musk and Reperfusion-Injury

Reperfusion Injury Acute ischemic stroke is increasing in people recently and Musk, as a commonly used Traditional Chinese Medicine (TCM), has been suggested as a potential agent against acute ischemic stroke, but the efficacies and underlying mechanisms of it remain unknown.. This study was aimed to test the hypotheses that volatile compounds of musk could attenuate nerve injury and identify the bioactive compounds and potential mechanisms of Musk.. Transient middle cerebral artery occlusion (MCAO) model in vivo in Sprague-Dawley rats (SD rats) was used to test this hypothesis. Collecting ingredients of Musk and their related targets were discerned from the Gas chromatography-olfactory mass spectrometry (GC-O-MS) experiment. Then the potential mechanisms and targets of the compounds were searched by network pharmacology techniques. Finally, the pathway was verified by Western Bolt (WB).. First, Musk treatment significantly up-regulated the relative levels of AKT1, PI3KA, and VEGFA in the hippocampus, and improved the sport functions in the post-MCAO ischemic rats in vivo. Next, twenty potential flavor active compounds were recognized by GC-O-MS. A total of 89 key targets including HIF-1, PIK3CA, TNF signaling pathway, and VEGF were identified. AKT1, HIF1A, PIK3CA, and VEGFA were viewed as the most important genes, which were validated by molecular docking simulation.. The Volatile compounds of musk can attenuate nerve injury and improving post-cerebral ischemic exercise functions by HIF1A pathways, and the combined data provide novel insight for Musk volatile compounds developed as new drug for improving reperfusion injury in acute ischemic stroke.

Topics: Animals; Class I Phosphatidylinositol 3-Kinases; Drugs, Chinese Herbal; Fatty Acids, Monounsaturated; Humans; Infarction, Middle Cerebral Artery; Ischemic Stroke; Molecular Docking Simulation; Rats; Rats, Sprague-Dawley; Receptor Protein-Tyrosine Kinases; Receptors, Cholinergic; Reperfusion Injury

To investigate the mechanism of Musk and Borneol on cerebral ischemia and reperfusion injury at different time points of acute phase in rats.. 180 rats were divided into seven groups including sham, ischemia-reperfusion after 24 h and 72 h model group, Musk 50 and 25 mg/kg groups, Borneol 50 and 25 mg/kg groups, and Xingnaojing 10 mL/kg group. Ischemia-reperfusion model was made after administration of each drug. The neurologic impairment scores at different time points after ischemia and reperfusion was evaluated, activities of cyclooxygenase (COX-2) and 5-lipoxygenase (5-LOX) in brain tissue were determined, and the expression of CysLT2 protein and mRNA in hippocampus were explored.. Musk and Borneol significantly improved the neurologic impairment scores of ischemia-reperfusion injury rats, improved the pathological morphology of rats brain tissue, reduced the activities of COX-2 and 5-LOX in brain homogenates,and inhibited the expression of CysLT2 protein in hippocampus.. Musk and Borneol have protective effect on inflammatory injury of acute injury in ischemia-reperfusion injury rats, the mechanism is related to inhibition the activity of COX-2 and 5-LOX in brain.

Topics: Animals; Anti-Inflammatory Agents; Arachidonate 5-Lipoxygenase; Brain; Brain Ischemia; Camphanes; Cyclooxygenase 2; Fatty Acids, Monounsaturated; Rats; Rats, Sprague-Dawley; Reperfusion Injury

To study the metabolomics of focal cerebral ischemia reperfusion injury in rats' brain treated by musk combined with borneol.. Amino acids, fatty acids, organic acids, glucose,and sterols were transferred to ethers or esters which were heat stable and evaporated easily. The chromatographic conditions were optimized to analyze the endogenous metabolites from serum of the rats.. The metabolic fingerprints of the endogenous metabolites were obtained by the optimum method. Twenty-nine chromatographic peaks in the metabolic fingerprints were identified by mass data and standard references. And the difference between normal, model rats, and model rats treated by musk with borneol was analyzed by the Principal Component Analysis (PCA).. The metabolic fingerprints based on the derivation reaction combined with GC-MS could analyze the endogenous metabolites; The variation between different groups was related to the quantity of the biomarkers which could be in accordance with focal cerebral ischemia reperfusion injury.

Topics: Amino Acids; Animals; Biomarkers; Blood Chemical Analysis; Brain Ischemia; Camphanes; Disease Models, Animal; Fatty Acids; Fatty Acids, Monounsaturated; Gas Chromatography-Mass Spectrometry; Glucose; Metabolomics; Principal Component Analysis; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury

To research the effects of moschus, borneol, styrax and benzoinum on the structure and function of blood brain barrier in cerebral ischemia-reperfusion injury model rats.. Focal middle cerebral artery occlusion (MCAO) was introduced as an in vivo ischemic model in rats. After 2 h MCAO, nylon suture was pulled up 1 cm to give blood reperfusion. After 22 h reperfusion, all animals were decapitated. The ultramicrostructure of blood brain barrier of ischemia hemisphere side in fronto-parietal cortex region by transmission electron microscope, and the content of VEGF and MMP-9 in ischemia side brain tissue were measured by ELISA.. In model and solvent group rats, the capillary endothelium cells, astro-glial cells and nerve cells in ischemia hemisphere side in fronto-parietal region were emerged in different degree compared with sham-operated groups, which exhibited tight junction between endothelial cells being opened, basal lamina being dissolved, and permeability increasing, and cellularedema. In borneol (0.2 g x kg(-1)) group rats, the structure of three kinds of cells were nearly normal, which tight junction structure was clear, rough endoplasmic reticulum and polyribosome could be found in cytoplasm. In moschus (66.6 mg x kg(-1)) group rats, the structure of capillary endothelium cells and astrocytes were nearly normal as well as the basal lamina, but the electrons in neurons was maldistribution. In styrax (1.332 g x kg(-1)) group rats, astrocytes were nearly normal, while capillary endothelial cells and neurons exhibited oedema in different degrees. And the basal lamina was discontinuous, augmentation of cell spaces in endothelial cells increased the permeability, some endoplasmic reticulum broadened and ribosome ablated. In benzoinum (1.0 g x kg(-1)) group rats, oedema of capillary endothelial cells and astrocytes was significant, basal lamina broke. Meanwhile endoplasmic reticulum broadened as vacuole, the number of ribosome in rough endoplasmic reticulum decreased, crista mitochondriales in some neurons disappeared as vacuole which hint oedema happened. Results also showed that borneol decrease the level of VEGF in ischemia side brain tissue significantly, while has little influence on the level of MMP-9. Moschus showed the tendency to decrease the level of VEGF and MMP-9 in ischemia side brain tissue.. Aromatic resuscitation drugs showed the protection effect on blood brain barrier in cerebral ischemia-reperfusion injury rats, which the protection effect of moschus and borneol were better than that of styrax and benzoinum. The mechanism of protection effect maybe related to decrease the level of VEGF and MMP-9.

Topics: Animals; Benzoin; Blood-Brain Barrier; Brain Ischemia; Camphanes; Disease Models, Animal; Fatty Acids, Monounsaturated; Infarction, Middle Cerebral Artery; Male; Matrix Metalloproteinase 9; Neuroprotective Agents; Plant Extracts; Rats; Reperfusion Injury; Styrax; Vascular Endothelial Growth Factor A