Acute Toxicity of Jinchuan Formula Plum Wine Extract and Its Protective Effect on Mice with Liver Injury

[Objectives]To investigate the acute toxicity and hepatoprotective effect of Jinchuan formula plum wine extract on mice,determine its safety range,and evaluate its hepatoprotective effect.[Methods]The median lethal dose(LD_(50))was determined by acute toxicity test with the toxic reaction and mortality of mice as indexes.Sixty Kunming mice were randomly divided into 6 groups:normal control group,model group(ConA-induced liver injury model),Jinchuan formula plum wine high,medium and low dose groups(1.0,0.5,0.25 g/kg)and silybin group(0.1 g/kg).The levels of ALT,AST,LDH in serum and TG,VLDL in liver were measured.After HE staining,the pathological changes of liver tissue in mice were observed,and the liver protective effect of Jinchuan formula plum wine extract was analyzed and evaluated.[Results]LD_(50)was 11.18 g/kg,and the 95%confidence limit of LD_(50)was 10.31-12.05 g/kg.The high-dose group of Jinchuan formula plum wine extract could significantly reduce the serum ALT and AST activities of ConA-induced liver injury mice(P<0.05).[Conclusions]Jinchuan formula plum wine extract is relatively safe,and also has a protective effect on liver injury.

Protective Effect of Ethanol Extract from Sweet Potato Leaves on CCL_(4)-Induced Liver Injury in Mice

[Objectives]To investigate the protective effect of ethanol extract from sweet potato leaves on liver injury induced by CCl_(4)in mice.[Methods]25 ICR mice were randomly divided into blank group,model group,high-dose extract group(200 mg/kg),low-dose extract group(100 mg/kg)and positive control group(2 mg/kg colchicine),with 5 mice in each group.All groups except the blank group were given intraperitoneal injection of 20%CCl 4 olive oil solution(2 mL/kg),and the blank group was given the same dose of olive oil solution three times a week.After 4 weeks,each administration group was given the corresponding dose of drugs(10 mL/kg),and the blank group and model group were given the corresponding amount of normal saline for 2 weeks.After the last intragastric administration,fasting was required,but water was allowed,blood was taken from eyeballs,and upper serum was taken by static centrifugation.Serum AST,ALT,CRP,IL-6 and SOD levels were detected by the kit.[Results]Compared with the blank group,the serum AST and ALT levels in the model group were significantly increased;compared with the model group,the ethanol extract of sweet potato leaves could decrease the levels of ALT,AST,CRP,IL-6 and increase the level of SOD in serum.[Conclusions]The ethanol extract of sweet potato leaves had protective effect on the mice with liver injury induced by CCl_(4),and its mechanism may be to protect the liver by lowering enzymes,inhibiting inflammation and antioxidant stress.

Study on Protection Mechanism of Viscum coloratum (Kom.) Nakai f. lutescens kitag Fruit Polysaccharides on Mice with Acute Alcoholic Liver Injury

This study was conducted to investigate the protective mechanism of V. coloratum fruit polysaccharides（ VCFP） on mice with acute alcoholic liver injury. Acute liver injury model was built by one-time alcohol gavage. The mice were randomly divided into VCFP-treated groups（ low-,medium-,and highdose）,alcohol model group and normal control group at the same time. VCFP-treated groups were administrated polysaccharide intragastrically continuously for4 weeks; and the alcohol model group and normal control group were administrated intragastrically the same amount of normal saline. The general situation and liver tissue morphological structure changes were observed. The results showed that the levels of ALT,AST,TC,TG,MDA contents,and CAT and GSH-Px activity of mice in the model group increased significantly（ P 〈 0. 01）,while the activity of SOD and weight and liver index decreased significantly（ P 〈 0. 01） compared with the normal control group. After 4 weeks of gavage,VCFP could significantly improve weight,liver index and SOD activity,and significantly reduce ALT,AST,TC and TG levels,MDA content and CAT and GSH-Px activity. These results suggest that VCFP can improve antioxidant enzyme activity,remove oxygen free radical and reduce membrane lipid peroxidation reaction,thereby protecting liver cells.

Immunomodulation and liver protection of Yinchenhao decoction against concanavalin A-induced chronic liver injury in mice

OBJECTIVE：This study investigated the immunoregulatory and protective roles of Yinchenhao decoction,a compound of Chinese herbal medicine,in a mouse model of concanavalin A（Con A）-induced chronic liver injury.METHODS：Female Bal B/c mice were randomly divided into 4 groups：normal control,Con A model,Con A model treated with Yinchenhao decoction（400 mg/kg,orally）,and Con A model treated with dexamethasone（0.5 mg/kg,orally）.All treatments were given once a day for 28 d.Except of the normal control,mice received tail vein injection of Con A（10 mg/kg）on days 7,14,21,and 28,at 1 h after treatment with Yinchenhao decoction or dexamethasone or saline to induce chronic liver injury.RESULTS：Repeated Con A injection induced chronic liver injury,which was evidenced by infl ammatory cell infi ltration and necrosis,increased serum alanine aminotranferease activities,decreased albumin levels,and an imbalanced expression of immunoregulatory genes in the liver tissues including signifi cantly enhanced interferon-γ,interleukin-4,monocyte chemotactic protein-1,and cluster of differentiation 163 m RNA levels,and reduced tumor necrosis factor-αand interleukin-6 m RNA levels.Treatment with Yinchenhao decoction signifi cantly reversed the Con A-induced changes in immunoregulatory gene expression in the liver tissues,reduced serum alanine aminotranferease activity,enhanced serum albumin level,and attenuated the extent of liver infl ammation and necrosis.Furthermore,Yinchenhao decoction did not result in hepatocyte degeneration and spleen weight loss that were observed in mice received long-term treatment with dexamethasone.CONCLUSION：Yinchenhao decoction treatment protected liver against the Con A-induced chronic liver damage and improved liver function,which were associated with the modulation of gene expression related to immune/infl ammatory response.

Protective Effect of Mongolian Medicine Youning Bawei Powder on Liver Injury Induced by CCl4 in Mice

[Objectives]To study the protective effect of Mongolian medicine Youning Bawei Powder on liver injury induced by carbon tetrachloride(CCl_(4))in mice.[Methods]The experimental mice were divided into 5 groups:normal group,model group,positive control group,low-dose group and high-dose group of Mongolian medicine Youning Bawei Powder.The model group was induced by CCl_(4),the positive control group was treated with liver-protecting tablet,and the Mongolian medicine group was treated with Youning Bawei Powder for one month.The liver tissue injury of mice in each group was observed by HE staining,and the levels of serum ALT,AST,SOD and MDA were detected.[Results]Mongolian medicine Youning Bawei Powder significantly improved the pathological liver injury induced by CCl_(4),significantly decreased the content of ALT,AST and MDA in serum of mice with CCl_(4) liver injury,and significantly increased the activity of serum SOD.[Conclusions]Youning Bawei Powder,a Mongolian medicine,has a protective effect on liver injury induced by CCl_(4) in mice.

Experimental study on the protective effect of propofol on liver injury in rats with sepsis

Objective:To observe the protective effect of propofol on liver injury in rats with sepsis and explore its protective mechanism.Methods:24 Wister rats were randomly divided into 3 groups,with 8 rats in each group:the sham operation group,the saline group and the propofol group.An intraperitoneal injection of LPS 8 mg/kg was used in the saline group,with continuous infusion of normal saline.An intraperitoneal injection of LPS 8 mg/kg and continuous infusion of propofol saline solution were also performed in the propofol group.Results:Compared with the saline group,the levels of ALT,AST,IL-6 and TNF-αin the sham operation group and the propofol group were significantly lower than those in the saline group.Conclusions:Propofol has a certain protective effect on liver injury in rats with sepsis.

Liver protection strategies in liver transplantation

BACKGROUND： Liver transplantation is the therapy of choice for patients with end-stage liver diseases. However, the gap between the low availability of organs and high demand is continuously increasing. Innovative strategies for organ protection are necessary to expand donor pool and to achieve better outcomes for liver transplantation. The present review analyzed and compared various strategies of liver protection.DATA SOURCES： Databases such as PubM ed, Embase and Ovid were searched for the literature related to donor liver protection strategies using following key words： ＂ischemia reperfusion injury＂, ＂graft preservation＂, ＂liver transplantation＂, ＂machine perfusion＂ and ＂conditioning＂. Of the 146 studies identified,only those with cutting edge strategies were analyzed.RESULTS： A variety of therapeutic approaches were proposed to alleviate graft ischemia/reperfusion injury, which included static cold storage, machine perfusion （hypothermic, normothermic and subnormothermic）, manual conditioning （pre,post and remote）, and pharmacological conditioning. Evidences from animal experiments and clinical trials suggested that all these strategies could potentially protect liver graft; however, their clinical applications are limited partially due to their own disadvantages.CONCLUSIONS： There are a plenty of methods suggested to decrease the degree of donor liver transplantation-related injury. However, none of these approaches is perfect in clinical practice. More translational researches （molecular and clinical studies） are needed to improve the techniques in liver graft protection.

Experimental Study of Pratia Extact on Acute Liver Injury in Mice

[Objectives] This study was conducted to observe the protective effect of Pratia extract on acute liver injury in mice.[Methods] Mice were randomly divided into 6 groups according to body weight,10 in each group: normal control group,ethanol-induced/CCl4 liver injury model,low-dose,middle-dose and high-dose Pratia extract groups,and bifendatatum group.Except the blank group,other groups were given 50% ethanol intragastrically at a dose of 12 ml/kg to cause acute alcoholic liver injury,or intraperitoneally injected with 10% CCl4 soybean oil solution to cause acute CCl4 liver injury.The serum ALT and AST activity were measured as well as liver SOD and MDA concentrations.[Results] Pratia extract effectively reduced serum ALT and AST,decreased MDA content and increased liver tissue SOD activity.[Conclusions] Pratia extract has certain protective effect on acute liver injury.

Protective effects of C-phycocyanin on alcohol-induced acute liver injury in mice

Excessive alcohol consumption leads to liver disease. Extensive evidence suggests that C-phycocyanin(C-PC), a chromophore phycocyanobilin derived from Spirulina platensis, exerts protective eff ects against chemical-induced organ damage. In this study, we investigated whether C-PC could protect against ethanol-induced acute liver injury. Serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), triglyceride(TG), total cholesterol(CHOL), low-density lipoprotein(LDL), liver homogenate malondialdehyde(MDA), superoxide dismutase(SOD) content were measured, and pathological examination of liver sections were examined. C-PC showed obvious inhibitory eff ects on serum ALT, AST, TG, CHOL, LDL and MDA, and SOD content significantly increased in the liver. The structure of hepatic lobules was clear, liver sinus returned to normal, and liver cell cords were arranged in neat rows. Cloudiness, swelling, inflammatory cell infiltration and spotty necrosis of liver cells were significantly reduced. Therefore, C-PC can significantly protect against ethanol-induced acute liver injury.

Protective eff ect of Solanum Nigrum Linn green fruit ethanolic extract on alcoholic liver injury in mice

Alcoholic liver injury is a liver disease caused by excessive alcohol consumption,which can lead to chronic liver disease death.Solanum Nigrum Linn taste bitter,cold,has the effect of clearing heat and detoxification,promoting blood and detumescence.Solanum Nigrum Linn fruit contains a variety of antioxidant enzymes,can remove the body produced by aerobic metabolism harmful substances.In this paper,a model of alcohol-induced liver injury in C57BL/6 mice was established to evaluate the protective eff ect of Solanum Nigrum Linn green fruit(SNGF)ethanolic extract on alcohol-induced liver injury.H&E staining and oil red O(ORO)staining showed that hepatic lobules were clearly demarcated,vacuoles were signifi cantly reduced and lipid droplets were reduced in SNGF ethanolic extract treatment group.Serum levels of TC,TG,LDH,TBA,AKP,ALT and AST were decreased in the SNGF ethanolic extract treatment group,and SNGF ethanolic extract could clear reactive oxygen species(ROS)in time.MDA content was signifi cantly decreased after SNGF ethanolic extract treatment,while superoxide dismutase(SOD)and GSH-Px contents were increased after SNGF ethanolic extract treatment.These results suggest that SNGF ethanolic extract has a protective eff ect on alcohol-induced liver injury.

A new class of potent liver injury protective compounds: Structural elucidation, total synthesis and bioactivity study

A new class of potent liver injury protective compounds,phychetins A-D(1-4)featuring an unique 6/6/5/6/5 pentacyclic framework,were isolated and structurally characterized from a Chinese medicinal plant Phyllanthus franchetianus.Compounds 2-4 are three pairs of enantiomers that were initially obtained in a racemic manner,and were further separated by chiral HPLC preparation.Compounds 1-4 were proposed to be originated biosynthetically from a coexisting lignan via an intramolecular Friedel-Crafts reaction as the key step.A bioinspired total synthesis strategy was thus designated,and allowed the effective syntheses of compounds 2-4 in high yields.Some of compounds exhibited significant anti-inflammatory activities in vitro via suppressing the production of pro-inflammatory cytokine IL-1β.Notably,compound 4,the most active enantiomeric pair in vitro,displayed prominent potent protecting activity against liver injury at a low dose of 3 mg/kg in mice,which could serve as a promising lead for the development of acute liver injury therapeutic agent.

Protective effect of curcumin against liver warm ischemia/reperfusion injury in rat model is associated with regulation of heat shock protein and antioxidant enzymes

AIM: To investigate the hypothesis that the protective effects of curcumin in hepatic warm ischemia/reperfusion (I/R) injury are associated with increasing heat shock protein 70 (Hsp70) expression and antioxidant enzyme activity. METHODS: Sixty Sprague-Dawley male rats were randomly divided into sham, I/R, C + I/R groups. The model of reduced-size liver warm ischemia and reperfusion was used. Curcumin (50 mg/kg) was administered by injection through a branch of superior mesenteric vein at 30 min before ischemia in C + I/R group. Five rats were used to investigate the survival during 1 wk after operation in each group. Blood samples and liver tissues were obtained in the remaining animals after 3, 12, and 24 h of reperfusion to assess serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver tissue NO2- + NO3-, malondialdehyde (MDA) content, superoxide dismutase (SOD), catalase (CAT), nitricoxide synthase (NOS) and myeloperoxidase (MPO) activity, Hsp70 expression and apoptosis ratio. RESULTS: Compared with I/R group, curcumin pretreatment group showed less ischemia/reperfusion- induced injury. CAT and SOD activity and Hsp70 expression increased significantly. A higher rate of apoptosis was observed in I/R group than in C + I/R group, and a significant increase of MDA, NO2- + NO3- and MPO level in liver tissues and serum transaminase concentration was also observed in I/R group compared to C + I/R group. Curcumin also decreased the activity of inducible NO synthase (iNOS) in liver after reperfusion,but had no effect on the level of endothelial NO synthase (eNOS) after reperfusion in liver. The 7 d survival rate was significantly higher in C + I/R group than in I/R group. CONCLUSION: Curcumin has protective effects against hepatic I/R injury. Its mechanism might be related to the overexpression of Hsp70 and antioxidant enzymes.

Pharmacological research progress of ursolic acid for the treatment of liver diseases

Ursolic acid is a natural pentacyclic triterpenoid with various pharmacological activities such as anti-inflammatory,hepatoprotective,antitumor,and hypoglycemic activity.This natural product is widely present in many common Chinese herbal medicines such as Hedyotis diffusa and Prunella vulgaris.The present review highlights the pharmacological research progress of ursolic acid in liver disease,with a focus on providing directions for future research and clinical practice of ursolic acid.Modern studies have demonstrated that ursolic acid can adjust the activities of enzymes such as superoxide dismutase and NADPH oxidase to balance oxidative stress,reduce inflammation,as well as to repair damaged liver.Research also showed that ursolic acid targeted lipid metabolic genes,activating autophagy and reducing lipid deposition in hepatocytes,further preventing the progress of fatty liver.Besides,the combination of ursolic acid with caspase-3 was able to prevent apoptosis and relieve liver injury.Furthermore,ursolic acid was showed to target the intestine by alleviating mucosal injury and restoring the balance of the intestinal microecology and protect liver through the enterohepatic axis.In terms of antitumor activity,ursolic acid targeted several tumor suppressor genes including gene of phosphate and tension homology deleted on chromsome ten and p53,and affected the expression of cyclin and apoptosis-related proteins involving Bax,Bcl-2,and Bcl-x,which acted on signal transduction pathways including phosphatidylinositol-3-kinase/protein kinase B,extracellular regulated protein kinases and proteina fosforilata 21 wide-type actiated factorlp 1.The same compound interacted with caspases,resulting in inhibition of cell proliferation and induction of apoptosis.In addition,ursolic acid also exerted anticancer activity through inhibiting angiogenesis,tumor invasion and metastasis,and improving immunity.Other studies have noted the importance of nano-preparations of ursolic acid for its clinical applications.This review provides essential information on the role of ursolic acid in liver protection.Further research on the mechanisms of action of ursolic acid would be useful for its pharmaceutical development and clinical application.

Protective effect of hydrogen-rich saline on liver ischemia-reperfusion injury in mice

Objective To explore protective effect of hydrogen - rich saline on liver ischemia reperfusion ( IR) in mice and possible mechanisms. Methods Twenty - four C57BL /6 mice were randomly divided into 3 groups: sham - operated group,control group ( mice were injec-

Role of Nrf2 in chronic liver disease

Nuclear erythroid 2-related factor 2(Nrf2) is a central regulator of antioxidative response elements-mediated gene expression. It has a significant role in adaptive responses to oxidative stress by interacting with the antioxidant response element, which induces the expression of a variety of downstream targets aimed at cytoprotection. Previous studies suggested oxidative stress and associated damage could represent a common link between different forms of diseases. Oxidative stress has been implicated in various liver diseases, including viral hepatitis, nonalcoholic fatty liver disease/steatohepatitis, alcoholic liver disease and drug-induced liver injury. Nrf2 activation is initiated by oxidative or electrophilic stress, and aids in the detoxification and elimination of potentially harmful exogenous chemicals and their metabolites. The expression of Nrf2 has been observed throughout human tissue, with high expression in detoxification organs, especially the liver. Thus, Nrf2 may serve as a major regulator of several cellular defense associated pathways by which hepatic cells combat oxidative stress. We review the relevant literature concerning the crucial role of Nrf2 and its signaling pathways against oxidative stress to protect hepatic cell from oxidative damage during development of common chronic liver diseases. We also review the use of Nrf2 as a therapeutic target to prevent and treat liver diseases.

护肝片联合抗感颗粒治疗EBV肝损伤的网络药理学分析

目的:通过网络药理学联合分子对接技术探讨护肝片联合抗感颗粒治疗EB病毒(Epstein-Barr virus,EBV)肝损伤的分子机制。方法:利用TCMSP、HERB数据库和Swiss Target Prediction平台筛选和预测护肝片联合抗感颗粒的活性成分及潜在靶点。通过GeneCards数据库检索EBV肝损伤的相关基因。运用Cytoscape 3.9.1软件构建药物活性成分-靶点网络,并筛选出关键成分。对护肝片联合抗感颗粒治疗EBV肝损伤的潜在作用靶点进行GO及KEGG通路富集分析,并将其导入STRING平台,构建PPI网络,利用MCC和MNC算法筛选出核心靶点。最后,利用CB-Dock对关键成分与核心靶点进行分子对接。结果:共收集护肝片联合抗感颗粒的活性成分96个,护肝片联合抗感颗粒治疗EBV肝损伤的作用靶点57个。GO和KEGG通路富集分析结果主要与细胞因子受体结合、细胞因子活性、人巨细胞病毒感染等功能和通路相关。分子对接结果证实核心靶点STAT3、AKT1、JUN、TP53能稳定地与关键成分槲皮素、山柰酚、木犀草素、金合欢素、异鼠李素结合。结论:护肝片联合抗感颗粒主要通过槲皮素、山柰酚、木犀草素、金合欢素和异鼠李素等关键成分作用于STAT3、AKT1、JUN和TP53等核心靶点,参与细胞因子相关生物细胞过程的调节,最终起到治疗EBV肝损伤的作用。

益母草碱对急性酒精性肝损伤的保护作用

目的探究益母草碱对急性酒精性肝损伤的保护作用。方法将C57BL/6J小鼠随机分为对照组、模型组、益母草碱低剂量组、益母草碱高剂量组和联苯双酯组,每组8只。按确定药物与剂量给予益母草碱组和联苯双酯组灌胃,1次/日,连续10 d,对照组与模型组给予等体积注射用氯化钠溶液。末次给药12 h后,除对照组外,其余4组小鼠给予乙醇含量为56%的北京二锅头灌胃,连续3 d,每次间隔12 h。末次给予北京二锅头后,禁食4 h后处死小鼠,取肝脏称重,计算肝脏系数。检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、甘油三酯(TG)、丙二醛(MDA)含量。苏木素-伊红染色观察肝脏病理学变化,蛋白免疫印迹法检测相关蛋白。结果模型组小鼠ALT、AST、TG、MDA水平及肝脏指数显著高于对照组,差异有统计学意义(P<0.05);益母草碱低剂量组和高剂量组小鼠ALT、AST、TG、MDA水平及肝脏指数低于模型组(P<0.05)。肝脏组织病理检查及油红O染色揭示,益母草碱减轻乙醇对小鼠肝脏组织的损伤(P<0.05)。结论益母草碱对急性酒精性肝损伤具有保护作用。

TCDCA对四氯化碳所致大鼠肝损伤的影响

为了研究牛磺鹅去氧胆酸(TCDCA)对大鼠肝损伤的影响,试验采用大鼠四氯化碳肝损伤模型,观察TCDCA对肝损伤大鼠血清AST、AKP、T-Bil、总蛋白质含量及总抗氧化能力的影响。结果表明:TCDCA能显著降低CCl4所致大鼠急性肝损伤血清中AST、AKP、T-Bil含量;显著升高CCl4所致大鼠急性肝损伤血清中蛋白质含量和总抗氧化能力。因此,TCDCA对CCl4所致大鼠急性肝损伤有一定的保护作用。

爬岩红提取物对化学性肝损伤小鼠的保护作用

分别用体积分数0.5%CCl_(4)、50%乙醇溶液建立小鼠急性肝损伤模型,研究爬岩红水提物、醇提物对CCl_(4)和酒精所致的肝损伤小鼠的保护作用。结果显示,爬岩红水提物、醇提物均能降低CCl_(4)肝损伤小鼠血清ALT活性、肝组织MDA水平,升高肝组织GSH-PX、T-SOD、CAT、白蛋白水平,减轻CCl4肝损伤小鼠肝组织的病理变化程度,且二者的保肝作用无显著差异(P>0.05);爬岩红水提物、醇提物均能降低酒精性肝损伤小鼠血清ALT活性、肝组织MDA和TG水平,升高肝组织GSH、T-SOD水平,减轻酒精性肝损伤小鼠肝组织的病理变化程度,且水提物的效果更为显著(P<0.05)。爬岩红水提取物、醇提取物对CCl_(4)和酒精所致的肝损伤小鼠均有保护作用,水提物对酒精性肝损伤的保护作用更好。

苦瓜总皂苷对小鼠急性酒精性肝损伤的干预作用研究

为了探讨苦瓜总皂苷对小鼠急性酒精性肝损伤的干预作用。将60只健康昆明种小鼠随机分为6组,每组10只。依次为空白组、模型组、阳性对照组、苦瓜总皂苷高剂量组、苦瓜总皂苷中剂量组和苦瓜总皂苷低剂量组。除空白组外,其他各组连续10d上午9:00给予白酒,建立急性酒精性肝损伤模型,下午2:00除模型组和空白组给予生理盐水外,其他各组给予干预治疗。末次给药12h后,比较每组小鼠的酒精状态。称重肝脏,计算肝脏系数,取肝组织切片进行病理学分析,测量小鼠的血清和肝脏中生化指标。结果表明:苦瓜总皂苷可以显著提高肝指数;降低模型组小鼠血清中AST、ALT水平和肝脏中MDA含量,增加肝脏中GSH含量,增强肝脏SOD、CAT活力且肝细胞颗粒变性有不同程度的改善。苦瓜总皂苷可有效减轻白酒诱导的小鼠急性酒精性肝损伤,其作用机制可能与减轻自由基和脂质过氧化物对肝细胞损伤有关。