Isosilybin A
(Synonyms: 异水飞蓟宾A) 目录号 : GC36343
Isosilybin A 是一种从 silymarin 中分离出来的黄酮木脂素，具有抗前列腺癌 (PCA) 活性。Isosilybin A 抑制癌细胞增殖并诱导 G1 期停滞和凋亡，通过靶向 Akt-NF-κB-androgen receptor (AR) 轴激活前列腺癌细胞的凋亡机制。
Cas No.:142796-21-2
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Isosilybin A, a flavonolignan isolated from silymarin, has anti-prostate cancer (PCA) activity. Isosilybin A inhibits proliferation and induces G1 phase arrest and apoptosis in cancer cells, which activates apoptotic machinery in PCA cells via targeting Akt-NF-κB-androgen receptor (AR) axis[1][2].
[1]. Deep G, et al. Isosilybin B and isosilybin A inhibit growth, induce G1 arrest and cause apoptosis in human prostatecancer LNCaP and 22Rv1 cells. Carcinogenesis. 2007 Jul;28(7):1533-42. [2]. Deep G, et al. Isosilybin A induces apoptosis in human prostate cancer cells via targeting Akt, NF-κB, and androgen receptor signaling. Mol Carcinog. 2010 Oct;49(10):902-12.
| Cas No. | 142796-21-2 | SDF | |
| 别名 | 异水飞蓟宾A | ||
| Canonical SMILES | O=C1[C@H](O)[C@@H](C2=CC=C(O[C@H](C3=CC=C(O)C(OC)=C3)[C@@H](CO)O4)C4=C2)OC5=CC(O)=CC(O)=C15 | ||
| 分子式 | C25H22O10 | 分子量 | 482.44 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.0728 mL | 10.364 mL | 20.728 mL |
| 5 mM | 0.4146 mL | 2.0728 mL | 4.1456 mL |
| 10 mM | 0.2073 mL | 1.0364 mL | 2.0728 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Isosilybin B and Isosilybin A inhibit growth, induce G1 arrest and cause apoptosis in human prostate cancer LNCaP and 22Rv1 cells
Carcinogenesis 2007 Jul;28(7):1533-42.PMID:17389612DOI:10.1093/carcin/bgm069.
Silymarin and, one of its constituents, silibinin exert strong efficacy against prostate cancer (PCA); however, anticancer efficacy and associated mechanisms of other components of silymarin, which is a mixture of flavonolignans, are largely unknown. Here we have assessed the anticancer efficacy of two pure compounds isosilybin B and Isosilybin A, isolated from silymarin, in human prostate carcinoma LNCaP and 22Rv1 cells. Isosilybin B and Isosilybin A treatment resulted in growth inhibition and cell death together with a strong G(1) arrest and apoptosis in both the cell lines. In the studies examining changes in cell cycle and apoptosis regulators, isosilybin B and Isosilybin A resulted in a decrease in the levels of both cyclins (D1, D3, E and A) and cyclin-dependent kinases (Cdk2, Cdk4 and cell division cycle 25A), but caused an increase in p21, p27 and p53 levels, except in 22Rv1 cells where isosilybin B caused a decrease in p21 protein level. Isosilybin B- and isosilybin A-induced apoptosis was accompanied with an increase in the cleavage of poly (ADP-ribose) polymerase, caspase-9 and caspase-3 and a decrease in survivin levels. Compared with LNCaP and 22Rv1 cells, the antiproliferative and cytotoxic potentials of isosilybin B and Isosilybin A were of much lesser magnitude in non-neoplastic human prostate epithelial PWR-1E cells suggesting the transformation-selective effect of these compounds. Together, this study for the first time identified that isosilybin B and Isosilybin A, two diastereoisomers isolated from silymarin, have anti-PCA activity that is mediated via cell cycle arrest and apoptosis induction.
Isosilybin A induces apoptosis in human prostate cancer cells via targeting Akt, NF-κB, and androgen receptor signaling
Mol Carcinog 2010 Oct;49(10):902-12.PMID:20721970DOI:10.1002/mc.20670.
Prostate cancer (PCA) is the second most malignancy in American men. Advanced stage PCA cells possess unlimited replication potential as well as resistance to apoptosis. Therefore, targeting survival mechanisms and activating apoptotic machinery in PCA cells using nontoxic phytochemicals is suggested as an attractive strategy against this deadly malignancy. In the present study, we assessed the effect of one such botanical agent, namely Isosilybin A, on apoptotic machinery and key members of cell survival signaling [Akt, NF-κB, and androgen receptor (AR)] in different PCA cells. Results showed that Isosilybin A (90-180 µM) treatment significantly induces apoptotic death by activating both extrinsic (increased level of DR5 and cleaved caspase 8) and intrinsic pathways (caspase 9 and 3 activation) of apoptosis in three different human PCA cell lines namely 22Rv1, LAPC4, and LNCaP. Further, Isosilybin A treatment decreased the levels of phospho-Akt (serine-473), total Akt, and the nuclear levels of NF-κB constituents (p50 and p65). Isosilybin A treatment also decreased the AR and PSA level in 22Rv1, LAPC4, and LNCaP cells. Employing pan-caspase inhibitor (Z-VAD.fmk), we confirmed that isosilybin A-mediated decreased AR is independent of caspases activation. Temporal kinetics analysis showed that the primary effect of Isosilybin A is on AR, as decrease in AR was evident much earlier (4 h) relative to caspase activation and apoptosis induction (12 h). Overall, our results demonstrated that Isosilybin A activates apoptotic machinery in PCA cells via targeting Akt-NF-κB-AR axis; thereby, indicating a promising role for this phytochemical in the management of clinical PCA.
Identification of Isosilybin A from milk thistle seeds as an agonist of peroxisome proliferator-activated receptor gamma
J Nat Prod 2014 Apr 25;77(4):842-7.PMID:24597776DOI:10.1021/np400943b.
Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of glucose and lipid metabolism. Agonists of this nuclear receptor are used in the treatment of type 2 diabetes and are also studied as a potential treatment of other metabolic diseases, including nonalcoholic fatty liver disease. Silymarin, a concentrated phenolic mixture from milk thistle (Silybum marianum) seeds, is used widely as a supportive agent in the treatment of a variety of liver diseases. In this study, the PPARγ activation potential of silymarin and its main constituents was investigated. Isosilybin A (3) caused transactivation of a PPARγ-dependent luciferase reporter in a concentration-dependent manner. This effect could be reversed upon co-treatment with the PPARγ antagonist T0070907. In silico docking studies suggested a binding mode for 3 distinct from that of the inactive silymarin constituents, with one additional hydrogen bond to Ser342 in the entrance region of the ligand-binding domain of the receptor. Hence, Isosilybin A (3) has been identified as the first flavonolignan PPARγ agonist, suggesting its further investigation as a modulator of this nuclear receptor.
Absolute configuration of Isosilybin A by X-ray crystallography of the heavy atom analogue 7-(4-Bromobenzoyl)Isosilybin A
J Nat Prod 2012 Nov 26;75(11):1879-81.PMID:23116206DOI:10.1021/np3005369.
Isosilybin A (1) is one of the major flavonolignans that constitute silymarin, an extract of the fruits (achenes) of milk thistle (Silybum marianum). The chemistry of the Silybum flavonolignans has been studied for over four decades, and the absolute configuration of 1 has been determined previously by electronic circular dichroism and X-ray crystallography via correlating the relative configuration of the phenylpropanoid moiety to the established absolute configuration of the 3-hydroxyflavanone portion of the molecule. Herein we report the X-ray crystallographic structure of the product of the reaction of 1 with 4-bromobenzoyl chloride, and, thus, the absolute configuration of 1 was established as (2R, 3R, 7″R, 8″R) directly via X-ray crystallography of an analogue that incorporated a heavy atom. The results were consistent with previously reported assignments and verified the absolute configuration of the diastereoisomer of 1, isosilybin B, and the related diastereoisomeric regioisomers, silybin A and silybin B.
Molecular structure and stereochemistry of silybin A, silybin B, Isosilybin A, and isosilybin B, Isolated from Silybum marianum (milk thistle)
J Nat Prod 2003 Sep;66(9):1171-4.PMID:14510591DOI:10.1021/np030163b.
Two pairs of diastereoisomeric flavonolignans, silybin A, silybin B, Isosilybin A, and isosilybin B, were successfully separated from Silybum marianum by sequential silica gel column chromatography, preparative reversed-phase HPLC, and recrystallization. Complete stereochemical assignments at C-2, C-3, C-7', and C-8' of these flavonolignans have been achieved. On the basis of X-ray crystallographic analysis and optical rotation data, coupled with comprehensive (1)H and (13)C NMR spectral data interpretation including COSY, HMQC, and HMBC, the stereochemistry of these diastereoisomers was determined unambiguously as silybin A (4), 2R, 3R, 7'R, 8'R; silybin B (5), 2R, 3R, 7'S, 8'S; Isosilybin A (6), 2R, 3R, 7'R, 8'R; and isosilybin B (7), 2R, 3R, 7'S, 8'S.