Search Results (10)

Musk, a precious traditional Chinese medicine, is secreted by the male forest musk deer (Moschus berezovskii). The gut microbiota plays an essential role in host metabolism, yet its relationship with musk traits remains poorly understood. Here, 16S rRNA sequencing of 89 fecal samples was integrated with musk quality (color and moisture) and yield data to investigate how fecal bacterial communities influence these traits. Distinct microbial consortia were associated with musk traits. Aromatic and sulfur-metabolizing taxa (norank_f_Actinomycetaceae, Nocardioides, Rhodococcus, and Mailhella) were associated with degradation of aromatic compounds and sulfur-containing amino acids, potentially contributing to muscone and other bioactive aroma components. Short-chain fatty acid (SCFA) producing taxa (Blautia, Phascolarctobacterium, Oscillospiraceae UCG-005, unclassified_f_Lachnospiraceae, Anaerovorax, Parabacteroides, Prevotellaceae_UCG-003, Christensenellaceae R-7 group, and Bacteroides) were capable of fiber decomposition and may supply energy for steroid synthesis via SCFAs, favoring high-quality musk formation. Ketogulonicigenium vulgare was linked to anti-inflammatory polypeptides and steroids. These potential indicators may facilitate early selection of high-yielding deer, inform probiotic/prebiotic interventions, and support dietary strategies to improve gut health and musk productivity, thereby reducing poaching and promoting the sustainable conservation of this endangered species. Full article

Background: The NLRP3 inflammasome drives pathological inflammation in various diseases. PINK1/Parkin-associated mitophagy serves as a critical negative regulator of NLRP3 activation, yet pharmacological enhancers remain scarce. Muscone, a natural macrocyclic ketone with blood–brain barrier permeability, exhibits potent anti-inflammatory properties; however, its mechanistic role within the NLRP3-mitophagy axis remains undefined. Methods: LPS/ATP-stimulated macrophages were employed to assess stage-specific effects of muscone on NLRP3 priming (NF-κB signaling, NLRP3, and pro-IL-1β expression) and activation (ASC oligomerization, ASC–pro-caspase 1 complex formation, and IL-1β secretion). RNA sequencing and bioinformatic analysis were performed for pathway enrichment. Mitophagy was characterized by MitoSOX Red staining for mt-ROS detection, electron microscopy, Western blotting of LC3B-II in isolated mitochondria and PINK1 and Parkin in whole-cell lysates, and live-cell mitochondria–lysosome tracking. In vivo protective efficacy was assessed in an LPS-induced endotoxemia mouse model. Results: Muscone dose-dependently suppressed both the priming and activation stages of the NLRP3 inflammasome, maximally reducing IL-1β secretion by ~60% at 50 μM. Mechanistically, muscone amplified PINK1/Parkin-associated mitophagy, scavenging excessive mt-ROS and attenuating NLRP3 activation. These effects were corroborated by RNA-seq and comprehensive functional assays. In vivo, muscone (30 mg/kg) significantly improved survival (3/8 mice alive at 98 h when all LPS controls had died; 2/8 survived to the 132-h endpoint), with concomitant enhancement of mitophagy markers in peritoneal macrophages. Conclusions: Muscone functions as a PINK1/Parkin-associated mitophagy enhancer that maintains mitochondrial quality control during NLRP3-driven inflammatory responses. Its unique macrocyclic structure and blood–brain barrier permeability provide a promising scaffold for developing therapeutics against inflammatory disorders associated with NLRP3 inflammasome activation. Full article

Forest musk deer (Moschus berezovskii) are endangered ungulates, and captive breeding has been effective for its ex situ conservation and sustainable medicinal musk utilization in traditional Asian traditional medicine. Methods of focal sampling and all-occurrence recording were used to evaluate the intensity of stereotypic behaviors and personality traits in 25 captive male forest musk deer. Additionally, musk secretion was monitored in this study, and muscone content was measured with gas chromatography, thereby analyzing the interrelationship between their stereotypic behavior, personality traits, and musk secretion. The results revealed no significant differences in stereotypic behaviors or personality traits across age groups (p > 0.05). Individuals with stereotypic behaviors showed a tendency toward secreting higher amounts of musk and muscone content compared to those without stereotypic behaviors, although these differences were not statistically significant (p > 0.05). Furthermore, the exploratory behavior level and active behavior level were not significantly correlated with the secretion amount of musk. However, both the exploratory behavior level and active behavior level exhibited significant positive correlations with muscone content (p < 0.05). These findings provide valuable insights for the breeding, welfare, and ex situ conservation of endangered forest musk deer. Full article

Objective: Muscone (MUS), a primary active component of musk, is known for its significant pharmacological properties. However, its clinical application is limited due to poor water solubility and moderate stability. This study aims to address these limitations by encapsulating MUS within biodegradable γ-cyclodextrin metal–organic frameworks (γ-CD-MOFs) using a solvent-free method to enable oral MUS delivery by improving solubility and stability, pending in vivo validation. Methods: MUS was encapsulated into γ-CD-MOFs using a solvent-free method, achieving an optimal loading rate of 10.6 ± 0.7%. Comprehensive characterization was performed using scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). Biocompatibility was assessed using RAW264.7 cells, and molecular dynamics simulations were conducted to study the interactions between MUS and γ-CD-MOFs. Results: Characterization techniques confirmed the successful encapsulation of MUS into γ-CD-MOFs. Biocompatibility studies revealed no cytotoxicity, indicating that the system is safe for drug delivery. Molecular dynamics simulations showed that MUS preferentially occupies the large spherical cages of γ-CD-MOFs, driven by non-covalent interactions. Solubility tests and in vitro release studies demonstrated that the solubility of MUS was improved after encapsulation within γ-CD-MOFs. Stability assessments indicated that γ-CD-MOFs significantly enhanced the thermal and photostability of MUS, with high residual amounts remaining under various storage conditions. Conclusions: This study demonstrates the potential of γ-CD-MOFs to solidify MUS, enhance its solubility, and improve its storage stability, providing a foundation for its future use in pharmaceutical applications. Full article

Background/Objectives: Musk is a widely used traditional Chinese medicine derived from musk deer that has the pharmacological effects of “activating blood dredging collateral” and “consciousness-restoring resuscitation”. Its volatile compounds (VCs) play a key role in these effects, especially in the treatment of stroke. However, there have been no comprehensive studies on the differences in the VCs of these different musks. This study investigated the differences in the VCs of different musks and the potential targets and mechanisms of action for stroke. Methods: Different musks were studied via GC–MS, and the potential targets and mechanisms of VCs associated with stroke were investigated using network pharmacology. Results: A total of 99 VCs were detected in 79 musk samples. The most important VCs of different colours and forms were muscone, phenol, acetic acid, and isovaleric acid. Further study revealed that the change in organic acids and ketones was the cause of the significant difference between white musk and other types of musk. In addition, network pharmacological analyses identified 180 potential targets of the major volatile compounds of musk associated with stroke, and five key targets (SRC, EGFR, ESR1, PTGS2, and DRD2). Enrichment analysis showed that these key targets play an important role in neural related pathways. The molecular docking results confirmed that the key targets can effectively bind with the main VCs (muscone and phenol). Conclusions: These findings provide valuable insights into the distinct volatile compositions of various types of musk and underscore the significant potential of volatile compounds (VCs) in stroke treatment. Full article

The impact of organometallic chemistry on the terpene field only really blossomed in the 1960s and 1970s with the realisation that carbon–carbon bond formation under mild conditions could be achieved by using nickel or iron carbonyls as synthetic reagents. Concomitantly, the development of palladium derivatives capable of the controlled coupling of isoprene units attracted the attention of numerous highly talented researchers, including future Nobel laureates. We discuss briefly how early work on the syntheses of simple monoterpenes soon progressed to sesquiterpenes and diterpenes of increasing complexity, such as humulene, flexibilene, vitamin A, or pheromones of commercial value, in particular those used in perfumery (muscone, lavandulol), or grandisol and red scale pheromone as replacements for harmful pesticides. As the field progressed, there has been more emphasis on developing organometallic routes to enantiopure rather than racemic products, as well as gaining precise mechanistic data on the transformations, notably the course of metal-promoted molecular rearrangements that have long been a feature of terpene chemistry. We note the impact of the enormously enhanced analytical techniques, high-field NMR spectroscopy and X-ray crystallography, and their use to re-examine the originally proposed structures of terpenes and their organometallic derivatives. Finally, we highlight the very recent ground-breaking use of the crystalline sponge method to acquire structural data on low-melting or volatile terpenes. The literature cited herein covers the period 1959 to 2023. Full article

Gongjindan (GJD) is a traditional Korean medicine consisting of four herbal medicines and two animal-derived medicines, and is taken as a tonic in Republic of Korea. In this study, the goal was to develop and validate a simultaneous analytical method to quantify eight compounds in commercially available GJD samples using high-performance liquid chromatography (HPLC), ultra-performance liquid chromatography with tandem mass spectrometry (UPLC–MS/MS), and gas chromatography with tandem mass spectrometry (GC–MS/MS) systems. In HPLC and UPLC–MS/MS, seven components (gallic acid, 5-(hydroxymethyl)furfural, morroniside, loganin, nodakenin, decursin, and decursinol angelate) were separated and quantified using a distilled water–acetonitrile mobile phase system on a Capcell Pak UG80 C₁₈ column and an Acquity UPLC BEH C18 column, respectively. Muscone was quantified using GC–MS/MS. The developed assays were validated by evaluating the linearity, limit of detection, limit of quantitation, recovery, and precision. In the regression equations of all compounds, the coefficient of determination was ≥0.9917, showing good linearity. The recovery was 93.70–108.17%, and the relative standard deviation values in the precision test were all <1.50%. Using the developed analysis methods, GJD samples were determined to contain the eight target compounds in concentrations from non-detected to 10.75 mg/g. The analytical assays developed and validated in this study can be used to obtain data for the quality control of commercially available GJDs and for the further expansion of efficacy and clinical studies. Full article

Claudin 5 is one of the major proteins of tight junctions and is responsible for cerebrovascular integrity and BBB function. Muscone and (+)-borneol is the major ingredient of moschus and borneolum, respectively, with antioxidative and anti-inflammatory activities. This study investigated whether muscone and (+)-borneol combination protected claudin 5 by targeting ROS-mediated IL-1β accumulation. Muscone and (+)-borneol reduced cerebral infarct volume and cerebrovascular leakage with claudin 5 protection in mice after stroke, largely due to inhibiting ROS accumulation and inflammatory infiltrate of microglia. Muscone reduced ROS and then blocked the CaN/Erk1/2 pathway to decrease IL-1β release, while (+)-borneol removed mitochondrial ROS and attenuated the SDH/Hif-1α pathway to inhibit IL-1β transcription, thereby jointly reducing IL-1β production. Accumulated IL-1β disrupted cAMP/CREB activation and attenuated transcriptional regulation of claudin 5. Muscone and (+)-borneol combination cooperatively protected BBB function by blocking IL-1β-mediated cAMP/CREB/claudin 5 cascades. Mutation of Ser133 site of CREB or knockdown of claudin 5 weakened the effects of muscone and (+)-borneol on upregulation of TEER value and downregulation of FITC-dextran permeability, suggesting that targeting CREB/claudin 5 was an important strategy to protect vascular integrity. This study provided ideas for the studies of synergistic protection against ischemic brain injury about the active ingredients of traditional Chinese medicines (TCMs). Full article

Cisplatin, one of the most common antitumor agents, is widely applied to treat various cancerous diseases and is included in the World Health Organization Model List of Essential Medicines. Cisplatin therapy is used to treat 10–20% of all cancerous cases, and its cure rate is especially high in testicular cancer (over 90%). However, a major side effect of this anticancer drug is nephrotoxicity, limiting treatment effect and reducing the quality of life in cancer patients. Muscone, an odoriferous constituent of musk, was confirmed to inhibit cisplatin-induced LLC-PK1 kidney proximal tubule cell death in a dose-dependent manner. In term of renal protective mechanism, muscone inhibited cisplatin oxidative toxicity by decreasing reactive oxygen species (ROS) level and stimulating HO-1 expression. Muscone also exerted anti-inflammation effect through inhibition of p38 phosphorylation. Furthermore, muscone mitigated cisplatin-induced apoptosis in LLC-PK1 cells via both intrinsic and extrinsic pathways by inhibiting pro-apoptotic protein Bax expression, and cleaved caspase-3, 7, and 8; and increase of anti-apoptotic protein Bcl-2 level. In addition, the anti-apoptotic effect of muscone also was enhanced by preventing p53 expression and its phosphorylation. Our study showed that muscone may be a potential protective agent against cisplatin-induced nephrotoxicity. Full article

The present study evaluated the anti-inflammatory effects of 4-methylcyclopentadecanone (4-MCPC) on edema models in mice and aimed to determine the safety of 4-MCPC after acute exposure. The acute toxicity of 4-MCPC was evaluated by oral administration to rats of single doses of 0, 5, 50, 500 and 5000 mg/kg. Toxic symptoms were observed for 14 days. The anti-inflammatory activity was evaluated in xylene-induced mouse ear edema and carrageenan-induced mouse paw edema. The animals were treated with 4-MCPC once every day for seven consecutive days. Edema index, % inhibition, IL-1β, TNF-α, PGE₂ and MPO levels in paws were detected after the treatment with xylene or carrageenan. Our results indicated that the LD₅₀ value of 4-MCPC in rats is greater than 5000 mg/kg. The ED₅₀ of 4-MCPC in xylene-induced mouse ear edema model was 7.5 mg/kg. 4-MCPC (8 or 16 mg/kg) remarkably inhibited carrageenan-induced mouse paw edema. Further study revealed that 4-MCPC treatment also decreased IL-1β, TNF-α, PGE₂ and MPO levels in mice paws. Intragastric administration of 4-MCPC exhibited more significant anti-inflammatory activity than muscone at a dose of 16 mg/kg. Taken together, our results suggest that 4-MCPC has potent anti-inflammatory activity and the mechanisms might be related to the decreases of the levels of IL-1β, TNF-α, PGE₂ and MPO in inflamed paws. Full article