CHEMICAL & PHARMACEUTICAL BULLETIN
·
2011
·Vol. 59
·期 8
·1045-1047
·
IF 1.507
Yibing Guo,Xiaohong Li,Yahong Zhao,Yongxing Si,Hui Zhu,Yumin Yang
Salidroside is a phenylpropanoid glycoside isolated from Rhodiola rosea L., a traditional Chinese medicinal plant, and has displayed a broad spectrum of pharmacological properties. In this paper, two analogues were prepared with the glucosamine and N-acetylglucosamine as glycosyl donor, 2-(4-hydroxyphenyl)ethanol as glycosyl acceptor. The effects of them over PC12 cell model exposed to hypoglycemia and serum limitation were assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Flow Cytometry and Western blot analysis.
研究领域:
药理学
·
神经生物学
✓ 已验证
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2019
·Vol. 40
·期 8
·1106-1118
·
IF 4.01
Zhao Kai-jing,Chen Yang,Hong Shi-jin,Yang Yi-ting,Xu Jiong,Yang Han-yu,Zhu Liang,Liu Ming,Xie Qiu-shi,Tang Xian-ge,Yang Ting-ting,Zhou Ya-qian,Liu Li,Liu Xiao-dong
Cinnamic acid and its analogues (pyragrel and ozagrel) undergo chain-shortened (β-oxidative) and reductive metabolism on acyl side chain. In this study, we characterized the β-oxidative and reductive metabolism on acyl side chain of cinnamic acid and its analogues using primary rat hepatocytes, hepatic mitochondrial, and microsomal systems. A compartmental model including parent compounds and metabolites was developed to characterize in vivo β-oxidative and reductive metabolism following an intravenous dose of parent compounds to rats. The fitted total in vivo clearance values were further compared with the in vitro values predicted by the well-stirred model. We showed that hepatic microsomal CYP450s did not catalyze β-oxidative or reductive metabolism of the three compounds. Similar to β-oxidation of fatty acids, β-oxidative metabolism on their acyl side chain occurred mainly in mitochondria, which was highly dependent on ATP, CoA and NAD + . Fatty acids and NADH inhibited the β-oxidative metabolism. Reductive metabolism occurred in both mitochondria and microsomes. Reduction in mitochondria was ATP-, CoA-, and NAD(P)H-dependent and reversible, which was suppressed by enoyl reductase inhibitor triclosan. Reduction in microsomes was ATP-, CoA-, and NADPH-dependent but little affected by triclosan. Both plasma concentrations of β-oxidative metabolites and reductive metabolites were successfully fitted using the compartmental model. The estimated total in vivo clearance values were consistent with those predicted from hepatocytes and organelles, implicating significance of in vitro kinetics. These findings demonstrate the roles of hepatic mitochondria and microsomes in β-oxidative and reductive metabolism on acyl side chain of cinnamic acid and its analogues along with their metabolic characteristics.
研究领域:
药理学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2021
·
IF 4.384
Kunkun Guo,Xin Wang,Baolin Huang,Xiaoyun Wu,Shuimei Shen,Zimin Lin,Jie Zhao,Zheng Cai
Gastrodin is the main active constituent of Tianma, a famous traditional Chinese herbal medicine. Our previous research has found that gastrodin is absorbed rapidly in the intestine by the sodium-dependent glucose transporter 1 (SGLT1). In the current report, gastrodin is the best glycoside compound absorbed via the glucose transport pathway. This study aimed to investigate the effect of the slight difference in chemical structure on the drug intestinal absorption via the glucose transport pathway. Traditional biopharmaceutical and computer-aided molecular docking methods were used to evaluate the intestinal absorption characteristics of three gastrodin analogues, namely, salicin , arbutin and 4-methoxyphenyl-β-D-glucoside (4-MG). The oil–water partition coefficient (log P ) experiments showed that the log P values of the gastrodin analogues followed the order: 4-MG > salicin > arbutin. In vitro Caco-2 cell transport experiments demonstrated that the apparent permeability coefficient ( P app ) value of arbutin was higher than those of salicin and 4-MG. In situ single-pass intestinal perfusion experiments showed that the absorption of arbutin and 4-MG was better than that of salicin and that the absorption of the three compounds in the colon was lower than that in the small intestine. Quantitative real-time polymerase chain reaction results confirmed that the SGLT1 mRNA expression in the small intestine of rats was obviously higher than that in the colon of rats. In vivo pharmacokinetic experiments demonstrated that the oral bioavailability of salicin was lower than those of arbutin and 4-MG. In vitro and in vivo experiments showed that glucose or phlorizin (SGLT1 inhibitor) could decrease the intestinal absorption of the three compounds. Contrary to the above biopharmaceutical experiments, the computer-aided molecular docking test showed that the affinity of salicin to the v SGLT receptor was stronger than those of arbutin and 4-MG. In conclusion, the SGLT1 can facilitate the intestinal absorption of salicin, arbutin and 4-MG, and the slight difference in chemical structure can affect absorption.
研究领域:
药理学
·
生物医学工程
·
中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2013
·
IF 1.977
Hua Li,Juanjuan Pu,Yi Wang,Chuang Liu,Jie Yu,Tao Li,Ruiqiang Wang
The interactions between Trypsin and bifendate (DDB) or analogs (I, II and III) were investigated by fluorescence, UV–visible absorption, resonance light scattering, synchronous fluorescence and 3D spectroscopy under mimic physiological conditions. The results revealed that DDB and analogs caused the fluorescence quenching of Trypsin by the formation of DDB/I/II/III–Trypsin complex. The quenching and energy transfer mechanisms were discussed. The binding constants and thermodynamic parameters at three different temperatures were obtained. The hydrophobic interaction was the predominant intermolecular forces to stabilize the complex. Results showed that DDB was the stronger quencher and bound to Trypsin with higher affinity than other three analogs.
研究领域:
生物化学
·
药物化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2023
·
IF 9.8
Linfeng Peng,Hui Li,Wangjun Lin,Tangfu Xiao,Jianqiao Wang,Jinfeng Tang,Nana Wang
Antimony (Sb) pollution in water has attracted extensive attention due to the biotoxicity of Sb. Secondary iron minerals readily sorb heavy metal(loid)s and critically affect their cycling in terrestrial environments. However, compared with synthetic pure iron mineral phases, little is known about the Sb sorption behavior and mechanism on natural secondary iron minerals (nSIMs) composed of various mineral phases. In this study, sorption experiments were conducted to investigate the Sb(V) sorption properties of nSIMs from an acid mine drainage zone and corresponding single-component synthetic secondary mineral phases and to compare their sorption behaviors and mechanisms. Spectroscopic analyses indicated that the nSIMs structurally resembled a hybrid of schwertmannite , jarosite and goethite . Sb(V) sorption on nSIMs, schwertmannite, goethite and jarosite was controlled by chemisorption , with maximum Sb(V) sorption capacities of 217.39, 233.65, 32.17 and 35.61 mg/g, respectively. nSIMs demonstrated an excellent Sb(V) sorption capacity equivalent to or greater than that of the single-component phases. XRD, FTIR and Raman analyses indicated that Sb(V) was immobilized on nSIMs mainly through ion exchange with structural SO 4 2− and complexation interactions with surface Fe O and Fe OH; then, an Fe O Sb surface phase formed during the dissolution and further transformation of schwertmannite and jarosite into goethite. SEM revealed that nSIMs had an advantage in surface microstructure over the single components. These results suggested that despite the similarities in Sb(V) binding mechanism between nSIMs and schwertmannite, nSIMs might be more reactive for Sb(V) sorption since the nSIM components could mutually influence each other and facilitate Sb(V) sorption. This research suggests that nSIMs have potential for Sb(V) removal and helps elucidate the environmental behavior of Sb(V) associated with nSIMs.
研究领域:
环境科学
·
地球化学
✓ 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）