Vasoprotective Effects of Hyperoside against Cerebral Ischemia/Reperfusion Injury in Rats: Activation of Large-Conductance Ca2+-Activated K+ Channels.

Hyperoside (Hyp), a kind of Chinese herbal medicine, exerts multiple therapeutic effects on many diseases. However, the role and mechanisms of Hyp in vascular pathophysiology in ischemic stroke need to be further established. The study aimed to investigate the role of (large-conductance Ca2+-activated K+) BK channels on the vasoprotection of Hyp against cerebral ischemia and reperfusion (I/R) injury in rats. The concentration gradient of Hyp was pretreated in both the middle cerebral artery occlusion and reperfusion model and oxygen-glucose deprivation/reoxygenation (OGD/R) model of primary vascular smooth muscle cells (VSMCs) in rats. A series of indicators were detected, including neurological deficit score, infarct volume, malondialdehyde (MDA), superoxide dismutase (SOD), cerebral blood flow (CBF), cell viability, membrane potential, and BK channels α- and ß1-subunits expression. The results showed that Hyp significantly reduced infarct volume and ameliorated neurological dysfunction in I/R-injured rats. Besides, the effects of I/R-induced reduction of BK channels α- and ß1-subunits expression were significantly reversed by Hyp in endothelial-denudated cerebral basilar arteries. Furthermore, the protective effect against I/R-induced increases of MDA and reduction of SOD as well as CBF induced by Hyp was significantly reversed by iberiotoxin (IbTX). In OGD/R-injured VSMCs, downregulated cellular viability and BK channels ß1-subunits expression were remarkably reversed by Hyp. However, neither OGD/R nor Hyp affected BK channels α-subunits expression, and Hyp failed to induced hyperpolarization of VSMCs. Moreover, the protective effect against OGD/R-induced reduction of cell viability and SOD level and increases of MDA production induced by Hyp was significantly reversed by IbTX in VSMCs. The study indicates that Hyp has the therapeutic potential to improve vascular outcomes, and the mechanism is associated with suppressing oxidative stress and improving CBF through upregulating BK channels.

Simultaneous determination of five alkaloids from Rauvolfia vomitoria in rat plasma by LC-MS/MS: Application to a comparative pharmacokinetic study in normal and type 2 diabetic rats.

Rauvolfia vomitoria is widely distributed in the tropical regions of Africa and Asia, and has been used in traditional folk medicine in China. Indole alkaloids were found to be major bioactive components, while the effects of diabetes mellitus on the pharmacokinetic parameters of the components have not been reflected in vivo. In this study, an efficient and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous determination of five ingredients of R. vomitoria in rats. Detection was implemented in multiple-reaction-monitoring mode with an electrospray positive-ionization source. Validation parameters were all in accordance with the current criterion. The established method was effectively employed to compare the pharmacokinetic behaviors of five alkaloids (reserpine, yohimbine, ajmaline, ajmalicine, and serpentine) between normal and type 2 diabetic rats. The single-dose pharmacokinetic parameters of the five alkaloids were determined in normal and diabetic rats after oral administration of 100 and 200 mg/kg body weight. The results indicated that diabetes mellitus significantly altered the pharmacokinetic characteristics of yohimbine, ajmaline, and ajmalicine after oral administration in rats. This is an attempt to provide some evidence for clinicians that may serve as a guide for the use of antidiabetic medicine in clinical practice.