatic IRI when treated 10 min before reperfusion because of the higher pKa of NAC. In additional, DDD had no effect on the SDH both in hepatic IRI rats and in mitochondria. In conclusion, DDD had dose-dependent hepatocyte protections in the reperfusion stages in hepatic IRI rats, while the observed hepatocyte protections of DDD did not involve SDH activities. β-Diketone structures of DDD were crucial for the hepatocyte protections. The abilities of DDD to clear up the unsaturated aldehydes related with the enolate nucleophilicity and the pKa. DDD might be a promising candidate to treat hepatic IRI.Download high-res image (483KB)Download full-size image

BackgroundAnthraquinones extract from Rheum palmatum L. (rhubarb) including rhein, emodin, aloe-emodin, chrysophanol, physcion and sennoside A, has been widely used in China to treat various diseases.ObjectiveThis study was designed to explore the pharmacokinetic and pharmacodynamic properties of rhubarb anthraquinones extract in diabetic nephropathy and acute liver injury rats.MethodsThe diabetic nephropathy and acute liver injury rats were induced by intraperitoneal injection with streptozotocin (STZ) and carbon tetrachloride (CCL4), respectively. The rats were treated with different doses of rhubarb anthraquinones extract (37.5, 75 and 150 mg/kg) as administration groups. For pharmacokinetics, the drug concentrations of rhubarb anthraquinones consisting of rhein, emodin, aloe-emodin, chrysophanol, physcion and sennoside A were determined. For pharmacodynamics, the anti-diabetic nephropathy and hepatoprotective effects were assessed under different dosage regimens.ResultsThe rhein, emodin, aloe-emodin, chrysophanol were considered as pharmacokinetic markers at three doses of rhubarb anthraquinones extract. In diabetic nephropathy rats, no obvious pharmacokinetic change of the four ingredients was observed compared with control rats. However, the plasma exposures of the four ingredients increased in acute liver injury rats compared with control rats. The serum creatinine (SCr), blood urea nitrogen (BUN) and urine protein (UP) values in diabetic nephropathy rats decreased compared with those in the model group, which suggested that rhubarb anthraquinones extract displayed certain therapeutic and preventive effects against the diabetic nephropathy. However, rhubarb anthraquinones extract cannot ameliorate the CCL4-induced liver injury under the three different dosage regimens.ConclusionThere was no significant pharmacokinetic difference after a single oral administration of rhubarb anthraquinones extract between control and diabetic nephropathy rats. However, apparent pharmacokinetic differences were observed between control and liver injury rats. Also, rhubarb anthraquinones extract had beneficial effects on diabetic nephropathy rats, while no marked effect on liver injury rats under the same dosage regimens.Download high-res image (204KB)Download full-size image