Astragaloside IV attenuates cerebral ischemia and reperfusion injury and reduces activation of NLRP3 inflammasome and NF-κB phosphorylation in rats following a transient middle cerebral artery occlusion / 生理学报

The present study was aimed to investigate the protective effect and anti-inflammation mechanism of astragaloside IV (AST-IV) on cerebral ischemia and reperfusion injury. Following the establishment of cerebral ischemia and reperfusion model in rats by modified suture method, neurological deficit scores and cerebral infarct volume were used to evaluate the pharmacological effect of AST-IV against cerebral ischemia-reperfusion injury. Western blot was used to detect the expression levels of NLRP3, pro-Caspase-1, Caspase-1, pro-IL-1β, IL-1β, pro-IL-18, IL-18, phosphorylated and total nuclear factor kappa B (NF-κB)/p65 protein in the brain tissue. The results showed that compared with model group, the intervention of AST-IV decreased the neurological deficit scores, reduced the cerebral infarct volume, decreased the levels of NLRP3, Caspase-1, pro-IL-1β, IL-1β, pro-IL-18 and IL-18, and inhibited the expression of phosphorylated NF-κB in brain tissue. The results suggest that AST-IV has a protective effect against cerebral ischemia and reperfusion injury, and its mechanism is related to inhibiting the phosphorylation of NF-κB and NLRP3 inflammasome activation.

Effect of astragaloside Ⅳ combined with Panax notoginseng saponins on cerebral ischemia-reperfusion injury and study of pharmacokinetics in rats / 中国中药杂志

The aim is to study the effect of astragaloside Ⅳ (AST Ⅳ) combined with Panax notoginseng saponins (PNS) on cerebral ischemia-reperfusion injury, and to probe the synergistic mechanism through the pharmacokinetics of the four major components such as AST Ⅳ, ginsenoside Rg₁ (Rg₁), ginsenoside Rb₁ (Rb₁), notoginsenoside R₁ (R₁) in cerebral ischemia-reperfusion rats. Following the establishment of cerebral ischemia/reperfusion model in rats by modified suture method, neurological function score, cerebral infarction area and pathomorphology were used to evaluate the pharmacological effect that the combination of AST Ⅳ and PNS antagonized cerebral ischemia-reperfusion injury; the contents of AST Ⅳ, Rg₁, Rb₁, R₁ in rat plasma of different time points were determined with ultra performance liquid chromatography tandem massspectrometry (UPLC-MS/MS), pharmacokinetic parameters were calculated and pharmacokinetics changes of the main effective components were analyzed. The results showed that AST Ⅳ, PNS alone and their combination could reduce the cerebral infarction area of rats, relieve the behavioral scores of neurologic deficit, improve the pathological changes after cerebral ischemia, the effects of the combination were better. Among AST Ⅳ, Rg₁, Rb₁, R₁, the area under the curve (AUC) was significantly increased, the mean residence time of (MRT0-t) was delayed, the peak concentration (Cmax) was significantly raised, the apparent volume of distribution (Vz/F) was reduced, and the clearance rate in vivo was significantly slowed. It suggested that AST Ⅳ combined with PNS has synergistic enhancement on anti-cerebral ischemia/reperfusion injury, moreover, make the pharmacokinetic behavior of the main effective components change, the mechanism may be associated with prolonging the retention time of the effective components in cerebral ischemia condition, elevating the bioavailability.

In vitro microdialysis recoveries of nine active ingredients in Mahuang decoction / 中国中药杂志

To detect the in vitro probe microdialysis recoveries based on an HPLC-DAD method for simultaneous quantification of nine active ingredients (ephedrine, pseudoephedrine, methylephedrine, amygdalin, liquiritin, cinnamyl alcohol, cinnamic acid, cinnamaldehyde and glycyrrhizic acid) in Mahuang decoction, which provides reference for in vivo pharmacokinetic study. The concentrations of nine active ingredients in dialysate were detected by HPLC-DAD, to investigate the effect of flow rates (incremental method and subtraction method) and intraday stability of the probe recoveries and medium concentrations on the recoveries. Nine active ingredients could be well separated in 52 min. At the perfusion rate of 1.0 μL x min(-1), the relative recoveries of ephedrine, pseudoephedrine, methylephedrine, amygdalin, liquiritin, cinnamyl alcohol, cinnamic acid, cinnamaldehyde and glycyrrhizic acid were (50.95 ± 0.82)%, (52.74 ± 1.13)%, (51.29 ± 0.51)%, (32.56 ± 0.84)%, (45.36 ± 0.83)%, (70.94 ± 0.99)%, (69.98 ± 2.30)%, (71.68 ± 0.63)%, and (22.14 ± 0.48)%, respectively. And the probe kept steady in 7 hours. At the same medium concentration, the probe recoveries decreased exponentially with the increase in flow rates. The recoveries of seven ingredients detected by these two methods were similar at certain flow rates, except for amygdalin and cinnamaldehyde. At the same flow rate, the relative recoveries of cinnamyl alcohol, cinnamic acid and cinnamaldehyde changed greatly (9.55%-16.2%) and the others six ingredients had less change (3.27%-5.71%) with the changes in medium concentrations. Microdialysis method could be used to detect the in vitro recoveries of nine ingredients in Mahuang decoction. Reverse dialysis method could be used for the in vivo probe recovery calibration of ephedrine, pseudoephedrine, methylephedrine, liquiritin, cinnamyl alcohol and cinnamic acid at the flow rate of 2.0 μL x min(-1).

Autophagy in cerebral ischemia and the effects of traditional Chinese medicine / 中西医结合学报

Autophagy is a lysosome-mediated degradation process for non-essential or damaged cellular constituents, playing an important homeostatic role in cell survival, differentiation and development to maintain homeostasis. Autophagy is involved in tumors as well as neurodegenerative, cardiovascular and cerebrovascular diseases. Recently, active compounds from traditional Chinese medicine (TCM) have been found to modulate the levels of autophagy in tumor cells, nerve cells, myocardial cells and endothelial cells. Ischemic stroke is a major cause of neurological disability and places a heavy burden on family and society. Regaining function can significantly reduce dependence and improve the quality of life of stroke survivors. In healthy cells, autophagy plays a key role in adapting to nutritional deprivation and eliminating aggregated proteins, however inappropriate activation of autophagy may lead to cell death in cerebral ischemia. This paper reviews the process and the molecular basis of autophagy, as well as its roles in cerebral ischemia and the roles of TCM in modulating its activity.

Effect of active fraction of buyang huanwu decoction on caspase expression in rats after focal cerebral ischemic reperfusion / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate effect of the four kinds of active fractions extracted from Buyang Huanwu Decoction (BYHWD) on caspase expression in rats after focal cerebral ischemic reperfusion.</p><p><b>METHODS</b>The focal cerebral ischemia/reperfusion model rats were established by middle cerebral artery occlusion for 2 hrs followed with reperfusion for 46 hrs. Before and at 12th, 24th and 36th hour after cerebral ischemia, the rats were administered with alkaloid, glycoside, polysaccharide and aglycone from BYHWD respectively, and nimodipine was given as control medicine to observe the effect of them on protein expression of caspase-1, caspase-3 and caspase-8 using immunohistochemical method.</p><p><b>RESULTS</b>Protein expression of caspase-1 and caspase-3 increased in the injured lateral brain tissue after cerebral ischemia/reperfusion. Caspase-1 expression were observed mainly in choroids, while caspase-3 expression in hippocampus, cortex and medulla. All the four kinds of active fractions from BYHWD could inhibit caspase-1 expression, while nimodipine couldn't. Caspase-3 expression in hippocampus and medulla could be inhibited by alkaloid, that in hippocampus, cortex and medulla could be inhibited by glycoside and aglycone, and that in hippocampus and medulla by nimodipine, however, polysaccharide showd no effect on it. As for caspase-8 expression, no effect on it was shown in all groups.</p><p><b>CONCLUSION</b>Alkaloid, glycoside, polysaccharide and aglycone from BYHWD could relieve the inflammatory reaction occurred after cerebral ischemia/reperfusion by inhibiting caspase-1 expression to decrease production of inflammatory cytokine. Alkaloid, glycoside and aglycone could reduce neuronal apoptosis by inhibiting caspase-3 expression to antagonize the delayed neuronal death after cerebral ischemia. The 4 kinds of active fractions may be the main material basis for BYHWD in preventing ischemia/reperfusion cerebral injury.</p>