Pharmacological effects and mechanisms of polyphenols in Radix Puerariae on liver protection and anti-diabetes

In recent years,the incidence of liver diseases and diabetes is increasing year by year,and the patients are younger than before.Although the clinical medicine treatment is eff ective,but it would produce side eff ects.Radix Puerariae is the dried root of the Pueraria lobata(Willd.)Ohwi.Puerarin is an isofl avone compound with polyphenol structure.It is one of the main bioactive components of Radix Puerariae.Studies have found that the application of puerarin off ers beatifical act on liver protection,hypoglycemia,blood lipid,antioxidant,anti-osteoporosis,anti-cancer,anti-inflammatory and cardiovascular protection.Puerarin has been used in the treatment of liver disease and diabetes.In this study,the eff ect of puerarin on liver protection,diabetes treatment and the relationship between the two diseases were reviewed.The therapeutic mechanism and molecular targets of puerarin were explored in order to further improve the development of puerarin and increase its clinical application in protection against liver disease and diabetes.

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.

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.

Science Letters:A novel way of liver preservation improves rat liver viability upon reperfusion

Background/aim： Currently, the liver is cold-preserved at 0-4 ℃ for experimental and clinical purposes. Here, we investigated whether milder hypothermia during the initial phase of the preservation period was beneficial for liver viability upon reperfusion. Methods： In the first set of experiments, rat livers were preserved either conventionally in clinically used histidine-trypthopan-ketoglutarate （HTK） solution （Group A： 45 min and Group B： 24 h） or by slow cooling HTK solution （from 13 ℃ to 3 ℃） during the initial 45 min of preservation （Group C： 24 h）. In the second set of experiments, additional groups of livers were evaluated： Group BB-preservation according to Group B and Group CC-preservation according to Group C. Further, some livers were preserved at 13 ℃ for 24 h. Livers were then reperfused using a blood-free perfusion model. Results： Bile production was approximately 2-fold greater in Group C compared to Group B. Alanine transaminase （ALT） and aspartate transaminase （AST） release into perfusate were 2-3-fold higher in Group B compared to Group C. No significant differences were found in ALT and AST release between Group C and Group A. Livers in Group CC compared to Group BB exhibited significantly lower portal resistance, greater oxygen consumption and bromosulfophthalein excretion into bile and lower lactate dehydrogenase （LDH） release into perfusate. Histological evaluation of tissue sections in Group BB showed parenchymal dystrophy of hepatocytes, while dystrophy ofhepatocytes was absent in Group CC. Livers preserved at 13 ℃ for 24 h exhibited severe ischemic injury Conclusion： These results suggest that the conventional way of liver preservation is not suitable at least for rat livers and that slow cooling of HTK solution during the initial phase of cold storage can improve liver viability during reperfusion.

Effects of fermented soy milk on the liver lipids under oxidative stress

AIM： To investigate the effects of fermented soy milk powder on the antioxidative status and lipid metabolism in the livers of CCh-injected rats. METHODS： Forty-five healthy male Sprague-Dawley rats were randomly assigned to five groups according to five different diets： control （AIN-76）, AIN-76＋high- dose fermented soy milk powder, AIN-76＋low-dose fermented soy milk powder, AIN-76＋high-dose milk yogurt powder and AIN-76＋low-dose milk yogurt powder. The experiment lasted for 8 wk. After 4 wk, all the rats received intraperitoneal administration of CCh （0.2 mL/100 g body weight） every week. Total cholesterol （TC）, triglyceride （TG）, TBARS, ALP, and antioxidative enzymes in the liver were evaluated. RESULTS： There was also no significant difference in TBARS and antioxidative enzymes in the liver. TC and TG in the groups fed with fermented soy milk powder were generally lower than those fed with casein powder. CONCLUSION： Consumption of fermented soy milk was positive in lowering total cholesterol and TG accumulation in the liver under CCh-induced oxidative

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.

Cyclosporin A protects Balb/c mice from liver damage induced by superantigen SEB and D-GaIN

AIM To investigate the pathogenic effect ofSEB and D-GalN on liver and the protection ofcyclosporin A, the relationship between hepaticapoptosis and necrosis and the possiblemechanism of acute hepatic necrosis.METHODS After staphylococcal enterotoxin B(SEB ) mixed with D--galactosamine (D-GaiN )were injected intraperitoneally into Balb/c miceand those previously treated with cyclosporin A,blood samples were collected and livers wereisolated at 2, 6, 12 and 24 h. Patterns othepatocellular death were studiedmorphologically and biochemically, circulatingcytokines (TNF-a, IFN--y ) and mice mortalitywithin 24h was assessed.RESU’LTS The SEB could induce the typicalapoptotic changes of hepatocytes, the D-GaiNcould induce hepatocytes apoptosis anddegeneration at the same time, and the micehaving received the SEB + D-GaiN injectionsdeveloped apoptosis at 2 and 6 h, but after 12 hhepatocytes were characterized by severein jury, whereas all the examinations in thecyclosporin A treated mice were normal.CONCLUSION Hepatic cell apoptosis might berelated to necrosis, and massive hepatocyteapoptosis is likely the initiating step of acutehepatic necrosis in mice. The effects induced bySEB and D--GaiN on hepatocytes might bemediated by T cells, and could be prevented bycyclosporin A.

Screening on the Pharmacodynemic Active Parts of Protecting Liver of Peristrope japonica (thunb.)Bremek

The pharmacodynamic active parts of protecting liver of Peristrope japonica (thunb.)Bremek were identified. Rat acute liver injury model was induced by D-galactosamine (D-GlaN). The active parts were identified on the whole extraction and 4 fractions. The results showed that the pharmacodynamic active parts of Peristrope japonica were the n-BuOH fraction.

Bitter Melon Powder Protects against Obesity-associated Fatty Liver Disease by Improving Colonic Microenvironment in Rats with High-fat Diet-induced Obesity

This study explored how bitter melon powder （BMP） alters the colonic microenvironment during the development of obesity-associated fatty liver in rats. We observed that BMP effectively inhibited the body weight gain and lipid accumulation in the liver, ameliorated glucose intolerance, and increased the colon weight after an 8-week treatment compared to that in the high-fat diet （HFD） group. BMP significantly decreased fecal water toxicity towards HT-29 cells, as revealed by the cell counting kit （CCK）-8 assay results, and the mRNA expression of Toll-like receptor 4 （TLR4） in colon mucosa. Additionally, gut permeability in the BMP group was restored to normal levels. Finally, BMP alleviated the inflammatory state of the rat colon mucosa and liver tissues as well as the systemic inflammation.

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.

Protective Effect of Vitamin E on Liver Damage Induced by 2-Chloro-1, 3-butadiene

The present study was performed to determine the influence of lipid peroxidation and perturbance of Ca2+ homeostasis on liver damage induced by 2-chloro-1, 3-butadiene (CBD) and the protective effects of vitamin E in Wistar rats. Animals were given intraperitoneally different doses (8,40 or 200 mg·kg-1 daily) of CBD for 21 days, and the following dose-dependent events were observed: liver damage, significant increase in liver lipid peroxides, and decreases in activities of erythrocytic glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). The pretreatment of rats with vitamin E (po 150 mg·kg-1) before administering CBD (iP 60 mg·kg-1 ) daily for 21 days prevented the following CBD-induced changes, the increase in serum cholylglycine (CG), hepatic LP, hepatic mitochondrion LP, hepatic oxidized glutathione (GSSG) (while the significant increase of reduced glutathione (GSH) was not affected) and the decrease in activities of erythrocytic SOD and hepatic mitochondrial calcium sequestration. These results suggest that lipid peroxidation and perturbance of Ca2+ homeostasis appear to contribute to the hepatotoxicity of CBD, and vitamin E might prevent the liver damage induced by CBD. The decrease in activities of GSH-Px and SOD in erythrocytes might be used as biomarkers for adverse effects of CBD on defense system against lipid peroxidation.

Anti-tumor,Anti-allergy,Anti-angiogenesis and Hepatoprotective Effects of Deoxypodophyllotoxin and Its Molecular Mechanism

Deoxypodophyllotoxin not only has pharmacological effects such as anti-allergy,anti-angiogenesis and liver protection,but also has good anti-tumor activity.It can play an anti-tumor role by inhibiting cell viability,inducing apoptosis,blocking cell cycle and inhibiting cell migration.In this paper,the related research on pharmacological effect and mechanism of deoxypodophyllotoxin is reviewed,to lay a foundation for the follow-up study of deoxypodophyllotoxin and drug development.

Anti-cancer,Anti-inflammatory,Antioxidant and Other Pharmacological Effects of Wedelactone and Their Molecular Mechanisms

Wedelolide is a coumarin-like active substance extracted from Ecliptae Herba.It not only has pharmacological effects of anti-pulmonary fibrosis,anti-arthritis,blood vessel protection and liver protection,but also effectively inhibits the proliferation of cancer cells and induces apoptosis of cancer cells,thereby delaying the further development of malignant tumors.In this paper,the pharmacological effects and mechanisms of wedelactone were reviewed to lay a foundation for further study and clinical application of wedelactone.

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-

Hepatoprotective and Antioxidant Activity of Rhizome of Podophyllum hexandrum against Carbon Tetra Chloride Induced Hepatotoxicity in Rats

Objective To test possible antioxidant activity of n-hexane extract of Podophyllum hexandrum under in vitro and in vivo conditions. Methods The in vitro antioxidant activity was evaluated by the ability of the extract to interact with the stable free radical DPPH, Superoxide （02）, Hydroxyl （OH）, Hydrogen peroxide （H202） radicals, and reducing power ability of the extract was also evaluated. Under in vivo conditions the extract was evaluated for its hepatoprotective activity by measuring different biochemical parameters, such as serum alanine aminotransaminase, serum aspartate aminotransaminase and serum lactate dehydrogenase and antioxidant enzymes. Antioxidant status was estimated by determining the activities of antioxidative enzymes, glutathione reductase （GR）, glutathione peroxidase （GPx）, glutathione-S-transferase （GST） and superoxide dismutase （SOD）, and by determining the levels of reduced glutathione （GSH） and thiobarbituric acid reactive substances （TBARS）. Results Hexane extract of P. hexondrum exhibited good radical scavenging capacity in neutralization of DPPH, O2-, OH, and H202 radicals in a dose dependent manner, n-hexane extract of Podophyllum hexandrum at the doses of 20, 30, and 50 mg/kg-day produced hepatoprotective effect by decreasing the activity of serum marker enzymes, while it significantly increased the levels of glutathione （GSH）, glutathione peroxidase （GPx）, glutathione reductase （GR）, super oxide dismutase （SOD）, and glutathione-S-transferase （GST） in a dose dependant manner. The effect of n-hexane extract was comparable to that of standard antioxidant vitamin E. Conclusion The extract of Podophyllum hexandrum possess free radical scavenging activity under in vitro conditions and could protect the liver tissue against CCI4 induced oxidative stress probably by increasing antioxidant defense activities.

Research Progress on the Biological Activity of Pectolinarigenin

Pectolinarigenin is a kind of flavonoid,which is an active ingredient in Eupatorium odoratum.Some studies have confirmed that pectolinarigenin has many biological activities,including anti-oxidation,anti-allergy,anti-inflammation,anti-tumor and so on.In this paper,the biological activity and related mechanism of pectolinarigenin were summarized in order to provide theoretical basis and reference for the further development and utilization of pectolinarigenin.

Hepatoprotective and antioxidant activity of ethanolic extract of Artabotrys odoratissimus stem on rifampicin-induced hepatotoxicity in rats

The area of the existing examination was to explore the cancer prevention agent and hepatoprotective action of ethanolic stem concentrate of Artabotrys odoratissimus in rifampicin caused hepatotoxicity in albino wister rodents.The material was dehydrated in gloom;they were powdered,extricated with ethanol later primer phytochemical tests were finished.The hepatoprotective action of the ethanol extract was evaluated in albino wister rodents.Rifampicin(100 mg/kg)has upgraded the degrees of different biochemical markers of the liver like serum glutamic oxaloacetic transaminase,serum glutamate pyruvate transaminase,aspartate alkaline phosphatase and bilirubin.The different biochemical and histopathological examinations have done were aspartate alkaline phosphatase,aminotransferase,alanine transaminase,bilirubin,cell reinforcement movement by 1,1-diphenyl 2-picryl hydrazyl,nitro blue tetrazolium,hydrogen peroxide,lipid perioxidation,hydroxyl revolutionary and nitric oxide techniques.Treatment of ethanolic concentrate of the stem of Artabotrys odoratissimus(100 mg/kg,200 mg/kg and 400 mg/kg)has brought back the changed degrees of biochemical markers to the close ordinary levels in the portion subordinate way.Our discoveries proposed that Artabotrys odoratissimus ethanol stem extricate had an intense cell reinforcement and hepatoprotective action.

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.