Inhibitory effect of glycyrrhizin on lipopolysaccharide and d-galactosamine-induced mouse liver injury

The effects of glycyrrhizin isolated from licorice root were investigated on acute hepatitis induced by lipopolysaccharide (LPS) and d-galactosamine in mice. Serum alanine aminotransferase (ALT) activity was markedly increased 6 h to 8 h after administration of LPS/d-galactosamine. Levels in serum of cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10 and IL-12 reached a maximum by 2 h, whereas levels of IL-18, as well as of ALT, were maximal at 8 h. Glycyrrhizin (ED(50): 14.3 mg/kg) inhibited the increase in ALT levels when it was given to mice at 30 min before administration of LPS/d-galactosamine. Inflammatory responses, including infiltration of neutrophils and macrophages in the liver injury, were modulated by glycyrrhizin. Increases in ALT levels were reduced by an administration of glycyrrhizin at 10 min and 60 min but not 3 h, even after LPS/d-galactosamine treatment. However, glycyrrhizin had no effect on the production of TNF-alpha, IL-6, IL-10 and IL-12, whereas it significantly inhibited IL-18 production. Exogenous IL-18 further increased the elevation in ALT levels in mice treated with LPS/d-galactosamine. Glycyrrhizin completely suppressed the effect of IL-18 of increasing ALT levels. IL-18 was detected by immunohistochemistry in inflammatory cells such neutrophils and macrophages in liver injury. Glycyrrhizin reduced the responsiveness of cells to IL-18 in the liver injury. These results suggest that glycyrrhizin inhibits the LPS/d-galactosamine-induced liver injury through preventing inflammatory responses and IL-18 production. Furthermore, it seems that glycyrrhizin prevents IL-18-mediated inflammation in liver injury.     

Protective effect of baicalin against lipopolysaccharide/D-galactosamine-induced liver injury in mice by up-regulation of heme oxygenase-1

Baicalin, a traditional anti-inflammatory drug, has been found to protect against liver injury in several experimental animal hepatitis models; however, the mechanisms underlying the hepatoprotective properties of baicalin are poorly understood. In the present study,we investigated the effects of baicalin on the acute liver injury in mice induced by Lipopolysaccharide/D-galactosamine (LPS/D-GalN). Baicalin (50, 150, and 300 mg/kg) was pretreated intraperitoneally (i.p.) at 2, 24, and 48 h respectively before LPS/D-GalN injected in mice.The mortality, hepatic tissue histology, hepatic tissue Tumor necrosis factor-alpha (TNF-alpha) and myeloperoxidase (MPO), plasma levels of TNF-alpha and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed. Besides, western blotting analyses of nuclear factor kappa B (NF-kappaB) translocation and Heme oxygenase-1(HO-1) protein expression, as well as HO-1 activity were determined. The results showed that baicalin protected against LPS/D-GalN-induced liver injury, including dose-dependent alleviation of mortality and hepatic pathological damage, decrease of ALT/AST release and the rise of MPO. Baicalin reduced nuclear translocation of NF-kappa B, TNF-alpha mRNA and protein levels in hepatic tissues and plasma levels of TNF-alpha induced by LPS/D-GalN. Moreover, baicalin dose-dependently increased HO-1 protein expression and activity. Further, inhibition of HO-1 activity significantly reversed the protective effect of baicalin against LPS/D-GalN-induced liver injury. These results suggest that baicalin can effectively prevent LPS/D-GalN-induced liver injury by inhibition of NF-kappa B activity to reduce TNF-alpha production and the underlying mechanism may be related to up-regulation of HO-1 protein and activity.     

Protective effect of wedelolactone against CCl4-induced acute liver injury in mice

Eclipta, a traditional Chinese medicine, has been used to treat liver disease for centuries. However, the chemical basis and biological mechanisms of Eclipta remain elusive. The current study aims to investigate the hepatoprotective effect of wedelolactone (WEL), a major coumarin in Eclipta, using C57BL/6 mice with carbon tetrachloride CCl₄-induced acute liver injury (ALI). Our data showed that WEL markedly decreased the CCl₄-induced elevation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and improved hepatic histopathology changes. WEL also significantly decreased the content of MDA in liver tissues, meanwhile increased the activities of antioxidant enzymes SOD and GSH-Px. In addition, WEL reduced the protein expression of TNF-α, IL-1β and IL-6, as well as mRNA expression. Western blot results revealed that WEL repressed phosphorylation of extracellular signal-regulated kinase (ERK) and translocation of NF-κB p65 from cytoplasm to nucleus and enhanced the phosphorylation of c-Jun. N-terminal kinase (JNK). Moreover, results showed that WEL significantly inhibited CCl₄-induced hepatocytes apoptosis, markedly suppressed the down-regulation of Bax and active Caspase-3 expression and accelerated the expression of Bcl-2. Overall, the findings indicate that WEL exhibits a protective effect against CCl₄-induced ALI in mice by enhancing the antioxidative defense system, suppressing the inflammatory response and cell apoptosis of liver.     

丹参酮类化合物对小鼠应激性肝损伤的保护作用

目的研究4种丹参酮类化合物对拘束应激引起小鼠肝损伤的保护作用。方法采用拘束负荷法造成小鼠应激性肝损伤。应用赖氏法测定小鼠血浆中ALT活性，TBARS法测定血浆及肝组织匀浆中的MDA含量，抗氧化能力指数(ORAC)法测定血浆抗氧化能力指数，HPLC法测定血浆及肝组织匀浆中维生素C和GSH水平，以及ORAC法测定和观察丹参酮类化合物的体内和体外抗氧化活性。结果与拘束模型组相比，4种丹参酮类化合物均可明显降低应激小鼠血浆ALT水平，提高肝组织匀浆的抗氧化能力指数、维生素C和GSH水平，并降低MDA含量。4种丹参酮类化合物体外也显示出较强的抗氧化能力。在体内和体外实验中，二氢丹参酮的抗氧化作用均明显优于其他3种丹参酮类化合物。结论丹参酮类化合物对拘束应激引起的小鼠肝损伤具有一定的保护作用，其作用机制可能部分来自于其抗氧化活性。     

Protective effect of Cassia fistula fruit extract against bromobenzene-induced liver injury in mice

In the present study, hepatoprotective effect of Cassia fistula fruit extract was investigated in mice. Animals were divided into six groups receiving normal saline (1), bromobenzene (460 mg/kg) alone (2) and together with increasing doses (200, 400, 600, 800 mg/kg) of a crude hydro-alcoholic extract of Cassia fistula fruit (3-6, respectively). All administrations were carried out orally, daily, for 10 days. On the 11th day, animals were sacrificed. Serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (γGT) were determined; serum levels of direct and total bilirubin were measured; furthermore, livers were prepared for histological examination. Our results showed that bromobenzene treatment alone elicited a significant increase in activities of AST, ALT, ALP (but not γGT), and it significantly elevated the levels of direct and total bilirubin. Co-treatment with Cassia fistula fruit extract, however, significantly and dose-dependently decreased the above-mentioned enzyme activities (with exception of γGT) and bilirubin levels, producing a recovery to the naive state. The protective effect of Cassia fistula fruit extract against liver injury evoked by bromobenzene was confirmed by histological examination as well. In conclusion, the Cassia fistula fruit extract has significant hepatoprotective effect in our murine model.     

齐墩果醇酸对化学物质致小鼠急性肝损伤的保肝作用(英文)

目的:评价齐墩果醇酸(OA)对急性肝损伤的保肝作用.方法:小鼠sc OA 200 μmol·kg~(-1)三天,然后给予肝毒物.通过病理组织学观察及测定血清丙氨酸转氨酶和艾杜糖醇脱氢酶活性来估价肝损伤.结果:OA能明显减轻四氯化碳,溴苯,醋氨酚,速尿,硫代乙酰胺,鬼笔毒环肽,秋水仙硷,氯化镉,D—半乳糖胺和内毒素等所致小鼠急性坏死性肝损伤,降低这些肝毒物所引起的血清转氨酶和艾杜糖醇脱氢酶的升高,但对氯仿,二甲亚硝氨,鹅膏菌索和烯丙醇的毒性无作用.结论:OA能减轻多种化学物质(但并非全部)引起的肝损伤.其保肝机制可能是多方面的.     

Protective effect of fucoidan against acetaminophen-induced liver injury

Fucoidan, a sulfated polysaccharide extracted from various brown seaweeds, possesses a wide range of pharmacological properties. In this study, we investigated the protective effect of fucoidan on acetaminophen-induced acute liver injury in rats. Liver injury was induced by administration of acetaminophen (800 mg/kg, i.p.) and fucoidan was administered (100 mg kg, p.o.) 2 h before and after acetaminophen administration. After 24 h, co-treatment of fucoidan ameliorated liver damage and cell death induced by acetaminophen. Acetaminophen induced the overexpression of CYP2E1, one of the metabolizing enzymes of acetaminophen, but cotreatment with fucoidan suppressed its increased expression of CYP2E1. Fucoidan also reduced the hepatic apoptosis induced by acetaminophen exposure as shown in the protein expression of Bax, Bcl-2, and cleaved caspase-3. The anti-oxidative effect of fucoidan was observed from the increase of the production and expression of glutathione, superoxide dismutase, and glutathione peroxidase, both of which were decreased by acetaminophen. Also, fucoidan decreased the expression of inflammatory mediators, including tumor necrosis factoralpha, interleukin 1 beta, and inducible nitric oxide synthase. Taken together, the data demonstrate the hepato-protective effects of fucoidan against acetaminophen-induced liver injury via anti-oxidant, anti-inflammatory, and anti-apoptotic mechanisms.     

柞树皮水提浸膏对四氯化碳所致小鼠急性肝损伤的保护作用

目的 研究柞树皮水提浸膏对CCl<,4>所致小鼠急性肝损伤的保护作用.方法 用CCl<,4>造小鼠急性肝损伤模型,灌胃给药,用比色法测定小鼠血清中天冬氨酸转氨酶(AST)、丙氨酸氨基转移酶(ALT)活性、肝组织谷胱甘肽过氧化物酶(GSH-Px)的活性和丙二醛(MDA)的含量.结果 柞树皮水提浸膏能显著降低CCl<,4>所致小鼠各组血清中AST、ALT活性的升高(P<0.05),同时升高肝组织中GSH-Px的活性,降低肝组织中MDA的含量(P<0.05).结论 柞树皮水提浸膏对CCl<,4>所致小鼠急性肝损伤具有一定的保护作用.     

Protective effects of probiotic Lactobacillus casei Zhang against endotoxin- and d-galactosamine-induced liver injury in rats via anti-oxidative and anti-inflammatory capacities

Lactobacillus casei Zhang (LcZ) has been recently isolated from the traditional Mongolian beverage koumiss and has a set of favorable probiotic properties, including aciduricity, bile resistance and ability to colonize the gastrointestinal tract. We have previously reported the anti-oxidative properties of LcZ in the hyperlipidemic rats. In this study, the hepatoprotective effects of LcZ against lipopolysaccharide (LPS) and d-galactosamine (D-GalN)-induced liver injury were investigated. We found that pretreatment with LcZ significantly improved survival of rats challenged with LPS/D-GalN. In addition, pretreatment with LcZ significantly decreased alanine transaminase (ALT) and aspartate aminotransferase (AST) levels in LPS/D-GalN-challenged rats, which were accompanied by diminished liver injuries, reduced malondialdehyde (MDA) content and increased superoxide dismutase (SOD) activity in liver homogenates. Pretreatment with LcZ also markedly reduced LPS/D-GalN-induced production of hepatic nitric oxide (NO), activation of inducible nitric oxide synthase (iNOS) and expression of tumor necrosis factor-α (TNF-α). Furthermore, hepatic toll-like receptor 4 (TLR4) mRNA and protein levels, the phosphorylation of I-κB and translocation of nuclear factor κB (NF-κB) were significantly down-regulated by pretreatment with LcZ. These results suggest that pretreatment with LcZ protects against LPS/D-GalN-induced liver injury in rats via its anti-oxidative and anti-inflammatory capacities. The hepatoprotective effects of LcZ are associated with an inhibition of TLR4 expression and TLR4 signaling.     

Protective effect of andrographolide against concanavalin A-induced liver injury

This study was designed to investigate the hepatic protective effect and the molecular mechanisms of andrographolide in concanavalin A-induced liver injury model. Results showed that andrographolide (Ag) attenuated concanavalin A (Con-A)-induced liver injury and inhibited hepatocyte apoptosis. Further results showed that oxidative stress response genes were significantly elevated during the pathogenesis induced by Con-A. Meanwhile, gadolinium chloride and N-acetyl-l-cysteine (NAC) treatment, which inactivates Kupffer cells or reduces reactive oxygen species, respectively, prevented the liver injury. So the messenger RNA levels of the oxidative response genes mentioned above were detected, and the following results showed that Ag treatment reduced their expression. Besides, serum lactate dehydrogenase and myeloperoxidase activity was significantly reduced by Ag. Finally, Ag treatment did not further reduce serum tumor necrosis factor-α production compared with NAC treatment alone. Thus, our results indicate that Ag prevents Con-A-induced liver injury and reduced the hepatic oxidative stress response. The hepatic protective effect of Ag indicates that Ag supplementation may be beneficial in the treatment of immune-mediated liver injury.     

川芎嗪对大鼠肝脏缺血再灌注损伤的保护作用

目的：研究川芎嗪对大鼠肝脏缺血再灌注损伤的保护作用及其机制。方法：SD大鼠随机分为5组：空白对照组、假手术组、缺血再灌注组、生理盐水组和川芎嗪组。其中空白对照组大鼠直接处死;假手术组开腹后60 min关闭腹腔;缺血再灌注组阻断70%肝血流60 min,再灌注4 h;生理盐水组予腹腔内注射生理盐水8 ml/kg,30 min后阻断70%肝血流60 min,再灌注4 h;川芎嗪组予腹腔内注射川芎嗪80 mg/kg,30 min后阻断70%肝血流60 min,再灌注4 h。速率法测血清丙氨酸氨基转移酶（alanine aminotransferase,ALT）和天冬氨酸氨基转移酶（aspartate aminotransferase,AST）活性,酶联免疫吸附法（ELISA）测血白介素-1（IL-1）、白介素-10（IL-10）和肿瘤坏死因子-α（TNF-α）水平。苏木素-伊红染色观察肝脏病理改变。结果：川芎嗪组血清ALT、AST、IL-1和TNF-α水平均比缺血再灌注组和生理盐水组明显降低（P〈0.05）,而IL-10则明显高于缺血再灌注组和生理盐水组（P〈0.05）。病理结果显示,川芎嗪组大鼠肝细胞损伤较缺血再灌注组和生理盐水组为轻。结论：川芎嗪对大鼠肝脏缺血再灌注损伤具有保护作用,其机制可能与抑制炎性细胞因子生成及促进抗炎细胞因子表达有关。     

Protective effect of taraxasterol on acute lung injury induced by lipopolysaccharide in mice

Taraxasterol, a pentacyclic-triterpene isolated from Taraxacum officinale, has been reported to have potent anti-inflammatory properties. However, the effect of taraxasterol on lipopolysaccharide (LPS)-induced mice acute lung injury has not been investigated. The aims of this study were to investigate whether taraxasterol could ameliorate the inflammation response in LPS-induced acute lung injury and to clarify the possible mechanism. Male BALB/c mice were pretreated with taraxasterol 1 h before intranasal instillation of LPS. 7 h after LPS administration, the myeloperoxidase (MPO) in lung tissues, lung wet/dry ratio and inflammatory cells in the bronchoalveolar lavage fluid (BALF) were detected. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) in the BALF were measured by ELISA. The extent of phosphorylation of IκB-α, p65 NF-κB, p46–p54 JNK, p42–p44 ERK, and p38 were determined by western blotting. The results showed that taraxasterol attenuated the infiltration of inflammatory cells, the activity of myeloperoxidase (MPO), lung wet/dry ratio, and the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in a dose-dependent manner. Additionally, western blotting results showed that taraxasterol inhibited the phosphorylation of IκB-α, p65 NF-κB, p46–p54 JNK, p42–p44 ERK, and p38 caused by LPS. Our data suggest that anti-inflammatory effects of taraxasterol against the LPS-induced ALI may be due to its ability of inhibition of the NF-κB and MAPK signaling pathways.     

白芍总苷对卡介苗加脂多糖引起的小鼠免疫性肝损伤的保护作用

目的　研究白芍总苷对小鼠免疫性肝损伤的保护作用。方法　在建立BCG +LPS诱导免疫性肝损伤小鼠模型的基础上 ,分光光度法检测血清中ALT、AST、NO水平和肝匀浆MDA、GSH Px、SOD含量 ;放免法检测TNF α的生物学活性 ;细胞增殖法测定脾淋巴增殖反应。结果　白芍总苷 (6 0、12 0、2 4 0mg·kg-1)ig给药可明显降低免疫性肝损伤小鼠增高的血清ALT、AST活性 ,同时能减少肝匀浆MDA含量 ,使降低的肝匀浆GSH Px、SOD活性升高 ,进一步研究发现白芍总苷可明显抑制免疫性肝损伤小鼠血清NO和TNF α的产生。白芍总苷还可抑制小鼠腹腔巨噬细胞TNF α的产生 ,对ConA诱导的脾淋巴增殖反应具有恢复作用 ,而对LPS诱导的脾淋巴增殖反应无明显影响。结论　白芍总苷对免疫性肝损伤具有保护作用。     

Ellagic acid protects Lipopolysaccharide/d-galactosamine-induced acute hepatic injury in mice

Ellagic acid, a natural polyphenol found in certain fruits, nuts and vegetables, has been reported to have anti-inflammatory, anti-tumor, and antioxidant activities. However, the effects of ellagic acid on acute hepatic injury have not been reported. In the present study, we investigated the effects of ellagic acid on Lipopolysaccharide/d-galactosamine-induced acute hepatic injury in mice. The results showed that LPS/GalN increased hepatic malondialdehyde (MDA) content, TNF-α level, serum ALT and AST levels and TNF-α level. However, these changes were attenuated by ellagic acid. Western blot analysis showed that ellagic acid inhibited LPS/GalN-induced NF-κB activation. Furthermore, ellagic acid induced the expression of Nrf2 and heme oxygenase-1. In conclusion, our results showed that ellagic acid protected against LPS/GalN-induced liver injury by enhancing the antioxidative defense system and reducing inflammatory response.     

Protective effects of salecan against carbon tetrachloride-induced acute liver injury in mice

Carbon tetrachloride (CCl₄) is a well‐established model for screening hepato‐protective drugs. The aim of the present study was to evaluate the potential protective effects of a novel soluble β‐glucan salecan on acute liver injury induced by CCl₄ in mice and to further explore the underlying mechanisms. Mice were given salecan (40 mg kg^?1) or phosphate‐buffered saline for 3 days prior to treatment with a single intraperitoneal dose of CCl₄ (1 ml kg^?1 body weight). Animals were sacrificed at 0, 12, 24, 48, 72 and 96 h post‐injection of CCl₄. Serum liver enzyme levels, histology, lipid peroxidation, glutathione (GSH) content, expression of antioxidant enzymes and hepatocyte proliferation were subsequently evaluated. The serum levels of hepatic enzyme markers were markedly reduced in the salecan pretreatment group compared with the control group. Histopathological examination of the livers revealed that hepatocellular degeneration and necrosis were significantly attenuated at an early stage during CCl₄ intoxication and liver recovery was markedly accelerated at a later stage in salecan pre‐administered mice. Furthermore, salecan administration remarkably alleviated lipid peroxidation and restored GSH depletion. Meanwhile, the expression of antioxidant genes was significantly elevated in the salecan‐treated group. Interestingly, the administration of salecan remarkably enhanced hepatocyte proliferation in the recovery phase after CCl₄ injection. Taken together, these results demonstrated that salecan exhibits a protective action on acute hepatic injury induced by CCl₄ through attenuating oxidative stress and accelerating hepatocyte regeneration. Copyright © 2011 John Wiley & Sons, Ltd.