栀子提取物GJ-4急性毒性和长期毒性研究

Study on acute and long-term toxicity of GJ-4 extracted from Gardenia jasminoides J.Ellis

目的评价中药栀子提取物GJ-4的急性毒性和长期毒性,为其开发成为治疗老年痴呆的新药提供安全依据。方法在急性毒性实验中,将30只ICR小鼠按随机数字表法分为对照组、栀子提取物2.5 g/kg组和栀子提取物5.0 g/kg组,每组10只。栀子提取物2.5 g/kg组和栀子提取物5.0 g/kg组小鼠分别灌胃2.5、5.0 g/kg栀子提取物GJ-4混悬液。对照组灌胃等体积的0.5%羧甲基纤维素钠(sodium carboxymethyl cellulose,CMC-Na)。连续灌胃7 d。记录小鼠死亡率、体重和一般状况。计算小鼠的心脏指数、肝脏指数、肾脏指数,采用全自动生化检测仪检测血清中ALT、ALP、BUN、SCr水平。长期毒性实验中,将75只ICR小鼠按随机数字表法分为对照组及栀子提取物100、250、500、1000 mg/kg组,每组15只。栀子提取物100、250、500、1000 mg/kg组分别灌胃100、250、500、1000 mg/kg栀子提取物GJ-4混悬液,对照组灌胃等体积的0.5%CMC-Na,1次/d,连续给药30 d。记录小鼠的死亡率、体重、精神状态。计算小鼠的脏器指数,检测血清中ALT、ALP、BUN水平。结果急性毒性实验中,各组小鼠精神状态和饮食情况良好,观察7 d内小鼠未出现死亡。与对照组比较,给药组小鼠体重、心脏指数、肝脏指数、肾脏指数比较差异无统计学意义(P>0.05),栀子提取物2.5 g/kg组小鼠血清BUN[(10.17±0.82)mmol/L比(11.25±0.47)mmol/L]水平降低(P<0.05),栀子提取物5.0 g/kg组小鼠ALP[(116.0±10.75)U/L比(148.0±25.73)U/L]水平降低(P<0.05)。长期毒性实验中,各给药小鼠精神状态和饮食情况良好,均未出现死亡。与对照组比较,栀子提取物各剂量组小鼠体重、心脏指数、肾脏指数、脾脏指数及血清ALT、ALP、BUN水平比较差异无统计学意义(P>0.05),栀子提取物250 mg/kg组肝脏指数[(4.90±0.56)比(4.38±0.49)]升高(P<0.01),胸腺指数[(0.09±0.02)比(0.14±0.04)]降低(P<0.05)。结论栀子提取物GJ-4在小鼠急性毒性和长期毒性实验中未表现出明显毒性,安全性较好。

Objective To investigate the acute and long-term toxicity of GJ-4 extracted from Gardenia jasminoides J.Ellis,and to provide safety basis for its development as a new drug for the treatment of dementia.Methods In the acute toxicity experiment,30 ICR mice were randomly divided into control group,gardenia extract 2.5 g/kg group and gardenia extract 5.0 g/kg group,10 mice in each group.The mice in the 2.5 g/kg and 5.0 g/kg gardenia extract groups were administrated with GJ-4 suspension.The control group was given 0.5%sodium carboxymethyl cellulose(CMC-Na)by gavage.The mice were given continuous gavage for 7 days.The mortality,body weight and general condition of mice were recorded.The levels of ALT,ALP,BUN and creatinine(CRE)in serum were measured by automatic biochemical detector.In the long-term toxicity experiment,75 ICR mice were divided into control group and gardenia extract 100,250,500,1000 mg/kg group according to the random number table method,15 mice in each group.The GJ-4 suspension of Gardenia extract 100,250,500 and 1000 mg/kg were administrated to the stomach respectively in the gardenia extract 100,250,500 and 1000 mg/kg groups,and 0.5%CMC-Na of the same volume was administrated to the stomach in the control group once a day for 30 days.The mortality,weight and mental state of mice were recorded.The organ index and the levels of ALT,ALP and BUN in serum were observed.Results In the acute toxicity experiment,the mental state and diet of mice in each group were good,and there was no death within 7 days.Compared with the control group,there was no significant differences in body weight,heart index,liver index and kidney index between the two groups(P>0.05).Compared with the control group,the level of BUN(10.17±0.82 mmol/L vs.11.25±0.47 mmol/L)in the gardenia extract 2.5 g/kg group significantly decreased(P<0.05),and the level of ALP(116.0±10.75 U/L vs.148.0±25.73 U/L)in the gardenia extract 5.0 g/kg group significantly decreased(P<0.05).In the long-term toxicity experiment,the mice were in good mental state and had good diet,and no death occurred.Compared with the control group,there was no significant differences in body weight,heart index,kidney index,spleen index and serum ALT,ALP and BUN levels between the two groups(P>0.05).The liver index(4.9±0.56 vs.4.38±0.49)in the 250 mg/kg gardenia extract group significantly increased(P<0.01),and the thymus index(0.09±0.02 vs.0.14±0.04)significantly decreased(P<0.05).Conclusions The Gardenia jasminoides extract GJ-4 has no obvious toxicity in acute and long-term toxicity experiment,indicating that GJ-4 is safe.