Deguelin   中文名称: 鱼藤素

PI3K; Akt

Deguelin 下调具有活跃 PI3K/Akt 轴的白血病细胞系中的 Akt 磷酸化。 Deguelin 在浓度为 10 或 100 nmol/l 时可有效防止 Akt 磷酸化。德桂林总 Akt 表达不受影响。 Deguelin 对 U937 细胞中 p44/42 或 p38 MAP 激酶的磷酸化或表达也没有影响。德桂林使人类白血病细胞对化疗更敏感。 Deguelin 在 AML 母细胞中增加阿糖胞苷敏感性并使 Akt 去磷酸化，但在 CB CD34+ 中则不然。当以 10 nmol/l 的浓度使用 24 小时时，deguelin 将 U937 细胞阻滞在 S 期，并阻止它们进展到 G2/M 期。 Deguelin 在 10 nmol/l 浓度下单独使用 24 小时，不会显着增加 U937 细胞的凋亡率[1]。

Deguelin 可抑制鸡绒毛尿囊膜 (CAM) 的体内血管生成，且无细胞毒性作用，并可显着降低 AMD 小鼠模型中激光诱导的 CNV，且无明显的视网膜毒性[2]。它在不同癌症类型中表现出显着的体外和体内抗肿瘤发生和抗增殖活性。在临床前研究中，Deguelin 显着降低了肿瘤的发生率。当局部使用 Deguelin 时，可以显着减少由 UVB 暴露引起的皮肤肿瘤的数量，这表明它可能具有作为癌症化学预防剂的潜力。在暴露于烟草特异性致癌物苯并(a)芘 (Bap) 和其他致癌物的 A/J 小鼠中，德桂林显着降低了肿瘤的多样性和体积以及总体肿瘤负荷，且没有明显的毒性。然而，超过一定剂量的德桂林是有毒的，因此不应忽视这一点。帕金森氏病是由鱼腥草素治疗引起的，鱼腥草素是一种潜在的线粒体复合物 I 抑制剂，可减少酪氨酸羟化酶阳性神经元的数量。 Kim 等人表明，鱼胶素主要通过 Src/STAT 信号传导促进 PD 样综合征，因为 α-突触核蛋白（PD 发病机制中的关键蛋白功能）被鱼胶素激活的 Src 磷酸化[3]。

使用 Caspase-Glo-3 测定法测定 Caspase 3 活性。该测定在针对每种特定 caspase 活性进行优化的缓冲系统中提供发光底物。半胱天冬酶裂解底物后会产生发光信号。产生的信号与样品中存在的半胱天冬酶活性量成正比。将细胞样品中的蛋白质 (10 µg) 用水稀释至最终体积 50 µL，然后将 50 µL Caspase-Glo-3 试剂添加到白色 96 孔微量滴定板中。将板密封，以 300-500 rpm 轻轻混合 30 秒，然后在室温下孵育 30 分钟。在酶标仪 (TECAN Infinite 200) 中测量发光。

将 Deguelin 与乳腺癌细胞以递增的浓度孵育 24、48 和 72 小时。浓度范围为 31 nM 至 500 nM。最后，对细胞进行胰蛋白酶处理，并通过使用 Z 系列库尔特计数器对细胞进行计数来评估细胞增殖。数据显示为对照的 MeanSE%。

Female athymic mice (nu/nu), which are six to seven weeks old, are kept in barrier-free housing with 12-hour light/12-hour dark cycles in an environment with a temperature of 24°C and a relative humidity of 50%. Water is available at all times, along with sterile mouse food. The dorsal flank region of the animal is subcutaneously injected with a 23 g hypodermic needle after MDA-MB-231 cells (3.0 million cells/animal) are injected in sterile PBS suspension. A palpable tumor at the injection site is checked daily on the animals. The mice are divided randomly into three groups and given one of the following after the tumor (about 50 mm3) appears: 1) a vehicle as a control. 2) Deguelin therapy at a dose of 2 mg/kg body weight; or 3) Deguelin at a dose of 4 mg/kg body weight. Ten creatures make up each group. For a period of 21 days, vehicle or deguelin is given by i.p. injection. The toxicity of the drugs and vehicles is observed in animals every day, and they are weighed once per week. Every other day, the tumor's growth is observed, and every other day, calipers are used to measure the tumor's size. The widely used equation tumor volume (mm3)=π/6 lengthwidthdepth is used to calculate tumor volume. The information shown in each group's average tumor volume plus SE (mm3). Except when they appear to be moribund or tumors exhibit necrosis, the animals are sacrificed at the appointed time. At termination, the tumor is excised, freed from connective tissue and other organs, a small piece is fixed in 10% buffered formalin, and the remaining tumor is snap-frozen for a future biochemical analysis. The liver, lung, kidney, and spleen are removed and weighed.

---

Eight-week-old male and female C57BL/6 mice were used. The experimental procedures were approved by the Animal Ethics Committee of Southern Medical University. The mice were housed in a controlled environment with 12 h light/dark cycles, a temperature of 25 ± 2°C, humidity between 40% between 60%, and had free access to water and food. Referring to our previous study,11 the ALF model was induced by APAP (300 mg/kg, Macklin, Shanghai, China) via oral gavage at 8:00 PM. To investigate the protective role of deguelin (dissolved in sesame oil) in ALF, the APAP-treated mice were immediately injected intraperitoneally with deguelin (20 mg/kg, InvivoChem, Guangzhou, China) or sesame oil for 24 h. For inhibitor experiment, ML224 (10 mg/kg, InvivoChem, Guangzhou, China) was injected intraperitoneally into mice. Reference: Gut Microbes. 2024 Jan-Dec;16(1):2404138.

Rat LD oral >2 gm/kg

[1]. Br J Haematol. 2005 Jun;129(5):677-86.

[2]. J Pharmacol Exp Ther. 2008 Feb;324(2):643-7.

[3]. Mol Clin Oncol. 2013 Mar;1(2):215-219.

Deguelin is a rotenone that is 13,13a-dihydro-3H-chromeno[3,4-b]pyrano[2,3-h]chromen-7(7aH)-one substituted by methoxy groups at positions 9 and 10, and by two methyl groups at position 3 (the 7aS,13aS-stereoisomer). It exists in abundant quantities in the bark, roots, and leaves of the Leguminosae family of plants and reported to exert anti-tumour effects in various cancers. It has a role as an apoptosis inducer, an antineoplastic agent, a plant metabolite, an angiogenesis inhibitor, an antiviral agent, a mitochondrial NADH:ubiquinone reductase inhibitor, an anti-inflammatory agent and an EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor. It is a member of rotenones, an aromatic ether, an organic heteropentacyclic compound and a diether.
Deguelin has been reported in Piscidia piscipula, Derris elliptica, and other organisms with data available.

C23H22O6

394.4172

394.141

C, 70.04; H, 5.62; O, 24.34

522-17-8

522-17-8

107935

Light yellow to yellow solid powder

1.3±0.1 g/cm3

560.1±50.0 °C at 760 mmHg

85-87ºC(lit.)

244.7±30.2 °C

0.0±1.5 mmHg at 25°C

1.584

5.03

63.22

0

6

2

29

674

2

O1C2C3C([H])=C([H])C(C([H])([H])[H])(C([H])([H])[H])OC=3C([H])=C([H])C=2C([C@@]2([H])C3=C([H])C(=C(C([H])=C3OC([H])([H])[C@@]12[H])OC([H])([H])[H])OC([H])([H])[H])=O

ORDAZKGHSNRHTD-UXHICEINSA-N

InChI=1S/C23H22O6/c1-23(2)8-7-12-15(29-23)6-5-13-21(24)20-14-9-17(25-3)18(26-4)10-16(14)27-11-19(20)28-22(12)13/h5-10,19-20H,11H2,1-4H3/t19-,20+/m1/s1

(7aS,13aS)-9,10-dimethoxy-3,3-dimethyl-13,13a-dihydro-3H-pyrano[2,3-c:6,5-f'''']dichromen-7(7aH)-one.

(-)-Deguelin; (-)-cis-deguelin; DEGUELIN(-); CHEBI:4357; K5Z93K66IE; MFCD01740600; (-)-cis-Deguelin

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~78 mg/mL (197.8 mM)
Water: <1 mg/mL
Ethanol: 78 mg/mL (197.8 mM)

配方 1 中的溶解度: ≥ 2.5 mg/mL (6.34 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

---

配方 2 中的溶解度: 2.5 mg/mL (6.34 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

---

View More

配方 3 中的溶解度: ≥ 2.5 mg/mL (6.34 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

---

请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。