musk and muscone

Musk, the dried secretion from the preputial follicles of the male musk deer (genus Moschus), possesses various pharmacological activities and has been used extensively in traditional Chinese medicine for thousands of years. Muscone is the main active ingredient of musk and exerts pharmacological effects similar to those of musk. Although muscone was notably used to treat various disorders and diseases, such as neurological disorders, chronic inflammation and ischemia-reperfusion injury, most of the mechanisms of the pharmacological action of muscone remain unclear because of slow progress in research before the 21st century. In recent years, the pharmacological activities and mechanisms of muscone have been clarified. The present article summarizes the pharmacological and biological studies on cerebrovascular disease, cardiovascular disease, neurological effects, cancer and others and the associated mechanisms of the action of muscone to date.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Cerebrovascular Disorders; Cycloparaffins; Deer; Ethnopharmacology; Fatty Acids, Monounsaturated; Humans; Medicine, Chinese Traditional; Neoplasms; Odorants

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

Traditionally, musk has been used as an analgesic to treat pain associated with cancer. Hepatocellular carcinoma (HCC) is an aggressive tumor; however, patients with liver cancer that received musk were reported to live longer and have a higher quality of life. Thus, the present study aimed to investigate whether muscone, a macrocyclic compound of musk, demonstrated potential as an anti‑liver cancer drug for the non‑surgical treatment of advanced liver cancer. Briefly, liver cancer cells were treated with muscone and the rates of cellular apoptosis and autophagy were investigated using staining techniques and western blotting. The underlying molecular mechanisms of muscone were evaluated using high‑throughput sequencing and the in vitro effects of muscone were subsequently validated in vivo using a nude mouse model. Muscone increased the rates of apoptosis and autophagy in liver cancer cells; the increase in cellular apoptosis was observed to occur through endoplasmic reticulum stress responses, whereas muscone‑induced autophagy was closely associated with the AMP kinase/mTOR complex 1 signaling pathway. These findings were verified in vivo. Notably, sestrin‑2 expression levels were also significantly decreased in liver cancer tissues compared with paracancerous tissues. In conclusion, the present study suggests that muscone demonstrates potential as an anticancer drug, and the findings of the present study provide the basis for the development of effective anticancer drugs derived from natural compounds.

Topics: Adenylate Kinase; Animals; Apoptosis; Carcinoma, Hepatocellular; Cell Line, Tumor; Cycloparaffins; Endoplasmic Reticulum Stress; Fatty Acids, Monounsaturated; Gene Expression Regulation, Neoplastic; Heterografts; Humans; Liver Neoplasms; Mechanistic Target of Rapamycin Complex 1; Mice; Nuclear Proteins

Male musk deer secrete musk from the musk gland located between their naval and genitals. Unmated male forest musk deer generate a greater amount of musk than mated males, potentially allowing them to attract a greater number of females. In this study, we used gas chromatography and mass spectrometry (GC/MS) to explore musk chemical composition of the musk pods of captive mated and unmated sexually mature Chinese forest musk deer and used next-generation sequencing to intensively survey the bacterial communities within them. Analysis of the chemical composition of the musk showed that unmated males have more muscone and cholesterol. Features of the musk16S rRNA gene showed that mated Chinese forest musk deer have both a greater Shannon diversity (p < 0.01) and a greater number of estimated operational taxonomic units than unmated ones; many bacterial genera were overrepresented in unmated Chinese forest musk deer males. Members of these genera might be involved in musk odor fermentation. PICRUSt analysis revealed that metabolic pathways such as aldosterone-regulated sodium reabsorption, metabolism of terpenoids and polyketides, flavone and flavonol biosynthesis, and isoflavonoid biosynthesis were enriched in the musk of unmated Chinese forest musk deer males.

Topics: Aldosterone; Animals; Cholesterol; Cycloparaffins; Deer; Exocrine Glands; Fatty Acids, Monounsaturated; Female; Fermentation; Flavonoids; Forests; Male; Microbiota; Odorants; Polyketides; Sexual Behavior, Animal; Symbiosis; Terpenes

The vibrational theory of olfaction assumes that electron transfer occurs across odorants at the active sites of odorant receptors (ORs), serving as a sensitive measure of odorant vibrational frequencies, ultimately leading to olfactory perception. A previous study reported that human subjects differentiated hydrogen/deuterium isotopomers (isomers with isotopic atoms) of the musk compound cyclopentadecanone as evidence supporting the theory. Here, we find no evidence for such differentiation at the molecular level. In fact, we find that the human musk-recognizing receptor, OR5AN1, identified using a heterologous OR expression system and robustly responding to cyclopentadecanone and muscone, fails to distinguish isotopomers of these compounds in vitro. Furthermore, the mouse (methylthio)methanethiol-recognizing receptor, MOR244-3, as well as other selected human and mouse ORs, responded similarly to normal, deuterated, and (13)C isotopomers of their respective ligands, paralleling our results with the musk receptor OR5AN1. These findings suggest that the proposed vibration theory does not apply to the human musk receptor OR5AN1, mouse thiol receptor MOR244-3, or other ORs examined. Also, contrary to the vibration theory predictions, muscone-d30 lacks the 1,380- to 1,550-cm(-1) IR bands claimed to be essential for musk odor. Furthermore, our theoretical analysis shows that the proposed electron transfer mechanism of the vibrational frequencies of odorants could be easily suppressed by quantum effects of nonodorant molecular vibrational modes. These and other concerns about electron transfer at ORs, together with our extensive experimental data, argue against the plausibility of the vibration theory.

Topics: Animals; Carbon Isotopes; Cycloparaffins; Deuterium; Electron Transport; Fatty Acids, Monounsaturated; HEK293 Cells; Humans; Isomerism; Mice; Models, Biological; Odorants; Receptors, Odorant; Smell; Vibration

Musk odorants are used widely in cosmetic industries because of their fascinating animalic scent. However, how this aroma is perceived in the mammalian olfactory system remains a great mystery. Here, we show that muscone, one musk odor secreted by various animals from stink glands, activates a few glomeruli clustered in a neuroanatomically unique anteromedial olfactory bulb. The muscone-responsive glomeruli are highly specific to macrocyclic ketones; interestingly, other synthetic musk odorants with nitro or polycyclic moieties or ester bonds activate distinct but nearby glomeruli. Anterodorsal bulbar lesions cause muscone anosmia, suggesting that this region is involved in muscone perception. Finally, we identified the mouse olfactory receptor, MOR215-1, that was a specific muscone receptor expressed by neurons innervating the muscone-responsive anteromedial glomeruli and also the human muscone receptor, OR5AN1. The current study documents the olfactory neural pathway in mice that senses and transmits musk signals from receptor to brain.

Topics: Animals; Colforsin; Cycloparaffins; Dose-Response Relationship, Drug; Fatty Acids, Monounsaturated; Gene Expression Regulation; Green Fluorescent Proteins; Humans; Membrane Potentials; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neural Cell Adhesion Molecules; Odorants; Olfactory Bulb; Olfactory Pathways; Olfactory Receptor Neurons; Proto-Oncogene Proteins c-fos; Receptors, Odorant; Smell; Xenopus laevis

To study the possible pathway of the effect of musk on brain disorder, distributing into the brain through blood brain barrier.. We used the musk ketone (muscone), a main composition of musk, to inject through the tail vein of the rats into the blood and took the brain and other organs at different times to make samples. Then gas chromatography was used to measure the distribution of muscone in the brain and other organs.. Muscone could pass through the normal rat's blood brain barrier into the brain and soon reached the highest peak and remained in higher concentration, and more slowly metabolized as compared with other organs.. Musk distributing into the brain through blood brain barrier provides the basis for its effect in treating brain disorders. Chromatography is an effective method to study the active composition of Chinese herbal medicine distributing through the blood brain barrier into the brain.

Topics: Animals; Blood-Brain Barrier; Brain; Chromatography, Gas; Cycloparaffins; Fatty Acids, Monounsaturated; Female; Injections, Intravenous; Male; Rats; Rats, Sprague-Dawley

As a highly valued ingredient of Chinese medicinal remedies, musk is used as a detoxification agent and for treating fever, inflammation and swelling, and pain. Muscone (3-methylcyclopentadecanone-1), an odoriferous secretion from the ventral glands of male musk deer, is believed to be the active ingredient. A small amount of muscopyridine is also found in the secretion from the ventral glands of male musk deer. Common counterfeit ingredients are musk xylene, musk ambrette, musk ketone, and diphenhydramine. An extraction/GC-MS protocol/data evaluation scheme was developed and applied to study allegedly musk-containing Musk-Tiger Bone Plaster preparations and musk pods (or grains) from Chinese medicine stores and an airport customs. The content of muscone in a specific sample was estimated based on the percentage of the amount recovered from the first extraction. No muscone or counterfeit ingredients were found in all musk pod (or grain) samples from the customs and in the majority of Musk-Tiger Bone Plaster preparations, while muscone (alone or with counterfeit ingredients) was found in most of the musk pod (or grain) collected from Chinese medicine stores.

Topics: Animals; Cycloparaffins; Drugs, Chinese Herbal; Fatty Acids, Monounsaturated; Gas Chromatography-Mass Spectrometry; Materia Medica; Molecular Structure; Odorants

The widespread use of synthetic musk fragrances and the resultant presence of these substances and their metabolites in the aquatic environment (as well as their accumulation in human adipose tissue) raises the question of whether musk fragrances display endocrine and in particular estrogenic activity. A variety of musk fragrances were tested using the E-screen assay. A statistically significant increase in proliferation rate of human MCF-7 breast cancer cells was detected for two nitro musks (musk xylene, musk ketone), a major metabolite of musk xylene ( p-amino-musk xylene), and the polycyclic musk fragrance AHTN. This indicates that these substances do, in fact, demonstrate estrogenic activity. Coincubation with the antiestrogen tamoxifen showed that the increase in proliferation rate by the musk fragrances is estrogen receptor-mediated. It must be noted, however, that the effective estrogenic strength and estrogenic potency were low compared to 17 b-estradiol. The naturally occurring fragrance muscone from the group of macrocyclic musk fragrances, a group of substances that have not yet been well characterized in respect to their toxicological properties, has also been shown to be weakly estrogenically active in vitro. E-screen analysis showed that the nitro musk metabolites o-amino musk xylene and 2-amino-MK, the macrocyclic musk fragrances ethylene brassylate, ethylene dodecandioate, and cyclopentadecanolide, are not estrogenically active.

Topics: Biological Assay; Breast Neoplasms; Cell Division; Cycloparaffins; Estrogens; Fatty Acids, Monounsaturated; Female; Humans; Odorants; Receptors, Estrogen; Tumor Cells, Cultured

By using benzene as the extraction solvent and the method of internal standard, Shexiang Baoxin Pills was directly analyzed for muscone by GC. The method showed very good stability and linearity. The rate of recovery was 101.4%.

Topics: Chromatography, Gas; Cycloparaffins; Drug Combinations; Drugs, Chinese Herbal; Fatty Acids, Monounsaturated; Materia Medica

In this paper liquid crystal b-PBPeB was adopted as the GC-stationary liquid phase. From the ether extract of musk, androsterone, muscone and cholesterol were identified. Comparative analysis of 13 samples of musk has proved this method to be useful in the quality evaluation of musk.

Topics: Androsterone; Animals; Cholesterol; Chromatography, Gas; Cycloparaffins; Fatty Acids, Monounsaturated; Odorants; Quality Control

The ether extract of musk, artificially bred musk and original musk reacted with 2,4-dinitrophenylhydrazine to form corresponding phenylhydrazones. The products were determined by HPLC. The conditions of quantitative analysis of muscone hydrazone and qualitative analysis of delta 5-androstene-3 beta-hydroxy-17-one hydrazone and 3 alpha-hydroxy-5 alpha-androstan-17-one hydrazone, such as the choice of chromatographic columns and mobile phase were studied. The results of standard curve and recovery experiment are satisfactory. Dual detection and MS were used to identify and analyse the purity of the chromatographic peak of muscone hydrazone. Experiments of addition of standards were used to confirm the peaks of delta 5-androstene-3 beta-hydroxy-17-one hydrazone and 3 alpha-hydroxy-5 alpha-androstan-17-one hydrazone.

Topics: Androsterone; Chromatography, High Pressure Liquid; Cycloparaffins; Dehydroepiandrosterone; Fatty Acids, Monounsaturated; Materia Medica

The general pharmacological properties of musk were studied. After the application of musk, inhibition of acetic acid-induced writhing, hemolytic effect and excitation of spontaneous uterine motility of rats, inhibition of spontaneous motility in isolated ileum of rabbits, and anti-inflammatory effects and potentiation of beta-adrenergic action in isolated preparations of guinea pig trachea were observed. These effects were not observed after application of muscone or allantoin, constituents of musk.

Topics: Allantoin; Analgesics; Animals; Anticonvulsants; Cycloparaffins; Digestive System; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Female; Guinea Pigs; Hemodynamics; In Vitro Techniques; Male; Mice; Motor Activity; Muscle, Smooth; Muscles; Peripheral Nerves; Rats; Rats, Inbred Strains; Species Specificity

Topics: Animals; Arvicolinae; Cycloparaffins; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Male; Mass Spectrometry

Topics: Chromatography, Gas; Cycloparaffins; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Gas Chromatography-Mass Spectrometry; Odorants

Topics: Cycloparaffins; Drug Contamination; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Lactones; Medicine, Chinese Traditional