Pharmaceutics
·
2025
·Vol. 17
·期 4
·497
·
IF 5.5
Zifan Qiao,Lihua Chen,Mubarak G. Bello,Shiyu Huang
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.
研究领域:
药剂学
·
分子动力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CURRENT NEUROVASCULAR RESEARCH
·
2025
·Vol. 22
·期 1
·70-85
·
IF 1.7
Ziteng Yang,Yuanqi Zuo,Guangyun Wang,Ning Wang
Introduction: The endothelial barrier is composed of brain microvascular endothelial cells (BMECs) and tight junction (TJ) proteins. Musk is a valuable ingredient in Traditional Chinese Medicine (TCM). It is used in the treatment of stroke because of its ability to induce resuscitation. The core component of musk is muscone. Previous studies have evidenced that muscone may be involved in the treatment of ischemic stroke (IS), but the underlying mechanism is still unclear. The main objective of this study was to explore the protective effect of muscone on OGD/R-induced endothelial barrier disruption and determine its underlying mechanism. Methods: OGD/R-induced damage to BMECs was assessed using the MTT and LDH assays. The apoptosis level in BMECs was determined using western blot and Hoechst staining. Western blot, immunofluorescence, and phalloidin staining were used to assess the expressions of TJ proteins and pathway proteins expression. A monolayer cell barrier was constructed using BMECs in vitro, and the permeability of the barrier was assessed by TEER as well as the transmissivity of sodium fluorescein. Molecular docking, DARTS, and CETSA were used to verify the regulatory effect of muscone on the pathway. Results: Muscone reduced OGD/R-induced apoptosis of BMEC cells, inhibited the degradation of TJ proteins, promoted the coherent expression of ZO-1 on the membrane, and restored TEER. Mechanistic studies showed that H-89 reversed the promoting effects of muscone on pathway proteins and promoted the disassembly of the actin cytoskeleton, which, in turn, promotes BMEC apoptosis and TJ protein degradation, ultimately disrupting the endothelial barrier. Discussion: The inhibition of BMEC apoptosis and improvement of endothelial barrier damage by muscone may be an important mechanism for treating ischemic stroke. Conclusion: We demonstrated that muscone could reduce OGD/R-induced hyperpermeability of the brain endothelial barrier by activating the PKA/RHOA/MLC pathway.
研究领域:
神经科学
·
药理学
·
中医中药
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-16
·
IF 14.7
Wu Xin,Yu Yuanhuan,Wang Meiyan,Dai Di,Yin Jianli,Liu Wenjing,Kong Deqiang,Tang Shasha,Meng Meiyao,Gao Tian,Zhang Yuanjin,Zhou Yang,Guan Ningzi,Zhao Shangang,Ye Haifeng
Gene therapies provide treatment options for many diseases, but the safe and long-term control of therapeutic transgene expression remains a primary issue for clinical applications. Here, we develop a muscone-induced transgene system packaged into adeno-associated virus (AAV) vectors (AAV MUSE ) based on a G protein-coupled murine olfactory receptor (MOR215-1) and a synthetic cAMP-responsive promoter (P CRE ). Upon exposure to the trigger, muscone binds to MOR215-1 and activates the cAMP signaling pathway to initiate transgene expression. AAV MUSE enables remote, muscone dose- and exposure-time-dependent control of luciferase expression in the livers or lungs of mice for at least 20 weeks. Moreover, we apply this AAV MUSE to treat two chronic inflammatory diseases: nonalcoholic fatty liver disease (NAFLD) and allergic asthma, showing that inhalation of muscone—after only one injection of AAV MUSE —can achieve long-term controllable expression of therapeutic proteins (ΔhFGF21 or ΔmIL-4). Our odorant-molecule-controlled system can advance gene-based precision therapies for human diseases.
研究领域:
基因治疗
·
药理学
·
分子生物学
·
慢性病管理
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
·
2025
·Vol. 66
·期 5
·21-21
·
IF 4.7
Xianyang Liu,Hangjia Zuo,Chao Wu,Na Li,Qian Zhou,Fan Cao,Baorui Chu,Shuhao Zeng,Hui Feng,Yakun Wang,Fengyang Lei,Ke Hu,Shengping Hou
Purpose:Uveitis is an immune-mediated ocular disorder that poses a significant threat to vision, particularly among young and middle-aged adults. The treatment of uveitis is complicated by the presence of the blood-retinal barrier (BRB), which restricts the passage of large molecular drugs into the eye, thus limiting effective therapeutic options. The primary objective of this study is to identify a novel therapeutic agent capable of treating uveitis and explore its underlying mechanism.Methods:In this study, we used a mouse model of experimental autoimmune uveitis (EAU) induced by interphotoreceptor retinoid-binding protein (IRBP) and lipopolysaccharide (LPS) and interferon-gamma (IFN-γ)-induced inflammatory BV2 cells. Evans blue and fundus fluorescein angiography (FFA) experiments were performed to evaluate the destruction of BRB. Silt lamp and hematoxylin and eosin (H&E) staining were conducted to evaluate the inflammatory response. In vivo proteomics and Western blot were carried to investigate the underlying mechanisms.Results:Our study reveals that Muscone significantly alleviates EAU and restores the integrity of BRB. Moreover, Muscone treatment markedly downregulated inflammatory factors within the retinas and BV2 cells. In vivo proteomic combined with liquid chromatography-mass spectrometry (LC-MS) has elucidated that Muscone exerts its anti-inflammatory effects by modulating the PI3K-AKT signaling pathway. Moreover, by using LY294002 to specifically inhibit PI3K, we observed a marked decrease in inflammatory phenotype and BRB destruction of EAU.Conclusions:In summary, this study establishes the protective efficacy of Muscone against the progression of EAU and provides insights into the molecular mechanisms responsible for its therapeutic action.
研究领域:
免疫学
·
眼科学
·
药理学
·
分子生物学
·
神经炎症
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2025
·
IF 3.9
Gao Minjie,Yang Zongmei,Song Senchuan,Liu Xigui,Wang Fei
A series of Pd/N-doped graphene catalysts were designed for the efficient and highly selective synthesis of muscone through the hydrogenation of 3-methylcyclopentadecenone (XT). The catalysts were characterized using FT-IR, BET, XPS, XRD, Raman and SEM–EDS. All results indicated the uniform dispersion of Pd on NG. By optimizing reaction conditions, the hydrogenation of XT achieved a high yield and selectivity of muscone, producing a 99% yield at 2 MPa H 2 and 90 °C in 10 h using a 10 wt% Pd/N-doped graphene catalyst functionalized with melamine (Pd/NmG), which significantly outperformed conventional Pd/C catalysts. Graphical abstract
研究领域:
催化化学
·
有机合成
·
材料科学
·
化学工程
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
Separations
·
2023
·Vol. 10
·期 4
·231
·
IF 2.6
Chang-Seob Seo,Hyeun-Kyoo Shin
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 C18column 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.
研究领域:
中药学
·
分析化学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）