Parthenolide is an NF-κB inhibitor with IC50 values for Eca109, KYSE-510, SiHa and MCF-7 cells of approximately 10.3, 13.3, 8.42 and 9.54µM at 48h respectively[1][2]. Parthenolide, a sesquiterpene lactone derived from the plant Tanacetum parthenium, is recognized for its multifaceted biological activities, including anti-inflammatory, anti-tumor, and anti-viral properties. Parthenolide holds promise as a stable anti-inflammatory therapeutic and is currently under investigation in cancer clinical trials[3][4].
In vitro, Parthenolide (0, 5, 10, 20μM) treated human esophageal cancer Eca109 cells for 48h suppressed cell proliferation and migration by downregulating expression of NF-κB and VEGF in Eca109 cells[1]. Parthenolide (0.5, 1.0 and 5.0μM) exerted anti-inflammatory effect on lipopolysaccharide (LPS)-activated mouse macrophages by dose-dependently reducing IL-12 production through the downregulation of NFκB-mediated activation and binding to the p40-κB site[5]. After being applied to Vero cells infected with HSV-1 at a concentration of 2.5µg/mL for 24 hours, Parthenolide exhibited antiviral activity by disrupting cellular pathways crucial for effective virus replication. This was achieved by enhancing the expression of both caspase-8 and caspase-9, and by diminishing the accumulation of the NF-κB p65 subunit within the cell nucleus[6].
In vivo, 4mg/kg Parthenolide was intraperitoneal injected three times a week in human esophageal cancer cells bering mice for 4 weeks and exhibited anti-tumor-growth and anti-angiogenesis effect by negatively regulating the NF-κB/AP-1 pathway[1]. Parthenolide(10mg/kg)was administered by intraperitoneal (i.p.) injection and relieved colon inflammation in mice model by regulating Treg/Th17 balance in a gut-microbe dependent manner, mainly through the increased microbiota-derived SCFAs production[7]. Parthenolide exerted a protective effect from the liver injury after biliary duct ligation (BDL) in Phb1 KO mice. By intraperitoneal administered at a dose of 3mg/kg, 24 hours and 1 hour before BDL, or twice a week over a two-week period, Parthenolide effectively normalized the elevated levels of HDAC4 protein that resulted from the absence of Phb1[8].
References:
[1] Tian B.,Xiao YH,Ma JL,et al.Parthenolide Inhibits Angiogenesis in Esophageal Squamous Cell Carcinoma Through Suppression of VEGF.Onco Targets Ther.2020 Jul 29;13:7447–7458.
[2] Al-Fatlawi A.A., Atheer A Al-Fatlawi A.A., Irshad M, Rahisuddin, Ahmad A.Effect of parthenolide on growth and apoptosis regulatory genes of human cancer cell lines.Pharm Biol. 2015 Jan;53(1):104-9.
[3] Wang MT, Qiyan Li QY.Parthenolide could become a promising and stable drug with anti-inflammatory effects.Nat Prod Res. 2015;29(12):1092-101.
[4] Ghantous A, Sinjab A,Herceg Z,Darwiche N.Parthenolide: from plant shoots to cancer roots.Drug Discov Today.2013 Sep;18(17-18):894-905
[5] Kang BY,Chung SW,Kim TS.Inhibition of interleukin-12 production in lipopolysaccharide-activated mouse macrophages by parthenolide, a predominant sesquiterpene lactone in Tanacetum parthenium: involvement of nuclear factor-kappaB.Immunol Lett.2001 Jul 2;77(3):159-63.
[6] Benassi-Zanqueta E.,Marques C.F.,Nocchi S.R.,et al. Parthenolide Influences Herpes simplex virus 1 Replication in vitro.Intervirology. 2018;61(1):14-22.
[7] Liu YJ,Tang B,Wang FC,et al.Parthenolide ameliorates colon inflammation through regulating Treg/Th17 balance in a gut microbiota-dependent manner.Theranostics. 2020 Apr 6;10(12):5225-5241
[8] Barbier-Torres L.,Beraza N., Fernández-Tussy P.,et al.Histone deacetylase 4 promotes cholestatic liver injury in the absence of prohibitin-1.Hepatology.2015 Oct;62(4):1237-48.
Parthenolide是一种NF-κB抑制剂，对Eca109、KYSE-510、SiHa和MCF-7细胞48h的IC50值分别约为10.3、13.3、8.42和9.54µM[1][2]。Parthenolide是一种从植物小白菊中提取的倍半萜内酯，Parthenolide具有多方面的生物活性，包括抗炎、抗肿瘤和抗病毒特性。Parthenolide有望成为一种稳定的抗炎治疗药物，目前也作为抗癌药物进行临床研究[3][4]。
在体外，Parthenolide（0、5、10、20µM）作用于人ESCC（Esophageal Squamous Cell Carcinoma 食管鳞状细胞癌）细胞系Eca109 48h后，通过下调ESCC细胞NF-κB和VEGF的表达抑制细胞增殖和迁移[1]。Parthenolide（0.5、1.0和5.0µM）通过下调NFκB介导的激活和结合p40-κB位点，剂量依赖性地降低IL-12的产生，在脂多糖（LPS）激活的小鼠巨噬细胞中具有抗炎作用[5]。当以2.5µg/mL的浓度作用于HSV-1感染的Vero细胞24小时后，Parthenolide通过破坏对病毒有效复制至关重要的细胞途径显示出抗病毒活性，包括增强caspase-8和caspase-9的表达，以及减少细胞核内NF-κB p65亚基的积累[6]。
在体内，每周给荷人食管鳞状细胞癌小鼠腹腔注射4mg/kg的Parthenolide 3次，连续4周，通过负调控NF-κB/AP-1通路，表现出抗肿瘤生长和抗血管生成的作用[1]。通过腹腔注射Parthenolide（10mg/kg）增加了微生物来源的SCFAs产量，以肠道微生物依赖的方式调节Treg/Th17平衡，缓解了小鼠结肠炎症[7]。Parthenolide对Phb1 KO小鼠胆管结扎（BDL）后肝损伤具有保护作用。通过在BDL前24小时和1小时腹腔注射3mg/kg剂量，或每周两次注射，持续两周，Parthenolide有效地使Phb1缺失导致的HDAC4蛋白水平升高正常化[8]。