Asiatic Acid Exhibits Anti-inflammatory and Antioxidant Activities against Lipopolysaccharide and d-Galactosamine-Induced Fulminant Hepatic Failure.
Asiatic Acid Exhibits Anti-inflammatory and Antioxidant Activities against Lipopolysaccharide and d-Galactosamine-Induced Fulminant Hepatic Failure.
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积雪草酸具有抗炎和抗氧化活性，可对抗脂多糖和 D-半乳糖胺诱导的暴发性肝衰竭
DOI：
10.3389/fimmu.2017.00785
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发表时间：
2017
影响因子：
7.3
通讯作者：
Ci X
中科院分区：
文献类型：
--
作者：
Lv H;Qi Z;Wang S;Feng H;Deng X;Ci X
炎症和氧化应激在暴发性肝衰竭(FHF)的发病机制中起重要作用。积雪草酸(AA)是一种五环三萜类化合物，广泛存在于各种蔬菜和水果中，具有抗氧化和抗炎作用。本研究探讨了AA对内毒素(LPS)和D-氨基半乳糖(GalN)诱导的FHF的保护作用及其分子机制。结果表明，AA可通过降低肝组织丙氨酸转氨酶、天冬氨酸氨基转移酶、白介素1β、白介素6和肿瘤坏死因子α的生成、丙二醛的生成、髓过氧化物酶的水平和活性氧的产生(即H_2O_2、NO和)，提高谷胱甘肽和超氧化物歧化酶的含量，从而对脂多糖/d-半乳糖胺诱导的肝衰竭有有效的保护作用。此外，AA通过部分诱导参与炎症反应的程序性细胞死亡4(PDCD4)蛋白的表达，显著抑制丝裂原活化蛋白激酶(MAPK)和核因子-kappaB(NF-κB)信号通路的激活。此外，AA处理显著诱导了谷氨酸-半胱氨酸连接酶修饰亚基、谷氨酸-半胱氨酸连接酶催化亚基、血红素加氧酶-1和NAD(P)H：苯二酮氧化还原酶1的表达，这在很大程度上依赖于核因子-红系2相关因子2(NRF2)的激活，这在很大程度上依赖于AMPK和糖原合成酶β(GSK3β)的磷酸化。因此，AA通过抑制氧化应激和炎症反应，对内毒素/d-GalN诱导的FHF具有保护作用。其机制可能与抑制MAPK和NF-κB的活化有关，其机制可能是通过部分诱导pDCD4和上调NRF2而依赖于β通路的激活。
Inflammation and oxidative stress are essential for the pathogenesis of fulminant hepatic failure (FHF). Asiatic acid (AA), which is a pentacyclic triterpene that widely occurs in various vegetables and fruits, has been reported to possess antioxidant and anti-inflammatory properties. In this study, we investigated the protective effects of AA against lipopolysaccharide (LPS) and d-galactosamine (GalN)-induced FHF and the underlying molecular mechanisms. Our findings suggested that AA treatment effectively protected against LPS/d-GalN-induced FHF by lessening the lethality; decreasing the alanine transaminase and aspartate aminotransferase levels, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α production, malondialdehyde formation, myeloperoxidase level and reactive oxygen species generation (i.e., H2O2, NO, and ), and increasing the glutathione and superoxide dismutase contents. Moreover, AA treatment significantly inhibited mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathway activation via the partial induction of programmed cell death 4 (PDCD4) protein expressions, which are involved in inflammatory responses. Furthermore, AA treatment dramatically induced the expression of the glutamate-cysteine ligase modifier subunit, the glutamate-cysteine ligase catalytic subunit, heme oxygenase-1, and NAD (P) H: quinoneoxidoreductase 1 (NQO1), which are largely dependent on activation of the nuclear factor-erythroid 2-related factor 2 (Nrf2) through the induction of AMP-activated protein kinase (AMPK) and glycogen synthase kinase-3β (GSK3β) phosphorylation. Accordingly, AA exhibited protective roles against LPS/d-GalN-induced FHF by inhibiting oxidative stress and inflammation. The underlying mechanism may be associated with the inhibition of MAPK and NF-κB activation via the partial induction of PDCD4 and upregulation of Nrf2 in an AMPK/GSK3β pathway activation-dependent manner.
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影响因子：
14.9
作者：
Malhotra D;Portales-Casamar E;Singh A;Srivastava S;Arenillas D;Happel C;Shyr C;Wakabayashi N;Kensler TW;Wasserman WW;Biswal S
通讯作者：
Biswal S
影响因子：
6.6
作者：
Mo, Chunfen;Wang, Ling;Xiao, Hengyi
通讯作者：
Xiao, Hengyi
影响因子：
7.3
作者：
Endo, Y;Shibazaki, M;Kumagai, K
通讯作者：
Kumagai, K
影响因子：
5.6
作者：
Huang, Chi-Chang;Lin, Kun-Ju;Shyur, Lie-Fen
通讯作者：
Shyur, Lie-Fen
影响因子：
7.4
作者：
Pang, Chun;Zheng, Zhiyong;Ji, Lili
通讯作者：
Ji, Lili