长形肉豆蔻化学成分及炮制工艺研究
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摘要
目的:
肉豆蔻(学名)为《中国药典》2005版收载的中药,现在市场上出售的肉豆蔻有两种,一种是圆形肉豆蔻,一种是长形肉豆蔻。在印度尼西亚市场上圆形的作为香料,而长形的却作为药用。国内正好相反,所以本研究旨在中医药理论的指导下,欲应用现代科学技术手段,首次对长形肉豆蔻(学名)进行全而深入的研究,制定炮制工艺,对其化学成分及药理作用与圆形肉豆蔻进行比较研究,并制定长形肉豆蔻的质量标准。
材料与方法:
1.材料:长形肉豆蔻药材购于安徽毫州,经辽宁中医药大学翟延君教授鉴定为肉豆蔻科植物长形肉豆蔻(Mystica argentea Warb.)的干燥成熟种仁。
圆形肉豆蔻药材购于沈阳市药材公司,经辽宁中医药大学翟延君教授鉴定为肉豆蔻科植物肉豆蔻(Mystica fragrans Houtt.)的干燥成熟种仁。
2.方法:
(1)通过高效液相色谱法、薄层色谱法、气质联用色谱法和电感耦合等离子体质谱法对两种肉豆蔻的化学成分进行比较,并通过硅胶柱层析,凝胶柱层析,重结晶等多种手段,从长形肉豆蔻的挥发性和非挥发性成分中分离纯化得到单体化合物。
(2)以甲基丁香酚、异甲基丁香酚和黄樟醚为指标,采用高效液相色谱法对两种肉豆蔻面煨、滑石粉煨、麸煨、泡后麸煨四种炮制工艺进行比较,并采用正交设计L_9(3~4)优选长形肉豆蔻的最佳炮制工艺。
(3)应用急性毒性实验方法,观察并用改良寇氏法计算小鼠的LD_(50)值。通过对正常小鼠的肠推进方法和抑制新斯的明引起的小鼠小肠功能亢进的方法,比较两种肉豆蔻生品及其炮制品涩肠止泻的作用功效。
(4)通过对长形肉豆蔻生品及麸煨长形肉豆蔻十批放大样品的水分、总灰分及酸不溶灰分的测定以及重金属限量检查、砷盐检查等,制定长形肉豆蔻生品及麸煨长形肉豆蔻的质量标准。
结果:
1.两种肉豆蔻的化学成分比较研究
通过对两种肉豆蔻的挥发性成分和非挥发性成分进行初步比较,发现两者成分大致相同,但在含量上有显著性差异,特别是长形肉豆蔻中肉豆蔻醚含量较少,因此对长形肉豆蔻挥发性和非挥发性成分做进一步的研究,分离出12个化合物,分别为黄樟醚(Ⅰ),甲基丁香酚(Ⅱ),异甲基丁香酚(Ⅲ):(E)-3-(benzo[d][1,3】dioxol-5-yl)prop-2-en-1-ol(1),7-hydroxy-3.4′-methylene-flavan(2),1,4苯二甲酸甲酯(3),内消旋二氢愈创木酸(4),erythro-1-(4-hydroxy-3-methoxyphenyl)-4-(3,4-methylenedioxyphenyl)-2,3-dimethy Ibutane(5),赤式-1-(3-甲氧基-4-羟基苯基)-2-(4-丙烯基-2-甲氧基苯氧基)-丙烷-1-醇(6),(7S,7′R,8S,8′R)-7,7′-Di-(4-hydrox y-3-methoxyphenyl)-8,8′-dimethyltetro-hydrofuran(7),β-谷甾醇(8),胡萝卜苷(9),其中化合物Ⅰ、Ⅱ、Ⅲ:1、2、3、6、8、9是首次从长形肉豆蔻植物中分离得到。采用GC/MS和ICP/MS方法分析长形肉豆蔻和圆形肉豆蔻的挥发油和无机元素,在挥发油中鉴定出长形肉豆蔻生品32个化合物,其炮制品29个化合物,圆形肉豆蔻生品35个化合物,其炮制品36个化合物。两种肉豆蔻在炮制前后无机元素的含量情况:Mg、Ca、Fe、Na的含量在炮制后有所升高:K有所降低。而且圆形肉豆蔻中的必需元素含量比长形肉豆蔻中的含量多。
2.两种肉豆蔻的炮制工艺比较研究
两种肉豆蔻经炮制后,挥发油含量都有不同程度的降低,止泻的有效成分甲基丁香酚和异甲基丁香酚含量也都有所增加,但圆形肉豆蔻炮制品增加的较为显著。两种肉豆蔻的毒性成分黄樟醚经炮制后都略微有所下降。
优选出长形肉豆蔻的最佳炮制工艺为:长形肉豆蔻用水浸泡6小时后,麸煨温度160～170℃,麸煨时间25min,每100kg长形肉豆蔻,用40kg麦麸。
3.两种肉豆蔻的药效学初步比较研究
长形肉豆蔻生品的LD_(50)=17.5g/kg,麸煨长形肉豆蔻的LD_(50)=23.5g/kg
两种肉豆蔻经炮制后均能明显的抑制小鼠小肠推动运动,并能抑制新斯的明引起的小肠推进功能亢进。且圆形肉豆蔻炮制品的止泻作用更为显著。
4.长形肉豆蔻生品及其麸煨品的质量标准。
初步制定长形肉豆蔻生品及其麸煨品的质量标准。暂定:长形肉豆蔻生品中:甲基丁香酚不少于0.035%;异甲基丁香酚不少于0.007%;黄樟醚不多于1.004%。麸煨长形肉豆蔻中:甲基丁香酚不少于0.056%:异甲基丁香酚不少于0.0089%;黄樟醚不可多于0.85%。
结论:
根据长形肉豆蔻与圆形肉豆蔻的化学成分、炮制工艺、药理作用、质量标准等全面的比较研究,初步认为长形肉豆蔻可以作为肉豆蔻的一种使用。
Purpose:
Nutmeg is embodied by Chinese Pharmacopoeia <2005>.Now the market has two varieties of nutmeg,one is Mystica fragrans Houtt.,the other is Mystica argentea Warb.In Indonesia,Mystica fragrans Houtt.is used for spices and Mystica argentea Warb is used for medicine.While in China,it is different.So our laboratory carried out comprehensive study, include comparative study of chemical composition and pharmacology of M.argentea Warb and M.fragrans Houtt.,then establish optimum processing technology and quality standard.
Material and method.
1.Material:Mystica argentea Warb.and Mystica fragrans Houtt was purchased from Bozhou Chinese Medicine Market,Anhui Province.A voucher specimen was deposited at our laboratory.
2.method:
(1)Though HPLC,TLC,GC-MS and ICP-MS methods,we compared the chemical compositions of M.argentea and M.fragrans.We applied silica-gel,sephadex LH-20, preparative TLC and recrystallization to separate and isolate the chemical compounds from M. argentea.
(2) The content of methyleugenol,methylisoeugenol,and safrol in volatile oil of M. argentea,M.fragrans and their different processed products were determined by HPLC.And the optimum processing technology was obtained using orthogonal design.
(3)Through acute toxicity experiment,we obtaind the spastics of LD_(50) by koushi.Via carbon powder drive experiment in small intestine of rats,we compared the anti-diarrheal action of Nutmeg and its different processed products.
(4) We established quality standard of M.argentea and its processed products,include moisture content,heavy metal limit examine,arsenic salt examine and ani-malcule limit examine of ten batch magnifying processing samples.
Results:
1.Comparative study of chemical compositions of Mystica argentea Warb.and Mystica fragrans Houtt.
Through HPLC analysis,we observed that the chemical compositions had no significant difference between them,but the content of main chemical constituents had remarkable difference.So we isolated the chemical conctituents of Mystica argentea Warb.for further study,and 12 compounds were elucidated.
Via UV,IR,NMR and MS,these compounds were identified as safrol(Ⅰ), methyleugenol(Ⅱ),methylisoeugenol(Ⅲ),(E)-3-(benzo[d][1,3]dioxol-5-yl)prop-2-en-1-ol (1),7-hydroxy-3′,4′-methylene-flavan(2),1,4-benzenedicarboxylic acid dimethyl ester(3), erythro-1,4-di(4-hydroxy-3-methoxyphenyl)-2,3-dimethylbutane(4),erythro-1-(4-hydroxy-3-methoxyphenyl)-4-(3,4-methylenedioxyphenyl)-2,3-dimethylbutane(5),rel-1-(3-methoxy -4-hydroxylbenzyl)-2-(4-allyl-2-methoxyphenoxies)-propane-1-ol(6),(7S,7′R,8S,8′R) -7,7′-Di-(4-hydroxy-3-methoxyphenyl)-8,8′-dimethyltetro-hydrofuran(7),β-sitosterol((?)), daucosterol((?)).Compound ofⅠ,Ⅱ,Ⅲ,1,2,3,6,8,9 were isolated from Mystica argentea Warb.for the first time.
Volatile oil of two varieties was analysed by GC-MS.We determined 32 compounds from M.argentea,29 compounds from the processed products of M.argentea;35 compounds from M.fragrans and 36 compounds from its processed products.
Inorganic elements of two varieties was analysed by ICP-MS.The content of Mg,Ca,Fe, Na was increased after processing,while the content of K was decreased.
2.Comparative Research on processing technology of the Mystica argentea Warb.and Mystica fragrans Houtt.
After processing,the content of methyleugenol and isomethyleugeno was increased,while the content of safrol was reduced.
The optimal processing technology of Mystica argentea Warb was obtained by orthogonal design using safrol,methyleugenol,methylisoeugenol as index substance,soaked the drug (100 Kg)with water for 6 hr,then roasted with wheat bran(40 Kg) at 160-170℃pot temperature for 25 min.
3.Comparative Research on Pharmacology of Mystica argentea Warb.and Mystica fragrans Houtt.
LD_(50) of Mystica argentea Warb.is 17.5g/kg,and its processed product is 23.5g/kg.The processed products of M.argentea and M.fragrans both had significant inhibitive effect on the small intestinal propulsive motion in normal rats and rats of motion hyperfunction induced by neostigmine.
4.Quality Standard Study of Mystica argentea Warb.and its Processed Product.
We established quality standard of Mystica argentea Warb.and its processed product. For M.argentea,the content of methyleugenol and isomethyleugenol were not less than 0.035%and 0.007%respectively.And the content of safrol was no higher than 1.004%.
Conclusion:
We considered that Mystica argentea.Warb can be used as one of variety of Nutmeg based on comparative study with M.fragrans from chemical composition,processing technology,and pharmacology etc.
肉豆蔻(学名)为《中国药典》2005版收载的中药,现在市场上出售的肉豆蔻有两种,一种是圆形肉豆蔻,一种是长形肉豆蔻。在印度尼西亚市场上圆形的作为香料,而长形的却作为药用。国内正好相反,所以本研究旨在中医药理论的指导下,欲应用现代科学技术手段,首次对长形肉豆蔻(学名)进行全而深入的研究,制定炮制工艺,对其化学成分及药理作用与圆形肉豆蔻进行比较研究,并制定长形肉豆蔻的质量标准。
材料与方法:
1.材料:长形肉豆蔻药材购于安徽毫州,经辽宁中医药大学翟延君教授鉴定为肉豆蔻科植物长形肉豆蔻(Mystica argentea Warb.)的干燥成熟种仁。
圆形肉豆蔻药材购于沈阳市药材公司,经辽宁中医药大学翟延君教授鉴定为肉豆蔻科植物肉豆蔻(Mystica fragrans Houtt.)的干燥成熟种仁。
2.方法:
(1)通过高效液相色谱法、薄层色谱法、气质联用色谱法和电感耦合等离子体质谱法对两种肉豆蔻的化学成分进行比较,并通过硅胶柱层析,凝胶柱层析,重结晶等多种手段,从长形肉豆蔻的挥发性和非挥发性成分中分离纯化得到单体化合物。
(2)以甲基丁香酚、异甲基丁香酚和黄樟醚为指标,采用高效液相色谱法对两种肉豆蔻面煨、滑石粉煨、麸煨、泡后麸煨四种炮制工艺进行比较,并采用正交设计L_9(3~4)优选长形肉豆蔻的最佳炮制工艺。
(3)应用急性毒性实验方法,观察并用改良寇氏法计算小鼠的LD_(50)值。通过对正常小鼠的肠推进方法和抑制新斯的明引起的小鼠小肠功能亢进的方法,比较两种肉豆蔻生品及其炮制品涩肠止泻的作用功效。
(4)通过对长形肉豆蔻生品及麸煨长形肉豆蔻十批放大样品的水分、总灰分及酸不溶灰分的测定以及重金属限量检查、砷盐检查等,制定长形肉豆蔻生品及麸煨长形肉豆蔻的质量标准。
结果:
1.两种肉豆蔻的化学成分比较研究
通过对两种肉豆蔻的挥发性成分和非挥发性成分进行初步比较,发现两者成分大致相同,但在含量上有显著性差异,特别是长形肉豆蔻中肉豆蔻醚含量较少,因此对长形肉豆蔻挥发性和非挥发性成分做进一步的研究,分离出12个化合物,分别为黄樟醚(Ⅰ),甲基丁香酚(Ⅱ),异甲基丁香酚(Ⅲ):(E)-3-(benzo[d][1,3】dioxol-5-yl)prop-2-en-1-ol(1),7-hydroxy-3.4′-methylene-flavan(2),1,4苯二甲酸甲酯(3),内消旋二氢愈创木酸(4),erythro-1-(4-hydroxy-3-methoxyphenyl)-4-(3,4-methylenedioxyphenyl)-2,3-dimethy Ibutane(5),赤式-1-(3-甲氧基-4-羟基苯基)-2-(4-丙烯基-2-甲氧基苯氧基)-丙烷-1-醇(6),(7S,7′R,8S,8′R)-7,7′-Di-(4-hydrox y-3-methoxyphenyl)-8,8′-dimethyltetro-hydrofuran(7),β-谷甾醇(8),胡萝卜苷(9),其中化合物Ⅰ、Ⅱ、Ⅲ:1、2、3、6、8、9是首次从长形肉豆蔻植物中分离得到。采用GC/MS和ICP/MS方法分析长形肉豆蔻和圆形肉豆蔻的挥发油和无机元素,在挥发油中鉴定出长形肉豆蔻生品32个化合物,其炮制品29个化合物,圆形肉豆蔻生品35个化合物,其炮制品36个化合物。两种肉豆蔻在炮制前后无机元素的含量情况:Mg、Ca、Fe、Na的含量在炮制后有所升高:K有所降低。而且圆形肉豆蔻中的必需元素含量比长形肉豆蔻中的含量多。
2.两种肉豆蔻的炮制工艺比较研究
两种肉豆蔻经炮制后,挥发油含量都有不同程度的降低,止泻的有效成分甲基丁香酚和异甲基丁香酚含量也都有所增加,但圆形肉豆蔻炮制品增加的较为显著。两种肉豆蔻的毒性成分黄樟醚经炮制后都略微有所下降。
优选出长形肉豆蔻的最佳炮制工艺为:长形肉豆蔻用水浸泡6小时后,麸煨温度160～170℃,麸煨时间25min,每100kg长形肉豆蔻,用40kg麦麸。
3.两种肉豆蔻的药效学初步比较研究
长形肉豆蔻生品的LD_(50)=17.5g/kg,麸煨长形肉豆蔻的LD_(50)=23.5g/kg
两种肉豆蔻经炮制后均能明显的抑制小鼠小肠推动运动,并能抑制新斯的明引起的小肠推进功能亢进。且圆形肉豆蔻炮制品的止泻作用更为显著。
4.长形肉豆蔻生品及其麸煨品的质量标准。
初步制定长形肉豆蔻生品及其麸煨品的质量标准。暂定:长形肉豆蔻生品中:甲基丁香酚不少于0.035%;异甲基丁香酚不少于0.007%;黄樟醚不多于1.004%。麸煨长形肉豆蔻中:甲基丁香酚不少于0.056%:异甲基丁香酚不少于0.0089%;黄樟醚不可多于0.85%。
结论:
根据长形肉豆蔻与圆形肉豆蔻的化学成分、炮制工艺、药理作用、质量标准等全面的比较研究,初步认为长形肉豆蔻可以作为肉豆蔻的一种使用。
Purpose:
Nutmeg is embodied by Chinese Pharmacopoeia <2005>.Now the market has two varieties of nutmeg,one is Mystica fragrans Houtt.,the other is Mystica argentea Warb.In Indonesia,Mystica fragrans Houtt.is used for spices and Mystica argentea Warb is used for medicine.While in China,it is different.So our laboratory carried out comprehensive study, include comparative study of chemical composition and pharmacology of M.argentea Warb and M.fragrans Houtt.,then establish optimum processing technology and quality standard.
Material and method.
1.Material:Mystica argentea Warb.and Mystica fragrans Houtt was purchased from Bozhou Chinese Medicine Market,Anhui Province.A voucher specimen was deposited at our laboratory.
2.method:
(1)Though HPLC,TLC,GC-MS and ICP-MS methods,we compared the chemical compositions of M.argentea and M.fragrans.We applied silica-gel,sephadex LH-20, preparative TLC and recrystallization to separate and isolate the chemical compounds from M. argentea.
(2) The content of methyleugenol,methylisoeugenol,and safrol in volatile oil of M. argentea,M.fragrans and their different processed products were determined by HPLC.And the optimum processing technology was obtained using orthogonal design.
(3)Through acute toxicity experiment,we obtaind the spastics of LD_(50) by koushi.Via carbon powder drive experiment in small intestine of rats,we compared the anti-diarrheal action of Nutmeg and its different processed products.
(4) We established quality standard of M.argentea and its processed products,include moisture content,heavy metal limit examine,arsenic salt examine and ani-malcule limit examine of ten batch magnifying processing samples.
Results:
1.Comparative study of chemical compositions of Mystica argentea Warb.and Mystica fragrans Houtt.
Through HPLC analysis,we observed that the chemical compositions had no significant difference between them,but the content of main chemical constituents had remarkable difference.So we isolated the chemical conctituents of Mystica argentea Warb.for further study,and 12 compounds were elucidated.
Via UV,IR,NMR and MS,these compounds were identified as safrol(Ⅰ), methyleugenol(Ⅱ),methylisoeugenol(Ⅲ),(E)-3-(benzo[d][1,3]dioxol-5-yl)prop-2-en-1-ol (1),7-hydroxy-3′,4′-methylene-flavan(2),1,4-benzenedicarboxylic acid dimethyl ester(3), erythro-1,4-di(4-hydroxy-3-methoxyphenyl)-2,3-dimethylbutane(4),erythro-1-(4-hydroxy-3-methoxyphenyl)-4-(3,4-methylenedioxyphenyl)-2,3-dimethylbutane(5),rel-1-(3-methoxy -4-hydroxylbenzyl)-2-(4-allyl-2-methoxyphenoxies)-propane-1-ol(6),(7S,7′R,8S,8′R) -7,7′-Di-(4-hydroxy-3-methoxyphenyl)-8,8′-dimethyltetro-hydrofuran(7),β-sitosterol((?)), daucosterol((?)).Compound ofⅠ,Ⅱ,Ⅲ,1,2,3,6,8,9 were isolated from Mystica argentea Warb.for the first time.
Volatile oil of two varieties was analysed by GC-MS.We determined 32 compounds from M.argentea,29 compounds from the processed products of M.argentea;35 compounds from M.fragrans and 36 compounds from its processed products.
Inorganic elements of two varieties was analysed by ICP-MS.The content of Mg,Ca,Fe, Na was increased after processing,while the content of K was decreased.
2.Comparative Research on processing technology of the Mystica argentea Warb.and Mystica fragrans Houtt.
After processing,the content of methyleugenol and isomethyleugeno was increased,while the content of safrol was reduced.
The optimal processing technology of Mystica argentea Warb was obtained by orthogonal design using safrol,methyleugenol,methylisoeugenol as index substance,soaked the drug (100 Kg)with water for 6 hr,then roasted with wheat bran(40 Kg) at 160-170℃pot temperature for 25 min.
3.Comparative Research on Pharmacology of Mystica argentea Warb.and Mystica fragrans Houtt.
LD_(50) of Mystica argentea Warb.is 17.5g/kg,and its processed product is 23.5g/kg.The processed products of M.argentea and M.fragrans both had significant inhibitive effect on the small intestinal propulsive motion in normal rats and rats of motion hyperfunction induced by neostigmine.
4.Quality Standard Study of Mystica argentea Warb.and its Processed Product.
We established quality standard of Mystica argentea Warb.and its processed product. For M.argentea,the content of methyleugenol and isomethyleugenol were not less than 0.035%and 0.007%respectively.And the content of safrol was no higher than 1.004%.
Conclusion:
We considered that Mystica argentea.Warb can be used as one of variety of Nutmeg based on comparative study with M.fragrans from chemical composition,processing technology,and pharmacology etc.
引文
[1]国家药典委员会.中国药典,Ⅰ部[S].北京:化学工业出版社,2005:1-1.
[2].贾天柱.肉豆蔻的研究进展[J].中草药,1996,27(11):690-93
[3].全国中草药汇编(下册).人民卫生出版社1978:247
[4].郭希圣,俞波.肉豆蔻的质量研究Ⅰ肉豆蔻化学成分的分离和鉴定[J].药物分析杂志,1985,5(5):258-262.
[5].李铁林,周杰,徐植灵,等.炮制对肉豆蔻挥发油含量的影响及肉豆蔻挥发油化学成分的研究[J].中国中药杂志,1990,15(7):21-23.
[6].李铁林,周杰,江文君,等.炮制对肉豆蔻挥发油成分及肉豆蔻醚含量影响的研究.中国中药杂志1990;15(8):23-25
[7].赖文玲,曾志,陈亿新,等.中药复方中后下组分化学成分研究(Ⅱ)肉豆蔻挥发油[J].中草药,2002,33(7):596-598.
[8].刘博,陈开勋,陈渭萍,等.肉豆蔻超临界二氧化碳萃取工艺及其精油的GC-MS分析研究[J].香料香精化妆品,2003(4):17.19
[9].王莹,杨秀伟,陶海燕,等.商品肉豆蔻挥发油成分的GC.MS分析[J].中国中药杂志,2004,29(4):339.342.
[10].陈迪华.海南岛引种的与马来西亚进口肉豆蔻(种子和叶)挥发油的比较研究.中药通报1987:12(10):655-657
[11].郭希圣,俞波.肉豆蔻的质量研究--Ⅱ.肉豆蔻挥发油中主要活性成分的高效液相色谱法测定。药物分析杂志。1987;7(6):331-334
[12].贾天柱,等.肉豆蔻不同炮制品挥发油中肉豆蔻醚、黄樟醚的薄层扫描测定[J].中国中药杂志,1991,16(5):275-277
[13].杨秀伟,高继山,等.肉豆蔻化学成分研究.中成药1994;16(5):38-40
[14].贾天柱,李军.肉豆蔻和肉豆蔻衣及其炮制品中脂肪酸成分分析。中药材.1995:18(11):564-565
[15].贾天柱,沙明.肉豆蔻不同炮制品挥发油中肉豆蔻醚、黄樟醚的HPLC法测定[J].中国中药杂志,1997,22(7):410-411.
[16].贾天柱,沙明,曹爱民,等.肉豆蔻不同炮制品挥发油中丁香酚类成分测定[J].中国中药杂志,1997,22(8):477-475.
[17]Shin K,H,et al.Arch Pharm Res,1988,11(3):240
[18]李建北,丁怡.云南肉豆蔻化学成分研究[J]。中国中药杂志,2001,26(7):479-481
[19]中岛嘉次郎等.肉豆蔻中的血管平滑肌收缩抑制作用[J].国外医学中医中药分册,1998,20(5):62.
[20].Filleur F.长形肉豆蔻中的木脂素具抗增殖,抗芳香酶,抗1713一羟基类固醇脱氢酶和抗氧化活性[J].国外医药,植物药分册,2002,17(6):254
[21].李秀芳,吴立军.肉豆蔻的化学成分[J].沈阳药科大学学报,2006,23:698-734
[22].Shin BK,Lee EH,Kiin HM.Suppression of L-histidine decar-boxylase mRNA expression by methyleugenol[J],ochem Biophys Res Commun,1997,Mar 6,232(1):188-191.
[23].A1-Bataina BA,Maslat AO,A1--Kofahil MM.Element analysis and biological studies on ten oriental spices using XRF and Trace Elem Med Biol[J].J Trace Elem MedBiol,2003,17(2):85-91
[24].Hallstrom H,Thuvander A.Toxicological evaluation of myristici--ni[J].Nat Toxins,1997,5(5):186.192
[25].陈丽坤,李韶华.肉豆蔻炮制研究[J].中药材,2002,25(3):174-176
[26].王正益,张振凌,吴建刚,等.肉豆蔻炮制的初步研究(摘要)[J].河南医药,1984,4(6):386-387.
[27].贾天柱,李洁.肉豆蔻不同炮制品止泻作用及急性毒性比较[J].中国中药杂志,1997,22(4):216-218.
[28].周燕华,谭建宁.不同炮制条件对肉豆蔻挥发油、脂肪油及肉豆蔻醚含量的影响[J].中国中药杂志,1998,23(4):217-219
[29].Niyas Z,Variyar PS,Gholap AS,et al.Effect of gamma--irradiation DB the lipid profile of(Myristica fragrans Houtt.)[J].g-ric Food Chem,2003,Oct 22,51(22):650245504.
[30].Calucci L,Pinzino C,Zandomeneghi M,et al.Effects of galnma.irradiation on the free radical and antioxidant contents in nine aromatic herbs and spices[J].J Agric Food Chem,2003,Feb 12,51(4):927-934.
[31].李宏斌.肉豆蔻炮制工艺的改进[J].基层中药杂志,2001,15(5):36-37.
[32].贾天柱,单福永.肉豆蔻不同炮制品的质量比较[J].中药材,1997,20(11):561-563.
[33].李军东,刘月霞.肉豆蔻炮制方法的改进[J].基层中药杂志,1996.10(1):22.
[34].Lahlou S,Figueiredo AF,Magalhaes P J,et al.Cardiovasculareffects of methyleugenol,a natural constituent of many plant essentialoils,in normotensive rats[J].L/re Sci,2004,Mar26,74(19):2401-2412.
[35]Ram A,Lauria P,Gupta R,et al.Hypolipidaemic effect of My-ristica fragrans fruit extract inrabbits[J].J Ethnopharmacol,1996,Dec,55(1):49-53.
[36].Saleh M.Pharmacology action about nutmeg[J].Planta Med,1989,32:82.
[37].Ozaki Y,KilauraY,Yashikawa C.A method for the determination of serum guanase using guanine as the substrate[J].Japan J Pharm,1984,49:155
[38].Sangalli BC,Chiang W.Toxicology of nutmeg abuse[J].JToxi-col Clin Toxicol,2000,38(6):6714578.
[39].Sonavane GS,Sarveiya VP,Kasture VS,et al.Anxiogenie activ-ity of Myristiea fragrans seeds[J].Pharmacol Biochem Behav,2002,Jan-Feb,71(1-2):239-244.
[40].中国科学医学研究所.中药志[M].北京:人民卫生出版社,1986:339-341.
[41].天津市药品检验所中药组.关于肉豆蔻炮制方面有关问题的探讨[J].中草药通讯,1979,10(1):16.
[42].Grover K,Khandkar S,Vats V,et al.Pharmacological studiesr'n Mvristica fragrans·antidiarrheal,hypnotic,analgesic and hmodynamic(blood pressure)paramete-[J].Metho& Find Exp Clin Pharmacol,2002,Dec,24(10):6754580
[43].Lima CC,Criddle DN,Coelho-de.Souza AN,et al.Relaxant and antispasmodic actions of methyleugenol on guinea-pig isolatedileum[J].Planta Med,2000,Jun,66(5):408-41
[44].Husan S,Jannul.The action of anti-tumor in uterme about Myristica fragrans Houtt[J].Cancer Lett,1991,56(3):231.
[45].Jannul,Husan S.The action of anti-minor in derma aboutMyristica fragrans Houtt[J].Cancer Lett,1991,56(1) 59
[46].Chhabra S K,Rao A R.Transmammary modulation of xenobiot2ic metabolizing enzymes in liver of mouse pups by mace(Myristi2ca fragrans Houtt)[J].J Ethnopharmacol,1994,42(3):169.
[47].Zheng G,Zhang D.Involvement of bioantioxidants in throm-bosis in mice [J].Carcinogenesis,1992,13(10):1921.
[48].贾天柱,姜涛.肉豆蔻不同炮制品抗炎、镇痛及抑菌作用比较[J].辽宁中医杂志, 1996,23(10):474.
[49].Broadhu-t CL,Polansky MM,Ande-on RA.Insulin.like bio.logical activity of culinary and medicinal plant aqueous extracts invitro[j].J Agric od Chem,2000,Mar,48(3):849.852.
[50].周慧秋,于滨,乔婉红,等.甲基丁香酚药理作用研究[J].中医药学报,2000,2:79-80.
[51].Meepagala KM,Sturtz G,Wedge DE.Antifungal constituents of the essential oil fraction of Artemisia dracunculus L.Vat.dracun.cuius[J].J Agric Food Chem,2002,Nov 20,50(24):6989-6992
[52].ShinoharaC,Mori S,Ando T,etal.Arg.gingipain inhibition and anti-bacterial activity selective for Porphyromonas gingivalis by malabaricone C[J].Biosci Biotechnol Biochem,1999,Aug,63(8):1475-1477.
[53].De M,Krishna De A,Banerjee AB.Antimierobial screening of some Indian spices[J].Phytother Res,1999 Nov,13(7):616-618
[54].Smith-Palmer A,Stewart J,Vyfe L.Antimierobial properties of plant essential oils and essences against five important food-borne pathogens[J].Lett AppZ Microbiol,1998,Feb,26(2):118-122
[55].Ejechi BO,Souzey JA,Akpomedaye DE.Microbial stability of mango(Mangifera indica L.)juice preserved by combined appli-cation of mild heat and extracts of two tropical spices[J].J FoodProt,1998,Jun,61(6):725-727
[56].Mureia MA,Egea I,Romojaro F,et al.Antioxidant evaluation in dessert spices compared with common food additives[J],g-r/c Food Chem,2004,Apr 7,52(7):1872-1881.
[57].Tajuddin,Ahmad S,Latif A,et al.Aphrodisiac activity of 50%ethanolic extracts of Myristiea fragrans Houtt.and Syzygium aro-maticum(L)Merr.&Perry.(clove)in male mice:a compara-live study[j].BMC Complement Ahem Med,2003,Oct 20,3(1):6.
[58].Capasso R,Pinto L,Vuotto ML,et al.Preventive effect of euge-nol on PAF and ethanol-induced gastric mucosal damage Fitotera-pia,2000,Aug,71 Suppl 1:S131-137.
[59]. Kreydiyyeh SI, Usta J, Copti R. Effect of cinnamon, clove and some of their constituents on the Na(+)-K(+)-ATPase activity and alanine absorption in the rat jejunum[J]. Food ChemToxi-col, 2000, Sep, 38(9): 755-762.
[2].贾天柱.肉豆蔻的研究进展[J].中草药,1996,27(11):690-93
[3].全国中草药汇编(下册).人民卫生出版社1978:247
[4].郭希圣,俞波.肉豆蔻的质量研究Ⅰ肉豆蔻化学成分的分离和鉴定[J].药物分析杂志,1985,5(5):258-262.
[5].李铁林,周杰,徐植灵,等.炮制对肉豆蔻挥发油含量的影响及肉豆蔻挥发油化学成分的研究[J].中国中药杂志,1990,15(7):21-23.
[6].李铁林,周杰,江文君,等.炮制对肉豆蔻挥发油成分及肉豆蔻醚含量影响的研究.中国中药杂志1990;15(8):23-25
[7].赖文玲,曾志,陈亿新,等.中药复方中后下组分化学成分研究(Ⅱ)肉豆蔻挥发油[J].中草药,2002,33(7):596-598.
[8].刘博,陈开勋,陈渭萍,等.肉豆蔻超临界二氧化碳萃取工艺及其精油的GC-MS分析研究[J].香料香精化妆品,2003(4):17.19
[9].王莹,杨秀伟,陶海燕,等.商品肉豆蔻挥发油成分的GC.MS分析[J].中国中药杂志,2004,29(4):339.342.
[10].陈迪华.海南岛引种的与马来西亚进口肉豆蔻(种子和叶)挥发油的比较研究.中药通报1987:12(10):655-657
[11].郭希圣,俞波.肉豆蔻的质量研究--Ⅱ.肉豆蔻挥发油中主要活性成分的高效液相色谱法测定。药物分析杂志。1987;7(6):331-334
[12].贾天柱,等.肉豆蔻不同炮制品挥发油中肉豆蔻醚、黄樟醚的薄层扫描测定[J].中国中药杂志,1991,16(5):275-277
[13].杨秀伟,高继山,等.肉豆蔻化学成分研究.中成药1994;16(5):38-40
[14].贾天柱,李军.肉豆蔻和肉豆蔻衣及其炮制品中脂肪酸成分分析。中药材.1995:18(11):564-565
[15].贾天柱,沙明.肉豆蔻不同炮制品挥发油中肉豆蔻醚、黄樟醚的HPLC法测定[J].中国中药杂志,1997,22(7):410-411.
[16].贾天柱,沙明,曹爱民,等.肉豆蔻不同炮制品挥发油中丁香酚类成分测定[J].中国中药杂志,1997,22(8):477-475.
[17]Shin K,H,et al.Arch Pharm Res,1988,11(3):240
[18]李建北,丁怡.云南肉豆蔻化学成分研究[J]。中国中药杂志,2001,26(7):479-481
[19]中岛嘉次郎等.肉豆蔻中的血管平滑肌收缩抑制作用[J].国外医学中医中药分册,1998,20(5):62.
[20].Filleur F.长形肉豆蔻中的木脂素具抗增殖,抗芳香酶,抗1713一羟基类固醇脱氢酶和抗氧化活性[J].国外医药,植物药分册,2002,17(6):254
[21].李秀芳,吴立军.肉豆蔻的化学成分[J].沈阳药科大学学报,2006,23:698-734
[22].Shin BK,Lee EH,Kiin HM.Suppression of L-histidine decar-boxylase mRNA expression by methyleugenol[J],ochem Biophys Res Commun,1997,Mar 6,232(1):188-191.
[23].A1-Bataina BA,Maslat AO,A1--Kofahil MM.Element analysis and biological studies on ten oriental spices using XRF and Trace Elem Med Biol[J].J Trace Elem MedBiol,2003,17(2):85-91
[24].Hallstrom H,Thuvander A.Toxicological evaluation of myristici--ni[J].Nat Toxins,1997,5(5):186.192
[25].陈丽坤,李韶华.肉豆蔻炮制研究[J].中药材,2002,25(3):174-176
[26].王正益,张振凌,吴建刚,等.肉豆蔻炮制的初步研究(摘要)[J].河南医药,1984,4(6):386-387.
[27].贾天柱,李洁.肉豆蔻不同炮制品止泻作用及急性毒性比较[J].中国中药杂志,1997,22(4):216-218.
[28].周燕华,谭建宁.不同炮制条件对肉豆蔻挥发油、脂肪油及肉豆蔻醚含量的影响[J].中国中药杂志,1998,23(4):217-219
[29].Niyas Z,Variyar PS,Gholap AS,et al.Effect of gamma--irradiation DB the lipid profile of(Myristica fragrans Houtt.)[J].g-ric Food Chem,2003,Oct 22,51(22):650245504.
[30].Calucci L,Pinzino C,Zandomeneghi M,et al.Effects of galnma.irradiation on the free radical and antioxidant contents in nine aromatic herbs and spices[J].J Agric Food Chem,2003,Feb 12,51(4):927-934.
[31].李宏斌.肉豆蔻炮制工艺的改进[J].基层中药杂志,2001,15(5):36-37.
[32].贾天柱,单福永.肉豆蔻不同炮制品的质量比较[J].中药材,1997,20(11):561-563.
[33].李军东,刘月霞.肉豆蔻炮制方法的改进[J].基层中药杂志,1996.10(1):22.
[34].Lahlou S,Figueiredo AF,Magalhaes P J,et al.Cardiovasculareffects of methyleugenol,a natural constituent of many plant essentialoils,in normotensive rats[J].L/re Sci,2004,Mar26,74(19):2401-2412.
[35]Ram A,Lauria P,Gupta R,et al.Hypolipidaemic effect of My-ristica fragrans fruit extract inrabbits[J].J Ethnopharmacol,1996,Dec,55(1):49-53.
[36].Saleh M.Pharmacology action about nutmeg[J].Planta Med,1989,32:82.
[37].Ozaki Y,KilauraY,Yashikawa C.A method for the determination of serum guanase using guanine as the substrate[J].Japan J Pharm,1984,49:155
[38].Sangalli BC,Chiang W.Toxicology of nutmeg abuse[J].JToxi-col Clin Toxicol,2000,38(6):6714578.
[39].Sonavane GS,Sarveiya VP,Kasture VS,et al.Anxiogenie activ-ity of Myristiea fragrans seeds[J].Pharmacol Biochem Behav,2002,Jan-Feb,71(1-2):239-244.
[40].中国科学医学研究所.中药志[M].北京:人民卫生出版社,1986:339-341.
[41].天津市药品检验所中药组.关于肉豆蔻炮制方面有关问题的探讨[J].中草药通讯,1979,10(1):16.
[42].Grover K,Khandkar S,Vats V,et al.Pharmacological studiesr'n Mvristica fragrans·antidiarrheal,hypnotic,analgesic and hmodynamic(blood pressure)paramete-[J].Metho& Find Exp Clin Pharmacol,2002,Dec,24(10):6754580
[43].Lima CC,Criddle DN,Coelho-de.Souza AN,et al.Relaxant and antispasmodic actions of methyleugenol on guinea-pig isolatedileum[J].Planta Med,2000,Jun,66(5):408-41
[44].Husan S,Jannul.The action of anti-tumor in uterme about Myristica fragrans Houtt[J].Cancer Lett,1991,56(3):231.
[45].Jannul,Husan S.The action of anti-minor in derma aboutMyristica fragrans Houtt[J].Cancer Lett,1991,56(1) 59
[46].Chhabra S K,Rao A R.Transmammary modulation of xenobiot2ic metabolizing enzymes in liver of mouse pups by mace(Myristi2ca fragrans Houtt)[J].J Ethnopharmacol,1994,42(3):169.
[47].Zheng G,Zhang D.Involvement of bioantioxidants in throm-bosis in mice [J].Carcinogenesis,1992,13(10):1921.
[48].贾天柱,姜涛.肉豆蔻不同炮制品抗炎、镇痛及抑菌作用比较[J].辽宁中医杂志, 1996,23(10):474.
[49].Broadhu-t CL,Polansky MM,Ande-on RA.Insulin.like bio.logical activity of culinary and medicinal plant aqueous extracts invitro[j].J Agric od Chem,2000,Mar,48(3):849.852.
[50].周慧秋,于滨,乔婉红,等.甲基丁香酚药理作用研究[J].中医药学报,2000,2:79-80.
[51].Meepagala KM,Sturtz G,Wedge DE.Antifungal constituents of the essential oil fraction of Artemisia dracunculus L.Vat.dracun.cuius[J].J Agric Food Chem,2002,Nov 20,50(24):6989-6992
[52].ShinoharaC,Mori S,Ando T,etal.Arg.gingipain inhibition and anti-bacterial activity selective for Porphyromonas gingivalis by malabaricone C[J].Biosci Biotechnol Biochem,1999,Aug,63(8):1475-1477.
[53].De M,Krishna De A,Banerjee AB.Antimierobial screening of some Indian spices[J].Phytother Res,1999 Nov,13(7):616-618
[54].Smith-Palmer A,Stewart J,Vyfe L.Antimierobial properties of plant essential oils and essences against five important food-borne pathogens[J].Lett AppZ Microbiol,1998,Feb,26(2):118-122
[55].Ejechi BO,Souzey JA,Akpomedaye DE.Microbial stability of mango(Mangifera indica L.)juice preserved by combined appli-cation of mild heat and extracts of two tropical spices[J].J FoodProt,1998,Jun,61(6):725-727
[56].Mureia MA,Egea I,Romojaro F,et al.Antioxidant evaluation in dessert spices compared with common food additives[J],g-r/c Food Chem,2004,Apr 7,52(7):1872-1881.
[57].Tajuddin,Ahmad S,Latif A,et al.Aphrodisiac activity of 50%ethanolic extracts of Myristiea fragrans Houtt.and Syzygium aro-maticum(L)Merr.&Perry.(clove)in male mice:a compara-live study[j].BMC Complement Ahem Med,2003,Oct 20,3(1):6.
[58].Capasso R,Pinto L,Vuotto ML,et al.Preventive effect of euge-nol on PAF and ethanol-induced gastric mucosal damage Fitotera-pia,2000,Aug,71 Suppl 1:S131-137.
[59]. Kreydiyyeh SI, Usta J, Copti R. Effect of cinnamon, clove and some of their constituents on the Na(+)-K(+)-ATPase activity and alanine absorption in the rat jejunum[J]. Food ChemToxi-col, 2000, Sep, 38(9): 755-762.
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