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从桃金娘科白千层中分离得到的 Praecoxin A 对四氯化碳诱导的小鼠肝毒性的肝保护活性。对氧化应激、炎症和细胞凋亡的影响。

Hepatoprotective activity of praecoxin A isolated from Melaleuca ericifolia against carbon tetrachloride-induced hepatotoxicity in mice. Impact on oxidative stress, inflammation, and apoptosis.

机构信息

Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Cairo, Egypt.

Department of Pharmacology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt.

出版信息

Phytother Res. 2019 Feb;33(2):461-470. doi: 10.1002/ptr.6242. Epub 2018 Dec 3.

DOI:10.1002/ptr.6242
PMID:30506741
Abstract

The hepatoprotective activity of praecoxin A, an ellagitannin from Melaleuca ericifolia, was determined against CCl -induced toxicity in mice. Praecoxin A was administered (25, 50, and 100 mg/kg) for 5 days followed by CCl . Praecoxin A markedly ameliorated the CCl -induced increase in AST (by 19, 52, and 56%), ALP (22, 45, and 48%), ALT (11, 47, and 54%), total bilirubin (14, 27, and 28%), and MDA (26, 44, and 51%) at the tested doses, respectively, as compared with CCl group. It was evident that praecoxin A significantly (p < 0.001) increased the antioxidant parameters GSH (45, 99, and 137%) and SOD (61, 129, and 159%). Histological findings revealed a marked amelioration of hepatocyte degeneration, necrosis, inflammatory cell infiltration, and hemorrhage in the groups treated with praecoxin A. COX-2 and caspase-3 hepatic expressions were significantly downregulated (p < 0.001) in praecoxin A-treated groups (up to 57, 83, and 93% for COX-2 and by 30, 82, and 99% for caspase-3). These findings suggest that praecoxin A exerts a beneficial effect against oxidative stress by reducing lipid peroxidation, enhancing the antioxidant defense status, and protecting against the histopathological changes induced by CCl . This study highlights a promising natural hepatoprotective candidate derived from M. ericifolia that might be an alternative to silymarin.

摘要

从桃金娘科白千层中提取的鞣花单宁 Praecoxin A 对 CCl4 诱导的小鼠肝毒性的保护作用。Praecoxin A 连续给药 5 天(25、50 和 100mg/kg),然后给予 CCl4。与 CCl4 组相比,Praecoxin A 分别显著改善 CCl4 诱导的 AST(增加 19%、52%和 56%)、ALP(增加 22%、45%和 48%)、ALT(增加 11%、47%和 54%)、总胆红素(增加 14%、27%和 28%)和 MDA(增加 26%、44%和 51%)。显然,Praecoxin A 显著(p<0.001)增加了抗氧化参数 GSH(增加 45%、99%和 137%)和 SOD(增加 61%、129%和 159%)。组织学发现,用 Praecoxin A 治疗的各组肝细胞变性、坏死、炎性细胞浸润和出血明显改善。COX-2 和 caspase-3 的肝表达均显著下调(p<0.001)(COX-2 下调高达 57%、83%和 93%,caspase-3 下调 30%、82%和 99%)。这些发现表明,Praecoxin A 通过减少脂质过氧化、增强抗氧化防御状态和防止 CCl4 诱导的组织病理学变化,对氧化应激发挥有益作用。本研究突出了一种有希望的源自白千层的天然肝保护候选物,它可能是水飞蓟素的替代品。

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