Kamebakaurin
目录号 : GC39093
Kamebakaurin, a compound of kaurane diterpenes was isolated from traditional Chinese medicinal plant Isodon excia.
Cas No.:73981-34-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
HCT116 cells |
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Preparation Method |
HCT116 cells were seeded in 96-well plates and incubated overnight. Kamebakaurin was dissolved in DMSO. After 24 h, the cells were pretreated with different concentrations of kamebakaurin for 24 h. Measurement of cell viability by MTT assay. |
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Reaction Conditions |
0-30µM;24 h |
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Applications |
Treated with different concentrations of kamebakaurin for 24 h, The activity of HCT116 cells did not decrease significantly. |
| Animal experiment [2]: | |
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Animal models |
Six weeks old specific-pathogen-free Crj:BALB/c nu/nu female athymic nude mice |
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Preparation Method |
mice were randomly assigned to three groups, each of which consists of five mice, and then were subcutaneously inoculated with HCT116 cells in the left flank region. Kamebakaurin, dissolved in DMSO, was administered orally every other day for 40 days at a dose of 15 and 50 mg/kg body weight starting from day 10 post cell implantation to mice. |
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Dosage form |
15 and 50 mg/kg;40 days;p.o. |
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Applications |
Kamebakaurin (50 mg/kg) produced significant growth inhibition of HCT116 cells in tumor xenograft model. |
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References: [1]. Wang KS, Ma J, et,al. Kamebakaurin inhibits the expression of hypoxia-inducible factor-1α and its target genes to confer antitumor activity. Oncol Rep. 2016 Apr;35(4):2045-52. doi: 10.3892/or.2016.4576. Epub 2016 Jan 19. PMID: 26781327. |
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Kamebakaurin, a compound of kaurane diterpenes was isolated from traditional Chinese medicinal plant Isodon excia. It is a potent inhibitor of NF-kappaB activation by directly targeting DNA-binding activity of p50[6].
Treated with different concentrations of kamebakaurin (0-30μM;24 h), The activity of HCT116 cells did not decrease significantly, but Kamebakaurin inhibits HIF-1α protein expression in cells [1]. Kamebakaurin (0.1, 1.0, 5 μM) significantly inhibited the LPS-induced production of nitric oxide (NO) in a concentration-dependent fashion in activated microglial cells[2]. Kamebakaurin (0-500ng/ml;4h)dose-dependently attenuated iNOS gene expression in LPS-activated dendritic cells (DCs). Kamebakaurin significantly inhibited the gene expression and protein production of the inflammatory cytokines TNF-α, IL-12, and IL-1β[4].
Kamebakaurin (50 mg/kg;40 days;p.o.) produced significant growth inhibition of HCT116 cells in tumor xenograft model[1]. Kamebakaurin dose-dependently suppressed the inflammation in an adjuvant arthritis model. Oral administration of 20 mg/kg kamebakaurin resulted in the 75% decrease of paw volume[3]. Pretreatment with Kamebakaurin reduced the magnitude of Acetaminophen (N-acetyl-p-aminophenol, APAP)-induced increases in plasma levels of hepatic injury markers, lipid peroxidation, and inflammatory response[5].
References:
[1]. Wang KS, Ma J, et,al. Kamebakaurin inhibits the expression of hypoxia-inducible factor-1α and its target genes to confer antitumor activity. Oncol Rep. 2016 Apr;35(4):2045-52. doi: 10.3892/or.2016.4576. Epub 2016 Jan 19. PMID: 26781327.
[2]. Kim BW, Koppula S, et,al.Anti-neuroinflammatory activity of Kamebakaurin from Isodon japonicus via inhibition of c-Jun NH?-terminal kinase and p38 mitogen-activated protein kinase pathway in activated microglial cells. J Pharmacol Sci. 2011;116(3):296-308. doi: 10.1254/jphs.10324fp. Epub 2011 Jun 25. PMID: 21705843.
[3]. Lee JH, Choi JK, et,al. Anti-inflammatory effect of kamebakaurin in in vivo animal models. Planta Med. 2004 Jun;70(6):526-30. doi: 10.1055/s-2004-827152. PMID: 15241890.
[4]. Kim JY, Kim HS, et,al. Inhibition of TAK1 by kamebakaurin in dendritic cells. Int Immunopharmacol. 2013 Jan;15(1):138-43. doi: 10.1016/j.intimp.2012.11.004. Epub 2012 Nov 15. PMID: 23159603.
[5]. Yoshioka H, Aoyagi Y, et,al. Suppressive effect of kamebakaurin on acetaminophen-induced hepatotoxicity by inhibiting lipid peroxidation and inflammatory response in mice. Pharmacol Rep. 2017 Oct;69(5):903-907. doi: 10.1016/j.pharep.2017.04.004. Epub 2017 Apr 12. PMID: 28624597.
[6]. Lee JH, et,al.Kaurane diterpene, kamebakaurin, inhibits NF-kappa B by directly targeting the DNA-binding activity of p50 and blocks the expression of antiapoptotic NF-kappa B target genes. J Biol Chem. 2002 May 24;277(21):18411-20. doi: 10.1074/jbc.M201368200. Epub 2002 Mar 4. PMID: 11877450.
Kamebakaurin 是一种从传统中药植物 Isodon excia 中分离出来的贝壳杉烷二萜类化合物。它是一种有效的 NF-kappaB 激活抑制剂，可直接靶向 p50[6] 的 DNA 结合活性。
Kamebakaurin处理不同浓度(0-30μM;24 h)后，HCT116细胞的活性没有明显下降，但Kamebakaurin抑制细胞内HIF-1α蛋白的表达[1]。 Kamebakaurin (0.1, 1.0, 5 μM) 在活化的小胶质细胞中以浓度依赖性方式显着抑制 LPS 诱导的一氧化氮 (NO) 的产生[2]。 Kamebakaurin (0-500ng/ml;4h)剂量依赖性地减弱 LPS 激活的树突细胞 (DC) 中的 iNOS 基因表达。 Kamebakaurin显着抑制炎性细胞因子TNF-α、IL-12和IL-1β的基因表达和蛋白生成[4]。
Kamebakaurin（50 mg/kg；40 天；口服）在肿瘤异种移植模型中对 HCT116 细胞产生显着的生长抑制作用[1]。 Kamebakaurin 以剂量依赖性方式抑制辅助性关节炎模型中的炎症。口服 20 mg/kg 的龟贝卡林可使足爪体积减少 75%[3]。使用 Kamebakaurin 预处理可降低对乙酰氨基酚（N-乙酰基-对氨基苯酚，APAP）诱导的肝损伤标志物、脂质过氧化和炎症反应血浆水平升高的程度[5]。
| Cas No. | 73981-34-7 | SDF | |
| Canonical SMILES | O[C@]1([C@@]2(C3=O)[C@](CC[C@H]1C3=C)([H])[C@]4([C@](C(C)(CC[C@@H]4O)C)([H])C[C@H]2O)CO)[H] | ||
| 分子式 | C20H30O5 | 分子量 | 350.45 |
| 溶解度 | Soluble in DMSO | 储存条件 | 4°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 | 2.8535 mL | 14.2674 mL | 28.5347 mL |
| 5 mM | 0.5707 mL | 2.8535 mL | 5.7069 mL |
| 10 mM | 0.2853 mL | 1.4267 mL | 2.8535 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。
Kamebakaurin inhibits the expression of hypoxia-inducible factor-1α and its target genes to confer antitumor activity
Oncol Rep 2016 Apr;35(4):2045-52.PMID:26781327DOI:10.3892/or.2016.4576.
Hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor that mediates the adaptation of tumor cells and tissues to the hypoxic microenvironment, has attracted considerable interest as a potential therapeutic target. Kamebakaurin is a diterpenoid compound isolated from Isodon excia (Maxin.) Hara, which has been used for anti-inflammatory activities. However, its antitumor activity along with molecular mechanism has not been reported. Kamebakaurin showed potent inhibitory activity against HIF-1 activation induced by hypoxia or CoCl2 in various human cancer cell lines. This compound significantly decreased the hypoxia-induced accumulation of HIF-1α protein, whereas it did not affect the expression of topoisomerase-I (Topo-I). Further analysis revealed that Kamebakaurin inhibited HIF-1α protein synthesis, without affecting the expression level of HIF-1α mRNA or degradation of HIF-1α protein. Furthermore, Kamebakaurin prevented hypoxia-induced expression of HIF-1 target genes for vascular endothelial growth factor (VEGF) and erythropoietin (EPO). However, Kamebakaurin caused cell growth inhibition via cell cycle arrest at G1 phase in tumor cells. In vivo studies, we further confirmed the inhibitory effect of Kamebakaurin on the expression of HIF-1α proteins, leading to growth inhibition of HCT116 cells in a xenograft tumor model. These results show that Kamebakaurin is an effective inhibitor of HIF-1 and provide new perspectives into its anticancer activity.
1O, 20O-diacetyl Kamebakaurin protects against acetaminophen-induced hepatotoxicity in mice
Biomed Res 2018;39(5):251-260.PMID:30333432DOI:10.2220/biomedres.39.251.
The present study aimed to investigate the protective effects of Kamebakaurin (KA) and 1O, 20O-diacetyl Kamebakaurin (Ac2KA) on acetaminophen (APAP)-induced hepatotoxicity and compare the hepatoprotective mechanisms of the two chemicals. Seven-week-old male C57BL/6J mice were orally administered KA, Ac2KA, or an ethanol/olive oil emulsion once per day for 7-days. Twenty-four hours after the final administration, the mice were fasted and then intraperitoneally injected with 450 mg/kg APAP or saline. At 16 h after injection, the mice were euthanized and blood samples were collected for plasma analysis. Pretreatment with KA and Ac2KA significantly attenuated APAP-induced hepatic injury. The protective effect of Ac2KA was stronger than that of KA. These two chemicals attenuated oxidative stress, inflammatory cytokine production, c-jun N-terminal kinase activation, and receptor-interacting protein (RIP)-3 activation. Ac2KA also decreased APAP-induced RIP-1 activation and nuclear factor kappa B (NF-κB) p65 translocation. Moreover, Ac2KA repressed mRNA expression of Cyp1a2/2e1 in the liver. Our results showed that KA and Ac2KA exerted protective effects against APAP-induced hepatotoxicity. The responsible mechanisms may be related to the chemicals' antioxidant activity and the inhibition of c-jun N-terminal kinase activation and RIP-3 activation. The effects of Ac2KA included those of KA, as well as RIP-1 inactivation, NF-κB inhibition, and Cyp inhibition.
Inhibition of TAK1 by Kamebakaurin in dendritic cells
Int Immunopharmacol 2013 Jan;15(1):138-43.PMID:23159603DOI:10.1016/j.intimp.2012.11.004.
Kamebakaurin (KA) has anti-cancer and anti-inflammatory activities through direct inhibition of DNA-binding activity of nuclear factor-kappa B (NF-κB) p50. We suggest here another molecular target of KA by the use of lipopolysaccharide-treated dendritic cells. In cell- and enzyme-based assays, KA directly inhibited autophosphorylation and kinase activity of TAK1, followed by the inhibition of TAK1-downstream signaling cascades, such as IKK phosphorylation-IκBα degradation-nuclear translocation of NF-κB, phosphorylation of MEK3/6-p38 mitogen activated protein kinase (MAPK), and MKK4/7-c-Jun N-terminal kinase MAPK. These results demonstrated that TAK1 might be the direct molecular target of KA.
Kaurane diterpene, Kamebakaurin, inhibits NF-kappa B by directly targeting the DNA-binding activity of p50 and blocks the expression of antiapoptotic NF-kappa B target genes
J Biol Chem 2002 May 24;277(21):18411-20.PMID:11877450DOI:10.1074/jbc.M201368200.
Kaurane diterpenes have been identified from numerous medicinal plants, which have been used for treatment of inflammation and cancer, however, their molecular mechanism of action remains unclear. We have previously shown that Kamebakaurin and other three kaurane diterpenes selectively inhibit activation of transcription factor NF-kappaB, a central mediator of apoptosis and immune responses. We here demonstrate that Kamebakaurin is a potent inhibitor of NF-kappaB activation by directly targeting DNA-binding activity of p50. Kamebakaurin prevented the activation of NF-kappaB by different stimuli in various cell types. Kamebakaurin did not prevent either stimuli-induced degradation of IkappaB-alpha or nuclear translocation of NF-kappaB, however, it significantly interfered DNA binding activity of activated NF-kappaB in cell and in vitro and preferentially prevented p50-mediated DNA-binding activity of NF-kappaB rather than that of RelA as measured using in vitro translated p50 and RelA proteins. Moreover, a p50 mutant with a Cys-62 --> Ser mutation was not inhibited with Kamebakaurin, indicating that the effect of Kamebakaurin was probably due to its interaction with cysteine 62 in p50. The covalent modification of p50 by Kamebakaurin was further demonstrated by mass spectrometry analysis that showed an increase in the molecular mass of kamebakaurin-treated p50, and this modification was not reverted by addition of dithiothreitol. These results suggested that Kamebakaurin exhibited its inhibitory activity by a direct covalent modification of cysteine 62 in the p50. Also, treatment of cells with Kamebakaurin prevented the tumor necrosis factor-alpha (TNF-alpha)-induced expression of antiapoptotic NF-kappaB target genes encoding c-IAP1 (hiap-2) and c-IAP2 (hiap-1), members of the inhibitor of apoptosis family, and Bfl-1/A1, a prosurvival Bcl-2 homologue, and augmented the TNF-alpha-induced caspase 8 activity, thereby resulting in sensitizing MCF-7 cells to TNF-alpha-induced apoptosis. Taken together, Kamebakaurin is a valuable candidate for the intervention of NF-kappaB-dependent pathological conditions such as inflammation and cancer.
Anti-inflammatory effect of Kamebakaurin in in vivo animal models
Planta Med 2004 Jun;70(6):526-30.PMID:15241890DOI:10.1055/s-2004-827152.
We have identified Kamebakaurin as an inhibitor of NF-KB and elucidated its molecular mechanism as a specific inhibitor in the DNA-binding activity of the p50 subunit of NF-KB. Here, we describe its anti-inflammatory activity in in vitro and in vivo models. Kamebakaurin dose-dependently inhibited not only the expression of inflammatory NF-KB target genes such as iNOS,COX-2, and TNF-x, but also the production of PGE2 and TNF-a in LPS-stimulated RAW264.7 cells. Moreover, in an air pouch model of inflammation, it suppressed the recruitment of neutrophils,production of TNF-a as well as PGE2 in the pouch exudates induced by carrageenan. In addition, Kamebakaurin dose-dependently suppressed the inflammation in an adjuvant arthritis model. Oral administration of 20 mg/kg Kamebakaurin resulted in the 75% decrease of paw volume. Taken together, Kamebakaurin, a specific inhibitor of DNA-binding activity of the p50 subunit, is a valuable candidate for the intervention in NF-KB-dependent pathological conditions such as inflammation.