Abstract
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 150mg/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.
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