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胡椒碱衍生物PL 1-3负载白蛋白纳米粒对脂多糖/d-半乳糖胺诱导的小鼠急性肝损伤的肝保护作用评价

Evaluation of Hepatoprotective Effects of Piperlongumine Derivative PL 1-3-Loaded Albumin Nanoparticles on Lipopolysaccharide/d-Galactosamine-Induced Acute Liver Injury in Mice.

作者信息

Li Pengxiao, Guo Xiaoyuan, Liu Ting, Liu Qing, Yang Jie, Liu Guoyun

机构信息

School of Pharmaceutical Sciences, Liaocheng University, 1 Hunan Street, Liaocheng, Shandong 252059, China.

出版信息

Mol Pharm. 2022 Dec 5;19(12):4576-4587. doi: 10.1021/acs.molpharmaceut.2c00215. Epub 2022 Aug 16.

Abstract

In recent years, piperlongumine (PL) having specific cytotoxicity has attracted considerable attention for anticancer activity. Through structural modification, the active derivative PL 1-3 shows potential anti-inflammatory activity and low cytotoxicity, but its water solubility is low. Here, PL 1-3-loaded bovine serum albumin nanoparticles (1-3 NPs) were prepared and characterized, which can improve the dissolution. 1-3 NPs exhibited effective hepatoprotective effects on lipopolysaccharide/d-galactosamine-induced acute liver injury of mice, which was similar to liver injury in clinical settings. 1-3 NPs treatment can inhibit inflammation, oxidative stress, and apoptosis via the downregulation of NF-κB signaling pathways, the activation of Nrf2/HO-1 signaling pathways, and the inhibition of expression of Bax and caspase 3 proteins. The above results demonstrated that PL 1-3-loaded bovine serum albumin nanoparticles possessed potential value in intervention of inflammation-based liver injury.

摘要

近年来,具有特定细胞毒性的胡椒碱(PL)因其抗癌活性而备受关注。通过结构修饰,活性衍生物PL 1-3显示出潜在的抗炎活性和低细胞毒性,但其水溶性较低。在此,制备并表征了负载PL 1-3的牛血清白蛋白纳米颗粒(1-3 NPs),其可提高药物的溶解性。1-3 NPs对脂多糖/d-半乳糖胺诱导的小鼠急性肝损伤表现出有效的肝保护作用,这与临床环境中的肝损伤相似。1-3 NPs处理可通过下调NF-κB信号通路、激活Nrf2/HO-1信号通路以及抑制Bax和caspase 3蛋白的表达来抑制炎症、氧化应激和细胞凋亡。上述结果表明,负载PL 1-3的牛血清白蛋白纳米颗粒在干预炎症性肝损伤方面具有潜在价值。

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