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Environmental pollutant N-N′ethylnitrosourea-induced leukemic NLRP3 inflammasome activation and its amelioration by Eclipta prostrata and its active compound wedelolactone
Environmental Toxicology ( IF 4.5 ) Pub Date : 2021-11-02 , DOI: 10.1002/tox.23400
Subhashree Bhattacharyya 1 , Sujata Law 1
Affiliation  

Environmental exposure of N-nitroso compounds (NOCs) from various sources like tobacco smoke, pesticides, smoked meat, and rubber manufacturing industries has been an alarming cause of carcinogenesis. Neonatal exposure to the carcinogenic N-N′ethylnitrosourea (ENU), a NOC has been established to cause leukemogenesis. Our world is constantly battling against cancer with consistent investigations of new anti-cancer therapeutics. Plant derived compounds have grasped worldwide attention of researchers for their promising anti-cancer potentials. Eclipta prostrata is one such ayurvedic herb, renowned for its anti-inflammatory properties. Currently, it has been explored in various cancer cell lines to establish its anti-cancer effect, but rarely in in-vivo cancer models. Wedelolactone (WDL), the major coumestan of E. prostrata is recognized as an inhibitor of IKK, a master regulator of the NF-kB inflammatory pathway. As persistent inflammation and activated inflammasome contribute to leukemogenesis, we tried to observe anti-leukemogenic efficacy of E. prostrata and its active compound WDL on the marrow cells of ENU induced experimental leukemic mice. Treatment groups were administered an oral gavage at a dose of 1200 mg/kg and 50 mg/kg b.w of crude extract and WDL respectively for 4 weeks. Various parameters like hemogram, survivability, cytological and histological investigations, migration assay, cell culture, flowcytometry and confocal microscopy were taken into consideration pre- and post-treatment. Interestingly, the plant concoction portrayed maximum effects in comparison to WDL alone. The study suggests E. prostrata and WDL as vital complementary adjuncts for anti-inflammasome mechanism in ENU-induced leukemia.

中文翻译:

环境污染物NN'乙基亚硝基脲诱导的白血病NLRP3炎症小体活化及旱莲草及其活性化合物菝葜内酯的改善作用

来自烟草烟雾、杀虫剂、熏肉和橡胶制造行业等各种来源的 N-亚硝基化合物 (NOC) 的环境暴露一直是致癌的一个令人担忧的原因。新生儿暴露于致癌的 NN'乙基亚硝基脲 (ENU),已确定一种 NOC 可导致白血病发生。我们的世界一直在与癌症作斗争,不断研究新的抗癌疗法。植物衍生化合物因其具有良好的抗癌潜力而受到全世界研究人员的关注。Eclipta prostrata就是这样一种阿育吠陀草药,以其抗炎特性而闻名。目前,已在各种癌细胞系中探索其抗癌作用,但在体内癌症模型中很少见。Wedelolactone (WDL),主要的香豆素E. prostrata被认为是 IKK 的抑制剂,IKK 是 NF-kB 炎症通路的主要调节剂。由于持续的炎症和活化的炎症小体有助于白血病的发生,我们试图观察E. prostrata的抗白血病功效及其活性化合物WDL对ENU诱导的实验性白血病小鼠骨髓细胞的作用。治疗组分别以 1200 mg/kg 和 50 mg/kg bw 粗提物和 WDL 的剂量口服管饲法,持续 4 周。各种参数,如血象、存活率、细胞学和组织学研究、迁移测定、细胞培养、流式细胞术和共聚焦显微镜在治疗前和治疗后都被考虑在内。有趣的是,与单独的 WDL 相比,植物混合物表现出最大的效果。该研究表明E. prostrata和 WDL 是 ENU 诱导的白血病中抗炎体机制的重要补充辅助剂。
更新日期:2022-01-02
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