Protective Mechanism Of Jinzhao Capsules Against Alcohol-induced Liver And Stomach Injury

Objectives:In recent years,excessive drinking has become a social and public issue of great concern throughout the world.Excessive drinking can cause serious harm to the health of the body.It is believed that excessive drinking can cause damp and hot poisonous evil to restrain the spleen and stomach,or damage the liver and gallbladder to cause liver loss and drainage.in traditional Chinese medicine.Jinzhao Capsule is a product that Infinitus has listed.It is composed of Radix Puerariae,Semen Hoveniae,Gardenia Jasminoide and has the function of protecting liver damage and can treat and prevent liver diseases.This experiment mainly explores the advantages of its products,explores its protective mechanism against alcoholic liver and stomach injury,and enhances the scientific and technological content.This experiment first studied the effects of Jinzhao Capsules on the drunkenness,liver function,liver lipids and ethanol metabolizing enzymes,liver and stomach antioxidant enzymes in mice with acute alcoholic liver and stomach injury models.The protective effect mechanism of Jinzhao Capsule on acute alcoholic liver and stomach injury were preliminary discussed,and the experimental basis for its clinical application was provided.Secondly,to study the effects of Jinzhao Capsule on liver function,liver lipid and ethanol metabolism enzymes,antioxidant enzymes,inflammatory factors,Keap1-Nrf2-NF-κB pathway and other indicators in chronic alcoholic liver injury model mice,and to explore Jinzhao Capsule on chronic alcohol Protective effects of liver injury and its mechanism of action.Material and Methods:Experiment 1:Protective effect mechanism of Jinzhao capsules on mice with acute alcoholic liver injurySPF male ICR mice,aged 8 to 10 weeks,weighing 25 to 35 g.After adaptive feeding,they were randomly divided into control group(Control),model group(Model),positive drug Yinzhihuang(YZH)group,Jinzhao capsule low-dose group(GZZ-L),Jinzhao capsule mediumdose group(GZZ-M),Jinzhao capsule high-dose group(GZZ-H),a total of 6 groups,10 in each group.Jinzhao capsule low-dose,medium-dose,and high-dose mice were given a daily intragastric suspension of Jinzhao capsules 0.21g/kg,0.42g/kg,and 0.84g/kg,with an intragastric volume of 20ml/kg.Yin Zhihuang Granule Suspension was administered with 1.5g/kg,20ml/kg;the blank control group and the model control group were given an equal volume of distilled water orally once a day.The general condition of the animals was observed and weighed 1 time/week,and the amount of gavage was adjusted according to the weight of the animal.After 4 weeks of continuous dosing,the mice in each group were fasted for 12 hours,except for the blank group,the other groups were administrated with 50%ethanol solution 12 mL/kg,and the blank group was irrigated with an equal volume of distilled water to establish mouse model of acute alcoholic liver injury.After removing the eyeballs and taking blood,the liver was taken.Observation indicators:the behavioral state,mental state,second stool state,number of drunks,and drunkenness of mice after drinking.Serum indicators:alanine aminotransferase(ALT),aspartate aminotransferase(AST).Liver indicators:malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT),reduced glutathione(GSH),total cholesterol(TC),triglycerides(TG),Alcohol dehydrogenase(ADH),acetaldehyde dehydrogenase(ALDH),liver pathological sections.Experiment 2:Protective effect mechanism of Jinzhao Capsule on mice with acute alcoholic gastric injuryThe experimental method is the same as that in experiment 1.After removing the eyeballs and taking blood,the stomach is taken.Gastric indicators:malondialdehyde(MDA),superoxide dismutase(SOD),nitric oxide(NO),and prostaglandin E2(PEG2)levels.Experiment 3:Protective effect of Jinzhao capsule on mice with chronic alcoholic liver injurySPF male ICR mice,aged 8 to 10 weeks,weighing 25 to 35 g.After adaptive feeding,they were randomly divided into control group(Control),model group(Model),positive drug Hugan tablet(HGP)group,Jinzhao capsule low-dose group(GZZ-L),Jinzhao capsule medium-dose group(GZZ-M),Jinzhao capsule high-dose group(GZZ-H),a total of 6 groups,10 in each group.Except for the blank group,the mice in each group were administrated with 50%ethanol 10ml/kg daily.The positive drug group was administrated with a liver-protective tablet suspension 0.7g/kg daily,20ml/kg.Jinzhao capsule low,medium and high-dose mice gavage Jinzhao capsule 0.21,0.42,0.84g/kg,20ml/kg.JinZhao capsule and alcohol were administered to the stomach once a day for 4 weeks.After removing the eyeballs and taking blood,the liver was taken.Observation indicators:behavioral state,mental state,and fecal state of the mice.Serum indicators:alanine aminotransferase(ALT),aspartate aminotransferase(AST).Liver indicators:total cholesterol(TC),triglycerides(TG),Alcohol dehydrogenase(ADH),acetaldehyde dehydrogenase(ALDH),liver pathological sections.Experiment 4:Protective mechanism of Jinzhao capsule on mice with chronic alcoholic liver injuryThe experimental method is the same as that in experiment 3.After removing the eyeballs and taking blood,the liver was taken.Liver indicators:Activity level of malondialdehyde MDA,superoxide dismutase(SOD),catalase(CAT),reduced glutathione(GSH),tumor necrosis factor-α(TNF-α),interleukin-6(IL6)and interleukin-10(IL-10).MRNA of Kelch-like epichlorohydrin related protein-1(keapl),nuclear factor E2 related factor(Nrf2),nuclear transcription factor-κB p65(NF-κB p65).Protein expression of kelch-like epichlorohydrin related protein-1(keap1),nuclear factor E2 related factor(Nrf2),nuclear transcription factor-κB p65(NF-κB p65),heme oxygenase 1(HO1),phosphorylated nuclear Factor κB inhibits protein α(pIκ-Bα).Results:1 Experiment 1:Compared with the model group,the drunk state of the mice in the low,medium and high dose groups of Jinzhao Capsule was significantly improved,the number of drunks and the rate of drunkenness were significantly reduced,and the serum ALT and AST levels were significantly reduced(P<0.01,P<0.05).The levels of MDA,TC and TG in liver tissue of mice in the low-dose group were significantly reduced(P<0.01),and ADH levels were significantly increased(P<0.01).In the middle-dose group,MDA,TC,and TG levels in liver tissue of mice significantly decreased(P<0.01),and ALDH,GSH,and ADH levels increased significantly(P<0.01).MDA,TC,and TG levels in liver tissue of mice in the highdose group were significantly reduced(P<0.01),and GSH,ADH,CAT,SOD,and ALDH levels were significantly increased(P<0.01).The pathological section of Jinzhao Capsule improved in all groups.2 Experiment 2:Compared with the model group,the levels of MDA in the gastric tissues of mice in the low,medium and high dose groups of Jinzhao Capsules were significantly reduced(P<0.01).The SOD level in the gastric tissue of mice in the low-dose group increased significantly(P<0.01).The levels of NO and SOD in the gastric tissue of mice in the middledose group were significantly increased(P<0.01).The levels of PGE2,SOD and NO in the gastric tissue of mice in the high-dose group were significantly increased(P<0.01,P<0.05).3 Experiment 3:Compared with the model group,the drunk state of the mice in the low,medium and high dose groups of Jinzhao Capsule was significantly improved,the serum ALT and AST levels of the Jinzhao capsules in the low-dose and high-dose groups were significantly reduced(P<0.01,P<0.05),and those in the middle-dose group were significantly reduced(P<0.01).The levels of TC and TG in the liver tissues of mice in Jinzhao Capsule’s low,medium and high dose groups were significantly reduced(P<0.01).The levels of ADH and ALDH in the liver tissue of the low-dose group were significantly increased(P<0.01),the levels of ADH and ALDH in the liver tissue of the middle-dose group were significantly increased(P<0.01,P<0.05),the liver of the high-dose group The levels of ADH and ALDH increased significantly(P<0.01).The pathological section of Jinzhao Capsule improved in all groups.4 Experiment 4:Compared with the model group,the levels of MDA,TNF-α and IL-6 in the liver tissue of mice in the low and high dose groups of Jinzhao Capsule were significantly reduced(P<0.01,P<0.05),MDA and IL-6 levels in liver tissue of mice in the middle-dose group were significantly reduced(P<0.01,P<0.05).The levels of CAT and GSH in liver tissue of mice in the low-dose group were significantly increased(P<0.01).In the middle-dose group,the levels of CAT and GSH in the liver tissue of mice increased significantly(P<0.01,P<0.05).The levels of CAT,SOD,GSH and IL-10 in liver tissue of mice in the high-dose group were significantly increased(P<0.01).Compared with the model group,the expression levels of keapl,NF-κB mRNA in the liver tissue of mice in the low and high dose groups of Jinzhao Capsule were significantly reduced(P<0.01,P<0.05).In the middle-dose group,the expression level of NF-κB mRNA in liver tissue of mice was significantly reduced(P<0.01).The expression levels of Nrf2 mRNA in liver tissues of mice in the low,medium and high dose groups were significantly increased(P<0.01).Compared with the model group,the expression levels of keap1,NF-κB p65 and pIκ-Ba protein in the liver tissues of mice in the low,medium and high dose groups of Jinzhao Capsules decreased,while the expression levels of Nrf2 and HO-1 proteins increased.Conclusions:1 Jinzhao Capsule has the effect of relieving alcohol and protecting the liver and protecting acute alcoholic liver injury.Its mechanism of action is related to enhancing the activities of key enzymes and antioxidant enzymes in ethanol metabolism in liver tissues,reducing the production of lipid peroxides,protecting the integrity of liver cell membranes,and reducing the release of transaminase.2 Jinzhao Capsule has the effect of protecting acute alcoholic gastric injury.Its mechanism is related to enhancing gastric antioxidant enzyme activity and protecting gastric mucosal injury.3 Jinzhao Capsule which has the effect of protecting chronic alcoholic liver injury is related to enhancing the activity of key enzymes of ethanol metabolism in the liver tissue of the body,reducing the production of lipid peroxides,and reducing the release of transaminase.4 The mechanism of Jinzhao Capsule to protect chronic alcoholic liver injury is related to enhancing the activity of antioxidant enzymes in the liver tissue,protecting the integrity of liver cell membrane,regulating the level of inflammatory factors,and regulating the keap1/Nrf2/NF-κB pathway mRNA and index protein expression levels.