Wen Da-Chao, Hu Xiao-Yu, Wang Yan-Yan, Luo Jian-Xing, Lin Wu, Jia Ling-Yan, Gong Xin-Yue
School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China; Department of Infectious Diseases, Teaching Hospital of Chengdu University of Traditional Chinese Medicine, 610072 Sichuan Province, China.
Department of Infectious Diseases, Teaching Hospital of Chengdu University of Traditional Chinese Medicine, 610072 Sichuan Province, China.
J Ethnopharmacol. 2016 Nov 4;192:67-73. doi: 10.1016/j.jep.2016.06.063. Epub 2016 Jul 1.
Acute alcohol intoxication (AAI) is a frequent emergency, but therapeutic drugs with superior efficacy and safety are lacking. Panax ginseng (PG) and Hippophae rhamnoides (HR) respectively has a wide application as a complementary therapeutic agent in China for the treatment of AAI and liver injury induced by alcohol. We investigated the effects of aqueous extracts from PG and HR (AEPH) on AAI mice and identified its underlying mechanisms.
Models of AAI were induced by intragastric administration of ethanol (8g/kg). Seventy-two Specific pathogen-free (SPF) male Kunming mice were randomly divided into six groups: normal group, positive control group, AEPH of low dosage (100mg/kg) group, AEPH of medium dose (200mg/kg) group, AEPH of high dosage (400mg/kg) group and model group. The mice were treated with metadoxine (MTD, 500mg/kg) and AEPH. Thirty minutes later, the normal group was given normal saline, while the other groups were given ethanol (i.g., 8g/kg). The impact of AEPH was observed. In the same way, another seventy-two Kunming mice were randomly divided into six groups equally. The blood ethanol concentration at 0.5, 1, 1.5, 2, 3 and 6h after ethanol intake was determined by way of gas chromatography. The activity of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) and microsomal ethanol oxidase (EO) in liver, and the concentration of β-endorphin (β-EP), leucine-enkephalin (LENK) in the brain were determined by enzyme-linked-immunosorbent serologic assay (ELISA).
AEPH markedly prolonged alcohol tolerance time and shortened sober-up time after acute ethanol administration. AEPH decreased blood ethanol levels in six tests after ethanol intake. The 7-day survival rate of AEPH group was obviously superior to model group. AEPH increased the activities of ADH, ALDH, and decreased EO activity in liver. The crucial find was that AEPH markedly decreased β-EP and LENK concentration in the brain.
AEPH can markedly increase the levels of ADH, ALDH, decrease EO activity in liver and decrease the concentration of β-EP and LENK in the brain to against acute alcohol intoxication in mice.
急性酒精中毒(AAI)是一种常见的急症,但缺乏疗效和安全性俱佳的治疗药物。人参(PG)和沙棘(HR)在中国分别作为辅助治疗药物广泛应用于AAI及酒精所致肝损伤的治疗。我们研究了PG和HR水提取物(AEPH)对AAI小鼠的影响,并确定其潜在机制。
通过灌胃给予乙醇(8g/kg)诱导建立AAI模型。将72只无特定病原体(SPF)雄性昆明小鼠随机分为6组:正常组、阳性对照组、低剂量AEPH(100mg/kg)组、中剂量AEPH(200mg/kg)组、高剂量AEPH(400mg/kg)组和模型组。小鼠分别用美他多辛(MTD,500mg/kg)和AEPH进行处理。30分钟后,正常组给予生理盐水,其他组给予乙醇(灌胃,8g/kg)。观察AEPH的作用。同样,将另外72只昆明小鼠随机均分为6组。通过气相色谱法测定乙醇摄入后0.5、1、1.5、2、3和6小时的血乙醇浓度。采用酶联免疫吸附测定法(ELISA)测定肝脏中乙醇脱氢酶(ADH)、乙醛脱氢酶(ALDH)和微粒体乙醇氧化酶(EO)的活性,以及脑中β-内啡肽(β-EP)、亮氨酸脑啡肽(LENK)的浓度。
AEPH显著延长急性乙醇给药后的酒精耐受时间并缩短清醒时间。AEPH在乙醇摄入后的6次检测中均降低了血乙醇水平。AEPH组的7天生存率明显优于模型组。AEPH增加了肝脏中ADH、ALDH的活性,并降低了EO活性。关键发现是AEPH显著降低了脑中β-EP和LENK的浓度。
AEPH可显著提高肝脏中ADH、ALDH的水平,降低EO活性,并降低脑中β-EP和LENK的浓度,从而对抗小鼠急性酒精中毒。