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Euphol Sale

(Synonyms: 大戟二烯醇) 目录号 : GC38638

Euphol 是一种四环三萜醇,是从 Euphorbia tirucalli 的汁液中分离出来的,具有抗炎和免疫调节作用,具有口服活性。 Euphol 通过一种可逆机制抑制单酰基甘油脂肪酶 (MGL) 的活性,IC50=315 nM。 外周 MGL 抑制可调节内源性大麻素系统从而阻止炎症性疼痛的发展。

Euphol Chemical Structure

Cas No.:514-47-6

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1mg
¥909.00
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5mg
¥2,727.00
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10mg
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Sample solution is provided at 25 µL, 10mM.

产品文档

Quality Control & SDS

View current batch:

实验参考方法

Kinase experiment: [1,2]:

Preparation method

Samples containing either euphol, MGL (1.4 pM), or both euphol and MGL were incubated at 37℃ for 30 min in assay buffer.

At various time points, the reaction was stopped with an equal volume of ice-cold methanol and was directly analyzed in positive ionization mode by LC/MS.

Applications

Euphol inhibits MGL protein with an IC50 of 315±1 nM.

Cell experiment [3]:

Cell lines

Gastric cancer CS12 cells

Preparation method

Samples containing either euphol, MGL (1.4 pM), or both euphol and MGL were incubated at 37℃ for 30 min in assay buffer.

Reaction Conditions

2- 60 µg/mL;72h

Applications

Euphol inhibits MGL protein with an IC50 of 315±1 nM.

Animal experiment [4]:

Animal models

Male CD1 mice (8-10 weeks of age)

Preparation method

Mices were orally treated by gavage with 3, 10, or 30 mg/kg of euphol twice a day from day 0 to day 7 (preventive treatment) or with 30 mg/kg from day 3 to day 7 (therapeutic treatment).

Dosage form

3, 10, or 30 mg/kg;p.o.;7 day

Applications

Euphol treatment alleviates the severity of DSS-induced acute colitis in mice.

References:

[1].  King AR, Duranti A,et,al. URB602 inhibits monoacylglycerol lipase and selectively blocks 2-arachidonoylglycerol degradation in intact brain slices. Chem Biol. 2007 Dec;14(12):1357-65. doi: 10.1016/j.chembiol.2007.10.017. PMID: 18096504; PMCID: PMC2225625.

[2].King AR, Dotsey EY, et,al.Discovery of potent and reversible monoacylglycerol lipase inhibitors. Chem Biol. 2009 Oct 30;16(10):1045-52. doi: 10.1016/j.chembiol.2009.09.012. PMID: 19875078; PMCID: PMC3034734.

[3]. Lin MW, Lin AS, et,al. Euphol from Euphorbia tirucalli selectively inhibits human gastric cancer cell growth through the induction of ERK1/2-mediated apoptosis. Food Chem Toxicol. 2012 Dec;50(12):4333-9. doi: 10.1016/j.fct.2012.05.029. Epub 2012 May 23. PMID: 22634261.

[4].Dutra RC, Claudino RF, et,al. Preventive and therapeutic euphol treatment attenuates experimental colitis in mice. PLoS One. 2011;6(11):e27122. doi: 10.1371/journal.pone.0027122. Epub 2011 Nov 2. PMID: 22073270; PMCID: PMC3206917.

产品描述

Euphol, a major constituent found in Euphorbia tirucalli effectively inhibited via a reversible mechanism, the monoacylglycerol lipase (MGL) activity (IC50 = 315 nM), which is a serine hydrolase involved in the biological deactivation of the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG) [1-3]. Euphol exhibits diverse biological activities, such as anti-viral, anti-inflammatory, and anti-cancer effects[4].

Euphol-induced(0-125ug/ml) poptosis revealed by elevated caspase 3/7 activity, was correlated with a significant inhibition of MAP kinase/Erk 1/2 and PI3K/Akt signaling pathway in glioblastoma U87 MG cells[5]. Euphol(2- 60 µg/mL;72h) can inhibit the proliferation of gastric cancer CS12 cells. Euphol induces ERK1/2 phosphorylation in CS12 cells[6]. In T47D human breast cancer cells, treatment of cells with different doses of euphol(0.01mM-0.3mM) for 24, 48, 72 h resulted in decreased cell viability, accompanied by G1 phase cell accumulation[7].

Euphol treatment decreased cyclin D1 expression and low phosphorylation of Rb. Euphol(10 mg/kg; p.o.) attenuates the clinical signs of experimental autoimmune encephalomyelitis (EAE), It inhibited EAE induced dyskinesia [8].Mice treated with euphol (30 mg/kg;p.o.) were protected from marked body weight loss and recovered a healthy appearance that was similar to that of control healthy mice (non-colitic) [9].

真酚(Euphol)是Euphorbia tirucalli中的主要成分,真酚可逆的抑制丝氨酸水解酶MGL活性(IC50 = 315 nM)[1-3]。并且真酚具有抗病毒、抗炎、抗癌等多种生物活性[4]。

真酚(0-125ug/ml)在在胶质母细胞瘤U87 MG细胞中诱导的caspase 3/7活性升高,这与Erk 1/2和PI3K/Akt信号通路的显著抑制相关[5]。真酚(2- 60 µg/mL;72h)对CS12细胞增殖有抑制作用,真酚可以诱导CS12细胞ERK1/2磷酸化[6]。在T47D人乳腺癌细胞中,用不同剂量的真酚(0.01mM-0.3mM;24、48、72 h)处理细胞会导致细胞活力下降,细胞聚集在G1期[7]。

真酚处理降低了cyclin D1的表达,降低了Rb的磷酸化水平。真酚(10 mg/kg; p.o.)可以减轻实验性自身免疫性脑脊髓炎(EAE)的临床症状,抑制EAE诱导的运动障碍[8]。用真酚(30 mg/kg;p.o.)治疗的小鼠体重不会减轻,和健康小鼠(非结肠炎)在外观上无差距[9]。

References:
[1]. Dutra RC, SimÃo da Silva KA, et,al. Euphol, a tetracyclic triterpene produces antinociceptive effects in inflammatory and neuropathic pain: the involvement of cannabinoid system. Neuropharmacology. 2012 Sep;63(4):593-605. doi: 10.1016/j.neuropharm.2012.05.008. Epub 2012 May 18. PMID: 22613837.
[2]. King AR, Dotsey EY, et,al. Discovery of potent and reversible monoacylglycerol lipase inhibitors. Chem Biol. 2009 Oct 30;16(10):1045-52. doi: 10.1016/j.chembiol.2009.09.012. PMID: 19875078; PMCID: PMC3034734.
[3]. King AR, Duranti A, et,al. URB602 inhibits monoacylglycerol lipase and selectively blocks 2-arachidonoylglycerol degradation in intact brain slices. Chem Biol. 2007 Dec;14(12):1357-65. doi: 10.1016/j.chembiol.2007.10.017. PMID: 18096504; PMCID: PMC2225625.
[4]. Kasperczyk H, La Ferla-BrÜhl K, et,al. Betulinic acid as new activator of NF-kappaB: molecular mechanisms and implications for cancer therapy. Oncogene. 2005 Oct 20;24(46):6945-56. doi: 10.1038/sj.onc.1208842. PMID: 16007147.
[5]. Gade IS, ChadÉneau C, et,al.Induces Apoptosis and Affects Signaling Proteins in Glioblastoma and Prostate Cancer Cells. Asian Pac J Cancer Prev. 2022 Dec 1;23(12):4205-4212. doi: 10.31557/APJCP.2022.23.12.4205. PMID: 36580003; PMCID: PMC9971480.
[6]. Lin MW, Lin AS, et,al. Euphol from Euphorbia tirucalli selectively inhibits human gastric cancer cell growth through the induction of ERK1/2-mediated apoptosis. Food Chem Toxicol. 2012 Dec;50(12):4333-9. doi: 10.1016/j.fct.2012.05.029. Epub 2012 May 23. PMID: 22634261.
[7]. Wang L, Wang G, et,al. Euphol arrests breast cancer cells at the G1 phase through the modulation of cyclin D1, p21 and p27 expression. Mol Med Rep. 2013 Oct;8(4):1279-85. doi: 10.3892/mmr.2013.1650. Epub 2013 Aug 22. PMID: 23969579.
[8]. Dutra RC, de Souza PR, et,al. Euphol prevents experimental autoimmune encephalomyelitis in mice: evidence for the underlying mechanisms. Biochem Pharmacol. 2012 Feb 15;83(4):531-42. doi: 10.1016/j.bcp.2011.11.026. Epub 2011 Dec 1. PMID: 22155310.
[9]. Dutra RC, Claudino RF, et,al. Preventive and therapeutic euphol treatment attenuates experimental colitis in mice. PLoS One. 2011;6(11):e27122. doi: 10.1371/journal.pone.0027122. Epub 2011 Nov 2. PMID: 22073270; PMCID: PMC3206917.

Chemical Properties

Cas No. 514-47-6 SDF
别名 大戟二烯醇
Canonical SMILES C[C@@]1(CC2)[C@@](CC[C@]1([C@H](C)CC/C=C(C)/C)[H])(C)C3=C2[C@]4(C)[C@](CC3)([H])C(C)(C)[C@@H](O)CC4
分子式 C30H50O 分子量 426.72
溶解度 Soluble in DMSO 储存条件 -20°C, protect from light
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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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溶解性数据

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1 mg 5 mg 10 mg
1 mM 2.3435 mL 11.7173 mL 23.4346 mL
5 mM 0.4687 mL 2.3435 mL 4.6869 mL
10 mM 0.2343 mL 1.1717 mL 2.3435 mL
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Research Update

Immunomodulatory and cytotoxic activities of Euphol

Life Sci 2021 Sep 1;280:119700.PMID:34111465DOI:10.1016/j.lfs.2021.119700.

Aims: This study evaluated the effect of Euphol isolated from Euphorbia umbellata (Pax) Bruyns latex on the activation of complement pathways (classical (CP), alternative (AP) and lectin (LP)), neutrophil chemotaxis, cytotoxic activity, cell morphology and death in HRT-18 and 3T3 cells lines. Main methods: CP and AP were assessed using hemolytic assays and ELISA for LP; neutrophil chemotaxis was performed using Boyden's chamber; cytotoxicity was evaluated by neutral red methodology and characteristics of cell death were assessed by cell morphology with hematological staining. Key findings: Although Euphol increased CP activation (38% at a concentration of 976.1 μM), an inhibitory effect on AP, LP (31% and 32% reduction in the concentration of 976.1 μM) and neutrophil chemotaxis (inhibit 84% of neutrophil migration at a concentration 292.9 μM) was observed. In addiction Euphol was able to induce significant cell death in a time-dependent manner, presenting an IC50 of 70.8 μM and 39.2 μM for HRT-18 and 3T3 cell lines respectively and it was also observed apoptotic characteristics as cellular rounding, chromatin condensation and blebs formation for both cell lines. Significance: Euphol has a potential use for the treatment of complement-related inflammatory diseases due to its ability to downregulate inflammation. On the other hand, the controlled activation of CP can contribute to complement-dependent cytotoxicity in the context of monoclonal antibody-based cancer treatment.

Euphol from Tapinanthus sp. Induces Apoptosis and Affects Signaling Proteins in Glioblastoma and Prostate Cancer Cells

Asian Pac J Cancer Prev 2022 Dec 1;23(12):4205-4212.PMID:36580003DOI:10.31557/APJCP.2022.23.12.4205.

Background: Plants play an important role in cancer therapy. They are source of natural molecules which can induce apoptosis in cancer cells by affecting molecular mechanisms implicated in cancer progression. The MAP Kinase/ERK1/2 and PI3K/AKT signaling pathways are two classical signaling pathways implicated in cancer progression and constitute therapeutic targets against cancer. This study aimed to evaluate the effect of Euphol on MAP Kinase/ERK1/2 and PI3K/AKT signaling pathways in glioblastoma and prostate cancer cells. Euphol is a tetracyclique triterpene alcohol isolated from Tapinanthus sp. which is a hemi parasitic plant belonging to Loranthaceae family. Methods: Plant powder was extracted by maceration and Euphol was isolated and described using respectively column chromatography separation on silica gel and spectroscopic data. Cytotoxic effect of Euphol was evaluated using XTT assay and its effect on MAP Kinase/ERK1/2 and PI3K/AKT protein expression was investigated by Western immunoblot analysis. Apotosis was analyzed by evaluating caspase-3/7 activity. Results: Our investigations demonstrated that this compound has an important cytotoxic effect on C6 and U87 MG glioblastoma (GBM) cells and PC-3 prostate cancer cells. Furthermore, euphol-induced apoptosis revealed by elevated caspase 3/7 activity, was correlated with a significant inhibition of MAP kinase/Erk 1/2 and PI3K/Akt signaling pathway in glioblastoma U87 MG cells. The reverse effect was observed in C6 glioblastoma cells, where apoptosis was correlated with a long-lasting activation of Erk 1/2. In PC-3 cells, Euphol had no or limited effect on Erk 1/2 and Akt activity. Conclusion: These results indicate that Euphol induces cell death in glioblastoma and prostate cancer cells and regulates significantly Erk1/2 and Akt activity in glioblastoma cells.

Euphol, a tetracyclic triterpene, from Euphorbia tirucalli induces autophagy and sensitizes temozolomide cytotoxicity on glioblastoma cells

Invest New Drugs 2019 Apr;37(2):223-237.PMID:29931585DOI:10.1007/s10637-018-0620-y.

Glioblastoma (GBM) is the most frequent and aggressive type of brain tumor. There are limited therapeutic options for GBM so that new and effective agents are urgently needed. Euphol is a tetracyclic triterpene alcohol, and it is the main constituent of the sap of the medicinal plant Euphorbia tirucalli. We previously identified anti-cancer activity in Euphol based on the cytotoxicity screening of 73 human cancer cells. We now expand the toxicological screening of the inhibitory effect and bioactivity of Euphol using two additional glioma primary cultures. Euphol exposure showed similar cytotoxicity against primary glioma cultures compared to commercial glioma cells. Euphol has concentration-dependent cytotoxic effects on cancer cell lines, with more than a five-fold difference in the IC50 values in some cell lines. Euphol treatment had a higher selective cytotoxicity index (0.64-3.36) than temozolomide (0.11-1.13) and reduced both proliferation and cell motility. However, no effect was found on cell cycle distribution, invasion and colony formation. Importantly, the expression of the autophagy-associated protein LC3-II and acidic vesicular organelle formation were markedly increased, with Bafilomycin A1 potentiating cytotoxicity. Finally, Euphol also exhibited antitumoral and antiangiogenic activity in vivo, using the chicken chorioallantoic membrane assay, with synergistic temozolomide interactions in most cell lines. In conclusion, Euphol exerted in vitro and in vivo cytotoxicity against glioma cells, through several cancer pathways, including the activation of autophagy-associated cell death. These findings provide experimental support for further development of Euphol as a novel therapeutic agent for GBM, either alone or in combination chemotherapy.

Natural Plant Compounds: Does Caffeine, Dipotassium Glycyrrhizinate, Curcumin, and Euphol Play Roles as Antitumoral Compounds in Glioblastoma Cell Lines?

Front Neurol 2022 Feb 17;12:784330.PMID:35300350DOI:10.3389/fneur.2021.784330.

Many plant-derived compounds are shown to be promising antitumor therapeutic agents by enhancing apoptosis-related pathways and cell cycle impairment in tumor cells, including glioblastoma (GBM) cell lines. We aimed to review four natural plant compounds effective in GBM cell lines as caffeine, dipotassium glycyrrhizinate (DPG), curcumin, and Euphol. Furthermore, antitumoral effect of these plant compounds on GBM cell lines through microRNAs (miRs) modulation was investigated. However, only DPG and curcumin were found as effective on miR modulation. Caffeine arrests GBM cell cycle in G0/G1 phase by cyclin-dependent kinases (CDK) complex inhibition and by decreasing BCL-2 and increasing FOXO1 expression levels causing greater apoptotic activity. Caffeine can also directly inhibit IP3R3, p38 phosphorylation, and rho-associated protein kinase (ROCK), decreasing cell invasion and migration capacity or indirectly by inhibiting the tissue inhibitor metalloproteinase-1 (TIMP-1) and integrins β1 and β3, leading to lower matrix metalloproteinases, MMP-2 and MMP-9. DPG presents antitumoral effect in GBM cells related to nuclear factor kappa B (NF-κB) pathway suppression by IRAK2 and TRAF6-mediating miR-16 and miR-146a, respectively. More recently, it was observed that DPG upregulated miR-4443 and miR-3620, responsible for post-transcriptional inhibition of the NF-κB pathway by CD209 and TNC modulation, respectively leading to lower MMP-9 and migration capacity. Curcumin is able to increase miR-223-3p, miR-133a-3p, miR-181a-5p, miR-34a-5p, miR-30c-5p, and miR-1290 expression leading to serine or threonine kinase (AKT) pathway impairment and also it decreases miR-27a-5p, miR-221-3p, miR-21-5p, miR-125b-5p, and miR-151-3p expression causing p53-BCL2 pathway inhibition and consequently, cellular apoptosis. Interestingly, lower expression of miR-27a by curcumin action enhanced the C/EBP homologous protein(CHOP) expression, leading to paraptosis. Curcumin can inhibit miR-21 expression and consequently activate apoptosis through caspase 3 and death receptor (DR) 4 and 5 activation. Autophagy is controlled by the LC-3 protein that interacts with Atg family for the LC3-II formation and autophagy activation. Euphol can enhance LC3-II levels directly in GBM cells or inhibits tumor invasion and migration through PDK1 modulation.

De Novo Biosynthesis of the Anticancer Compound Euphol in Saccharomyces cerevisiae

ACS Synth Biol 2021 Sep 17;10(9):2351-2358.PMID:34445867DOI:10.1021/acssynbio.1c00257.

Euphol is a euphane-type tetracyclic triterpene which is primarily found in the Euphorbia genus. Euphol has been renowned because of its great potential as a promising anticancer drug. Surprisingly, despite its diverse antitumor effects, the respective gene for Euphol biosynthesis had not been identified until this study. In our experiments with Euphorbia tirucalli, Euphol was detected predominantly in latex, the element that is often used for cancer treatments in Brazil. Two latex-specifically expressed oxidosqualene cyclases (OSCs) from E. tirucalli, designated as EtOSC5 and EtOSC6, were functionally characterized by expression in a lanosterol synthase knockout yeast strain GIL77. EtOSC5 produces Euphol and its 20S-isomer tirucallol as two of the major products, while EtOSC6 produces taraxasterol and β-amyrin as the major products. These four compounds were also detected as the major triterpenes in the E. tirucalli latex, suggesting that EtOSC5 and EtOSC6 are the primary catalysts for the formation of E. tirucalli latex triterpene alcohols. Based on a model structure of EtOSC5 followed with site-mutagenesis experiments, the mechanism for the EtOSC5 activity was proposed. By applying state-of-the-art engineering techniques, the expression of EtOSC5 together with three other known precursor genes were chromosomally integrated into Saccharomyces cerevisiae. The resulting engineered yeast strain YS5E-1 produced 1.84 ± 0.17 mg/L of Euphol in shake flasks.