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Phosphorylated-cyclic adenosine monophosphate response element-binding protein (Phospho-CREB) has an important role in the pathogenesis of myocardial ischemia. We isolated the iridoid glycoside cornin from the fruit of Verbena officinalis L, investigated its effects against myocardial ischemia and reperfusion (I/R) injury in vivo, and elucidated its potential mechanism in vitro. Effects of cornin on cell viability, as well as expression of phospho-CREB and phospho-Akt in hypoxic H9c2 cells in vitro, and myocardial I/R injury in vivo, were investigated. Cornin attenuated hypoxia-induced cytotoxicity significantly in H9c2 cells in a concentration-dependent manner. Treatment of H9c2 cells with cornin (10 µM) blocked the reduction of expression of phospho-CREB and phospho-Akt in a hypoxic condition. Treatment of rats with cornin (30 mg/kg, iv) protected them from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics, and reduction of severity of myocardial damage. Cornin treatment also attenuated the reduction of expression of phospho-CREB and phospho-Akt in ischemic myocardial tissue. These data suggest that cornin exerts protective effects due to an increase in expression of phospho-CREB and phospho-Akt.

BACKGROUND:The plasma concentration of paraquat is closely related to the prognosis of patients with paraquat toxication, and the most common cause of death from paraquat poisoning is multiple organ failure (MOF). This study aimed to evaluate therapeutic effect of smecta on the plasma concentrations of paraquat and multi-organ injury induced by paraquat intoxication in rats.METHODS:A total of 76 healthy adult SD rats were randomly divided into group A (control group, n=6), group B (poisoned group, n=30) and group C (smecta-treated group, n=30). Rats in groups B and C were treated intragastrically with PQ at 50 mg/kg, and rats in group A was treated intragastrically with saline (1 mL). Rats in group C were given intragastrically smecta at 400 mg/kg 10 minutes after administration of PQ, while rats in other two groups were treated intragastrically with 1 mL saline at the same time. Live rats in groups B and C were sacrificed at 2, 6, 24, 48, 72 hours after administration of PQ for the determination of paraquat plasma concentrations and for HE staining of the lung, stomach and jejunum. The rats were executed at the end of trial by the same way in group A.RESULTS:The plasma concentration of paraquat (ng/mL) ranged from 440.314±49.776 to 4320.6150±413.947. Distinctive pathological changes were seen in the lung, stomach and jejunum in group B. Lung injuries deteriorated gradually, edema, leukocyte infiltration, pneumorrhagia, incrassated septa and lung consolidation were observed. Abruption of mucosa, hyperemic gastric mucosa and leukocyte infiltration were obvious in the stomach. The hemorrhage of jejunum mucosa, the abruption of villus, the gland damage with the addition of inflammatory cell infiltration were found. Compared to group B, the plasma concentration of paraquat reduced (P<0.01) and the pathological changes mentioned above were obviously alleviated in group C (P<0.05, P<0.01).CONCLUSION:Smecta reduced the plasma concentration of paraquat and alleviated pathologic injury of rats with PQ poisoning.