Protective mechanism of Coprinus comatus polysaccharide on acute alcoholic liver injury in mice,the metabolomics and gut microbiota investigation

Coprinus comatus polysaccharide(CCP)has significant hepatoprotective effect.To explore hepatoprotective mechanism of CCP,the study analyzed preventive effect of CCP on acute alcoholic liver injury in mice by histopathological examination and biochemical analysis.Simultaneously,hepatoprotective mechanism was also analyzed in conjunction with metabolomics and proliferation of gut microbiota.The results showed that CCP significantly decreased alanine aminotransferase(ALT),aspartate aminotransferase(AST)and triglyceride(TG)levels in serum of alcoholic liver disease(ALD)mice.Histopathological examination showed that CCP can significantly improve liver damage.Metabolomics results showed that there were significant differences in the level of metabolites in liver tissue of control group,ALD group and CCP group,including taurine,xanthosine,fumaric acid and arachidonic acid,among others.Metabolites pathways analysis showed that hepatoprotective effect of CCP was related to energy metabolism,biosynthesis of unsaturated fatty acids,amino acids metabolism and lipid metabolism.Additionally,CCP inhibited an increase in the number of Clostridium perfringens,Enterobacteriaceae and Enterococcus,and a decrease in the number of Lactobacillus and Bifidobacterium in the gut of ALD mice.All these findings suggested that CCP treatment reversed the phenotype of ethanol-induced liver injury and the associated metabolites pathways.

Optimization of Extraction Conditions of Pomegranate Peel Polyphenols and Its Protective Effect on Acute Alcoholic Liver Injury in Mice

[Objectives]This study was conducted to explore the optimization of ultrasonic-assisted organic solvent extraction of pomegranate peel polyphenols(PPPs),and to study the protective effect of PPPs on acute alcoholic liver injury in mice.[Methods]The optimal extraction conditions of PPPs were determined by single factor and orthogonal experiments,and an acute alcoholic liver injury model in mice was established.Bifendate was used as the positive control group to investigate the protective effect of low,medium and high doses of PPPs on acute alcoholic liver injury.[Results]The optimum extraction process parameters were followed as 60%ethanol concentration,solid-liquid ratio of 1:40(w/v),extraction temperature of 50℃,and extraction time of 1.5 h,and the yield was 1.42%.The results of animal experiments showed that PPPs could effectively reduce the degree of alcoholic liver injury in mice,reduce the levels of serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST),and reduce the inflammation and necrosis of liver tissue in mice.Meanwhile,the total polyphenols from pomegranate peel also significantly reduced the expression levels of malondialdehyde(MDA),tumor necrosis factor(TNF-α)and interleukin-6(IL-6)in mice,and increased the levels of superoxide dismutase(SOD)and reduced glutathione(GSH)in liver tissue of mice,indicating its antioxidant and anti-inflammatory effects,further illustrating its protective effect on alcoholic liver injury.[Conclusions]PPPs could reduce the expression levels of TNF-α,IL-6 and MDA in mice,and increase the expression levels of SOD and GSH to achieve the protective effect on acute alcoholic liver injury in mice.This study will provide new ideas for the development of new anti-alcoholic liver injury drug resources.

Protective effect of gingerol dropping pills against alcoholic liver injury in mice

OBJECTIVE To prepare gingerol dropping pills and to investigate its protective effect on alcoholic liver injury. METHODS The prescription was selected by orthogonal design method and the effect of the option and ratio of ground substance,the temperature of drug. The hardness,circular degree,the tail formation and the dissolution time were studied. Totally 40 KM mice were randomly divided into control group,model group,gingerol dropping pill group(400 mg·kg^(-1)·d^(-1)) and positive control group(bifendate,150 mg·kg^(-1)·d^(-1)) of 10 mice each. The mice from the model and two drug groups were administrated with liqueur[0.15 mL/(10 g·d)]daily by gavage for 3 weeks,Two hours later,drug group mice were treated corresponding gingerol dropping pill and bifendate. Meanwhile,the control group were gavaged same amount of normal saline. Finally,when the model of acute alcoholic liver injury was established on the 22 stday,Biochemical indicators of ocular blood in mice were observed.We also observed the change of liver morphology. RESULTS Under optimum conditions,we can obtain dropping pills having circular shape,touching with hardness and short dissolution time. Compared with the control group,the levels of alanine transaminase(ALT),glutamic-oxaloacetic transaminase(AST) and malondialdehyde(MDA) in model group were obviously increased(P<0.01),While the activity of Superoxide dismutase(SOD) were decreased. In addition,In model group,mice liver disorders,hepatic lobule fusion,accompanying a large number of patchy sample liver cell vacuoles,various sizes of fat vacuoles appeared in cytoplasm and inflammatory cell infiltration were visible around the central vein. On the contrary,compared with the model group,drug groups attenuated or even reversed hepatic pathological changes. Form gingerol dropping pill group,an increase in hepatic SOD activity and serum ALT and AST activities were found and a significant decrease in hepatic MDA content were also observed(P<0.01). CONCLUSION The prescription of gingerol dropping pills was reasonable,and the preparation process was simple. Gingerol dropping pills can protect liver from alcoholic liver injury to some extend,and the mechanism may be related to its antioxidant effect.

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.

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.

Alcoholic liver injury:Influence of gender and hormones

This article discusses several subjects pertinent to a consideration of the role of gender and hormones in alcoholic liver injury (ALI). Beginning with an overview of factors involved in the pathogenesis of ALI, we review changes in sex hormone metabolism resulting from alcohol ingestion, summarize research that points to estrogen as a cofactor in ALI, consider evidence that gut injury is linked to liver injury in the setting of alcohol, and briefly review the limited evidence regarding sex hormones and gut barrier function. In both women and female animals, most studies reveal a propensity toward greater alcohol-induced liver injury due to female gender, although exact hormonal influences are not yet understood. Thus, women and their physicians should be alert to the dangers of excess alcohol consumption and the increased potential for liver injury in females.

Hepatoprotective effects of Hovenia dulcis seeds against alcoholic liver injury and related mechanisms investigated via network pharmacology

BACKGROUND Alcoholic liver disease(ALD)is a worldwide health problem,and natural products have been shown to improve ALD due to their antioxidant activities.Some parts of Hovenia dulcis(H.dulcis),such as roots,peduncles,and stems,provide health benefits.Nevertheless,the effects and mechanisms of H.dulcis seeds on ALD have not yet been fully elucidated.AIM To determine H.dulcis antioxidant activity,evaluate its effects against ALD,and investigate the related mechanisms via network pharmacology.METHODS The antioxidant activity of H.dulcis seed was determined by both ferric-reducing antioxidant power and trolox equivalent antioxidant capacity assays.The total phenolic and flavonoid contents were determined by Folin–Ciocalteu method and aluminum chloride colorimetry,respectively,and polysaccharide was determined by phenol-sulfuric acid method.The effects of H.dulcis seeds against alcoholic liver injury were investigated in mice with water extract pretreatment for 7 days followed by alcohol administration.Moreover,the mechanisms of action were explored with network pharmacology.RESULTS The results showed that H.dulcis seeds possessed strong antioxidant activity(245.11±10.17μmol Fe2+/g by ferric-reducing antioxidant power and 284.35±23.57μmol TE/g by trolox equivalent antioxidant capacity)and contained remarkable phenols and flavonoids,as well as a few polysaccharides.H.dulcis seeds attenuated alcohol-induced oxidative liver injury,showing reduced serum alanine and aspartate aminotransferases,alkaline phosphatase,and triglyceride,elevated hepatic glutathione,increased activities of superoxide dismutase and catalase,and reduced malondialdehyde and hepatic triglyceride.The results of network pharmacology analysis indicated that kaempferol,stigmasterol,and naringenin were the main bioactive compounds in H.dulcis seeds and that modulation of oxidative stress,inflammation,gut-derived products,and apoptosis were underlying mechanisms of the protective effects of H.dulcis seeds on ALD.CONCLUSION The results of this study demonstrate that H.dulcis seeds could be a good natural antioxidant source with protective effects on oxidative diseases such as ALD.

Study on the Protective Effect and Mechanism of Tibetan Medicine Ershiwuwei Songshi Pill on Acute Alcoholic Liver Injury in Rats

[Objectives]To investigate the protective effect and mechanism of Ershiwuwei Songshi Pill on acute alcoholic liver injury in rats.[Methods]Sixty male SD rats were randomly divided into normal control group,model group,polyene phosphatidylcholine(82.08 mg/kg)positive control group and Ershiwuwei Songshi Pill high(180 mg/kg),medium(90 mg/kg)and low(45 mg/kg)dose groups.The rats in each group were given corresponding drugs by intragastric administration for 3 d and fed normally.From the 4th d,all groups except the normal control group were fed with 15 mL/kg liquor(56%vol)for 7 d after 2 h of administration.After the last modeling,the levels of AST,ALT,TC,TG,SOD,GSH in serum and IL-1β,IL-6,TNF-αin liver tissue were measured.The protein expressions of Bax,Bcl-2 and Caspase3 were determined by Western blotting.HE staining was used to observe the pathological changes of liver tissue under light microscope.[Results]Compared with the model group,the body weight and the levels of SOD and GSH in the treatment group were significantly higher than those in the model group;liver index,serum ALT,AST,TC,TG,IL-1β,IL-6 and TNF-αlevels decreased significantly(P<0.01 or P<0.05);HE staining showed that there was a small amount of collagen proliferation and lymphocyte infiltration in connective tissue around the hepatic portal area in the model group,multiple inflammatory foci could be seen in the lobules,and round fat vacuoles could be seen in the cytoplasm;in each administration group,the pathological condition of the liver was mild.[Conclusions]Ershiwuwei Songshi Pill had a certain protective effect on acute alcoholic liver injury in rats,and its mechanism might be related to reducing enzyme,promoting lipid metabolism and anti-inflammation.

Lignans from Seeds of Herpetospermum caudigerum Wall.Protect Against Alcoholic Liver Injury via TGF-β/Smads Pathway in Rats

[Objectives]This study aimed to investigate the effects of lignans from seeds of Herpetospermum caudigerum Wall.(SHC)on expression of TGF-β/Smads in liver tissue of hepatic alcohol-injuried rats,and to explore its protective mechanism.[Methods]A total of 60 SD rats were randomly divided into six groups.The rats in all the groups except those in the normal group were given with white spirit by gavage for 8 weeks to establish alcoholic liver injury models.After rat models were established successfully,they were administered intragastrically with 400,200 and 100 mg/kg of lignans,respectively.The rats in the normal group were administered intragastrically with 50 mg/kg of silymarin.The administration lasted for 8 weeks,once a day.The changes in the general state,liver tissue pathology and collagen deposition of the rats were observed.The expression of TGF-β,TGF-β1 receptor 1(TβR-I),TGF-β1 receptor 2(TβR-II),Smad2/p-Smad2 and Smad3/p-Smad3 in the hepatic tissue was detected.[Results]The expression levels of TGF-β1,Smad2,p-Smad2,and p-Smad3 significantly declined,and the expression levels of TβR-I,TβR-II and Smad3 did not change significantly in the liver tissue of rats in the lignans groups and the expression levels of TGF-β,Smad2,and p-Smad3 significantly declined.Meanwhile,the expression levels of TβR-I,TβR-II,p-Smad2 and Smad3 did not change significantly in the silymarin group.[Conclusions]The lignans from SHC have significant intervention effects on alcoholic livery injury.The mechanism may be related to the inhibition of hepatic stellate cell(HSC)activation,TGF-βsecretion and p-Smad2,p-Smad3 expression in the signaling pathway.

Insights into skullcap herb-induced liver injury

This editorial addresses the growing concern of herb-induced liver injury(HILI),focusing on a unique case of Skullcap-induced HILI report.This editorial underscore the significant mortality rate linked to Skullcap-induced HILI,emphasizing the importance of vigilant monitoring and intervention.As herbal supplement usage rises,collaboration among clinicians and researchers is crucial to comprehend and address the complexities of HILI,particularly those involving Skullcap.

Hyperhomocysteinemia, endoplasmic reticulum stress, and alcoholic liver injury

Deficiencies in vitamins or other factors (B6, B12, folic acid, betaine) and genetic disorders for the metabolism of the non-protein amino acid-homocysteine (Hcy) lead to hyperhomocysteinemia (HHcy). HHcy is an integral component of several disorders including cardiovascular disease, neurodegeneration, diabetes and alcoholic liver disease. HHcy unleashes mediators of inflammation such as NFkB, IL-1β, IL-6, and IL-8, increases production of intracellular superoxide anion causing oxidative stress and reducing intracellular level of nitric oxide (NO), and induces endoplasmic reticulum (ER) stress which can explain many processes of Hcy-promoted cell injury such as apoptosis, fat accumulation, and inflammation. Animal models have played an important role in determining the biological effects of HHcy. ER stress may also be involved in other liver diseases such as a1-antitrypsin (a1-AT) deficiency and hepatitis C and/or B virus infection. Future research should evaluate the possible potentiative effects of alcohol and hepatic virus infection on ER stress-induced liver injury, study potentially beneficial effects of lowering Hcy and preventing ER stress in alcoholic humans, and examine polymorphism of Hcy metabolizing enzymes as potential risk-factors for the development of HHcy and liver disease.

Association of Cytokines with Clinical Indicators in Patients with Drug-Induced Liver Injury

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators.Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),antiinfective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed.Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group.Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-αand IL-6 may partake the inflammatory process of DILI.

Biochemistry and transcriptome analysis reveal condensed tannins alleviate liver injury induced by regulating cholesterol metabolism pathway

Free cholesterol has been considered to be a critical risk factor of nonalcoholic fatty liver disease(NAFLD).It remains unknown whether dietary intake of condensed tannins(CTs)have distinguishable effects to alleviate liver damage caused by a high cholesterol diet.Male C57BL/6 mice were fed a high cholesterol diet for 6 weeks,and given CTs treatment at a dosage of 200 mg/(kg·day)at the same time.The results indicated that compared with mice fed a normal diet,a high cholesterol diet group resulted in significant weight loss,dysregulation of lipid metabolism in blood and liver,and oxidative stress in the liver,but CTs treatment dramatically reversed these negative effects.Hematoxylin and eosin(H&E)staining and frozen section observation manifested that CTs treatment could effectively reduce the deposition of liver cholesterol and tissue necrosis caused by high cholesterol intake.CTs alleviated liver injury mainly by regulating the expression of related genes in cholesterol metabolism pathway and AMPK phosphorylation.Our results confirmed that CTs have remarkable cholesterol lowering and anti-liver injury effects in vivo.

Effi cacy of partial and complete resuscitative endovascular balloon occlusion of the aorta in the hemorrhagic shock model of liver injury

BACKGROUND:Resuscitative endovascular balloon occlusion of the aorta(REBOA)can temporarily control traumatic bleeding.However,its prolonged use potentially leads to ischemia-reperfusion injury(IRI).Partial REBOA(pREBOA)can alleviate ischemic burden;however,its security and eff ectiveness prior to operative hemorrhage control remains unknown.Hence,we aimed to estimate the effi cacy of pREBOA in a swine model of liver injury using an experimental sliding-chamber ballistic gun.METHODS:Twenty Landrace pigs were randomized into control(no aortic occlusion)(n=5),intervention with complete REBOA(cREBOA)(n=5),continuous pREBOA(C-pREBOA)(n=5),and sequential pREBOA(S-pREBOA)(n=5)groups.In the cREBOA and C-pREBOA groups,the balloon was inflated for 60 min.The hemodynamic and laboratory values were compared at various observation time points.Tissue samples immediately after animal euthanasia from the myocardium,liver,kidneys,and duodenum were collected for histological assessment using hematoxylin and eosin staining.RESULTS:Compared with the control group,the survival rate of the REBOA groups was prominently improved(all P<0.05).The total volume of blood loss was markedly lower in the cREBOA group(493.14±127.31 mL)compared with other groups(P<0.01).The pH was significantly lower at 180 min in the cREBOA and S-pREBOA groups(P<0.05).At 120 min,the S-pREBOA group showed higher alanine aminotransferase(P<0.05)but lower blood urea nitrogen compared with the cREBOA group(P<0.05).CONCLUSION:In this trauma model with liver injury,a 60-minute pREBOA resulted in improved survival rate and was effective in maintaining reliable aortic pressure,despite persistent hemorrhage.Extended tolerance time for aortic occlusion in Zone I for non-compressible torso hemorrhage was feasible with both continuous partial and sequential partial measures,and the significant improvement in the severity of acidosis and distal organ injury was observed in the sequential pREBOA.

Acetaminophen overdose-induced acute liver injury can be alleviated by static magnetic field

Acetaminophen(APAP),the most frequently used mild analgesic and antipyretic drug worldwide,is implicated in causing 46%of all acute liver failures in the USA and between 40%and 70%in Europe.The predominant pharmacological intervention approved for mitigating such overdose is the antioxidant N-acetylcysteine(NAC);however,its efficacy is limited in cases of advanced liver injury or when administered at a late stage.In the current study,we discovered that treatment with a moderate intensity static magnetic field(SMF)notably reduced the mortality rate in mice subjected to high-dose APAP from 40%to 0%,proving effective at both the initial liver injury stage and the subsequent recovery stage.During the early phase of liver injury,SMF markedly reduced APAPinduced oxidative stress,free radicals,and liver damage,resulting in a reduction in multiple oxidative stress markers and an increase in the antioxidant glutathione(GSH).During the later stage of liver recovery,application of vertically downward SMF increased DNA synthesis and hepatocyte proliferation.Moreover,the combination of NAC and SMF significantly mitigated liver damage induced by high-dose APAP and increased liver recovery,even 24 h post overdose,when the effectiveness of NAC alone substantially declines.Overall,this study provides a noninvasive non-pharmaceutical tool that offers dual benefits in the injury and repair stages following APAP overdose.Of note,this tool can work as an alternative to or in combination with NAC to prevent or minimize liver damage induced by APAP,and potentially other toxic overdoses.

Recent advances in the diagnosis of drug-induced liver injury

Drug-induced liver injury(DILI)is a major problem in the United States,commonly leading to hospital admission.Diagnosing DILI is difficult as it is a diagnosis of exclusion requiring a temporal relationship between drug exposure and liver injury and a thorough work up for other causes.In addition,DILI has a very variable clinical and histologic presentation that can mimic many different etiologies of liver disease.Objective scoring systems can assess the probability that a drug caused the liver injury but liver biopsy findings are not part of the criteria used in these systems.This review will address some of the recent updates to the scoring systems and the role of liver biopsy in the diagnosis of DILI.

Severe liver injury and clinical characteristics of occupational exposure to 2-amino-5-chloro-N,3-dimethylbenzamide: A case series

Background:The 2-amino-5-chloro-N,3-dimethylbenzamide is a key intermediate in the synthesis of pesticides and pharmaceuticals.However,no literature currently exists on 2-amino-5-chloro-N,3-dimethylbenzamide poisoning in humans.This study aimed to reveal the health hazard of this chemical for humans and summarize the clinical characteristics of patients with occupational 2-amino-5-chloro-N,3-dimethylbenzamide poisoning.Methods:This observational study included four patients with 2-amino-5-chloro-N,3-dimethylbenzamide poisoning from June 2022 to July 2022.The entire course of the incidents was described in detail.Blood 2-amino-5-chloro-N,3-dimethylbenzamide concentrations were detected by a mass spectrometer.Hema-toxylin and eosin staining was performed to assess liver injury,and immunofluorescence was used to evaluate hepatic mitophagy.Results:The 2-amino-5-chloro-N,3-dimethylbenzamide powder(99%purity)entered the human body mainly via the skin and respiratory tract due to poor personal protective measures.The typical course of 2-amino-5-chloro-N,3-dimethylbenzamide poisoning was divided into latency,rash,fever,organic dam-age,and recovery phases in accordance with the clinical evolution.Rash and fever may be the important premonitory symptoms for further organ injuries.The chemical was detected in the blood of all patients and caused multiple organ injuries,predominantly liver injury,including kidney,myocardium,and micro-circulation.Three patients recovered smoothly after comprehensive treatments,including artificial liver therapy,continuous renal replacement therapy,glucocorticoids,and other symptomatic and supportive treatments.One patient survived by liver transplantation.The postoperative pathological findings of the removed liver showed acute liver failure,and immunofluorescence staining confirmed the abundance of mitophagy in residual hepatocytes.Conclusions:This study is the first to elaborate the clinical characteristics of patients with 2-amino-5-chloro-N,3-dimethylbenzamide poisoning.The chemical enters the body through the respiratory tract and skin during industrial production.The 2-amino-5-chloro-N,3-dimethylbenzamide poisoning causes multiple-organ dysfunction with a predominance of liver injury.Liver transplantation may be an effective option for patients with severe liver failure.The mechanisms of liver injury induced by 2-amino-5-chloro-N,3-dimethylbenzamide might involve abnormal mitochondrial function and mitophagy.

Protective mechanism of Paeoniae Radix Alba against chemical liver injury based on network pharmacology,molecular docking,and in vitro experiments

Objective:To explore and validate the potential targets of Paeoniae Radix Alba(P.Radix,Bai Shao)in protecting against chemical liver injury through network pharmacology,molecular docking technology,and in vitro cell experiments.Methods:Network pharmacology was used to identify the common potential targets of P.Radix and chemical liver injury.Molecular docking was used to fit the components,which were subsequently verified in vitro.A cell model of hepatic fibrosis was established by activating hepatic stellate cell(HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1.The cells were exposed to different concentrations of total glucosides of paeony(TGP),the active substance of P.Radix,and then evaluated using the cell counting kit-8 assay,enzyme-linked immunosorbent assay,and western blot.Results:Analysis through network pharmacology revealed 13 key compounds of P.Radix,and the potential targets for preventing chemical liver injury were IL-6,AKT serine/threonine kinase 1,jun protooncogene,heat shock protein 90 alpha family class A member 1(HSP90AA1),peroxisome proliferator activated receptor gamma(PPARG),PTGS2,and CASP3.Gene Ontology(GO)enrichment analysis indicated the involvement of response to drugs,membrane rafts,and peptide binding.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation.Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1,PTGS2,PPARG,and CASP3.Different concentrations of TGP can inhibit the expression of COL-I,COL-III,IL-6,TNF-a,IL-1β,HSP-90a,and PTGS2 while increasing the expression of PPAR-γand CASP3 in activated HSC-LX2 cells.Conclusion:P.Radix primarily can regulate targets such as HSP90AA1,PTGS2,PPARG,CASP3.TGP,the main active compound of P.Radix,protects against chemical liver injury by reducing the inflammatory response,activating apoptotic proteins,and promoting the apoptosis of activated HSCs.

Spectrum of COVID-19 induced liver injury:A review report

The coronavirus disease 2019(COVID-19)pandemic has caused changes in the global health system,causing significant setbacks in healthcare systems worldwide.This pandemic has also shown resilience,flexibility,and creativity in reacting to the tragedy.The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection targets most of the respiratory tract,resulting in a severe sickness called acute respiratory distress syndrome that may be fatal in some individuals.Although the lung is the primary organ targeted by COVID-19 viruses,the clinical aspect of the disease is varied and ranges from asymptomatic to respiratory failure.However,due to an unorganized immune response and several affected mechanisms,the liver may also experience liver cell injury,ischemic liver dysfunction,and drug-induced liver injury,which can result in respiratory failure because of the immune system’s disordered response and other compromised processes that can end in multisystem organ failure.Patients with liver cirrhosis or those who have impaired immune systems may be more likely than other groups to experience worse results from the SARS-CoV-2 infection.We thus intend to examine the pathogenesis,current therapy,and consequences of liver damage concerning COVID-19.

Salivary metabolites are promising noninvasive biomarkers of druginduced liver injury

BACKGROUND Drug-induced liver injury(DILI)is one of the most common adverse events of medication use,and its incidence is increasing.However,early detection of DILI is a crucial challenge due to a lack of biomarkers and noninvasive tests.AIM To identify salivary metabolic biomarkers of DILI for the future development of noninvasive diagnostic tools.METHODS Saliva samples from 31 DILI patients and 35 healthy controls(HCs)were subjected to untargeted metabolomics using ultrahigh-pressure liquid chromatography coupled with tandem mass spectrometry.Subsequent analyses,including partial least squares-discriminant analysis modeling,t tests and weighted metabolite coexpression network analysis(WMCNA),were conducted to identify key differentially expressed metabolites(DEMs)and metabolite sets.Furthermore we utilized least absolute shrinkage and selection operato and random fores analyses for biomarker prediction.The use of each metabolite and metabolite set to detect DILI was evaluated with area under the receiver operating characteristic curves.RESULTS We found 247 differentially expressed salivary metabolites between the DILI group and the HC group.Using WMCNA,we identified a set of 8 DEMs closely related to liver injury for further prediction testing.Interestingly,the distinct separation of DILI patients and HCs was achieved with five metabolites,namely,12-hydroxydodecanoic acid,3-hydroxydecanoic acid,tetradecanedioic acid,hypoxanthine,and inosine(area under the curve:0.733-1).CONCLUSION Salivary metabolomics revealed previously unreported metabolic alterations and diagnostic biomarkers in the saliva of DILI patients.Our study may provide a potentially feasible and noninvasive diagnostic method for DILI,but further validation is needed.