Sagittaria sagittifolia polysaccharide protects against isoniazid- and rifampicin-induced hepatic injury via activation of nuclear factor E2-related factor 2 signaling in mice.
Sagittaria sagittifolia polysaccharide protects against isoniazid- and rifampicin-induced hepatic injury via activation of nuclear factor E2-related factor 2 signaling in mice.
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慈姑多糖通过激活小鼠核因子 E2 相关因子 2 信号传导，防止异烟肼和利福平诱导的肝损伤。
DOI：
10.1016/j.jep.2018.09.002
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发表时间：
2018-12
影响因子：
5.4
通讯作者：
Liao Yan
中科院分区：
文献类型：
--
作者：
Wang Jing;Luo Weizao;Li Bing;Lv Junping;Ke Xiuhui;Ge Dongyu;Dong Ruijuan;Wang Chunguo;Han Yue;Zhang Cong;Yu Haichuan;Liao Yan
民族药理学相关性慈姑 (Sagittaria sagittifolia L.)多糖（SSP）是从SSP的块根中分离出来的均质多糖的纯化形式。 sagittifolia，已被用作针对异烟肼和利福平联合用药引起的肝毒性的保护剂。然而，SSP对异烟肼和利福平诱导的肝损伤的保护作用尚未被研究。研究目的本研究旨在探讨SSP对异烟肼和利福平诱导的肝损伤小鼠的保肝作用及其潜在机制。材料与方法通过异烟肼和利福平灌胃诱导小鼠肝损伤，将小鼠分为以下六组：标准对照组（生理盐水灌胃给药）、模型（异烟肼和利福平各 100mg/kg/天灌胃）、阳性对照（异烟肼和利福平给药后 4 小时灌胃水飞蓟素 100mg/kg/天）和 SSP 处理（异烟肼和利福平给药后 4 小时灌胃 SSP 200、400 或 800mg/kg/天）利福平给药）。随后，采集所有动物的血液和肝脏样本并进行评估。结果SSP显着减轻了肝损伤，表现为血清中丙氨酸转氨酶、天门冬氨酸转氨酶和乳酸脱氢酶活性降低，肝脏中丙二醛水平降低，以及肝脏中谷胱甘肽水平升高，超氧化物歧化酶和过氧化氢酶活性增加。 SSP还有效减少了病理组织损伤。 SSP抑制细胞色素P450（CYP）2E1和CYP3A4的基因和蛋白表达。 SSP可诱导核因子红细胞2相关因子2（NRF2）、谷氨酸半胱氨酸连接酶和血红素加氧酶1的基因和蛋白表达，而抑制Kelch样ECH相关蛋白1的基因和蛋白表达。结论SSP对异烟肼和利福平诱导的小鼠肝损伤具有保护作用。潜在机制可能涉及 NRF2 及其靶抗氧化酶的激活以及 CYP 表达的抑制。
Ethnopharmacological relevanceTheSagittaria sagittifoliaL. polysaccharide (SSP) is a purified form of a homogeneous polysaccharide isolated from the root tubers ofS. sagittifolia, which has been used as a protectant against hepatotoxicity induced by coadministration of isoniazid and rifampicin. However, the protective effect of SSP against isoniazid- and rifampicin-induced liver injury has never been studied.Aim of the studyIn this study, the hepatoprotective effect of SSP and its underlying mechanism were investigated in mice with isoniazid- and rifampicin-induced liver injury.Materials and methodsLiver injury was induced in mice by intragastric administration of isoniazid and rifampicin, and the mice were divided into the following six groups: standard control (administration of saline by gavage), model (intragastric administration of isoniazid and rifampicin at 100 mg/kg/day each), positive control (100 mg/kg/day silymarin by gavage 4 h after isoniazid and rifampicin administration), and SSP-treated (200, 400, or 800 mg/kg/day SSP by gavage after isoniazid and rifampicin administration). Subsequently, blood and liver samples were collected from all the animals and were assessed.ResultsSSP significantly alleviated the liver injury, as evidenced by decreased activities of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase in the serum and a decreased level of malondialdehyde in the liver, as well as by an increased level of glutathione and increased activities of superoxide dismutase and catalase in the liver. SSP also effectively reduced the pathological tissue damage. The gene and protein expression of cytochrome P450 (CYP) 2E1 and CYP3A4 was inhibited by SSP. The gene and protein expression of nuclear factor erythroid 2-related factor 2 (NRF2), glutamate-cysteine ligase, and heme oxygenase-1 were induced by SSP, whereas that of Kelch-like ECH-associated protein 1 was inhibited.ConclusionsSSP exerts a protective effect against isoniazid- and rifampicin-induced liver injury in mice. The underlying mechanisms may involve activation of NRF2 and its target antioxidant enzymes and inhibition of the expression of CYPs.
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DOI：
10.1124/dmd.108.022723
发表时间：
2008-12
期刊：
Drug metabolism and disposition: the biological fate of chemicals
影响因子：
--
作者：
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影响因子：
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DOI：
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发表时间：
2017-08-25
期刊：
Molecules (Basel, Switzerland)
影响因子：
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作者：
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通讯作者：
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影响因子：
3.7
作者：
Li J;Shen F;Guan C;Wang W;Sun X;Fu X;Huang M;Jin J;Huang Z
通讯作者：
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DOI：
10.1016/j.etp.2014.04.004
发表时间：
2014-10
期刊：
Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie
影响因子：
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作者：
Kewei Wang
通讯作者：
Kewei Wang