Effects And Mechanism Of Epigallocatechin-3-gallate On Alcohol Absorption In Mice With Acute Alcoholism

Tea leaves which can attenuate alcoholism in traditional Chinese ancient medical literature are rich in polyphones, purine alkaloids, vitamins and amino acid. Some studies have been showed that tea extracts and tea polyphenols have decreased the symptom of alcoholism. Although epigallocatechin-3-gallate (EGCG) is one of the major pharmacological components in tea polyphenols, the role of EGCG in acute alcoholism has not been reported. In this study, Mice were infused 56% (v/v)"Er Guo Tou"with 5 g/kg to establish model of acute alcoholism. Then it was observed that acute neurological alcoholism indicators (locomotors activity, Morris water maze, balance beam test), blood alcohol concentration, alcohol dehydrogenase (ADH) activity in liver and stomach, P-gp expression in liver and ileum. These founding were used to reveal the possible mechanism of ethanol absorption.Objective: To establish mice model of acute alcoholism, and to investigate the effect of EGCG on acute alcoholism neurological indicators, blood alcohol concentration and its possible mechanism.Methods: Mice were randomly divided into normal group, model group, EGCG 25mg/kg group, EGCG 75 mg / kg group, EGCG 225 mg / kg group, and Ge Gen capsule group (180 mg / kg). Mice of normal group and model group were given saline by intragastric pathway. Mice of Drugs-treated group were given different doses of drugs by the same way. After 0.5h, the model group and drugs-treated group was treated with 5g/kg 56% (v/v) Er Guotou to establish model of acute alcoholism. Locomotors activity, Morris water maze and balance beam test were used to investigate the preventive effects of EGCG in acute alcoholism mice. Blood alcohol concentration was detected by headspace gas chromatography. The protein concentration and the activity of alcohol dehygrgenase in liver and stomach homogenates were determined by spectrophotometry. The expression of P-gp in liver and ileum were detected by Western blot.Results: 1. Compared with normal group,locomotor activities increased significantly in model group. Compared with model group, the locomotor activity was decreased in EGCG (75,225 mg / kg) group at 0.25 ~ 1h, especially in EGCG 225 mg / kg group (P <0.01) at 1h. EGCG 225 mg / kg and Pueraria capsule could significantly attenuate the effect of spatial disorder (P <0.01) in alcoholism mice. EGCG (75, 225 mg/kg) and Pueraria capsule could improve the out of balance at 0.75 ~ 2h (P <0.01).2. Compared with model group, blood alcohol concentration was decreased in EGCG (75,225 mg / kg) group at 0.5-1h (P <0.05), especially in EGCG 225 mg/kg at 1h (P <0.01). Compared with normal group, ADH activity in liver and stomach was decreased in model group. Compared with model group, the ADH activity in liver was significantly increased in EGCG 75mg/kg, 225 mg / kg group from 0.25h to 2h, particularly in EGCG 225 mg/kg (P <0.01); the ADH activity in stomach was significantly increased in EGCG 75 mg/kg group and 225 mg / kg group from 0.25h to 2h (P <0.01). It suggested that EGCG may enhance the ADH activity of liver and stomach to reduce blood alcohol concentration.3. Compared with normal group, the expression of P-gp in liver and ileum was increased significantly in model group. Compared with model group, the difference of P-gp expression of liver was significant in EGCG 25 mg/kg group and 225 mg/kg group at 1h (P <0.05) and in EGCG 25 mg/kg group and 75 mg/kg group at 2h; the difference of P-gp expression in ileum was significant in EGCG 25 mg/kg group and 75 mg/kg group at 1h (P <0.01) and 2h (P <0.05). It suggested that EGCG may inhibit the expression of P-gp of the liver and ileum.Conclusion: 1. EGCG could inhibit the addition of locomotors activity , prevent spatial barriers and improve the out of balance induced by alcohol;2. The mechanism of EGCG attenuating the alcoholism may be enhance ADH activity of liver and stomach, thereby reducing the blood alcohol concentration to improve neurological symptoms of acute alcoholism;3. Ethanol may enhance the P-gp expression of liver and ileum, EGCG has inhibitory effect on P-gp expression.