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Phyllanthin exerts neuroprotective effect against ischaemic/reperfusion injury via alteration of NF kB and AMPK/Nrf2 pathway
Journal of Environmental Pathology, Toxicology and Oncology ( IF 2.4 ) Pub Date : 2020-12-01 , DOI: 10.1615/jenvironpatholtoxicoloncol.2020036307
Jing Chen

Cerebral ischemia-reperfusion (CIR) is a common feature of ischemic stroke and is a major causative of disability and death among the patients, due to stroke worldwide. Phyllanthin, a lignin polyphenol is known for varied biological properties such as anti-inflammatory and anti-oxidative functions. Eventually, the protective effect against CIR has not been reported. Hence, the neuroprotective property of phyllanthin against CIR was evaluated in the present investigation and the involvement of AMP-activated protein kinase/nuclear factor erythroid 2-related factor 2 (AMPK/Nrf2) mediated nuclear factor kappa B (NF-kB) signaling pathway was studied in vitro and in vivo Wistar rats. CIR injury was induced by transient occlusion of the middle cerebral artery and the rats were divided 5 groups as control group (Sham-operated), ischemia induced-group (CIR) and CIR rats administered with phyllanthin (2.5, 5 and 10 mg/kg) and elucidated for neurological functions, various signaling genes, and inflammatory clues. The prima evidences of in vitro results demonstrated that phyllanthin assertively improved the cellular functions through abrogation of Nrf2 pathway. On the other hand, rats with CIR injury demonstrated neurological function deficit with a compromised permeability of blood-brain barrier (BBB) in rats. While the ischemic severity was evidenced by the activation of neuroinflammation cytokines and tissue oxidative stress. Moreover, the expression of apoptosis markers such as Bax, B-cell lymphoma (Bcl-2), and caspase-3 was abruptly increased with cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expressions. W

中文翻译:

菊磷脂通过改变NF kB和AMPK / Nrf2途径发挥对缺血/再灌注损伤的神经保护作用

脑缺血-再灌注(CIR)是缺血性中风的常见特征,并且是全球范围内因中风而导致患者致残和死亡的主要原因。木质素多酚Phyllanthin具有多种生物学特性,例如抗炎和抗氧化功能。最终,尚未报道对CIR的保护作用。因此,在本研究中评估了phyllanthin对CIR的神经保护作用,并参与了AMP激活的蛋白激酶/核因子红系2相关因子2(AMPK / Nrf2)介导的核因子κB(NF-kB)信号通路在体外和体内对Wistar大鼠进行了研究。CIR损伤是由大脑中动脉短暂闭塞引起的,将大鼠分为5组作为对照组(假手术),缺血诱导组(CIR)和CIR大鼠给予叶绿素(2.5、5和10 mg / kg),并阐明其神经功能,各种信号转导基因和炎症线索。体外结果的初步证据表明,phyllanthin可通过废除Nrf2途径来肯定地改善细胞功能。另一方面,CIR损伤的大鼠表现出神经功能缺陷,并损害了大鼠的血脑屏障(BBB)通透性。虽然缺血性严重程度通过神经炎症细胞因子的激活和组织氧化应激来证明。此外,环氧合酶2(COX-2)突然增加了Bax,B细胞淋巴瘤(Bcl-2)和caspase-3等凋亡标志物的表达,前列腺素E2(PGE2)和凝集素样氧化型低密度脂蛋白受体1(LOX-1)的表达。w ^
更新日期:2020-12-22
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