佛手苷內(nèi)酯作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetBergaptenCat. No.: HY-N0370CAS No.: 484-20-8分式: CHO分量: 216.19作靶點(diǎn): Cytochrome P450; Autophagy作通路: Metabolic Enzyme/Protease; Autophagy儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 10 mg/mL (46.26 mM; Need ultrasonic)H2O : 0.1 mg/mL (insoluble

2、)SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)備液1 mM 4.6256 mL 23.1278 mL 46.2556 mL5 mM 0.9251 mL 4.6256 mL 9.2511 mL10 mM 0.4626 mL 2.3128 mL 4.6256 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇

3、適當(dāng)?shù)娜芙獍?。以下溶解案都?qǐng)先按照 In Vitro 式配制澄清的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 1 mg/mL (4.63 mM); Suspended solution; Need ultrasonic此案可獲得 1 mg/mL (4.63 mM) 的均勻懸

4、濁液，懸濁液可于服和腹腔注射。以 1 mL 作液為例，取 100 L 10.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 1 mg/mL (4.63 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 1 mg/mL (4.63 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個(gè)以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 10.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L

5、油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Bergapten種天然的抗炎劑和抗腫瘤劑。Bergapten抑制和CYP 亞型。IC & Target CYP1體外研究 There is decreased N-acetyltransferase (NAT) activity in SC-M1 cells at concentrations of Bergapten (5-Methoxypsoralen, 5-MOP) from 0.05 mM to 25 mM, but no obvious dose-dependent effect is found between the

6、sedoses (r=0.5687). In COLO 205 cells, there is decreased NAT activity at low doses of Bergapten (0.05 mM and 0.5 mM)and increased NAT activity at a high dose (50 mM). Bergapten induces a dosedependent effect in our experimentalconcentrations on COLO 205 cells (r=0.8912); a promotion effect at a hig

7、her dose (50 mM) and an inhibition effect atlower doses (0.05-0.5 mM), while the concentrations 5-25 mM has no significant difference compared with thecontrol regimen1. Bergapten (5-Methoxypsoralen) exerts inhibitory effects on diabetes-related osteoporosis via theregulation of the PI3K/AKT, JNK/MAP

8、K and NF-B signaling pathways in osteoprotegerin knockout mice. Bergaptenhas also been shown to significantly inhibit the production of pro-inflammatory cytokines. Bergapten exhibits theability to significantly inhibit RANKL-RANK signaling transduction, and to suppress the activation of the PI3K/AKT

9、,JNK/MAPK and NF-B signaling pathways, thus protecting trabecular structure and decreasing osteoclastogenicdifferentiation2.體內(nèi)研究 The metabolic activity of NAT of the rat colon is higher than that of the stomach, and Bergapten (5-Methoxypsoralen,5-MOP) causes a decrease of AF concentration in the sto

10、mach at the 24-h time-period. The concentrations of AAF inthe stomach and colon are low. Although DMSO (solvent) influenced the metabolism of AAF, compared with thecontrol regimen, Bergapten still causes an increase in the further metabolism of AAF, and a decrease in theconcentration of AAF in the s

11、tomach at 24 h, and in the colon during the 24- to 72-h time-period1.PROTOCOLCell Assay 1 The human colon adenocarcinoma cell line (COLO 205, from a 70-year-old male Caucasian) sre placed into 75-cm2tissue culture flasks and grown in RPMI1640 medium, supplemented with 10% fetal bovine serum, contain

12、ingpenicillin and streptomycin (100 g/mL) and 1 mM glutamine, at 37C in a humidified atmosphere of 5% CO2 and95% O2. The human stomach adenocarcinoma cell line are placed into 75-cm2 tissue culture flasks and grown inRPMI 1640 medium, supplemented with 10% fetal bovine serum, containing penicillin a

13、nd streptomycin (100 g/mL)and 1 mM glutamine, at 37C in a humidified atmosphere of 5% CO2 and 95% O2. SC-M1 and COLO 205 cells aretreated with different concentrations of Bergapten (0.05, 0.5, 5, 10, 25 and 50 mM) and incubated for 72 h for thedose-effect study of Bergapten on NAT activity. To deter

14、mine the time-course effect of 0.5 mM Bergapten on NATactivity, the cells are incubated at 37AC and harvested at 12, 24, 48 and 72 h, respectively. Bergapten is dissolved inDMSO and the final concentration of vehicle is 0.1%. Only DMSO (solvent) is added for the control regimen1.MCE has not independ

15、ently confirmed the accuracy of these methods. They are for reference only.Animal Rats1Administration 1 Seventy-two male Sprague-Dawley (SD) rats, weighing approximately 200 g are used. A total of 72 rats are subjectedto 3 different regimens, each regimen divided into 4 groups with 6 rats in each gr

16、oup. Gastric intubation is used fordelivery of the test compounds into each animal. The first regimen received 1 mL Bergapten (dissolved in DMSO) at adose of 0.5 mmol per Kg of body weight. Regimen 2, the control regimen, received only 1 mL solvent (DMSO),Page 2 of 3 www.MedChemEwithout any Bergapte

17、n. Regimen 3, the contrast regimen, received nothing at that time. Twenty-four h later, all of therats from the 3 regimens received 1mL AF (dissolved in DMSO) at a dose of 0.3 mmol per Kg of body weight. Thegroups are divided by different collecting time: 12, 24, 48 and 72 h after AF administration,

18、 and then the animals aretransferred to individual metabolism cages. The stomachs and the colons of the rats from each regimen are collectedand are immediately extracted with ethyl acetate/methanol (95:5). The solvent is evaporated and the residueredissolved in methanol and assayed for AF and AAF by HPLC.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Lee YM, et al. Effects of 5-methoxypsoralen (5-MOP) on