musk and Disease-Models--Animal

Musk is a representative drug of aroma-relieving traditional Chinese medicine, and it is a commonly used traditional Chinese medicine for the treatment of ischemic stroke. Muscone is the core medicinal component of musk.. We sought to identify the target of muscone in the treatment of ischemic stroke using network pharmacology, an animal model of ischemic stroke, and differential proteomics.. The drug targets of muscone in the treatment of ischemic stroke were predicted and analyzed using information derived from sources such as the Traditional Chinese Medicine Systems Pharmacology database and Swiss Target Prediction tool. The animal model of focal cerebral ischemia was established by suture-based occlusion of the middle cerebral artery of rats. The rats were divided into six groups: sham-operated control, model, musk, muscone1, muscone2, and muscone3. Neurological deficit scores were calculated after intragastric administration of musk or muscone. The microcirculation blood flow of the pia mater was detected using a laser speckle blood flow meter. The cerebral infarction rate was detected by 2,3,5-triphenyltetrazolium chloride staining. The necrosis rate of the cerebral cortex and the hippocampal neurons was detected by hematoxylin and eosin staining. Blood-brain barrier damage was detected by the Evans blue method. Quantitative proteomics analysis in the sham-operated control, model, and muscone groups was performed using tandem-mass-tags. Considering fold changes exceeding 1.2 as differential protein expression, the quantitative values were compared among groups by analysis of variance. Furthermore, a protein-protein interaction network was constructed, and differentially expressed proteins were analyzed by gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.. Network pharmacology identified 339 targets for the intersection of 17 components of musk and cerebral ischemia-reperfusion injury. The GO and KEGG enrichment items mainly identified regulation of neuronal synaptic structure and transfer function, synaptic neurotransmitters, and receptor activity. Zoopery showed that the model group had a higher behavioral score, cerebral infarction rate, cortical and hippocampal neuron death rate, Evans blue exudation in the brain, and bilateral pia mater microcirculation blood flow differences than the sham-operated control group (P <0.01). Compared with the model group, the behavioral score, infarction rate, hippocampal neuronal mortality, and Evans blue content decreased significantly in the musk, muscone2, and muscone3 groups (P <0.05). Proteomic analysis showed that 160 genes were differentially expressed among the sham-operated control, model, and muscone groups. GO items with high enrichment included neuronal synapses, postsynaptic signal transduction, etc. KEGG items with high enrichment included cholinergic synapses, calcium signaling pathway, dopaminergic synapses, etc. Protein interaction analysis revealed that the top three protein pairs were Ndufa10/Ndufa6, Kcna2/Kcnab2, and Gsk3b/Traf6.. Muscone can reduce neuronal necrosis, protect the blood-brain barrier, and improve the neurological damage caused by cerebral ischemia via molecular mechanisms mainly involving the regulation of neuronal synaptic connections. Muscone is an important active component responsible for the "consciousness-restoring resuscitation" effect of musk on ischemic stroke.

Topics: Animals; Brain Ischemia; Cerebral Infarction; Consciousness; Cycloparaffins; Disease Models, Animal; Evans Blue; Fatty Acids, Monounsaturated; Infarction, Middle Cerebral Artery; Ischemic Stroke; Necrosis; Proteomics; Rats; Stroke

This study aimed to evaluate the effect induced by musk on Alzheimer's disease-such as neurodegenerative changes in mice exposed to chronic unpredictable mild stress (CUMS).. Forty male Swiss albino mice were divided into 4 groups (n = 10); control, CUMS, CUMS + fluoxetine, CUMS + musk. At the end of the experiment, behavior of the mice was assessed. Serum corticosterone level, hippocampal protein level of the glucocorticoid receptors, and brain-derived neurotropic factor were also assessed. Hippocampus was histopathologically examined.. Musk improved depressive status induced after exposure to CUMS as evidenced by the forced swimming and open field tests and improved the short-term memory as evidenced by the elevated plus maze test. Musk reduced both corticosterone levels and the hippocampal neurodegenerative changes observed after exposure to CUMS. These improvements were comparable to those induced by fluoxetine.. Musk alleviated the memory impairment and neurodegenerative changes induced after exposure to the chronic stress.

Topics: Animals; Behavior, Animal; Brain-Derived Neurotrophic Factor; Corticosterone; Disease Models, Animal; Fatty Acids, Monounsaturated; Fluoxetine; Hippocampus; Male; Mice; Receptors, Glucocorticoid; Selective Serotonin Reuptake Inhibitors; Stress, Psychological

Depression has become a common public health problem that is showing increasing prevalence. Slow onset of action, low response rates and drug resistance are potential limitations of the current antidepressant drugs. Alternative therapy using natural substances, specifically aromatherapy, is currently tried to treat depression. This work aimed to assess the efficacy of musk in relieving the behavioral, biochemical and hippocampal histopathological changes induced by exposure to chronic mild stress in mice and explore the possible mechanism behind this antidepressant-like effect. Forty male albino mice were divided into four groups (n = 10): control, a group exposed to chronic unpredictable mild stress (CUMS) and two groups exposed to CUMS and then treated with fluoxetine or musk. Behavioral changes and serum corticosterone levels were assessed at the end of the experiment. Protein and gene expressions of brain-derived neurotropic factor (BDNF) and glucocorticoid receptors (GRs) in the hippocampus were assessed using ELISA and real-time RT-PCR, respectively. Histopathological examination of the hippocampus and immunohistochemical techniques using glial fibrillary acidic protein (GFAP), Ki67, caspase-3, BDNF and GR were performed. Inhalation of musk had an antidepressant-like effect in an animal model of depression. Musk alleviated the behavioral changes and elevated serum corticosterone levels induced by exposure to chronic stress. It reduced the hippocampal neuronal apoptosis and stimulated neurogenesis in the dentate gyrus. Musk's action may be related to the upregulation of hippocampal GR and BDNF expressions. Musk is considered a potential antidepressant so it is advisable to assess its efficacy in treating depressed patient.

Topics: Administration, Inhalation; Animals; Antidepressive Agents; Behavior; Brain-Derived Neurotrophic Factor; Corticosterone; Depression; Disease Models, Animal; Fatty Acids, Monounsaturated; Fluoxetine; Gene Expression; Hippocampus; Male; Mice; Receptors, Glucocorticoid; Stress, Psychological

Depression is a significant public health concern all over the world, especially in modern communities. This study aims to assess the efficacy of musk in alleviating the behavioral, biochemical and histopathological changes induced by chronic unpredictable mild stress (CUMS) in an animal model of depression and to explore the underlying mechanism of this effect. Male Swiss albino mice were divided into four groups (n = 10): control, CUMS, CUMS+fluoxetine and CUMS+musk. At the end of the experiment, behavioral tests were administered and serum corticosterone and testosterone levels were assessed. Surface markers, proteins and gene expressions of brain-derived neurotropic factor (BDNF) and glucocorticoid receptors (GRs) in the hippocampus were assessed. The immunoexpression of glial fibrillary acidic protein, Ki67 and caspase-3 was also assessed. Data were analyzed using the Statistical Package for the Social Sciences and a P value of less than 0.05 was considered significant. Musk alleviated the behavioral changes caused by CUMS and reduced elevated corticosterone levels. It reduced CUMS-induced neuronal atrophy in the CA3 and dentate gyrus of the hippocampus and restored astrocytes. Musk reduced the neuro- and glial apoptosis observed in stressed mice in a manner comparable to that of fluoxetine. Musk induced these effects through up-regulating both BDNF and GR gene and protein expressions. Musk has an antidepressant-like effect in an animal model of depression, so it is advisable to assess its efficacy in people continually exposed to stressors.

Topics: Animals; Antidepressive Agents; Brain-Derived Neurotrophic Factor; Caspase 3; Corticosterone; Depression; Disease Models, Animal; Fatty Acids, Monounsaturated; Gas Chromatography-Mass Spectrometry; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Hippocampus; Ki-67 Antigen; Maze Learning; Mice; Receptors, Glucocorticoid; RNA, Messenger; Testosterone

To observe the effects of musk and carterii birdw on the pathology and the expressions of inflammatory cytokines in chronic non-bacterial prostatitis (CNBP) rats treated with polygonum extract.. Five male Wistar rats were used for the preparation of SC purified prostate protein solution, and another 48 randomly divided into four groups: polygonum extract, polygonum extract + musk and carterii birdw, CNBP model control and normal control. CNBP models were established by injecting SC purified prostate protein solution and Freund's complete adjuvant. At 60 days after modeling, the CNBP model control and normal control rats were treated with normal saline, and the other two groups with polygonum extract and polygonum extract + musk and carterii birdw, respectively (polygonum 1.575 g per kg per d, musk 0.021 g per kg per d, and carterii birdw 1.05 g per kg per d). After 14 days of continuous intragastric medication, all the rats were sacrificed for pathological examination, determination of the levels of TNF-alpha, IL-1beta, IL-6 and IL-8 in the prostate tissue homogenate by ELISA, and detection of the mRNA and protein expressions of inflammatory cytokines MCP-1 (CCL2) and CCR2 by RT-PCR and Western blot.. The polygonum extract + musk and carterii birdw group showed apparent improvement in the structure of the prostate tissue but no inflammatory infiltration, as was quite obvious in the polygonum extract group. Polygonum extract + musk and carterii birdw significantly decreased the inflammatory cytokines TNF-alpha ( [11.04 +/- 4.07] pg/ml), IL-1beta ([16.94 +/- 4.26] pg/ml), IL-6 ([110.08 +/- 28.42] pg/ml) and IL-8 ([26.28 +/- 7.36] pg/ml) in the prostate tissue, as compared with polygonum extract alone ([63.21 +/- 21.37] pg/ml, [41.32 +/- 14.62] pg/ml, [177.64 +/- 42.65] pg/ml and [96.37 +/- 37.61] pg/ml) (P < 0.05, P < 0.01). The former also exhibited significantly lower expressions of MCP-1 mRNA (0.32 +/- 0.17), MCP-1 protein (0.28 +/- 0.15), CCR2 mRNA (0.28 +/- 0.11) and CCR2 protein (0.11 +/- 0.04) than either the model control group (1.15 +/- 0.39, 0.93 +/- 0.34, 0.83 +/- 0.26 and 0.93 +/- 0.34) (P < 0.01), or the polygonum extract group (0.65 +/- 0.27, 0.56 +/- 0.22, 0.78 +/- 0.24 and 0.25 +/- 0.09) (P < 0.05, P < 0.01).. Musk and carterii birdw can enhance the effect of polygonum extract on chronic prostatitis, reduce inflammatory response and improve tissue repair of the prostate in rats.

Topics: Animals; Chronic Disease; Disease Models, Animal; Drugs, Chinese Herbal; Fatty Acids, Monounsaturated; Inflammation; Male; Phytotherapy; Plant Extracts; Polygonum; Prostatitis; Rats; Rats, Wistar

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