Er-xian ameliorates myocardial ischemia-reperfusion injury in rats through RISK pathway involving estrogen receptors.

Curculigo orchioides (CUR) and Epimedium (EPI) are traditional Chinese medicines with estrogen-like biological activity, called Xianmao and Xianlingpi (Er-xian) in Chinese. However, whether Er-xian exerts protective effects on myocardial ischemia-reperfusion injury (MIRI) is unknown. This study aimed to investigate the cardioprotective effects of Er-xian preconditioning against MIRI and the underlying mechanisms. CUR or EPI was administered intragastrically to aged female rats as a monotherapy or combination therapy. 2 weeks later, a rat MIRI model was established. Myocardial infarction size, myocardial morphology, cTnT, cell apoptosis rate, intracellular calcium concentration, mitochondrial permeability transition pore (MPTP) opening and reperfusion injury salvage kinase (RISK) signaling pathway molecules were observed after the surgery. To evaluate the mechanisms of Er-xian, estrogen receptors antagonists ICI 182780 and G15 were used. In this study, Er-xian notably alleviated myocardial tissue damage, maintained mitochondrial morphology, reduced infarct size and cardiac markers, and increased sera levels of E2. Moreover, Er-xian inhibited calcium overload and mPTP opening, and decreased cardiomyocyte apoptosis. We found that the dual therapy of CUR and EPI elicited more noticeable results than CUR or EPI monotherapy. The significant protective effects of Er-xian on ischemia-reperfusion myocardium were attributed to the up-regulation of AKT, ERK1/2 and GSK-3ß phosphorylation levels. The cardioprotective effects of Er-xian were significantly reduced after estrogen receptor blockade, especially GPER30. These results indicate that Er-xian attenuates MIRI through RISK signaling pathway and estrogen receptors are the critical mediators.

Protective effect of the combinations of glycyrrhizic, ferulic and cinnamic acid pretreatment on myocardial ischemia-reperfusion injury in rats.

The aim of this study was to find an effective drug cocktail pretreatment to protect myocardial tissue of the heart from ischemia-reperfusion (I/R) injury. The mechanisms underlying the effects of the drug cocktail were subsequently explored in order to expand the application of Dang-gui-si-ni-tang (DGSN), a Traditional Chinese Medicine. The active components of DGSN in the serum following oral administration were investigated using high-performance liquid chromatography. The activity of superoxide dismutase (SOD) and malondialdehyde (MDA) levels were then analyzed to show the effect of the active components in the treatment of myocardial I/R injury. An L16 (44) orthogonal experiment was utilized to determine the most effective cocktail mix and the mechanism underlying the effect of this mix on myocardial I/R injury was investigated. It was observed that FCG, a mixture of glycyrrhizic (50 mg/kg), cinnamic (200 mg/kg) and ferulic (300 mg/kg) acid, was the optimal drug cocktail present in DGSN. This was absorbed into the blood following oral administration and was shown to decrease MDA levels and increase the activity of SOD. In conclusion, the findings suggest that FCG, a combination of active ingredients in the DGSN decoction, can be absorbed into the blood and protect the myocardium from I/R injury.

[Determination of cinnamic acid and glycyrrhizic acid in rat serum and its pharmacokinetics after oral administration of Dangguisini decoction].

OBJECTIVE: To mensurate concentrations and pharmacokinetics of cinnamic acid and glycyrrhizic acid in rats after oral adiministration Dangguisini decoction. METHODS: To Determine serum concentration of cinnamic acid and glycyrrhizic acid by High-Performance Liquid Chromatography and calculate its parameter of pharmacokinetics in rats after oral administration of Dangguisini decoction via 3P97 software. RESULTS: Parameters of Pharmacokinetics of cinnamic acid and glycyrrhizic acid were Cmax 9.2008 (mg/L), AUC 304.0734 (mg/L) x min and Cmax 51.1330(mg/L), AUC 21476.9688 (mg/L) x min respectively in rats after oral administration of Dangguisini decoction. CONCLUSION: Absorption of cinnamic acid is quick and its metabolize is quick too, but metabolism of glycyrrhizic acid is oppositely slow in rats after oral administration of Dangguisini decoction.