[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 li...[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.展开更多
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...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.展开更多
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...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.展开更多
AIM:To test whether ethanol feeding could induce Toll-like receptor 4(TLR4)responses,assess the hepatoprotective effect of betaine and its inhibitive effect on TLR4 in animal models of alcoholic liver injury.METHODS:F...AIM:To test whether ethanol feeding could induce Toll-like receptor 4(TLR4)responses,assess the hepatoprotective effect of betaine and its inhibitive effect on TLR4 in animal models of alcoholic liver injury.METHODS:Forty-eight female Sprague-Dawley rats were randomly divided into four groups as control,model,low and high dose betaine groups.Except control group,all rats were fed with high fat-containing diet plus ethanol and fish oil gavages for 8 wk.Betaine was administered intragastrically after exposure of ethanol for 4 wk.The changes of liver histology were examined.The expression of TLR4 mRNA and protein was detected by RT-PCR and Western blotting,respectively.The serum aminotransferase activity alanine transarninase(ALT),aspartate aminotransferase(AST),serum endotoxin,and liver inflammatory factors tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),interleukin-18(IL-18)were also assayed.RESULTS:Compared with control group,rats of model group developed marked liver injury,accompanied by an increase of ALT(159.41±7.74 U/L vs 59.47± 2.34 U/L,P<0.0001),AST(248.25±1.40 U/L vs 116.89±3.48 U/L,P<0.0001),endotoxin(135.37± 30.17 ng/L vs 44.15±7.54 ng/L,P<0.0001),TNF-α(20.81±8.58 pg/mL vs 9.34±2.57 pg/mL,P=0.0003),IFN-γ(30.18±7.60 pg/mL vs 16.86±9.49 pg/mL,P= 0.0039)and IL-18(40.99±8.25 pg/mL vs 19.73±9.31 pg/mL,P=0.0001).At the same time,the expression of TLR4 mRNA and protein was markedly induced in the liver after chronic ethanol consumption(1.45±0.07 vs 0.44±0.04,P<0.0001;1.83±0.13 vs 0.56±0.08,P<0.0001).Compared with model group,betaine feeding resulted in significant decreases of ALT(64.93 ±6.06 U/L vs 159.41±7.74 U/L,P<0.0001),AST(188.73±1.11 U/L vs 248.25±1.40 U/L,P<0.0001),endotoxin(61.80±12.56 ng/L vs 135.37±30.17 ng/L,P<0.0001),TNF-α(9.79±1.32 pg/mL vs 20.81± 8.58 pg/mL,P=0.0003),IFN-γ(18.02±5.96 pg/mL vs 30.18±7.60 pg/mL,P=0.0008)and IL-18(18.23±7.01 pg/mL vs 40.99±8.25 pg/mL,P<0.0001).Betaine also improved liver steatosis.The expression levels of TLR4 mRNA or protein in liver tissues were significantly lowered(0.62±0.04 vs 1.45±0.07,P<0.0001;and 0.65±0.06 vs 1.83±0.13,P<0.0001).There was a statistical difference of TLR4 mRNA and protein expression between high-and low-dose betaine groups(0.62±0.04 vs 0.73±0.05,P<0.0001,and 0.65±0.06 vs 0.81±0.09,P<0.0001).CONCLUSION:Betaine can prevent the alcoholinduced liver injury effectively and improve the liver function.The expression of TLR4 increases significantly in ethanol-fed rats and betaine administration can inhibit TLR4 expression.展开更多
Alcohol abuse leads to alcoholic liver disease and no effective therapy is currently available.Wuzhi Tablet(WZ), a preparation of extract from Schisandra sphenanthera that is a traditional hepatoprotective herb, exert...Alcohol abuse leads to alcoholic liver disease and no effective therapy is currently available.Wuzhi Tablet(WZ), a preparation of extract from Schisandra sphenanthera that is a traditional hepatoprotective herb, exerted a significant protective effect against acetaminophen-induced liver injury in our recent studies, but whether WZ can alleviate alcohol-induced toxicity remains unclear. This study aimed to investigate the contribution of WZ to alcohol-induced liver injury by using chronic-binge and acute models of alcohol feeding. The activities of ALT and AST in serum were assessed as well as the level of GSH and the activity of SOD in the liver. The expression of CYP2E1 and proteins in the NRF2-ARE signaling pathway including NRF2, GCLC, GCLM, HO-1 were measured, and the effect of WZ on NRF2 transcriptional activity was determined. We found that both models resulted in liver steatosis accompanied by increased transaminase activities, but that liver injury was significantly attenuated by WZ. WZ administration also inhibited CYP2E1 expression induced by alcohol, and elevated the level of GSH and the activity of SOD in the liver. Moreover, the NRF2-ARE signaling pathway was activated by WZ andthe target genes were all upregulated. Furthermore, WZ significantly activated NRF2 transcriptional activity. Collectively, our study demonstrates that WZ protected against alcohol-induced liver injury by reducing oxidative stress and improving antioxidant defense, possibly by activating the NRF2-ARE pathway.展开更多
Betulin is main component of triterpenoids in bark extract of Betula platyphylla,and has antibacterial,antiviral,liver protecting,cholagogic,antitumorus and other functions.This paper reviews the pharmacological effec...Betulin is main component of triterpenoids in bark extract of Betula platyphylla,and has antibacterial,antiviral,liver protecting,cholagogic,antitumorus and other functions.This paper reviews the pharmacological effects and mechanisms of betulin.展开更多
基金Supported by Provincial Key College Students Innovation and Entrepreneurship Training Program Project (202211834033).
文摘[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.
基金The project supported by Col ege Students Of Science and Technology Innovation Project of Tai'an City(2015D064)the National College Students'Innovative and Entrepreneurial Training Project(201510439078)
文摘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.
文摘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.
文摘AIM:To test whether ethanol feeding could induce Toll-like receptor 4(TLR4)responses,assess the hepatoprotective effect of betaine and its inhibitive effect on TLR4 in animal models of alcoholic liver injury.METHODS:Forty-eight female Sprague-Dawley rats were randomly divided into four groups as control,model,low and high dose betaine groups.Except control group,all rats were fed with high fat-containing diet plus ethanol and fish oil gavages for 8 wk.Betaine was administered intragastrically after exposure of ethanol for 4 wk.The changes of liver histology were examined.The expression of TLR4 mRNA and protein was detected by RT-PCR and Western blotting,respectively.The serum aminotransferase activity alanine transarninase(ALT),aspartate aminotransferase(AST),serum endotoxin,and liver inflammatory factors tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),interleukin-18(IL-18)were also assayed.RESULTS:Compared with control group,rats of model group developed marked liver injury,accompanied by an increase of ALT(159.41±7.74 U/L vs 59.47± 2.34 U/L,P<0.0001),AST(248.25±1.40 U/L vs 116.89±3.48 U/L,P<0.0001),endotoxin(135.37± 30.17 ng/L vs 44.15±7.54 ng/L,P<0.0001),TNF-α(20.81±8.58 pg/mL vs 9.34±2.57 pg/mL,P=0.0003),IFN-γ(30.18±7.60 pg/mL vs 16.86±9.49 pg/mL,P= 0.0039)and IL-18(40.99±8.25 pg/mL vs 19.73±9.31 pg/mL,P=0.0001).At the same time,the expression of TLR4 mRNA and protein was markedly induced in the liver after chronic ethanol consumption(1.45±0.07 vs 0.44±0.04,P<0.0001;1.83±0.13 vs 0.56±0.08,P<0.0001).Compared with model group,betaine feeding resulted in significant decreases of ALT(64.93 ±6.06 U/L vs 159.41±7.74 U/L,P<0.0001),AST(188.73±1.11 U/L vs 248.25±1.40 U/L,P<0.0001),endotoxin(61.80±12.56 ng/L vs 135.37±30.17 ng/L,P<0.0001),TNF-α(9.79±1.32 pg/mL vs 20.81± 8.58 pg/mL,P=0.0003),IFN-γ(18.02±5.96 pg/mL vs 30.18±7.60 pg/mL,P=0.0008)and IL-18(18.23±7.01 pg/mL vs 40.99±8.25 pg/mL,P<0.0001).Betaine also improved liver steatosis.The expression levels of TLR4 mRNA or protein in liver tissues were significantly lowered(0.62±0.04 vs 1.45±0.07,P<0.0001;and 0.65±0.06 vs 1.83±0.13,P<0.0001).There was a statistical difference of TLR4 mRNA and protein expression between high-and low-dose betaine groups(0.62±0.04 vs 0.73±0.05,P<0.0001,and 0.65±0.06 vs 0.81±0.09,P<0.0001).CONCLUSION:Betaine can prevent the alcoholinduced liver injury effectively and improve the liver function.The expression of TLR4 increases significantly in ethanol-fed rats and betaine administration can inhibit TLR4 expression.
基金supported by the National Natural Science Foundation of China (Grant Nos. 81373470, 81573489, 81522047 and 81402998)the Natural Science Foundation of Guangdong Province (No. 2015A030313124)
文摘Alcohol abuse leads to alcoholic liver disease and no effective therapy is currently available.Wuzhi Tablet(WZ), a preparation of extract from Schisandra sphenanthera that is a traditional hepatoprotective herb, exerted a significant protective effect against acetaminophen-induced liver injury in our recent studies, but whether WZ can alleviate alcohol-induced toxicity remains unclear. This study aimed to investigate the contribution of WZ to alcohol-induced liver injury by using chronic-binge and acute models of alcohol feeding. The activities of ALT and AST in serum were assessed as well as the level of GSH and the activity of SOD in the liver. The expression of CYP2E1 and proteins in the NRF2-ARE signaling pathway including NRF2, GCLC, GCLM, HO-1 were measured, and the effect of WZ on NRF2 transcriptional activity was determined. We found that both models resulted in liver steatosis accompanied by increased transaminase activities, but that liver injury was significantly attenuated by WZ. WZ administration also inhibited CYP2E1 expression induced by alcohol, and elevated the level of GSH and the activity of SOD in the liver. Moreover, the NRF2-ARE signaling pathway was activated by WZ andthe target genes were all upregulated. Furthermore, WZ significantly activated NRF2 transcriptional activity. Collectively, our study demonstrates that WZ protected against alcohol-induced liver injury by reducing oxidative stress and improving antioxidant defense, possibly by activating the NRF2-ARE pathway.
基金Supported by Talent Training Project of the Central Support Fund for the Reform and Development of Local Colleges and Universities(2020GSP16)。
文摘Betulin is main component of triterpenoids in bark extract of Betula platyphylla,and has antibacterial,antiviral,liver protecting,cholagogic,antitumorus and other functions.This paper reviews the pharmacological effects and mechanisms of betulin.
