Antioxidants
·
2022
·Vol. 11
·期 12
·2406
·
IF 7.675
Xiang-Rong Cheng,Bu-Tao Yu,Jie Song,Jia-Hui Ma,Yu-Yao Chen,Chen-Xi Zhang,Piao-Han Tu,Mitchell N. Muskat,Ze-Gang Zhu
Food-derived electrophilic compounds (FECs) are small molecules with electrophilic groups with potential cytoprotective effects. This study investigated the differential effects of six prevalent FECs on colitis in dextran sodium sulfate (DSS)-induced mice and the underlying relationship with molecular characteristics. Fumaric acid (FMA), isoliquiritigenin (ISO), cinnamaldehyde (CA), ferulic acid (FA), sulforaphane (SFN), and chlorogenic acid (CGA) exhibited varying improvements in colitis on clinical signs, colonic histopathology, inflammatory and oxidative indicators, and Nrf2 pathway in a sequence of SFN, ISO > FA, CA > FMA, CGA. Representative molecular characteristics of the “penetration-affinity–covalent binding” procedure, logPvalue, Keap1 affinity energy, and electrophilic index of FECs were theoretically calculated, among which logPvalue revealed a strong correlation with colitis improvements, which was related to the expression of Nrf2 and its downstream proteins. Above all, SFN and ISO possessed high logPvalues and effectively improving DSS-induced colitis by activating the Keap1–Nrf2 pathway to alleviate oxidative stress and inflammatory responses.Keywords:electrophilic compound;colitis;molecular characteristic;logP
研究领域:
药理学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2022
·
IF 5.518
Shiyu Luo,Yanping He,Linhua Zhu,Tian Si,Yanlin Sun
Core oils’ properties are significant for the microencapsulation process. 12 representative single componential core oils with different chemical structures , logP , solubility, interfacial tension (IFT) and viscosity were specially selected to fabricate melamine-formaldehyde (MF) microcapsules. Afterward, the effect of core oils’ properties on the performance of microcapsules was investigated. It was found that the morphology, the average particle sizes (7.83 µm∼27.06 µm), the encapsulation efficiencies (47.35 ± 3%∼92.86 ± 4%), zeta potentials (−52.37 ± 2.97 mV∼−65.03 ± 0.79 mV) and the rupture forces (0.28 ± 0.20mN∼0.82 ± 0.3mN) of microcapsules were influenced by core oils’ properties. Further comprehensive analysis indicated that logP≥ 1.66 and the solubility≥ 0.055 mL 3 /g were the premises for the successful encapsulation processes. Moreover, by increasing logP, IFT and viscosity, the size of microcapsules increased; as microcapsules size increased, the release rate decreased; the high IFT and the solubility increased the encapsulation efficiency of microcapsules; the mechanical property was influenced by logP. This work provided to use logP as the criterion to predict the encapsulation work, which hasn’t been studied before; and the correlations between microcapsules’ various performances and core oils’ properties were initially established. This work was meaningful since logP was used as a clear criterion to select core oils for encapsulation work and core oils’ properties were used to predict the application performances of microcapsules.
研究领域:
材料科学
·
化学工程
✓ 已验证
产品关联
DOI
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Xin Zhao,Ting Hao,Jianmin Sang,Miaomiao Xia,Linxi Li,Ren-shan Ge,Congde Chen
Dithiocarbamates have been widely used in various industrial applications, such as insecticides (ferbam) or drug (disulfiram). This study explored the inhibitory effects of dithiocarbamates on human and rat gonadal 3β-hydroxysteroid dehydrogenases (3β-HSD) and investigated the structure-activity relationship and mechanistic insights. The inhibitory activity of six dithiocarbamates and thiourea on the conversion of pregnenolone to progesterone was evaluated using human KGN cell and rat testicular microsomes, with subsequent progesterone measurement using HPLC-MS/MS. The study found that among the tested compounds disulfiram, ferbam, and thiram exhibited significant inhibitory activity against human 3β-HSD2 and rat 3β-HSD1, with ferbam demonstrating the highest potency. The mode of action for these compounds was characterized, showing mixed inhibition for human 3β-HSD2 and mixed/noncompetitive inhibition for rat 3β-HSD1. Additionally, it was observed that dithiothreitol dose-dependently reversed the inhibitory effects of dithiocarbamates on both human and rat gonadal 3β-HSD enzymes. The study also delved into the penetration of these dithiocarbamates through the human KGN cell membrane and their impact on progesterone production, highlighting their potency in inhibiting human 3β-HSD2. Furthermore, bivariate correlation analysis revealed a positive correlation of LogP (lipophilicity) with IC 50 values for both enzymes. Docking analysis indicated that dithiocarbamates bind to NAD + and steroid-binding sites, with some interactions with cysteine residues. In conclusion, this study provides valuable insights into the structure-activity relationship and mechanistic aspects of dithiocarbamates as inhibitors of human and rat gonadal 3β-HSDs, suggesting that these compounds likely exert their inhibitory effects through binding to cysteine residues.
研究领域:
药理学
·
毒理学
·
内分泌学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）