Protective Effect of Gallotannin-Enriched Extract Isolated from Galla Rhois against CCl₄-Induced Hepatotoxicity in ICR Mice.
Protective Effect of Gallotannin-Enriched Extract Isolated from Galla Rhois against CCl₄-Induced Hepatotoxicity in ICR Mice.
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DOI：
10.3390/nu8030107
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发表时间：
2016-02-23
期刊：
影响因子：
5.9
通讯作者：
Hwang DY
中科院分区：
文献类型：
--
作者：
Go J;Kim JE;Koh EK;Song SH;Sung JE;Lee HA;Lee YH;Lim Y;Hong JT;Hwang DY
为了研究半Galla Rhois提取物（GEGR）对四氯化碳（CCl4）诱导的小鼠肝毒性、保护作用和作用机制，在注射CCl4前，用GEGR预处理5天小鼠，测定其血清生化指标、组织病理结构、抗氧化状态、肝凋亡相关蛋白和肝纤维化调节因子的变化。GEGR/CCl4处理组显示三种代表肝毒性的血清标记酶（ALP、AST和ALT）水平下降，但LDH水平保持不变。肝细胞坏死区明显受到抑制，丙二醛（MDA）浓度和超氧化物歧化酶（SOD）表达显著恢复。在GEGR的机制分析中，GEGR/CCl4处理组有效抑制了活性caspase-3的形成和Bax/Bcl-2表达的增强。GEGR/CCl4治疗组促炎细胞因子、TNF-α、IL-6水平及TNF-α下游信号通路p38、JNK磷酸化水平迅速恢复，抗炎细胞因子（IL-10）略有升高。此外，GEGR/CCl4处理组由于MMP-2表达、TGF-β1分泌和Smad2/3磷酸化的减轻，胶原积累明显减少。综上所述，这些结果表明，GEGR可能通过上调抗炎和抗氧化系统，对CCl4诱导的肝损伤具有显著的保护作用。
To investigate the toxicity, protective effects, and action mechanism of gallotannin-enriched extracts isolated from Galla Rhois (GEGR) against carbon tetrachloride (CCl4)-induced hepatotoxicity in Institute for Cancer Research (ICR) mice, alterations in serum biochemical indicators, histopathological structure, antioxidative status, hepatic apoptosis-related proteins, and liver fibrosis regulating factors were measured in mice pretreated with GEGR for five days before CCl4 injection. The GEGR/CCl4 treated group showed decreased levels of three serum marker enzymes (ALP, AST, and ALT) representing liver toxicity, although LDH levels remained constant. Necrotic area indicating hepatic cell death significantly inhibited, while malondialdehyde (MDA) concentration and superoxide dismutase (SOD) expression were dramatically recovered in the GEGR preadministrated group. In mechanism analyses of GEGR, the formation of active caspase-3 and enhancement of Bax/Bcl-2 expression was effectively inhibited in the GEGR/CCl4 treated group. The level of pro-inflammatory cytokines, TNF-α and IL-6, as well as the phosphorylation of p38 and JNK in the TNF-α downstream signaling pathway was rapidly recovered in the GEGR/CCl4 treated group, while anti-inflammatory cytokine (IL-10) increased slightly in the same group. Furthermore, the GEGR/CCl4 treated group showed a significant decrease in collagen accumulation results from alleviation of MMP-2 expression, TGF-β1 secretion and the phosphorylation of Smad2/3. Taken together, these results suggest that GEGR may induce remarkable protective effects against hepatic injury induced by CCl4 treatment through upregulation of the anti-inflammatory and antioxidant system.