BAY-7598-DataSheet-MedChemExpress

常用染料、电泳缓冲液、凝胶加样液和杂交液的配制：1.1%溴酚蓝（bromophenol blue）:加1g水溶性钠型溴酚蓝于100ml水中，搅拌或涡旋混合直到完全溶解。

2.1%二甲苯青FF（xylene cyanole FF）:溶解1g二甲苯青FF于足量水中，定容到100ml。

3.5mg/ml的溴化乙锭（EB，ethidium bromide）：小心称取0.5g溴化乙锭，转移到广口瓶中，加100ml水，用磁力搅拌器搅拌直到完全溶解。

用铝箔包裹装液管，于4℃储存。

工作浓度0.5mg/L水溶液。

一、DNA电泳1. Tris-乙酸（TAE：Tris/Acetate/EDTA）浓贮存液/L（50×）：2mol/L Tris-碱，1 mol/L 乙酸，50 mmol/L EDTA方法：242.2 g Tris-碱，用300mL水加热搅拌溶解后，加57mL冰乙酸，加入100mL 0.5mol/L EDTA（pH8.0），用冰乙酸调pH值至8.0，定容为1L。

2. Tris-硼酸（TBE：Tris/Borate/EDTA）浓贮存液/L (5×) : 90mmol/L Tris-碱，890mmol/L 硼酸盐，20mmol/L EDTA(pH8.0)方法：54g Tris碱、27.5硼酸、20ml 0.5mol/L EDTA(pH8.0)，水定容至1L。

使用液：（0.5×）：0.045mol/L Tris-磷酸，0.001mol/L EDTA注：进行聚丙烯酰胺凝胶电泳使用的是1×TBE，琼脂糖凝胶电泳使0.5×TBE，这是因为聚丙烯酰胺凝胶垂直槽的缓冲液槽较小，需加强离子强度，提供稍高一些的电流。

3. Tris-磷酸（TPE）浓贮存液/L（10×）：0.9mol/L Tris-磷酸、0.02mol/L EDTA方法：108g Tris碱、15.5ml 85%磷酸（1.679g/ml）、40ml 0.5mol/L EDTA(pH8.0)，水定容至1L。

Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:HSF1A is a cell–permeable activator of heat shock transcription factor 1 (HSF1).IC50 & Target: HSF1[1]In Vitro: HSF1A protects cells from stress–induced apoptosis, binds TRiC subunits and inhibits TRiC activity without perturbation of ATP hydrolysis. Genetic inactivation or depletion of the TRiC complex results in human HSF1 activation and HSF1A inhibits the direct interaction between purified TRiC and HSF1 in vitro. Moreover, fluorescence anisotropy experiments using FITC coupled to HSF1A demonstrates that HSF1A–FITC binds to a purified Tcp1 subunit of TRiC with an affinity of approximately 600 nM. This is validated qualitatively via titration of purified Tcp1 into binding reactions containing 500 nM Biotin or HSF1A–Biotin [1]. Quantification bycounting the number of cell containing aggregates as a function of the total number of cells reveals that at HSF1A concentrations as low as 2 μM, a reduced number of aggregate–containing cells are observed. The fraction of cells containing aggregates continued to decrease in a dose–dependent manner such that pretreatment with 12 μM HSF1A resulta in ~20% of the cells exhibiting aggregates visible by fluorescence microscopy [2].In Vivo: HSF1A enhances HSF1 activity, stabilizes HSF1 expression and minimizes Doxorubicin (DOX)–induced cardiac damage. WKY rats are challenged with DOX (accumulated dose: 30 mg/kgw), and DOX combined with HSF1A (100 mg/kgw/day). Supplementation with HSF1A significantly elevates cardiac functions back to the levels of the control group. HSF1A has been shown to stimulate human HSF1 nuclear translocation, elevate protein chaperone expression and ameliorate protein misfolding and cell death in aneurodegenerative disease model. The echocardiographic results show that HSF1A also alleviates DOX–induced failures in cardiac function [3].PROTOCOL (Extracted from published papers and Only for reference)Kinase Assay:[1]Protein extracts are generated from mammalian, yeast and E. coli cultures using biotin–binding buffer (20 mM HEPES,5 mM MgCl 2, 1 mM EDTA, 100 mM KCl, 0.03% NP–40) supplemented with 1% Trition–X100 and protease inhibitors. Approximately 0.5mg of protein extract is incubated with 100 μM HSF1A–Biotin for 4 h at 4°C and HSF1A–Biotin associated proteins captured by with NeutrAvidin Agarose Resin. After washing in biotin binding buffer proteins are eluted using 50 μL biotin elution buffer (100 mM Tris,150 mM NaCl, 0.1 mM EDTA, 2 mM D–biotin), resolved on a 4–20% SDS–PAGE, and immunoblotted. For purified TRiC and Hsp70analyses, 5 nM protein is incubated in biotin–binding buffer+0.5% Triton X–100 with 100 μM biotin or 100 μM HSF1A–Biotin for 4 h at 4°C and captured with NeutrAvidin Resin. For NiNTA purified yeast Tcp1, different concentrations of Tcp1 0.5 μM, 1 mM, 2 mM, 3 mM and 4 mM in 25 mM Hepes pH 7.5, 150 mM NaCl are incubated with 0.5 μM Biotin or HSF1A–Biotin for 4 h at 4°C and captured with NeutrAvidin Resin [1].Cell Assay:[2]PC12 cells seeded into a 96–well plate (5×104 cells/well) are treated with increasing concentrations of HSF1A (2, 4, 8 andProduct Name:HSF1A Cat. No.:HY-103000CAS No.:1196723-93-9Molecular Formula:C21H19N3O2S2Molecular Weight:409.52Target:HSP Pathway:Cell Cycle/DNA Damage; Metabolic Enzyme/Protease Solubility:DMSO: ≥ 150 mg/mL12 μM) for 15 h, at which time httQ74–GFP expression is stimulated by incubation in the presence of 1 μg/mL Doxycycline for 5 d. Cell viability is assessed via the XTT viability assay[2].Animal Administration:[3]Rat[3]Ten–week–old Wistar Kyoto rats (WKY) are used. The rats are housed at a constant temperature (22°C) on a 12–h light/dark cycle with food and tap water. The animals are arranged into three groups: WKY rats (the control group), DOX rats and DOX rats treated with HSF1A. Each group contain five animals. The DOX group is injected with DOX (5 mg/kg) for 6 consecutive weeks intraperitoneal injection to achieve a cumulative dose of 30 mg/kg, which has been well documented to achieve cardiotoxicity. The small molecular HSF1 activator HSF1A (100 mg/kg/day) is injected intraperitoneally.References:[1]. Neef DW, et al. A direct regulatory interaction between chaperonin TRiC and stress–responsive transcription factor HSF1. Cell Rep. 2014 Nov 6;9(3):955–66.[2]. Neef DW, et al. Modulation of heat shock transcription factor 1 as a therapeutic target for small molecule intervention in neurodegenerative disease. PLoS Biol. 2010 Jan 19;8(1):e1000291.[3]. Huang CY, et al. Doxorubicin attenuates CHIP–guarded HSF1 nuclear translocation and protein stability to trigger IGF–IIR–dependent cardiomyocyte death. Cell Death Dis. 2016 Nov 3;7(11):e2455.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。

Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:IBMX is a broad–spectrum phosphodiesterase (PDE ) inhibitor, with IC 50 of 6.5±1.2, 26.3±3.9 and 31.7±5.3 μM for PDE3, PDE4 and PDE5, respectively.IC50 & Target: IC50: 6.5±1.2 μM(PDE3), 26.3±3.9 μM (PDE4), 31.7±5.3 μM (PDE5)[1]In Vitro: At 100 μM, KMUP–1 (a xanthine derivative) and IBMX are the most effective at inducing tracheal relaxation; the magnitude of the relaxation responses induced by KMUP–1 and IBMX are not significantly different [1]. IBMX (100 μM) activates renal outer medullary K + (ROMK) channels (n=6, P<0.05) and prevents further channel activation by ANG II (n=6, P=NS) or cGMP. Of note is thatpretreatment of cortical collecting duct (CCDs) isolated from high–K + (HK)–fed rats with IBMX (100 μM) for 20 min leads to a significant increase in tubular cAMP content to 1.43±0.35 pg/mm tubule length (n=14) compare with that measured invehicle–treated controls (0.61±0.13 pg/mm tubule length, n=12, P<0.05)[2].In Vivo: IBMX, a non–selective PDE inhibitor significantly decreases the liver glycogen storage (mg/g, IBMX 22±1.5 P<0.001). IBMX potentiates insulin release and in hepatocytes and adipocytes, they increase glycogenolysis and lipolysis. In comparison with the control group, IBMX and mc5 significantly increase plasma glucose (blood glucose, mg/dl, control=141±3, IBMX=210±17 P<0.001and mc5=191±13 P<0.01) while other test compounds (mc1, mc6, MCPIP and milrinone) do not produce significant effect(control=141±3, mc1 160±7, mc6 175±9, MCPIP 179±8 and milrinone 116±2 P>0.05) also mc2 does not change plasma glucose (control=141±3 and mc2=145±5). IBMX has the highest efficacy on increasing plasma glucose [3]. Treatments with IBMX and Apocynin significantly decrease cold–induced elevation of right ventricular (RV) systolic pressure (23.5±1.8 and 24.2±0.6 mmHg,respectively) although they do not decrease RV pressure to the warm control levels. IBMX or Apocynin significantly reduces medial layer thickness (19.0±0.9, and 16.9±0.8 μm, respectively) and increases lumen diameter (62.7±4.2, and 59.5±4.3 μm, respectively) of small PAs in cold–exposed rats [4].PROTOCOL (Extracted from published papers and Only for reference)Cell Assay: IBMX is dissolved in DMSO (10 mM) and stored, and then diluted with appropriate media before use [2].[2]Cells are grown in 24–well plates 105 cells per well. At confluence, monolayer cells are washed with phosphate buffer solution (PBS) and thenincubated with KMUP–1 (0.1–100 μM) in the presence of 100 μM IBMX for 20 min. Incubation is terminated by the addition of 10%trichloroacetic acid (TCA). Cell suspensions are sonicated and then centrifuged at 2500× g for 15 min at 4°C. To remove TCA, the supernatants are extracted three times with 5 volumes of water–saturated diethyl ether. Then, the supernatants are lyophilized and the cyclic GMP or AMP of each sample is determined by using commercially available radioimmunoassay kits [2].Animal Administration: IBMX is dissolved in DMSO and diluted to desire concentration with less than 1% DMSO (Miceand Rat)[3][4].[3][4]Mice [3]Male mice (25–35 g) are used. For the experiment, the test compound (IBMX, milrinone, MCPIP, mc1, mc2, mc5 or mc6) or solvent (control) is injected subcutaneously to mice at 1 mg/kg dosage twice a day (8:00 a.m. and 8:00 p.m.) for 7 days. On day 8, animals areProduct Name:IBMX Cat. No.:HY-12318CAS No.:28822-58-4Molecular Formula:C 10H 14N 4O 2Molecular Weight:222.24Target:Phosphodiesterase (PDE)Pathway:Metabolic Enzyme/Protease Solubility:DMSO: ≥ 35 mg/mLanesthetized with intraperitoneal injection of thiopental (80 mg/kg) and blood samples are obtained from their hearts and then the liver is dissected. Each sample is centrifuged for 5 min and its serum is separated. The serum and the liver of each animal are kept frozen in less than –18 oC for the following measurements.Rat[4]Six groups of male Sprague–Dawley rats are used (150–180g, 6 rats/group). Three groups of rats are exposed to a climate–controlled walk–in chamber maintained at moderate cold (5.0±1°C). The remaining groups are kept in an identical chamber maintained at room temperature (23.5±1°C, warm) and served as controls. After eight weeks of exposure to cold, 3 groups in each temperature condition received continuous IV infusion of IBMX (PDE–1 inhibitor, 8.5 mg/kg/day), Apocynin (NADPH oxidase inhibitor, 25 mg/kg/day) and vehicle (DMSO, 50%), respectively. The doses of drugs have been validated for effective inhibition of PDE–1 and NADPH oxidase activity, respectively. Body weight is measured weekly. After one week of drug infusion, the animals’ right ventricular systolic blood pressure (RVBP) is measured under anesthesia. The RVP is a reliable indicator of pulmonary arterial blood pressure (PAP) and has been used by numerous investigators for evaluating PH.References:[1]. Wu BN, et al. KMUP–1, a xanthine derivative, induces relaxation of guinea–pig isolated trachea: the role of the epithelium, cyclic nucleotides and K+ channels. Br J Pharmacol. 2004 Aug;142(7):1105–14.[2]. Wei Y, et al. Angiotensin II type 2 receptor regulates ROMK–like K? channel activity in the renal cortical collecting duct during high dietary K? adaptation. Am J Physiol Renal Physiol. 2014 Oct 1;307(7):F833–43.[3]. Hosseini A, et al. Differential metabolic effects of novel cilostamide analogs, methyl carbostiryl derivatives, on mouse and hyperglycemic rat. Iran J Basic Med Sci. 2012 Jul;15(4):916–25.[4]. Crosswhite P, et al. Inhibition of phosphodiesterase–1 attenuates cold–induced pulmonary hypertension. Hypertension. 2013 Mar;61(3):585–92.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。

DAB Substrate Buffer 化学品安全技术说明书GHS product identifier :DAB Substrate Buffer化学品的推荐用途和限制用途GE001, GV800, GV823, GV825, GV900, GV925, K0620, K1492, K1494, K3467,K3468, K3954, K4065, K4071, K5007, K5204, K5207, K5361, K8000, K8002,K8023, SK001, SK005, SK006, SK050, SK110, SK310部件号:安全技术说明书根据 GB/ T 16483-2008 和 GB/ T 17519-2013GHS化学品标识:DAB稀释液推荐用途GE001 // EnVision FLEX Substrate Buffer (Dako Omnis) // HercepTest mAb pharmDx // 2 x 26 mLGV800 // EnVision FLEX Substrate Buffer (Dako Omnis) // EnVision FLEX,High pH (Dako Omnis) // 16x26 mLGV823 // EnVision FLEX Substrate Buffer (Dako Omnis) // EnVision FLEX Mini Kit, High pH (Dako Omnis) // 4x26 mLGV825 // EnVision FLEX Substrate Buffer (Dako Omnis) // EnVision FLEX DAB+ Substrate Chromogen System // 4x26 mLGV900 // EnVision FLEX Substrate Buffer (Dako Omnis) // EnVision FLEX HRP Magenta, High pH (Dako Omnis) // 3x26 mLGV925 // EnVision FLEX Substrate Buffer (Dako Omnis) // EnVision FLEX HRP Magenta Substrate Chromogen System (Dako Omnis) // 1x26 mLK0620 // DAB Substrate Buffer // GenPoint Tyramide Signal Amplification System for Biotinylated Probes // 10 mLK1492 // DAB+ Substrate Buffer // EGFR pharmDx // 1x10 mL K1494 // DAB+ Substrate Buffer // EGFR pharmDx // 10x11 mLK3467 // DAB+ Substrate Buffer // Dako Liquid DAB+ Substrate Chromogen System // 1x15 mLK3468 // DAB+ Substrate Buffer // Dako Liquid DAB+ Substrate Chromogen System // 1x110 mLK3954 // DAB+ Substrate Buffer // Dako ARK (Animal Research Kit),Peroxidase for Mouse Primary Antibodies // 1x18 mLK4065 // DAB+ Substrate Buffer // Dako EnVision+ Dual Link System-HRP (DAB+) // 1x18 mLK4071 // ER/PR pharmDx DAB+ Substrate Buffer // Dako ER/PR pharmDx Kit For the Dako Autostainer // 10x11 mLK5007 // Dako REAL Substrate Buffer // Dako REAL EnVision Detection System, Peroxidase/DAB+, Rabbit/Mouse // 1x250 mLK5204 // DAB Buffered Substrate // HercepTestTM // 1x10 mLK5207 // DAB Buffered Substrate // HercepTestfor the Dako Autostainer //15x11 mLK5361 // DAB+ Substrate Buffer // EnVision G|2 Doublestain System, Rabbit/Mouse (DAB+/Permanent Red) // 3x11 mLK8000 // EnVision FLEX Substrate Buffer // EnVision FLEX, High pH, (Link)// 12x20 mLK8002 // EnVision FLEX Substrate Buffer // EnVision FLEX+, Mouse, High pH,(Link) // 12x20 mLK8023 // EnVision FLEX Substrate Buffer // EnVision FLEX Mini Kit, High pH, (Link) // 5x20 mLSK001 // HercepTest DAB Substrate Buffer // HercepTest for Automated Link Platforms // 2x22 mLSK005 // DAB+ Substrate Buffer // PD-L1 IHC 28-8 pharmDx // 15x7.2 mL SK006 // DAB+ Substrate Buffer // PD-L1 IHC 22C3 pharmDx // 15x7.2 mL SK050 // DAB Substrate Buffer // Her2Low // 15x7.2 mlSK110 // EnVision DuoFLEX DAB+ Substrate Buffer // EnVision DuoFLEX Doublestain System, (Link) // 2x36 mLSK310 // ER/PR pharmDx DAB+ Substrate Buffer // Dako ER/PR pharmDx Kit (Link) // 2x50 mL 参考号码: SDS342:*************(24小时)应急咨询电话（带值班时间）:供应商/ 制造商:供应商/ 制造商: Agilent Technologies, Inc.（美国安捷伦科技有限公司）住所：5301 Stevens Creek Boulevard, Santa Clara, CA, 95051, United States 联系电话：+1 800 227 9770 供应商/ 制造商: Agilent Technologies Singapore (International) Pte Ltd.（安捷伦科技新加坡（国际）私人有限公司）住所：No. 1 Yishun Avenue 7, Singapore, 768923 联系电话：(65) 6276 2622供应商/ 制造商: Agilent Technologies Denmark ApS (安捷伦科技丹麦私人有限公司)住所：Produktionsvej 42， DK-2600 Glostrup, Denmark 联系电话： +45 44859500 本安全技术说明书责任人的e-mail地址:***************有关环境保护措施，请参阅第 12 节。

2021年第47卷第1期(总第421期)155㊀DOI:10.13995/ki.11-1802/ts.025185引用格式:陈琼,陈朋,李俊颖,等.酸枣仁提取物与茶氨酸复合配方对睡眠的改善作用[J].食品与发酵工业,2021,47(1):155-159.CHEN Qiong,CHEN Peng,LI Junying,et al.Sleeping quality improvement by Semen Ziziphi Spinosae and theanine com-pound formula[J].Food and Fermentation Industries,2021,47(1):155-159.酸枣仁提取物与茶氨酸复合配方对睡眠的改善作用陈琼∗,陈朋,李俊颖,徐旻珺(仙乐健康科技股份有限公司,广东汕头,515041)摘㊀要㊀为探究酸枣仁提取物与茶氨酸的复合配方对小鼠睡眠的影响及其作用机理,将雄性Balb-c 小鼠随机分成3组,酸枣仁提取物㊁茶叶茶氨酸低剂量组[酸枣仁提取物105mg /(kg ㊃d )㊁茶氨酸58mg /(kg ㊃d )]和高剂量组[酸枣仁提取物158mg /(kg ㊃d )㊁茶氨酸87mg /(kg ㊃d )],以及对照组(蒸馏水),连续灌胃30d ,测定各项睡眠指标以及血液和脑组织中各项指标㊂结果显示,与对照组相比,低剂量组与高剂量组小鼠催眠实验入睡率显著增加,脑组织中5-羟色胺浓度显著提高,β-内啡肽的浓度显著降低㊂此外,高剂量组小鼠睡眠时间显著延长(P <0.01),睡眠潜伏期显著缩短(P <0.01),血液中色氨酸的浓度显著提高(P <0.05)㊂以上结果表明,酸枣仁与茶氨酸复合配方,当酸枣仁提取物剂量为158mg /(kg ㊃d ),茶氨酸剂量为87mg /(kg ㊃d )时,具有改善睡眠的作用,这可能是通过影响小鼠血液中色氨酸,脑中5-羟色胺和β-内啡肽浓度实现的㊂关键词㊀酸枣仁;茶氨酸;改善睡眠;5-羟色胺;β-内啡肽第一作者:硕士,副主任药师(通讯作者,E-mail:806352951@)收稿日期:2020-07-28,改回日期:2020-09-15㊀㊀失眠是最常见的睡眠障碍疾病,我国每年有超过1/3的成年人睡眠质量低下[1]㊂目前用于治疗失眠的药物有很多,如唑吡坦㊁佐匹克隆等㊂镇静催眠药物已经发展到了第3代,疗效不断提升,但使用催眠镇静药物会产生乏力㊁头晕等不可避免的副作用[2],以食疗代替药物改善睡眠质量的方法受到越来越多的关注㊂文献报道酸枣仁㊁茶氨酸均有改善睡眠的作用[3-4]㊂酸枣仁是临床常用于治疗失眠的一味中药,最早用于汉代名医张仲景所写的‘金匮要略㊃血脾虚劳病脉证“,具有清热养血㊁安神除烦的功效[5]㊂酸枣仁中的有效成分已经被学者所发现,对其改善睡眠的作用机制的研究也越来越深入㊂L -茶氨酸是一种在20世纪90年代由日本科学家发现于茶叶中的非蛋白质游离氨基酸,具有改善睡眠的功效[6]㊂由于酸枣仁已被录入药食同源名单,茶氨酸被批准为新资源食品,作为食品原料安全性佳,必然会受到市场广泛关注㊂目前,关于酸枣仁改善睡眠的研究很多,但尚未见将酸枣仁与茶氨酸联用的报道㊂本研究在对这2种原料研究的基础上,通过动物实验探寻酸枣仁与茶氨酸联用的合适用量,并探究它们与小鼠部分血液和脑组织指标的关系,为助眠产品的研发提供数据支持㊂1㊀材料与方法1.1㊀材料与试剂酸枣仁提取物,杨凌萃健生物工程技术有限公司;茶氨酸,湖南金农生物资源股份有限公司;戊巴比妥钠㊁巴比妥钠,德国Sigma 公司;小鼠色氨酸㊁小鼠5-羟色胺㊁小鼠β-内啡肽ELISA 试剂盒,上海酶联生物科技有限公司㊂1.2㊀仪器与设备一次性注射器,江西洪达医疗器械集团;XS1003S 型电子天平,瑞士Mettler Toledo 公司;Cen-trifuge 5425离心机,德国Eppendorf 公司;Synergy H1酶标仪,美国Biotek 公司㊂1.3㊀动物与分组SPF 级Balb-c 健康雄性小鼠120只(8周龄,18~20g),小鼠随机分为4批,每批30只㊂各批间体质量无统计学差异㊂第1批用于直接睡眠以及延长戊巴比妥钠睡眠时间实验;第2批用于戊巴比妥钠阈下剂量催眠实验;第3批用于缩短巴比妥钠睡眠潜伏期时间实验;第4批用于小鼠血液中色氨酸㊁5-羟色胺含量,脑组织中5-羟色胺㊁β-内啡肽含量的测定㊂156㊀2021Vol.47No.1(Total 421)1.4㊀配方与剂量每批小鼠随机分成3组,每组各10只小鼠,分为空白对照组,低剂量组和高剂量组㊂空白对照组以与实验组同体积蒸馏水进行灌胃;低剂量组为酸枣仁提取物105mg /(kg㊃d),茶氨酸58mg /(kg㊃d),高剂量组为酸枣仁提取物158mg /(kg ㊃d ),茶氨酸87mg /(kg㊃d),依据剂量分别配制灌胃液,灌胃体积为0.2mL /10g,每日1次㊂1.5㊀实验方法1.5.1㊀直接睡眠实验将第1批小鼠按1.4中方法进行实验,连续给样品30d,末次以动物的翻正反射消失为入睡指标观察小鼠睡眠情况㊂1.5.2㊀延长戊巴比妥钠睡眠时间实验将用于直接睡眠实验的各组小鼠在末次给受试物后20min 经腹腔注射戊巴比妥钠0.2mL /20g,以动物的翻正反射消失为指标,观察样品能否延长戊巴比妥钠睡眠时间㊂1.5.3㊀戊巴比妥钠阈下剂量催眠实验将第2批小鼠按1.4中方法进行实验,连续给样品30d,末次给样品20min 后经腹腔注射戊巴比妥钠30mg /(kg㊃d),以动物的翻正反射消失为指标,观察30min 内小鼠睡眠情况㊂1.5.4㊀巴比妥钠睡眠潜伏期实验将第3批小鼠按1.4中方法进行实验,连续给样品30d 后㊂末次给样品20min 后经腹腔注射巴比妥钠0.2mL /20g,以翻正反射消失为指标,观察样品对巴比妥钠睡眠潜伏期的影响㊂1.5.5㊀小鼠血液中色氨酸㊁5-羟色胺含量检测将第4批小鼠按1.4中方法进行实验,连续给样品30d 后,将小鼠处死后取血,放置1h 待血液凝固,5000r /min 下离心10min,得到血清,严格按照小鼠色氨酸㊁小鼠5-羟色胺ELISA 检测试剂盒说明书方法,对小鼠血液中色氨酸㊁5-羟色胺含量进行检测㊂1.5.6㊀小鼠脑组织5-羟色胺㊁β-内啡肽含量检测将1.5.5中实验小鼠脑组织取出,参照杜正彩等[7]的方法制成匀浆液进行离心后备用,严格按照小鼠5-羟色胺㊁小鼠β-内啡肽ELISA 试剂盒说明书方法,对小鼠脑组织中5-羟色胺,β-内啡肽含量进行测定㊂1.6㊀数据处理与分析采用SAS 20.0软件进行数据分析,延长戊巴比妥钠睡眠时间实验㊁巴比妥钠睡眠潜伏期实验㊁小鼠血液中色氨酸㊁5-羟色胺含量和脑组织5-羟色胺㊁β-内啡肽含量的组间显著性比较采用单因素方差分析,数据以 均值ʃ标准差 表示㊂戊巴比妥钠阈下剂量催眠实验的组间显著性比较采用卡方检验分析㊂2㊀结果与分析酸枣仁提取物与茶氨酸复合配方作用于小鼠的各项实验与分析如下文所示㊂2.1㊀对小鼠直接睡眠的影响3组小鼠在给予样品之后均未出现翻正反射消失的现象,表明酸枣仁提取物与茶氨酸复合配方高低剂量组均无直接睡眠作用㊂2.2㊀对戊巴比妥钠诱导睡眠实验小鼠睡眠时间的影响延长戊巴比妥钠睡眠时间实验方法结果如图1-a 所示,与对照组相比,在经戊巴比妥钠诱导后,低剂量组小鼠睡眠时间并无增加,高剂量组小鼠睡眠时间较对照组显著增长(P <0.01)㊂2.3㊀对戊巴比妥钠阈下剂量催眠实验小鼠入睡率的影响戊巴比妥钠阈下剂量催眠实验结果如图1-b 所示,对照组入睡发生率仅为10%㊂与对照组相比,高低剂量组均显著提升了小鼠的入睡发生率,高剂量组入睡发生率上升尤为明显(P <0.01)㊂2.4㊀对巴比妥钠实验小鼠睡眠潜伏期时间的影响巴比妥钠睡眠潜伏期实验结果如图1-c 所示,与对照组相比,低剂量组小鼠睡眠潜伏时间有缩短趋势,但是不具有统计学上的显著性,高剂量组小鼠睡眠潜伏时间则显著缩短(P <0.01)㊂2.5㊀对小鼠体质量的影响对3项实验中高低剂量组小鼠在0㊁7㊁14㊁21㊁30天进行体质量测量后进行统一分析,结果如表1所示㊂实验前各组小鼠初始体质量无明显差异(P >0.05),在给予样品后,各组小鼠体质量也不呈现显著性差异(P >0.05),表明高㊁低剂量组均对小鼠体质量无明显影响㊂2.6㊀对小鼠血液指标(色氨酸㊁5-羟色胺)的影响小鼠血液中色氨酸㊁5-羟色胺含量如图2所示,与对照组相比,在灌胃酸枣仁提取物茶氨酸复合配方30d 后,低剂量组血清色氨酸含量有增加趋势,但不具有显著性;高剂量组血清色氨酸含量显著提高(P <0.05)㊂此外,高低剂量组血液中5-羟色胺的含量与对照组相比并无显著差异㊂2021年第47卷第1期(总第421期)157㊀a-延长戊巴比妥钠睡眠时间;b-戊巴比妥钠阈下剂量实验小鼠入睡率;c-巴比妥钠实验睡眠潜伏期时间图1㊀酸枣仁提取物与茶氨酸复合配方对小鼠睡眠的影响Fig.1㊀Effect of Semen Ziziphi Spinosae extract and theanine compound formula on the sleep quality of mice注:∗表示与对照组相比,具有显著性差异(P <0.05);∗∗表示与对照组相比,具有显著性差异(P <0.01)(下同)表1㊀酸枣仁提取物与茶氨酸复合配方对小鼠体质量的影响单位:gTable 1㊀Effect of Semen Ziziphi Spinosae extract andtheanine compound formula on mice body mass分组0d7d14d 21d 30d 对照组19.27ʃ1.2119.85ʃ1.4421.26ʃ1.6422.14ʃ1.5323.42ʃ1.85低剂量组18.90ʃ0.6719.66ʃ0.8121.18ʃ0.9521.75ʃ1.1123.25ʃ1.26高剂量组18.21ʃ1.6419.50ʃ1.4120.97ʃ1.4021.52ʃ1.0723.05ʃ1.422.7㊀对小鼠脑组织指标(5-羟色胺㊁β-内啡肽)的影响小鼠脑组织中5-羟色胺㊁β-内啡肽含量如图3所示㊂与对照组相比,给予样品后低剂量组与高剂量组小鼠脑组织中5-羟色胺的含量均显著升高(P <0.01),且具有一定的量效关系㊂与之相反,在服食样品后,与对照组相比,高低剂量组小鼠脑组织中β-内啡肽含量均显著性降低,且高剂量组更具显著性(P <0.01)㊂a-血清色氨酸;b-血清5-羟色胺图2㊀酸枣仁提取物-茶氨酸对小鼠血液中色氨酸㊁5-羟色胺的影响Fig.2㊀Effect of Semen Ziziphi Spinosae extract and theanine on tryptophan and 5-hydroxytryptamine in mouse blooda-5-羟色胺;b-β-内啡肽图3㊀酸枣仁提取物-茶氨酸对小鼠脑组织中5-羟色胺和β-内啡肽的影响Fig.3㊀Effect of Semen Ziziphi Spinosae extract and theanine compound formula on 5-hydroxytryptamineand β-endorphin in mouse brain 3㊀结论与讨论睡眠-觉醒的机制是一个十分复杂的过程,受到多种因素的调控[8],其中色氨酸在诱导睡眠的机制中起着重要的作用㊂色氨酸在血液中多以与白蛋白结合的形态存在,然而血液中的游离脂肪酸也竞争同样的结合位点㊂当血浆中游离脂肪酸水平升高时,会导致色氨酸与白蛋白分离,进而使血液中游离色氨酸含量上升㊂过量的游离色氨酸搭乘L -氨基酸转运蛋白穿过血脑屏障进入大脑,之后分别通过2条路径诱导睡眠:(1)合成5-羟色胺,当脑内5-羟色胺的浓度升高,就会使机体产生疲劳感和睡意,更容易进入睡眠状态[9],同时5-羟色胺作为褪黑素的前体也会促进褪黑素的形成[10],褪黑素是一种调节生物节律的158㊀2021Vol.47No.1(Total 421)激素,常用作治疗睡眠障碍;(2)激活色氨酸-犬尿酸通路,与神经元胶质细胞和神经元突触上的色氨酸㊁犬尿酸受体结合,诱发神经性疲劳,最终达到诱导睡眠的目的[11]㊂酸枣仁作为一种临床上治疗失眠的中药,包含多种活性成分,其中脂肪酸种类达41种,含量达32%,因此服用酸枣仁可引起瞬时的血浆游离脂肪酸浓度升高[12-13],进而使色氨酸和白蛋白解离,上调血浆色氨酸浓度㊂与此相一致,本文结果也显示高剂量组可显著升高小鼠血液中色氨酸的浓度(图2-a),进而上调脑中5-羟色胺浓度(图3-a),且与剂量呈现出正相关关系㊂同样,WANG 等[14]发现酸枣仁中斯皮诺素能显著抑制5-HT1A 激动剂,并作为5-HT1A 受体拮抗剂延长大鼠的睡眠时间;LIANG 等[15]研究发现酸枣仁皂苷成分能显著提高小鼠额叶皮层和海马中的5-羟色胺水平,与本实验相一致㊂实验结果还证明,酸枣仁提取物与茶氨酸联用,在剂量低时在延长小鼠睡眠时间和减少睡眠潜伏时间方面均无改善的趋势,只增加了入睡率㊂在剂量高时则显现出明显的改善睡眠作用㊂茶氨酸的结构与谷氨酸很相似,能在神经系统中与谷氨酸受体进行竞争性结合[16],有研究表明,茶氨酸能促进大脑中特别是纹状体多巴胺的释放[17],之后一部分茶氨酸会被分解成谷氨酸进入血液循环,另一部分则成为合成γ-氨基丁酸的原料[18]㊂但是,从李靓等[19]的实验结果得知,当茶氨酸剂量为50mg /(kg㊃d)时,也不体现出改善睡眠效果㊂同样,配方中所用酸枣仁量的不同,对小鼠睡眠的干预效果也有很大的差异[20-21]㊂本实验中低剂量组酸枣仁提取物用量为105mg /(kg ㊃d),茶氨酸剂量为58mg /(kg㊃d),无法达到改善睡眠的效果㊂此外,本实验中小鼠大脑中β-内啡肽的浓度随着酸枣仁提取物和茶氨酸剂量的升高而降低(图3-b)㊂β-内啡肽的浓度与睡眠有关,有文献报道猫服用β-内啡肽后会出现失眠症状[22],也有人体实验证实体内β-内啡肽的减少,能够改善其失眠症状[23],不过尚未有文献探究酸枣仁或者茶氨酸与β-内啡肽间的联系,从结果推测,酸枣仁与茶氨酸联用可降低脑组织中β-内啡肽的浓度,并且具有量效关系,对改善小鼠睡眠也有一定作用㊂综合上述实验结果,酸枣仁提取物与茶氨酸复合配方高剂量组显著延长戊巴比妥钠睡眠时间㊁增加戊巴比妥钠阈下剂量催眠实验入睡率和减少巴比妥钠睡眠潜伏实验睡眠潜伏时间,且无直接睡眠作用㊂根据‘保健食品检验与评价技术规范实施手册“[24]改善睡眠评价方法,酸枣仁提取物与茶氨酸复合配方在酸枣仁提取物158mg /(kg㊃d)㊁茶氨酸87mg /(kg㊃d)时,能显现出良好的协同效果,具有明显的改善睡眠作用,这种作用可能是通过提高血浆色氨酸浓度以及脑中色氨酸代谢产物含量和降低β-内啡肽含量来实现的㊂参考文献[1]㊀赵晓东,时晶,杨益昌,等.失眠的诊断与中西医治疗[J].中华中医药杂志,2011,26(11):2641-2643.ZHAO X D,SHI J,YANG Y C,et al.Diagnosis and treatment of in-somnia by integrated traditional Chinese and western medicine[J].China Journal of Traditional Chinese Medicine and Pharmacy,2011,26(11):2641-2643.[2]㊀姜春和.新型镇静催眠药物[J].医学综述,2014,20(19):3556-3558.JIANG C H.A new generation of sedative hypnotic drugs[J].Medi-cal Recapitulate,2014,20(19):3556-3558.[3]㊀张瑞鹏,赵仁邦,刘子慷,等.酸枣仁的功能作用及其产品开发[J].中国食物与营养,2018,24(10):26-30.ZHANG R P,ZHAO R B,LIU Z K,et al.Functional effect and prod-uct development of Semen Zippy Spinoza [J].Food and Nutrition in China,2018,24(10):26-30.[4]㊀李靓.茶氨酸保健功效研究及其保健食品开发[D].北京:中国农业科学院,2009.LI L.The development of health food based on health function re-search of theanine [D ].Beijing:Chinese Academy of Agricultural Sciences,2009.[5]㊀赵雪莹,陈燕.‘金匮要略“酸枣仁汤之酸枣仁刍议[J].陕西中医药大学学报,2018,41(2):102-104.ZHAO X Y,CHEN Y.Discussion on the Spina date seed of Ziziphi Spinosae decoction in Synopsis of Golden Chamber [J ].Journal of Shaanxi College of Traditional Chinese Medicine,2018,41(2):102-104.[6]㊀SYLLA S,OJALVO S P,KOMOROWSKI J,et al.The effect of a no-vel theanine complex (jds-mt-003)on sleep in a pentobarbital-in-duced sleep model in mice [J ].The FASEB Journal,2020,34:1-1.[7]㊀杜正彩,齐彪,张明哲,等.不同配伍比例栀子-肉桂水提物改善小鼠睡眠作用及相关机制研究[J].食品研究与开发,2019,40(21):49-54.DU Z C,QI B,ZHANG M Z,et al.Effects of different proportions of gardenia and Cinnamon cassia aqueous extract on sleep function and related mechanisms in mice [J].Food Research and Development,2019,40(21):49-54.[8]㊀张照环,刘振宇,张瀚文,等.从受体角度研究睡眠-觉醒调控机制[J].中国现代神经疾病杂志,2013,13(5):20-23.ZHANG Z H,LIU Z Y,ZHANG H W,et al.Regulatory mechanism in sleep-wake cycle:from a receptor view [J].Chinese Journal of Contemporary Neurology and Neurosurgery,2013,13(5):20-23.[9]㊀郑乐颖,季红光,王海明,等.睡眠剥夺对大鼠脑5-羟色胺代谢及行为的影响[J].中国行为医学科学,1998,7(4):256-257.ZHENG L Y,JI H G,WANG H M,et al.The effects of prolongedsleep deprivation on brain serotonin metabolism and behavior in rats [J].Chinese Journal of Behavioural Medical Science,1998,7(4):256-257.[10]㊀LI Y,HU N,YANG D,et al.Regulating the balance between thekynurenine and serotonin pathways of tryptophan metabolism[J].The FEBS Journal,2017,284(6):948-966.[11]㊀YAMASHITA M.Potential role of neuroactive tryptophan metabo-lites in central fatigue:Establishment of the fatigue circuit[J].In-ternational Journal of Tryptophan Research,2020,13:1-15. [12]㊀闫艳,张敏,崔小芳,等.酸枣仁化学成分体内过程及其质量标志物研究思路探讨[J].中草药,2019,50(2):40-50.YAN Y,ZHANG M,CUI X F,et al.Discussion on research ideasfor process in vivo of chemical compositions from Ziziphi spinosaeSemen and its quality marker[J].Chinese Traditional and HerbalDrugs,2019,50(2):40-50.[13]㊀刘世军,唐志书,崔春利,等.酸枣仁化学成分的研究进展[J].西部中医药,2016,29(9):143-146.LIU S J,TANG Z S,CUI C L,et al.The research progress of chemi-cal composition of suanzaoren[J].Western Journal of TraditionalChinese Medicine,2016,29(9):143-146.[14]㊀WANG X X,MA G J,XIE J B,et al.Influence of JuA in evokingcommunication changes between the small intestines and brain tis-sues of rats and the GABAA and GABAB receptor transcription lev-els of hippocampal neurons[J].Journal of Ethnopharmacology,2015,159:215-223.[15]㊀LIANG Y,YANG X,ZHANG X J,et al.Antidepressant-like effectof the saponins part of ethanol extract from SHF[J].Journal of Eth-nopharmacology,2016,191:307-314.[16]㊀陈淑珍,甄永苏.茶氨酸的药理学作用及机制[J].医学研究杂志,2013,42(11):17-20.CHEN S Z,ZHEN Y S.Pharmacological effects and mechanism oftheanine[J].Journal of Medical Research,2013,42(11):17-20.[17]㊀ADHIKARY R,MANDAL V.L-theanine:A potential multifacetednatural bioactive amide as health supplement[J].Asian PacificJournal of Tropical Biomedicine,2017,7(9):842-848[18]㊀DESAI M J,GILL M S,HSU W H,et al.Pharmacokinetics of thea-nine enantiomers in rats[J].Chirality,2005,17(3):154-162.[19]㊀李靓,林智,何普明,等.茶氨酸改善小鼠睡眠状况的实验研究[J].食品科学,2009,30(15):211-213.LI L,LIN Z,HE P M,et al.Sleep-promoting effect of L-theanine onmice[J].Food Science,2009,30(15):211-213. [20]㊀韩彦彬,姚思宇,赵鹏,等.酸枣仁茶改善小鼠睡眠作用的研究[J].中国热带医学,2009,9(9):305-306.HAN Y B,YAO S Y,ZHAO P,et al.Effect of Semen Ciziphi spi-nosae tea on sleeping quality of mice[J].China Tropical Medicine,2009,9(9):305-306.[21]㊀肖迪,刘俊,赵宾宾.酸枣仁汤对慢性睡眠剥夺大鼠海马5-HT1AR和5-HT2AR表达的影响[J].西部中医药,2019,32(5):12-15.XIAO D,LIU J,ZHAO B B.Impacts of Suan Zao Ren decoction onthe expressions of5-HT1AR and5-HT2AR in hippocampus of therats with chronic sleep deprivation[J].Western Journal of Tradi-tional Chinese Medicine,2019,32(5):12-15.[22]㊀KING C,MASSERANO J M,CODD E,et al.Effects of beta-endor-phin and morphine on the sleep-wakefulness behavior of cats[J].Sleep,1981,4(3):259-262.[23]㊀万秀琨,李铀,李亚琴,等.银屑病患者血浆中β-内啡肽与睡眠质量的相关性研究[J].医学文选,2006,25(3):376-378.WAN X K,LI Y,LI Y Q,et al.Association of serumβ-EP and thequality of sleep in patients with psoriasis[J].Anthology of Medi-cine,2006,25(3):376-378[24]㊀中华人民共和国卫生部.保健食品检验与评价技术规范(2003年版)[M].北京:中华人民共和国卫生部,2003:687.Ministry of Health of the People s Republic of China.Technicalstandards for testing&assessment of health food(2003edition)[M].Beijing:Ministry of Health of the People s Republic of Chi-na,2003:687.Sleeping quality improvement by Semen Ziziphi Spinosae andtheanine compound formulaCHEN Qiong∗,CHEN Peng,LI Junying,XU Minjun(SIRIO PHARMA CO.,LTD.,Shantou515041,China)ABSTRACT㊀To investigate the effect of the compound formula of Semen Ziziphi Spinosae extract and theanine on mice s sleeping quali-ty and its mechanism.Male Balb-c mice were randomly divided into3groups,low-dose group(Semen Ziziphi Spinosae extract:105 mg/(kg㊃d),theanine:58mg/(kg㊃d),high-dose group(Semen Ziziphi Spinosae extract:158mg/(kg㊃d),theanine:87 mg/(kg㊃d),and control group(distilled water)for30d continuous intragastric administration.The sleeping indicators and some inde-xes in blood and brain tissue were measured.The results showed that,compared with the control group,the hypnotic test sleep rate and the brain5-hydroxytryptamine concentration were significantly increased,while the brainβ-endorphin concentration was significantly de-creased both in low-dose group and high-dose group.Besides,mice in the high-dose group had prolonged sleeping time(P<0.01), shortened sleeping latency(P<0.01),and higher blood tryptophan concentrations(P<0.05)compared to the control group.The re-sults suggested that Semen Ziziphi Spinosae extract and theanine compound formula improved the sleeping quality with a dose of158 mg/(kg㊃d)Semen Ziziphi Spinosae extract and87mg/(kg㊃d)theanine.It may be achieved by affecting the tryptophan concentration in mouse blood,the5-hydroxytryptamine concentration andβ-endorphin concentration in mouse brain.Key words㊀Semen Ziziphi Spinosae;theanine;sleep improvement;5-hydroxytryptamine;β-endorphin2021年第47卷第1期(总第421期)159㊀。

Product Name:Aspirin CAS No.:50-78-2Cat. No.:HY-14654Product Data SheetMWt:180.16Formula:C9H8O4Purity :>98%Solubility:DMSO 36 mg/mL (199 mM); Water<1/L (<1M)Mechanisms:Biological Activity:Aspirin is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an anti-Pathways:Immunology/Inflammation; Target:COX <1 mg/mL (<1 mM)p y g,g p ,inflammatory compound that inhibits Cox-1.Target: Cox-1Aspirin (USAN), also known as acetylsalicylic acid , is a salicylate drug, often used as ananalgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatorymedication. The active ingredient of Aspirin was first discovered from the bark of the willow tree in 1763 by Edward Stone of Wadham College, Oxford University. Salicylic acid, the main metabolite of aspirin, is an integral part of human and animal metabolism. While in humans much of it isattributable to diet, a substantial part is synthesized endogenously.A i i i t f f di ti ll d t id l ti i fl t d (NSAID )b t References:[1]. Algra AM, et al. Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials. Lancet Oncol 2012May;13(5):518-27Aspirin is part of a group of medications called nonsteroidal anti-inflammatory drugs (NSAIDs), but differs from most other NSAIDs in the mechanism of action. Tho...Oncol. 2012 May;13(5):518-27.[2]. Krumholz HM, et al. Aspirin in the treatment of acute myocardial infarction in elderly Medicarebeneficiaries. Patterns of use and outcomes. Circulation. 1995 Nov 15;92(10):2841-7.Caution: Not fully tested. For research purposes onlyMedchemexpress LLC18W i l k i n s o n W a y , P r i n c e t o n , N J 08540,U S AE m a i l : i n f o @m e d c h e m e x p r e s s .c o m W e b : w w w .m e d c h e m e x p r e s s .c o m。

Table of ContentsLB Medium (1)NZ Medium (2)SM Buffer (3)SET Buffer (4)6X Prehyb Soln (5)10 X TBE (6)10 X TAE (7)20 X SSC (8)1% SDS, 0.2 M NaOH (9)14% PEG (8000), 2M NaCl, 10 mM MgSO4 (10)20% SDS (11)1.0 M Tris, pH 8.0, 1.5 M NaCl (12)10mM Tris-HCl, pH 7.5, 10mM MgSO4 (13)10 mM Tris, 50 mM EDTA, pH 7.5 (14)10 mM Tris-HCl, 1 mM EDTA, pH 7.5 (15)3 M Sodium Acetate, pH 4.8 (16)Electrophoresis dye (17)Labelling Stop dye (18)Sequencing gel dye (19)5% Acrylamide (20)6% Acrylamide in TBE, 50% Urea (21)40% Acrylamide (22)LB Medium (1 Liter)10g Bacto-tryptone5g Bacto-yeast extract10g NaClFor forty plates add 1% agar--1g. Autoclave media. When cool, add ampicillin and pour plates. For 1L of media, add 1.8 mL amp.NZ Medium (500 mL)5 g Bacto-tryptone2.5 g Bacto-yeast extract2.5 g NaCl1.25 g MgSO4For 20 plates add 1.2% agar--6g. Autoclave and pour plates at 50o CSM Buffer (1L)5.8 g NaCl1.2 g MgSo450 mL 1M Tris-HCl, pH 7.50.1 g Gelatin (doesn't dissolve)AutoclaveUsed for phage dilution and storage.SET Buffer50 mM Tris-HCl, pH 8.0, 50 mM EDTA, 20% w/v Sucroseto make 200mL:40 g Sucrose10 mL of 1M Tris20 mL of 0.5 M EDTA, disodium saltbring to 200 mL with H206X Prehybridization Solutionto make 500 mL300 mL ddH20150 mL 20X SSC50 mL 50X Denhardt's solution1 mL 0.5 M EDTA (disodium salt)2.5 mL 20% SDS6X refers to the concentration of SSC10X TBE Buffer (for polyacrylamide gels) to make one liter:60.75 g Tris3.7 g EDTA (tetrasodium salt)30 g Boric acid10X TAE Buffer (For agarose gels)to make one liter:48.20 g Tris6.75 g NaAce3.75 g EDTA (disodium salt)Adjust pH to 7.6 with acetic acid. (Approx. 20 mL)20X SSCto make one liter:175.3 g NaCl88.2 g NaCitrateadd water to bring volume to one liter.adjust to pH 7.0 with HCl.1% SDS, 0.2 M NaOHto make 100 mL:93 mL ddH205 mL 20% SDS2 mL 10 M NaOH14% PEG (8000), 2M NaCl, 10 mM MgSO4 to make one liter:140 g PEG117 g NaCl2.46 g MgSO4For use in phage DNA preparation.20% SDSto male 250 mL:50 g of SDS in a beakerAdd stir bar and H20 last.This solution will have to be heated for the SDS to dissolve.1.0 M Tris, pH 8.0, 1.5 M NaClto make one liter:121.1 g Trizma87.6 g NaClin a volume of water less than 1L. Adjust pH with HCl, then bring to 1L with H2010 mM Tris-HCl, pH 7.5, 10 mM MgSO4to make one liter:10 mL 1 M Tris-HCl2.46 g MgSO4for use in phage DNA preparation10 mM Tris, 50 mM EDTA, pH 7.5to make 200 mL:2 mL 1 M Tris20 mL 0.5 M EDTA (tetrasodium salt)178 mL ddH20adjust pH with HCl.10 mM Tris-HCl, 1 mM EDTA, pH 7.5to make 200 mL:2.0 mL 1 M Tris-HCl, pH 7.50.4 mL 0.5 M EDTA197.6 mL ddH203 M Sodium Acetate, pH 4.8to make one liter:408.1 g NaAce (trihydrate; gets cold in soln)about 700 mL H20adjust pH with glacial acetic acid (takes a lot)Measure tru pH by dilution with water; range will be between 4.8 and 5.5.Electrophoresis Dyeto make 4 mL:3 mL 50 mM EDTA, 10 mM Tris-HCl, pH 8.01 mL glycerol20 μL BPB10 μL Xylene cyanolStop dye for labelled probe1 mL 50 mM EDTA, 10 mM Tris, pH 7.5-8.5about 200 μl glyceroladd a few grains of blue dextran (8000)Sequencing gel dyefor approx 1 mL:1 mL formamide10 μL xylene cyanol10 μl BPB3 μL 10 M NaOH5% acrylamideto make 200 mL:20 mL 10X TBE25 mL 40% acrylamide155 mL H206% Acrylamide in TBE, 50% Ureato make 500 mL:50 mL 10X TBE75 mL 40% acrylamide250 g Ureabring to 500 mL with H2O40% Acrylamide (38:2 acrylamide:bis acrylamide) to make 200 mL:76 g acrylamide4 g bis acrylamidebring to 200 mL with H2O。

Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:TAK–875 is a potent, selective and orally bioavailable GPR40 agonist with EC 50 of 72 nM.IC50 & Target: EC50: 72 nM (GPR40)In Vitro: TAK–875 (0.01–10 μM) produces a concentration–dependent increase in intracellular IP production in CHO–hGPR40, with EC 50of 0.072 μM. TAK–875 (0.1–10 μM) dose–dependently augments intracellular IP production in CHO cells [1]. TAK–875 (3–30 μM)concentration–dependently augments [Ca 2+]i . In the presence of 10 mM glucose, TAK–875 (0.001–10 μM) dose–dependently stimulats insulin secretion from INS–1 833/15 cells [2].In Vivo: TAK–875 (10 mg/kg, p.o.) increases plasma insulin levels in ZDF rats. TAK–875 (30 mg/kg, p.o.) improves fasting hyperglycemia without affecting fasting normoglycemia. TAK–875 at 30 mg/kg, which is a 3– to 10–fold higher dose compared with the dose that improved glucose tolerance in diabetic rats, does not alter fasting glucose levels in SD rats with normal glucose homeostasis. Likewise,TAK–875 does not significantly alter insulin secretion in SD rats with normal fasting glucose levels [1].PROTOCOL (Extracted from published papers and Only for reference)Kinase Assay:[1]INS–1 832/13 cells are suspended in RPMI medium containing 11 mM glucose and the supplementsdescribed above. These cells are seeded at a density of 2×104 cells/well in a 96–well black plate coated with poly–D–lysine, and 1%BSA and 0.1% DMSO alone (control), palmitic acid (62.5, 125, 250, 500, and 1000 μM), oleic acid (62.5, 125, 250, 500, and 1000 μM), or TAK–875 (6.25, 12.5, 25, 50, and 100 μM) is added to the plate with 1% BSA and 0.1% DMSO, followed by culture for 72 h. After the culture, caspase 3/7 activity is measured with the Apo–one homogeneous caspase 3/7 assay according to the manufacturer's instructions. Fluorescence intensity is measured at an excitation of 485 nm and an emission at 535 nm.Cell Assay: TAK–875 is dissolved in 1% BSA and 0.1% DMSO. [1]INS–1 832/13 cells are suspended in RPMI medium and seeded in a 96–well plate at a density of 2×104 cells/well; 1% BSA and 0.1% DMSO alone (control), palmitic acid (10, 100, and 1000 μM), oleic acid (10, 100, and 1000 μM), or TAK–875 (1, 10, and 100 μM) is added to the plate. After 72–h culture, medium is discarded, and cells are preincubated for 2 h with KRBH containing 1 mM glucose and 0.2% BSA at 37°C. After discarding of the preincubation buffer, KRBH containing 1 or 20 mM glucose and 0.2% BSA is added, and the plate is further incubated for 2 h. The insulin concentration in the supernatant is measured as described above. To measure intracellular insulin content, INS–1 832/13 cells are exposed to 1% BSA and 0.1% DMSO alone (control), palmitic acid (1000 μM), oleic acid (1000 μM), or TAK–875 (100 μM) with 1% BSA and 0.1% DMSO. After incubation, cells are washed once with phosphate–buffered saline, and acid–ethanol solution is added to each well, followed by sonication on ice. Intracellular insulin is extracted by overnight incubation at -30°C, followed by separation of supernatant by centrifugation at 12,000 rpm×5 min at 4°C.Animal Administration: TAK–875 is formulated in 0.5% methylcellulose.[1]At 18 weeks of age, the N–STZ–1.5 rats are fasted overnight and orally given vehicle (0.5% methylcellulose) or TAK–875 (1, 3, and 10 mg/kg). Sixty minutes later, all animals receive an oral glucoseProduct Name:TAK–875Cat. No.:HY-10480CAS No.:1000413-72-8Molecular Formula:C 29H 32O 7S Molecular Weight:524.63Target:GPR40Pathway:GPCR/G Protein Solubility:DMSO: ≥ 128 mg/mLload (1 g/kg). Blood samples are collected from the tail vein before drug administration, before glucose load (time 0), and 10, 30, 60, and 120 min after the glucose load. Plasma glucose and insulin levels are measured with an AutoAnalyzer 7080 and radioimmunoassay, respectively. To see the effects of TAK–875 on fasting normoglycemia and hyperglycemia, SD rats (8 weeks old) or ZDF and ZL rats (12 weeks old) are fasted overnight and orally given vehicle (0.5% methylcellulose), TAK–875 (10 or 30 mg/kg), nateglinide (50 mg/kg), or glibenclamide (10 mg/kg). Blood samples are collected from the tail vein before drug administration (time 0) and 0.5, 1, 2, and 3 h (SD rats) and 0.5, 1, 2, 4, and 6 h (ZDF and ZL rats) after drug administration, and plasma glucose and insulin levels are measured as described above.References:[1]. Tsujihata Y,et al. TAK–875, an orally available G protein–coupled receptor 40/free fatty acid receptor 1 agonist, enhances glucose–dependent insulin secretion and improves both postprandial and fasting hyperglycemia in type 2 diabetic rats.J Pharmacol Exp[2]. Yoshiyuki Tsujihata, et al. TAK–875, an Orally Available GPR40/FFA1 Agonist Enhances Glucose–Dependent Insulin Secretion and Improves Both Postprandial and Fasting Hyperglycemia in Type 2 Diabetic Rats. JPET July 13, 2011Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。

Inhibitors, Agonists, Screening LibrariesSafety Data Sheet Revision Date:Oct.-11-2018Print Date:Oct.-11-20181. PRODUCT AND COMPANY IDENTIFICATION1.1 Product identifierProduct name :BAY-299Catalog No. :HY-107424CAS No. :2080306-23-41.2 Relevant identified uses of the substance or mixture and uses advised againstIdentified uses :Laboratory chemicals, manufacture of substances.1.3 Details of the supplier of the safety data sheetCompany:MedChemExpress USATel:609-228-6898Fax:609-228-5909E-mail:sales@1.4 Emergency telephone numberEmergency Phone #:609-228-68982. HAZARDS IDENTIFICATION2.1 Classification of the substance or mixtureNot a hazardous substance or mixture.2.2 GHS Label elements, including precautionary statementsNot a hazardous substance or mixture.2.3 Other hazardsNone.3. COMPOSITION/INFORMATION ON INGREDIENTS3.1 SubstancesSynonyms:NoneFormula:C25H23N3O4Molecular Weight:429.47CAS No. :2080306-23-44. FIRST AID MEASURES4.1 Description of first aid measuresEye contactRemove any contact lenses, locate eye-wash station, and flush eyes immediately with large amounts of water. Separate eyelids with fingers to ensure adequate flushing. Promptly call a physician.Skin contactRinse skin thoroughly with large amounts of water. Remove contaminated clothing and shoes and call a physician.InhalationImmediately relocate self or casualty to fresh air. If breathing is difficult, give cardiopulmonary resuscitation (CPR). Avoid mouth-to-mouth resuscitation.IngestionWash out mouth with water; Do NOT induce vomiting; call a physician.4.2 Most important symptoms and effects, both acute and delayedThe most important known symptoms and effects are described in the labelling (see section 2.2).4.3 Indication of any immediate medical attention and special treatment neededTreat symptomatically.5. FIRE FIGHTING MEASURES5.1 Extinguishing mediaSuitable extinguishing mediaUse water spray, dry chemical, foam, and carbon dioxide fire extinguisher.5.2 Special hazards arising from the substance or mixtureDuring combustion, may emit irritant fumes.5.3 Advice for firefightersWear self-contained breathing apparatus and protective clothing.6. ACCIDENTAL RELEASE MEASURES6.1 Personal precautions, protective equipment and emergency proceduresUse full personal protective equipment. Avoid breathing vapors, mist, dust or gas. Ensure adequate ventilation. Evacuate personnel to safe areas.Refer to protective measures listed in sections 8.6.2 Environmental precautionsTry to prevent further leakage or spillage. Keep the product away from drains or water courses.6.3 Methods and materials for containment and cleaning upAbsorb solutions with finely-powdered liquid-binding material (diatomite, universal binders); Decontaminate surfaces and equipment by scrubbing with alcohol; Dispose of contaminated material according to Section 13.7. HANDLING AND STORAGE7.1 Precautions for safe handlingAvoid inhalation, contact with eyes and skin. Avoid dust and aerosol formation. Use only in areas with appropriate exhaust ventilation.7.2 Conditions for safe storage, including any incompatibilitiesKeep container tightly sealed in cool, well-ventilated area. Keep away from direct sunlight and sources of ignition.Recommended storage temperature:Powder-20°C 3 years4°C 2 yearsIn solvent-80°C 6 months-20°C 1 monthShipping at room temperature if less than 2 weeks.7.3 Specific end use(s)No data available.8. EXPOSURE CONTROLS/PERSONAL PROTECTION8.1 Control parametersComponents with workplace control parametersThis product contains no substances with occupational exposure limit values.8.2 Exposure controlsEngineering controlsEnsure adequate ventilation. Provide accessible safety shower and eye wash station.Personal protective equipmentEye protection Safety goggles with side-shields.Hand protection Protective gloves.Skin and body protection Impervious clothing.Respiratory protection Suitable respirator.Environmental exposure controls Keep the product away from drains, water courses or the soil. Cleanspillages in a safe way as soon as possible.9. PHYSICAL AND CHEMICAL PROPERTIES9.1 Information on basic physical and chemical propertiesAppearance Light yellow to yellow (Solid)Odor No data availableOdor threshold No data availablepH No data availableMelting/freezing point No data availableBoiling point/range No data availableFlash point No data availableEvaporation rate No data availableFlammability (solid, gas)No data availableUpper/lower flammability or explosive limits No data availableVapor pressure No data availableVapor density No data availableRelative density No data availableWater Solubility No data availablePartition coefficient No data availableAuto-ignition temperature No data availableDecomposition temperature No data availableViscosity No data availableExplosive properties No data availableOxidizing properties No data available9.2 Other safety informationNo data available.10. STABILITY AND REACTIVITY10.1 ReactivityNo data available.10.2 Chemical stabilityStable under recommended storage conditions.10.3 Possibility of hazardous reactionsNo data available.10.4 Conditions to avoidNo data available.10.5 Incompatible materialsStrong acids/alkalis, strong oxidising/reducing agents.10.6 Hazardous decomposition productsUnder fire conditions, may decompose and emit toxic fumes.Other decomposition products - no data available.11.TOXICOLOGICAL INFORMATION11.1 Information on toxicological effectsAcute toxicityClassified based on available data. For more details, see section 2Skin corrosion/irritationClassified based on available data. For more details, see section 2Serious eye damage/irritationClassified based on available data. For more details, see section 2Respiratory or skin sensitizationClassified based on available data. For more details, see section 2Germ cell mutagenicityClassified based on available data. For more details, see section 2CarcinogenicityIARC: No component of this product present at a level equal to or greater than 0.1% is identified as probable, possible or confirmed human carcinogen by IARC.ACGIH: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by ACGIH.NTP: No component of this product present at a level equal to or greater than 0.1% is identified as a anticipated or confirmed carcinogen by NTP.OSHA: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by OSHA.Reproductive toxicityClassified based on available data. For more details, see section 2Specific target organ toxicity - single exposureClassified based on available data. For more details, see section 2Specific target organ toxicity - repeated exposureClassified based on available data. For more details, see section 2Aspiration hazardClassified based on available data. For more details, see section 212. ECOLOGICAL INFORMATION12.1 ToxicityNo data available.12.2 Persistence and degradabilityNo data available.12.3 Bioaccumlative potentialNo data available.12.4 Mobility in soilNo data available.12.5 Results of PBT and vPvB assessmentPBT/vPvB assessment unavailable as chemical safety assessment not required or not conducted.12.6 Other adverse effectsNo data available.13. DISPOSAL CONSIDERATIONS13.1 Waste treatment methodsProductDispose substance in accordance with prevailing country, federal, state and local regulations.Contaminated packagingConduct recycling or disposal in accordance with prevailing country, federal, state and local regulations.14. TRANSPORT INFORMATIONDOT (US)This substance is considered to be non-hazardous for transport.IMDGThis substance is considered to be non-hazardous for transport.IATAThis substance is considered to be non-hazardous for transport.15. REGULATORY INFORMATIONSARA 302 Components:No chemicals in this material are subject to the reporting requirements of SARA Title III, Section 302.SARA 313 Components:This material does not contain any chemical components with known CAS numbers that exceed the threshold (De Minimis) reporting levels established by SARA Title III, Section 313.SARA 311/312 Hazards:No SARA Hazards.Massachusetts Right To Know Components:No components are subject to the Massachusetts Right to Know Act.Pennsylvania Right To Know Components:No components are subject to the Pennsylvania Right to Know Act.New Jersey Right To Know Components:No components are subject to the New Jersey Right to Know Act.California Prop. 65 Components:This product does not contain any chemicals known to State of California to cause cancer, birth defects, or anyother reproductive harm.16. OTHER INFORMATIONCopyright 2018 MedChemExpress. The above information is correct to the best of our present knowledge but does not purport to be all inclusive and should be used only as a guide. The product is for research use only and for experienced personnel. It must only be handled by suitably qualified experienced scientists in appropriately equipped and authorized facilities. The burden of safe use of this material rests entirely with the user. MedChemExpress disclaims all liability for any damage resulting from handling or from contact with this product.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。

Total Cites Impact5-Year ImmediacyArticles (linked to journal informationFactor Impact Index1439CA-CANCER J CLIN0007-923513722153.45988.5527.0425 6399NEW ENGL J MED0028-479324560551.65850.80712.667360 7457REV MOD PHYS0034-68613572044.98251.882 6.47846 1675CHEM REV0009-266511259641.29845.79514.335176 6266NAT REV GENET1471-00562335841.06336.4 6.31470 5693LANCET0140-673616692239.0636.4279.556313 6278NATURE0028-0836********.59738.1599.243869 6269NAT REV MOL CELL BIO1471-00723134137.16244.026 5.98565 668ANNU REV IMMUNOL0732-05821596336.55643.7428.42928 6247NAT MATER1476-11224634835.74942.3768.411141 6240NAT GENET1061-40368118335.20934.52 5.511225 6260NAT REV CANCER1474-175X326283539.361 6.33369 277ADV PHYS0001-8732484934.29431.1670.8577 6267NAT REV IMMUNOL1474-173********.12935.851 4.83165 6263NAT REV DRUG DISCOV1474-177********.07833.2058.65143 6232NAT BIOTECHNOL1087-01563872832.43832.1827.08792 1565CELL0092-867417876231.95734.366 6.499415 6272NAT REV NEUROSCI1471-003X2693831.67335.888 5.06562 6250NAT NANOTECHNOL1748-33872192031.1736.011 5.876121 7624SCIENCE0036-807550848931.02733.587 6.691832 6948PHYSIOL REV0031-93332253730.17438.707 2.53839 5608JAMA-J AM MED ASSOC0098-748412150429.97829.2738.504232 652ANNU REV BIOCHEM0066-41541942027.68131.964 4.31232 6252NAT PHOTONICS1749-48851399327.25431.5677.492120 7140PROG POLYM SCI0079-67001445726.38331.706 4.60756 3430IEEE ENG MED BIOL0739-5175291326.3038.0190 6245NAT IMMUNOL1529-29083246526.19925.005 4.961128 677ANNU REV PATHOL-MECH1553-4006232225.79419.915 6.38918 1599CELL STEM CELL1934-59091259325.31527.361 4.336122 5696LANCET ONCOL1470-20451700525.11721.856 6.536153 1678CHEM SOC REV0306-00124764624.89230.1817.997390 1500CANCER CELL1535-61082220024.75527.059 4.465114 5695LANCET NEUROL1474-44221516023.91722.959 4.47289 682ANNU REV PLANT BIOL1543-50081343823.65429.248 3.18527 6249NAT METHODS1548-70911924123.56523.231 4.404151 651ANNU REV ASTRON ASTR0066-4146824023.33334.261 2.21414 7125PROG MATER 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1.297269 3374HUM MOL GENET0964-6906360417.6927.541 1.554478 7614SCI SIGNAL1937-914551687.6487.603 1.478182 4543J CONTROL RELEASE0168-3659297557.6338.078 1.136501 3024FRONT ECOL ENVIRON1540-929543167.61510.061 1.2560 7446REV MED VIROL1052-927617587.6157.024 1.35728 1204BIOMATERIALS0142-9612697927.6048.496 1.597898 5231J PATHOL0022-3417144687.585 6.928 2.376173 415AM J GASTROENTEROL0002-9270275217.5537.019 2.074188 4970J MAMMARY GLAND BIOL1083-302121207.524 5.838 1.225 656ANNU REV CHEM BIOMOL1947-54383317.5127.512 1.04522 7235Q REV BIOL0033-577033127.57.9040.1119 4037INT MATER REV0950-660822557.487.149 1.18816 876ARTHRITIS RHEUM-US0004-3591452007.4777.63 1.659411 1698CHEMSUSCHEM1864-563150567.4757.951 1.189286 2183CURR OPIN GENET DEV0959-437X81787.478.209 1.53880 7647SEMIN CANCER BIOL1044-579X42997.4367.107 2.22653 6140MOL ECOL RESOUR1755-098X47367.432 4.150.848132 7145PROG SOLID STATE CH0079-678614747.429 3.33806 675ANNU REV NUCL PART S0163-899821167.48.7770.73719 3210GONDWANA 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1.373378 929ASTROPHYS J0004-637X191940 6.733 5.945 2.0473075 1764CIRC-CARDIOVASC GENE1942-325X1641 6.728 6.398 1.17182 6921PHYS REV X2160-3308414 6.711 6.737 2.22571 6158MOL ONCOL1574-78911193 6.701 6.3790.91760 1768CIRC-HEART FAIL1941-32892007 6.684 6.67 1.41993 1309BMC MED1741-70152691 6.679 6.413 1.275109 1820CLIN GASTROENTEROL H1542-35658295 6.648 6.108 1.458179 6561ONCOTARGET1949-25531450 6.636 6.636 1.316114 2177CURR OPIN COLLOID IN1359-02944670 6.6297.0360.88443 2862EXPERT REV MOL MED1462-39941734 6.6230.78919 1417BRIT J PSYCHIAT0007-125021472 6.6067.112 1.872117 1019B AM METEOROL SOC0003-000711821 6.5917.704 2.48778 5280J PHYS CHEM LETT1948-71858575 6.585 6.651 1.301632 6902PHYS LIFE REV1571-0645659 6.583 6.699.45511 6990PLANT J0960-741232497 6.5827.113 1.5333456997PLANT PHYSIOL0032-088962407 6.5557.084 1.313469 5605JACC-CARDIOVASC INTE1936-87983378 6.552 6.834 1.603126 2396DRUG DISCOV TODAY1359-64468855 6.551 6.89 1.177158 271ADV MICROB PHYSIOL0065-29111006 6.545 6.267 1.25 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6.986 1.097370 636ANN SURG0003-493236761 6.3298.264 1.15301 6973PLANT BIOTECHNOL J1467-76443136 6.279 5.813 1.04101 6139MOL ECOL0962-108330411 6.275 6.792 1.369445 2110CRIT REV TOXICOL1040-84442955 6.253 5.9720.94335 6339NEUROIMAGE1053-811961770 6.2527.063 1.2911222 2595ENVIRON INT0160-41209059 6.248 6.1220.935199 5339J PSYCHIATR NEUROSCI1180-48822253 6.242 6.473 1.64734 6226NANOSCALE2040-33647835 6.233 6.262 1.1671015 7886STUD MYCOL0166-06161237 6.231 6.813 4.1676 6869PHILOS T R SOC B0962-843626581 6.237.298 3.522289 2310DEVELOPMENT0950-199151191 6.208 6.888 1.258434 7648SEMIN CELL DEV BIOL1084-95215613 6.202 6.51 1.034116 3764INT J CANCER0020-713644529 6.198 5.474 1.39738 4915J INVEST DERMATOL0022-202X23976 6.193 6.065 1.898264 471AM J TRANSPLANT1600-613516088 6.192 6.014 1.506348 6318NEURO-ONCOLOGY1522-85173845 6.18 5.9470.694157 231ADV COLLOID INTERFAC0001-86867115 6.1698.01 1.3250 6320NEUROBIOL AGING0197-458015479 6.166 6.098 1.583537 5604JACC-CARDIOVASC IMAG1936-878X2977 6.164 6.703 1.717113 2080CORTEX0010-94525265 6.161 5.042 2.745106 7864STROKE0039-249952524 6.158 6.831 1.086567 1640CHEM BIOL1074-55219695 6.157 6.097 1.486144 6621ORG LETT1523-706073440 6.142 5.563 1.5721608 4378J BONE MINER RES0884-043122111 6.128 6.227 1.101257 6165MOL PLANT1674-20522346 6.126 5.77 1.585118 2094CRIT CARE MED0090-349332733 6.124 6.401 2.614363 2371DIVERS DISTRIB1366-95164336 6.122 5.7430.935107 1863CLIN PHARMACOKINET0312-******** 6.109 5.4860.98154 8313WHO TECH REP SER0512-******** 6.1 3.2560.35714 8039THROMB HAEMOSTASIS0340-624517392 6.094 4.782 1.3462465510J THROMB HAEMOST1538-793314645 6.081 6.176 1.17265 5876MATER TODAY1369-70213769 6.0718.677 1.97744 1578CELL DEATH DIS2041-48891481 6.044 6.0440.565191 4548J COSMOL ASTROPART P1475-751613656 6.036 5.295 2.387555 1523CANCER TREAT REV0305-73724233 6.024 6.246 1.458107 7131PROG NUCL MAG RES SP0079-65651993 6.022 6.065 1.38918 1285BLOOD REV0268-960X17706 6.6620.76939 7877STRUCTURE0969-212612441 5.994 6.081 1.466191 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5.7690.9481479 6697P ROY SOC B-BIOL SCI0962-845237539 5.683 5.832 1.224624 8330WIRES NANOMED NANOBI1939-5116983 5.681 6.34 1.08547 1767CIRC-CARDIOVASC QUAL1941-77051551 5.658 5.647 1.43100 7369RETROVIROLOGY1742-46903084 5.657 4.857 1.505107 6713PAIN0304-395929370 5.644 6.125 1.264269 3917INT J NEUROPSYCHOPH1461-14574003 5.641 5.0920.805123 1530CARCINOGENESIS0143-333421223 5.635 5.5570.9553106383NEUROSCIENTIST1073-85843259 5.633 6.417 1.35645 7327RENEW SUST ENERG REV1364-032110347 5.627 6.5770.803584 6321NEUROBIOL DIS0969-996111288 5.624 5.482 1.493296 5925MBIO2150-75111260 5.621 5.621 1.536151 4817J HIGH ENERGY PHYS1126-670852898 5.618 4.712 2.6581861 1589CELL MOL LIFE SCI1420-682X17974 5.615 6.359 1.072290 5022J MED CHEM0022-262359227 5.614 5.383 1.225890 1362BRAIN BEHAV IMMUN0889-15916137 5.612 5.698 1.082147 6124MOL CANCER THER1535-716314654 5.599 5.72 1.201259 1873CLIN REV ALLERG IMMU1080-05491685 5.59 3.955 1.30662 7194PSYCHOL MED0033-291716680 5.587 6.1480.913230 2098CRIT REV 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Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:Alda–1 is a potent ALDH2 agonist, which significantly improves ALDH2 activity.In Vivo: Alda–1 treatment results in a significant decrease of 4–HNE–protein content in the plasma of apoE -/- mice. Alda–1administration leads to a slight increase in gene expression related to neurogenesis (Nog ), mitochondrial biogenesis (CYTB , ND1),and apoptosis (Bax , Gsk3b ) in the Hp of apoE -/- mice. Alda–1 administration leads to 2 and 10 differentially expressed proteins in theFCx and Hp of apoE -/- mice, respectively [1]. Alda–1 (1.5 mg/kg, b.w., i.p.) administration significantly increases the climbing time,tends to reduce the immobility time and increases the swimming time of the prenatally stressed rats in the forced swim test.Moreover, treatment of prenatally stressed rats with Alda–1 significantly increases number of entries into the open arms of the maze and the time spent therein, as assessed by elevated plus–maze test [2]. Alda–1 (8.5 mg/kg, i.p.) with glucose significantly lowers 4–HNE and FJB–positive cells in the cerebral cortex of Alda–1–treated rats than in DMSO–treated rats 24 h after glucose administration [3]. Alda–1 (10 mg/kg per day) treatment prevents aldehydic overload, mitochondrial dysfunction and improves ventricular function in post–MI cardiomyopathy rats [4].PROTOCOL (Extracted from published papers and Only for reference)Cell Assay:[2]Spleen cells (4×106 cells/mL) are stimulated by optimal concentrations of concanavalin A (Con A; 2.5μg/mL and 0.6 μg/mL) and lipopolysaccharide (LPS, 5 μg/mL) and are incubated in 96–well plates at final volume of 0.2mL for 72 h. Cell proliferation is determined by adding 0.5 μCi of [3H]–thymidine per well at 16 h before the end of the incubation.The cultures are harvested with an automatic cell harvester, and [3H] thymidine incorporation is assessed using a liquid scintillationcounter.Animal Administration: Alda–1 is dissolved in 1 mL/kg b.w. DMSO/water 50/50.[2]After behavioral verification at three months of age,the animals are divided into the following four groups: control, control + Alda–1, prenatally stressed and prenatally stressed + Alda–1(6 animals per group). Alda–1 injections are given intraperitoneally (i.p.) once daily at a dose of 1.5 mg/kg b.w. (dissolved in 1 mL/kg b.w. DMSO/water 50/50) for 14 days. At the same time, the control and prenatally stressed rats receive 1 mL/kg b.w. DMSO/water 50/50. The injections of Alda–1 and vehicle are given between 10 a.m and 11 a.m. In the last five days of Alda–1 treatment the behavioral parameters in the elevated plus maze test and then in the forced swim test are measured.References:[1]. Stachowicz A, et al. Proteomic Analysis of Mitochondria–Enriched Fraction Isolated from the Frontal Cortex and Hippocampus of Apolipoprotein E Knockout Mice Treated with Alda–1, an Activator of Mitochondrial Aldehyde Dehydrogenase (ALDH2). Int J Mol Sci.[2]. Stachowicz A, et al. The impact of mitochondrial aldehyde dehydrogenase (ALDH2) activation by Alda–1 on the behavioral and biochemical disturbances in animal model of depression. Brain Behav Immun. 2016 Jan;51:144–53.Product Name:Alda–1Cat. No.:HY-18936CAS No.:349438-38-6Molecular Formula:C 15H 11Cl 2NO 3Molecular Weight:324.16Target:Aldehyde Dehydrogenase (ALDH)Pathway:Metabolic Enzyme/Protease Solubility:DMSO: ≥ 51 mg/mL[3]. Ikeda T, et al. Effects of Alda–1, an Aldehyde Dehydrogenase–2 Agonist, on Hypoglycemic Neuronal Death. PLoS One. 2015 Jun 17;10(6):e0128844.[4]. Gomes KM, et al. Aldehydic load and aldehyde dehydrogenase 2 profile during the progression of post–myocardial infarction cardiomyopathy: benefits of Alda–1. Int J Cardiol. 2015 Jan 20;179:129–138.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。