Isoginkgetin
(Synonyms: 异银杏素) 目录号 : GC32758
A biflavonoid inhibitor of pre-mRNA splicing
Cas No.:548-19-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Isoginkgetin is a biflavonoid that has been found in G. biloba and is an inhibitor of pre-mRNA splicing.1 Isoginkgetin (33 μM) reduces the activity of an mRNA-dependent luciferase reporter by 5-fold, shifts the composition of total RNA extract from predominantly mRNA to pre-mRNA, and arrests cell growth in HEK293 cells. Isoginkgetin (10 μM) suppresses mouse lymphocyte proliferation induced by concanavalin A and LPS by approximately 87 and 90%, respectively.2 It also suppresses arachidonic acid release induced by phorbol 12-myristate 13-acetate and the calcium ionophore A23187 by 32.5 and 48.4%, respectively, in rat peritoneal macrophages when used at a concentration of 10 μM.3 Isoginkgetin (5-20 μM) reduces matrix metalloproteinase-9 (MMP-9) activity, expression, and mRNA levels in and decreases cell invasion by HT1080 fibrosarcoma cells in a concentration-dependent manner.4
1.O'Brien, K., Matlin, A.J., Lowell, A.M., et al.The biflavonoid isoginkgetin is a general inhibitor of pre-mRNA splicingJ. Biol. Chem.283(48)33147-33154(2008) 2.Lee, S.J., Choi, J.H., Son, K.H., et al.Suppression of mouse lymphocyte proliferation in vitro by naturally-occurring biflavonoidsLife Sci.57(6)551-558(1995) 3.Lee, S.J., Son, K.H., Chang, H.W., et al.Inhibition of arachidonate release from rat peritoneal macrophage by biflavonoidsArch. Pharm. Res.20(6)533-538(1997) 4.Yoon, S.-O., Shin, S.S., Lee, H.-J., et al.Isoginkgetin inhibits tumor cell invasion by regulating phosphatidylinositol 3-kinase/Akt-dependent matrix metalloproteinase-9 expressionMol. Cancer Ther.5(11)2666-2675(2006)
| Cas No. | 548-19-6 | SDF | |
| 别名 | 异银杏素 | ||
| Canonical SMILES | O=C1C=C(C2=CC=C(OC)C=C2)OC3=C(C4=CC(C5=CC(C6=C(O)C=C(O)C=C6O5)=O)=CC=C4OC)C(O)=CC(O)=C13 | ||
| 分子式 | C32H22O10 | 分子量 | 566.51 |
| 溶解度 | DMSO : ≥ 83.3 mg/mL (147.04 mM) | 储存条件 | Store at 2-8°C,protect from light |
| 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。 |
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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7652 mL | 8.826 mL | 17.6519 mL |
| 5 mM | 0.353 mL | 1.7652 mL | 3.5304 mL |
| 10 mM | 0.1765 mL | 0.8826 mL | 1.7652 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。
Isoginkgetin treatment attenuated lipopolysaccharide-induced monoamine neurotransmitter deficiency and depression-like behaviors through downregulating p38/NF-κB signaling pathway and suppressing microglia-induced apoptosis
J Psychopharmacol 2021 Oct;35(10):1285-1299.PMID:34281416DOI:10.1177/02698811211032473.
Background: Microglia activation-induced neuroinflammation may contribute to the etiology of depression. Podocarpus nagi containing high concentration of Isoginkgetin could effectively treat mental diseases in ancient times. However, the therapeutic role, peculiarly in the brain-immune modulation in depression is still unclear. This study aimed to determine effects of Isoginkgetin on lipopolysaccharide (LPS)-induced depression-like changes. Furthermore, its modulation on the p38/nuclear factor-kappa B (NF-κB) pathway in LPS-activated microglia was evaluated. Methods: Adult Kunming mice were intraperitoneally injected vehicle or Isoginkgetin (4 mg/kg) daily for 14 days before saline or LPS (0.83 mg/kg) administration. Depression-like behavior, neurotransmitter levels, and markers of neuroinflammation were determined. Isoginkgetin effect on LPS-induced microglial activation was then assessed in BV2 cells. Finally, conditioned medium (CM) derived from isoginkgetin-treated BV2 cells was co-cultured with SH-SY5Y cells for 24 h. Cell viability and apoptosis were evaluated. Results: LPS significantly induced helplessness and anxiety, which were associated with decreased 5-HT, noradrenaline, and dopamine concentrations. Meanwhile, LPS increased microglia M1 hallmark Iba1 expression and serum interleukin (IL)-1β concentration. These changes were attenuated by Isoginkgetin treatment. In vitro, Isoginkgetin markedly suppressed the production of IL-1β, IL-6, tumor necrosis factor-alpha, cyclooxygenase-2, inducible nitric oxide, and reactive oxygen species, which are released from LPS-stimulated BV2 cells. More interestingly, CM from isoginkgetin-treated BV2 cells significantly alleviated SH-SY5Y cell apoptosis and restored cell viability compared to LPS-treated group through the inhibition of p38/NF-κB signaling pathway. Conclusion: These data demonstrate that Isoginkgetin is an effective therapeutic agent for depression-like behaviors and neuropathological changes via potent anti-inflammatory property.
Isoginkgetin, a potential CDK6 inhibitor, suppresses SLC2A1/GLUT1 enhancer activity to induce AMPK-ULK1-mediated cytotoxic autophagy in hepatocellular carcinoma
Autophagy 2023 Apr;19(4):1221-1238.PMID:PMC10012924DOI:10.1080/15548627.2022.2119353.
Isoginkgetin (ISO), a natural biflavonoid, exhibited cytotoxic activity against several types of cancer cells. However, its effects on hepatocellular carcinoma (HCC) cells and mechanism remain unclear. Here, we revealed that ISO effectively inhibited HCC cell proliferation and migration in vitro. LC3-II expression and autophagosomes were increased under ISO treatment. In addition, ISO-induced cell death was attenuated by treatment with chloroquine or knockdown of autophagy-related genes (ATG5 or ULK1). ISO significantly suppressed SLC2A1/GLUT1 (solute carrier family 2 member 1) expression and glucose uptake, leading to activation of the AMPK-ULK1 axis in HepG2 cells. Overexpression of SLC2A1/GLUT1 abrogated ISO-induced autophagy. Combining molecular docking with thermal shift analysis, we confirmed that ISO directly bound to the N terminus of CDK6 (cyclin-dependent kinase 6) and promoted its degradation. Overexpression of CDK6 abrogated ISO-induced inhibition of SLC2A1/GLUT1 transcription and induction of autophagy. Furthermore, ISO treatment significantly decreased the H3K27ac, H4K8ac and H3K4me1 levels on the SLC2A1/GLUT1 enhancer in HepG2 cells. Finally, ISO suppressed the hepatocarcinogenesis in the HepG2 xenograft mice and the diethylnitrosamine+carbon tetrachloride (DEN+CCl4)-induced primary HCC mice and we confirmed SLC2A1/GLUT1 and CDK6 as promising oncogenes in HCC by analysis of TCGA data and human HCC tissues. Our results provide a new molecular mechanism by which ISO treatment or CDK6 deletion promotes autophagy; that is, ISO targeting the N terminus of CDK6 for degradation inhibits the expression of SLC2A1/GLUT1 by decreasing the enhancer activity of SLC2A1/GLUT1, resulting in decreased glucose levels and inducing the AMPK-ULK1 pathway.
Isoginkgetin derivative IP2 enhances the adaptive immune response against tumor antigens
Commun Biol 2021 Mar 1;4(1):269.PMID:33649389DOI:10.1038/s42003-021-01801-2.
The success of cancer immunotherapy relies on the induction of an immunoprotective response targeting tumor antigens (TAs) presented on MHC-I molecules. We demonstrated that the splicing inhibitor Isoginkgetin and its water-soluble and non-toxic derivative IP2 act at the production stage of the pioneer translation products (PTPs). We showed that IP2 increases PTP-derived antigen presentation in cancer cells in vitro and impairs tumor growth in vivo. IP2 action is long-lasting and dependent on the CD8+ T cell response against TAs. We observed that the antigen repertoire displayed on MHC-I molecules at the surface of MCA205 fibrosarcoma is modified upon treatment with IP2. In particular, IP2 enhances the presentation of an exon-derived epitope from the tumor suppressor nischarin. The combination of IP2 with a peptide vaccine targeting the nischarin-derived epitope showed a synergistic antitumor effect in vivo. These findings identify the spliceosome as a druggable target for the development of epitope-based immunotherapies.
Isoginkgetin leads to decreased protein synthesis and activates an ATF4-dependent transcriptional response
Biochim Biophys Acta Mol Cell Res 2021 Nov;1868(12):119123.PMID:34419492DOI:10.1016/j.bbamcr.2021.119123.
Isoginkgetin (IGG) is a small molecule inhibitor of pre-mRNA splicing. Failure to accurately remove introns could lead to the production of aberrant mRNAs and proteins. The cellular responses to splicing stress are not well defined. Here, we used oligonucleotide microarrays to assess genome wide changes in gene expression associated with exposure to IGG. Two of the 3 enriched pathways identified using PANTHER analysis of differentially expressed transcripts are linked to the ATF4 transcription factor. We confirmed that ATF4 was selectively translated and upregulated in response IGG despite an almost complete block to total protein synthesis. Importantly, partial disruption of the ATF4 gene using CRISPR-mediated gene editing prevented IGG-induced changes in gene expression. Remarkably, another spliceosome inhibitor, pladienolide B, did not inhibit translation, activate ATF4 or increase ATF4-dependent gene expression. Taken together, IGG activates ATF4 and an ATF4-dependent transcriptional response but these effects are not common to all spliceosome inhibitors.
Isoginkgetin attenuates endoplasmic reticulum stress-induced autophagy of brain after ischemic reperfusion injury
Bioengineered 2021 Nov 17.PMID:34787074DOI:10.1080/21655979.2021.1997564.
Statement of Retraction: Isoginkgetin attenuates endoplasmic reticulum stress-induced autophagy of brain after ischemic reperfusion injuryWe, the Editors and Publisher of the journal Bioengineered, have retracted the following article:Yueyong Li, Lingzhang Meng, Baosheng Li, Deyou Huang, Xiaohua Huang, Cheng Lin, Dong Li, Shaocai Qiu, Yingning Wu, Zhongheng Wei & Xuebin Li - 17. November 2021, Isoginkgetin attenuates endoplasmic reticulum stress-induced autophagy of brain after ischemic reperfusion injury (DOI: 10.1080/21655979.2021.1997564).Since publication, the authors have raised significant concerns about the reliability of the data presented in the article. As the Editor and Publisher also have concerns about the integrity of the reported results, all parties have agreed to retract the article to ensure correction of the scholarly record.We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions.The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as 'Retracted'.