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].
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.
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]。