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 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 effect 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 significantly 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 effect on alcohol-induced 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.

Immune-mediated liver injury following COVID-19 vaccination

Liver injury secondary to vaccination is a rare adverse event that has recently come under attention thanks to the continuous pharmacovigilance following the widespread implementation of coronavirus disease 2019(COVID-19)vaccination protocols.All three most widely distributed severe acute respiratory syndrome coronavirus 2 vaccine formulations,e.g.,BNT162b2,mRNA-1273,and ChAdOx1-S,can induce liver injury that may involve immune-mediated pathways and result in autoimmune hepatitis-like presentation that may require therapeutic intervention in the form of corticosteroid administration.Various mechanisms have been proposed in an attempt to highlight immune checkpoint inhibition and thus establish causality with vaccination.The autoimmune features of such a reaction also prompt an in-depth investigation of the newly employed vaccine technologies.Novel vaccine delivery platforms,e.g.,mRNA-containing lipid nanoparticles and adenoviral vectors,contribute to the inflammatory background that leads to an exaggerated immune response,while patterns of molecular mimicry between the spike(S)protein and prominent liver antigens may account for the autoimmune presentation.Immune mediators triggered by vaccination or vaccine ingredients per se,including autoreactive antibodies,cytokines,and cytotoxic T-cell populations,may inflict hepatocellular damage through wellestablished pathways.We aim to review available data associated with immunemediated liver injury associated with COVID-19 vaccination and elucidate potential mechanisms underlying its pathogenesis.

Protective effects of cyclosporine A on T-cell dependent ConA-induced liver injury in Kunming mice

INTRODUCTIONThe T-cell dependent specific liver injury in mice induced by concanavalin A(ConA) is a newly cstablished experimental liver injury model,which is considered more eligible for the study on pathophysiology of several human liver discascs,such as viral hepatitis and autommune hepatitis[1-9].T cell activation and several cytokines release had been proven to play a critical role in ConA -induced liver injury[10-19].Cyclosprine A(CsA),an effective inhibitor of activation of T lymphocytc,hes been used widely in clinical treatment,especially in autoimmune diseases and organ transplantation[20-25].In this study,we investigated the possible effect of CsA on ConA-induced liver injury in Kunning mice.

Progress of research on tetrahydrocurcumin against liver injury

Liver injury has become a serious liver disease worldwide,and its incidence is increasing year by year,bringing a serious health burden to people in all countries.Tetrahydrocurcumin is an active metabolite of curcumin,which has pharmacological effects such as antioxidant,anti-inflammatory,inhibition of apoptosis,anti-tumor,and anti-aging,and it can inhibit apoptosis in liver cells under the state of hepatic injury and reduce the level of oxidative stress and inflammation in liver tissues through the signaling pathways such as MAPK,PI3K/Akt,PPAR,AMPK,and Nrf2 to prevent and control liver injury.The purpose of preventing and controlling liver injury can be achieved.The active structure,pharmacological effects and application of tetrahydrocurcumin in liver injury were summarized by reviewing domestic and international literature,with a view to providing reference for further research on tetrahydrocurcumin in the field of 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 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.

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-

Liver injury associated with drug intake during pregnancy

Drug use during pregnancy is not common.Drug-induced liver injury(DILI)is a potential complication that is rare but can adversely affect both the mother and the fetus.Although many drugs can directly cause hepatotoxicity,idiosyncratic liver injury is common in pregnancy.Underreporting of adverse drug reactions,lack of adequate literature regarding drug safety in pregnancy,and the inherent difficulty in diagnosing DILI during pregnancy make the management of this condition challenging.This review attempts to describe the existing literature regarding DILI in pregnancy,which is mainly in the form of case reports;several studies have looked at the safety of antithyroid drugs,antiretroviral drugs,and paracetamol,which have an indication for use in pregnancy;the relevant data from these studies with regard to DILI has been presented.In addition,the review describes the diagnosis of DILI,grading the disease severity,assessment of causality linking the drug to the adverse event,regulatory guidelines for evaluating the potential of drugs to cause liver injury,efforts to ensure better participation of women in clinical trials and studies in pregnant women population in particular,and the challenges involved in generating adequate research evidence.The establishment of DILI registries in various countries is an encouraging development;however,there is a need for promoting active,spontaneous reporting of adverse events during pregnancy to ensure rapid generation of evidence regarding the safety of a drug in pregnant women.

Overview of drug induced liver injury in Brazil:What is the role of public health policy on the evidence?

BACKGROUND Adverse drug reactions are responsible for increased costs and morbidity in the health system.Hepatotoxicity can be induced both by non-prescription drugs and by those used for chronic diseases.It is the main cause of safety-related drug marketing withdrawals and could be responsible for irreversible and fatal injuries.AIM To identify and to summarize Brazilian studies reporting the drug-induced liver injury.METHODS A systematic review of Brazilian studies was carried out until June 2020.It was found 32 studies,being 10 retrospective cohorts,12 prospective cohorts,5 crosssectional,3 case-control,one case series and one randomized clinical trial.In most studies were investigated tuberculosis patients followed by other infectious conditions like human immunodeficiency virus(HIV)and hepatitis C virus.The hepatotoxicity ranged from one to 57%,led by isoniazid,rifampicin,and pyrazinamide.Few studies reported algorithm to assess causality.In most studies,there were moderate outcomes and it was necessary drug interruption.However,few severe outcomes,such as chronic liver damage and liver transplantation were reported.RESULTS Twenty-two different criteria for hepatotoxicity were found.The great heterogeneity did not allow a meta-analysis.Standardization of parameter of drug-induced liver injury and greater effort in pharmacovigilance could contribute to learn more about drug-induced liver injury(DILI)’s epidemiology in Brazil.CONCLUSION The development of strategic public health policies seems to have an influence on the DILI scientific evidence in Brazil due to main studies are in HIV and tuberculosis line care,two strategic health policies in Brazil.

Side effects of different doses of ephedrine in rats with cerebral ischemia/reperfusion injury

Ephedrine has a protective effect against cerebral ischemia,but its side effects limit its clinical application.Results from a previous study showed that 1.5 mg/kg per day ephedrine can promote motion recovery in rats following cerebral ischemia/reperfusion without significant side effects.In the present study,ephedrine at doses of 3.0,2.5 and 2.0 mg/kg was used to treat rats with cerebral ischemia/reperfusion and the effects of ephedrine on the heart,liver,kidney and cerebrum were observed.Results showed that the blood pressure of rats with cerebral ischemia/reperfusion injury following ephedrine treatment was lower than in rats that recovered naturally from cerebral ischemia/reperfusion,but the pressure decreased with increasing doses of ephedrine.In addition,serum aspartate transaminase,alkaline phosphatase and creatinine concentration in rats with cerebral ischemia/reperfusion injury following ephedrine treatment were greater than in rats that recovered naturally from cerebral ischemia/reperfusion.The concentrations of these enzymes were decreased with increasing doses of ephedrine.Ephedrine-treated rats displayed hyperemia,degeneration and edema in the cerebrum,liver,heart and kidney.Results demonstrated that ephedrine exhibited side effects on the cerebrum,heart,liver and kidney in rats following cerebral ischemia/reperfusion in a dose-dependent manner.

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.

Investigation of paeonol-geniposide on acute alcoholic liver injury based on uniform design method

Objective:To explore the optimal ratio and compatibility effect of paeonol-geniposide combination on acute alcoholic liver injury by uniform design.Methods:Lieber-DeCarli alcoholic liquid feed was used to induce acute alcoholic liver injury in mice.Uniform design was used to select the best dosage combination of paeonol and geniposide,and the related indexes of liver injury and oxidative stress were detected by kit.Serum inflammatory factors were detected by ELISA,and the expressions of p38 MAPK,JNK and NF-κB P65 related proteins in liver were detected by Western-blot.Results:The regression equation suggested that paeonol:geniposide=220:20 was the best ratio of paeonol and geniposide to resist alcoholic liver injury.Compared with the model group,the liver injury indexes and oxidation products of the paeonol+geniposide group decreased significantly,the antioxidant activity of liver tissue increased significantly,and the expression levels of p-p38 MAPK,p-JNK and NF-κB P65 protein decreased significantly.Conclusion:The optimal dosage of paeonolgeniposide was effectively optimized by uniform design and pharmacodynamic analysis.The combination of the two drugs could reduce the alcoholic liver injury by reducing the oxidative stress injury and inflammatory response in the liver tissue of mice,and its effect might be related to the targeting of p38 MAPK/JNK/NF-κB channel.

陈皮复合固体饮料制备工艺及其对急性酒精性肝损伤小鼠的保护作用

[目的]以药食同源的陈皮、山楂、葛根为主要原料,开发一种具有解酒功能的固体饮料,并探究其对急性酒精性肝损伤小鼠的保护作用。[方法]以浸膏得率和总黄酮含量为标准,采用正交试验选取最佳提取工艺;以感官评价、成型率、溶化性的综合评分为指标,采用单因素试验优化成型工艺。采用52%酒精灌胃的方法建立急性酒精性肝损伤小鼠模型,检测陈皮复合固体饮料对模型小鼠肝脏指数,血清中谷草转氨酶(AST)、谷丙转氨酶(ALT),肝组织中总胆固醇(TC)、甘油三酯(TG)、超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH)及炎症因子白细胞介素-1β(IL-1β)、白细胞介素6(IL-6)、肿瘤坏死因子-α(TNF-α)的影响,苏木素—伊红(HE)染色分析各组肝脏病理变化。[结果]陈皮复合固体饮料最佳制备工艺:3味药材浸泡30 min后提取2次,第一次料液比1∶12(g/mL)、提取时间2.0 h,第二次料液比1∶10(g/mL)、提取时间1.5 h;经浓缩、干燥、粉碎后得到干膏粉;干膏粉与麦芽糊精1∶1混合,加入1.0%的罗汉果甜苷,并以90%乙醇作为润湿剂进行湿法制粒。动物试验表明:与模型组相比,陈皮复合固体饮料组的AST、ALT、TG、TC、MDA、IL-1β、IL-6、TNF-α水平降低(P<0.01或P<0.05),GSH、SOD含量增加(P<0.01或P<0.05),且肝组织病理切片显示给药组小鼠肝损伤程度均有显著改善。[结论]陈皮复合固体饮料色泽均匀、溶解性好、甜度适中、口感细腻,对急性酒精性肝损伤具有良好的保护作用。

何首乌化学成分、药理作用及肝毒性的研究进展

从化学成分、药理作用及肝毒性3个方面综述何首乌的研究进展。何首乌含有二苯乙烯苷类、蒽醌类、磷脂类、黄酮类等多种化学成分,具有延缓衰老、抗癌、抗疲劳、抗炎镇痛、保护心血管等药理作用。目前,何首乌引起肝毒性的化学成分探讨主要集中于3类,即蒽醌类、二苯乙烯苷类及鞣质类。加大何首乌肝毒性成分、肝毒性机制研究的力度,加强中药安全用药知识宣教,规范其炮制及使用,可以在一定程度上降低何首乌肝毒性。

DHA单酰基甘油酯型藻油对小鼠急性酒精性肝损伤的保护作用

研究DHA单酰基甘油酯对小鼠急性酒精性肝损伤的保肝作用及机制。将雄性小鼠随机分为正常组、模型组、实验组(DHA单酰基甘油酯组)、阳性对照组(DHA三酰基甘油酯组和DHA乙酯组)5组。给药15 d后,检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、甘油三脂(TG)、总胆固醇(TC)、高密度脂蛋白(HDL)和低密度脂蛋白(LDL)含量,肝组织Toll样受体4(TLR 4)、髓样分化因子(MyD88)、核转录因子κB(NF-κB)基因表达水平。观察肝组织病理性改变;分析小鼠粪便细菌多样性。DHA单酰基甘油酯能显著降低急性酒精肝损伤小鼠血清ALT、AST、ALP、TG、TC和LDL浓度,而显著增加HDL浓度,改善酒精引起的肝组织病理性改变,而且DHA单酰基甘油酯对小鼠肝损伤改善效果优于DHA三酰基甘油酯和DHA乙酯。此外,DHA单酰基甘油酯能显著抑制酒精肝损伤小鼠肝组织TLR 4、MyD88、NF-κB基因表达,对酒精引起的肠道菌群紊乱具有一定恢复作用。DHA单酰基甘油酯对酒精诱导小鼠肝损伤具有一定保护作用,其机制可能与抑制TLR 4/NF-κB通路和改善肠道菌群有关。

不同灵芝菌丝体水提物对乙醇诱导LO2肝细胞损伤的保护作用

为了探讨不同灵芝菌丝体水提物对乙醇诱导LO2肝细胞损伤的保护作用,本文分析了7种不同灵芝菌株发酵菌丝体水提物对乙醇诱导LO2细胞损伤的保护作用。利用乙醇诱导LO2细胞建立体外肝损伤模型,并以细胞存活率、谷丙转氨酶(Alanine Aminotransferase,ALT)、谷草转氨酶(Aspartate Aminotransferase,AST)、活性氧(Reactive Oxygen Species,ROS)、超氧化物歧化酶(Superoxide dismutase,SOD)、谷胱甘肽(Glutathione,GSH)和丙二醛(Malondiadehyde,MDA)水平为指标考察灵芝菌丝体水提物对乙醇诱导LO2细胞损伤的保护效果。结果表明,7种灵芝菌株的菌丝体水提物均具有不同程度的保护作用。综合比较,G0119与G0154菌丝体的水提物作用效果较优,相较模型组,LO2细胞存活率显著提高(P<0.05),细胞培养液中的ALT、AST活力显著降低(P<0.05),细胞内ROS水平显著降低(P<0.05),SOD活力、GSH含量显著升高(P<0.05),MDA含量显著降低(P<0.05)。经相关性分析,发现水提物中多糖组分2的分子量大小与其保肝活性呈正相关,即分子量越大,活性越强。综上,灵芝菌丝体水提物对乙醇诱导的体外肝损伤起到保护作用,并且G0119与G0154菌株的作用效果较优,其保肝作用与提取物中多糖组分的分子量大小相关。

双环醇防治肝脏炎性损伤多学科专家共识

肝脏炎性损伤是许多慢性肝病的始动因素。肝脏炎性损伤可累及全身,反之,全身疾病也会导致肝损伤。肝病的诊治既要考虑肝脏病变本身,又需了解全身各系统疾病与肝脏炎性损伤之间相互影响及其病理生理发生机制。因此,针对肝损伤的诊治,常需多学科讨论,共同决策。肝病治疗的重要环节之一是保护和维持肝功能的稳定,其中如何进行抗炎护肝是制定治疗策略的重要考量因素之一。双环醇是由我国自主研发、用于治疗肝脏炎性损伤的一类化学药物,对各种原因所致的肝脏炎性损伤均具有较好的防治作用,已于“一带一路”沿线九国注册并上市。为此,我们组织了国内相关学科专家,根据肝病诊疗相关指南/共识/临床路径和循证医学证据,结合我国临床实践,总结双环醇在防治肝脏炎性损伤多学科临床应用方面的进展,旨在形成共识,提高双环醇临床使用的科学性和规范性,提升各学科对肝脏炎性损伤的防治水平。

基于网络药理学和体内实验探讨茯苓多糖抗对乙酰氨基酚致肝损伤的作用机制

目的利用网络药理学和体内实验,探讨茯苓多糖(PCP)抗对乙酰氨基酚(APAP)致肝损伤的作用靶点。方法通过SwissTargetPrediction数据库、SuperPred数据库和Pharmmapper数据库获取PCP的作用靶点,利用OMIM数据库、GeneCards数据库查找APAP致肝损伤相关作用靶点,使用String数据库构建蛋白互作网络(PPI)并筛选核心靶点。利用R软件进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路分析,通过AutoDuck vina软件对茯苓多糖和核心靶点进行分子对接。最后,用HE染色评估小鼠肝组织损伤情况,并且通过RT-PCR和免疫组化染色法(IHC)检测核心靶点的表达情况。结果共获得26个核心靶点,GO富集分析显示细胞凋亡、细胞周期、免疫等生物过程可能参与PCP抗APAP致肝损伤的进程。KEGG富集分析显示茯苓多糖抗APAP致肝损伤的信号通路主要集中在p53信号通路(p53 signaling pathway)、NOD样受体信号通路(NOD-like receptor signaling pathway)、TNF信号通路(TNF signaling pathway)等。分子对接结果显示,PCP与等核心靶点具有较好的结合能力。HE染色显示,APAP组小鼠肝组织形态结构出现异常,表现为细胞大面积坏死,而PCP干预后可以减轻肝组织损伤。RT-PCR和IHC结果表明,PCP通过逆转APAP暴露引起的CDK2、TNF、BCL2L1及MAOA水平升高来缓解小鼠肝损伤。结论通过网络药理学和体内实验找到了PCP抗APAP致肝损伤的可能潜在靶点,其作用机制可能与调节细胞周期、免疫反应、凋亡和药物代谢有关。