益智仁温脾止泻作用及盐炙对其影响的研究
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摘要
《中华人民共和国药典》2005年版一部规定：益智为姜科植物益智Alpinia oxyphylla Miq.的干燥成熟果实；辛、温,归脾、肾经；功能为温脾止泻,摄唾涎,暖肾,固精缩尿；主治脾寒泄泻,腹中冷痛,口多唾涎,肾虚遗尿,小便频数,遗精白浊。其“炮制”项下分列“益智仁”和“盐益智仁”两个饮片品种,其中“益智仁”由益智“除去杂质及外壳”而来,“盐益智仁”由益智仁“照盐水炙法炒干”而成。
目的
在国家“十一五”科技支撑计划项目“盐炙法——炮制共性技术”(编号：2006BAI09B06-09)课题的支持下,本课题组以益智仁为代表药物,基于对其“生品入脾,盐炙入肾,生熟有别”的传统认识,开展文献和实验研究,进行盐炙原理的探讨。前期已经完成益智仁“盐炙缩尿”部分的研究,因此本文以“温脾止泻”功效为切入点,在阐明这一功效作用机制和药效物质的基础上,探讨盐炙对其的影响,进一步来揭示盐炙原理,并为解析盐炙共性技术的科学内涵提供参考。
方法
采用文献学、药理学和化学相结合的手段开展益智仁盐炙的炮制学研究。
1采用文献学方法,整理中药益智的炮制历史沿革和现代研究进展,搞清中药益智炮制的历史情况和研究现状。
2采用药理学方法,开展益智仁温脾止泻功效的药效学研究,并探讨其可能的作用机制,认识益智仁温脾止泻的功效。
3采用化学方法,以药效为导向,筛选益智仁止泻作用的有效部位,并对有效部位进行的成分分离,揭示益智仁止泻功效的药效物质基础。
4在上述研究的基础上,开展益智仁盐炙前后药理作用的比较研究和化学成分的比较研究,阐明盐炙对其的影响,探讨盐炙的原理。
结果
1药理实验表明：益智仁对番泻叶所致的小鼠腹泻有对抗作用,对盐酸乙醇所致的大鼠胃溃疡有抑制作用,并且能够抑制小鼠在体胃肠的运动和家兔离体肠肌的收缩,降低脾虚泄泻模型大鼠血清胃泌素和血浆血管活性肠肽的含量。
2化学实验表明：益智仁止泻作用的有效部位为挥发油部位或石油醚和三氯甲烷萃取部位,通过对石油醚和三氯甲烷萃取部位的成分分离,得到了圆柚酮、β-谷甾醇、益智酮甲、Oxyphyllol B和胡萝卜苷五种化合物。其中圆柚酮能抑制盐酸乙醇所致的大鼠胃溃疡,益智酮甲能抑制家兔离体肠肌的收缩。
3益智仁盐炙前后对番泻叶所致的小鼠腹泻和对家兔离体肠肌收缩均有抑制作用,生品与盐炙品的作用无明显差异,而在水煎液中,生品的作用均强于盐炙品。益智仁生品与盐炙品中挥发油和圆柚酮的含量无明显差异,而在水煎液中,生品的含量均高于盐炙品。原因是益智仁盐炙后,水分含量降低,质地变得松脆,更加易于粉碎,同时表皮破碎,组织结构变得疏松,所含成分易于溶出,导致在水煎过程中,盐炙品中的药效成分较之生品,溶出更快,挥散更多,损失更大。
结论
益智仁具有一定的温脾止泻作用,其作用机制可能与抑制动物胃肠运动和调节胃肠激素水平有关。益智仁温脾止泻功效的有效部位为挥发油部位或石油醚和三氯甲烷萃取部位,圆柚酮和益智酮甲均为其有效成分。益智仁盐炙前后均有止泻作用,生品水煎液的作用强于盐炙品水煎液,这与“生品入脾,温脾止泻见长”的传统经验一致。结合课题组前期对于“盐炙缩尿”研究的结果,证明了益智仁“生品入脾,盐炙入肾,生熟有别”传统认识的正确性,认为用于温脾止泻,益智仁无需盐炙,生用即可；用于暖肾缩尿,则需要盐炙,以炙品为佳。
创新点
本文在中医药理论指导下,运用现代科学技术和方法,开展益智仁盐炙前后温脾止泻作用的研究,其创新性如下：
1揭示益智仁温脾止泻作用的药效机制,为其治疗脾寒泄泻提供现代药理学的依据,也为临床上进一步的合理用药提供参考。
2明确益智仁温脾止泻作用的物质基础,为进一步制定合理的质量标准,更好地评价与控制其质量提供参考。
3阐明盐炙对益智仁温脾止泻作用的影响,为进一步揭示益智仁盐炙原理和解析盐炙共性技术的科学内涵提供参考。
Fructus Alpiniae Oxyphyllae(FAO) is recorded in 'Pharmacopoeia of the People's Republic of China'(2005 edition). It is the dry ripe fruit of Alpinia oxyphylla Miq., pungent in flavour, warm, acting on the spleen channel and the kidney channel, and good at warming the spleen and anti-diarrhea, astringing and preserving the droll-spittle, specializing in conserving essence and arresting polyuria, usually being used to treat abdominal pain, diarrhoea, uncontrollable drolling and emissions, premature ejaculation, frequent micturition and enuresis resulted from kidney qi deficiency cold. There are two kinds of processed forms, which are'The Crude Seed Alpiniae Oxyphyllae (CSAO)'and'The Stir-heated Seed Alpiniae Oxyphyllae (SSAO)', CSAO is processed by excluding impurity and hull of FAO, and SSAO is stir-heating the CSAO with salt solution.
Objective
Being a part of'Technical Commonness in the Processing Method of Stir-heating with Salt Solution' project which is under the State Ministry of Science and Technology 11th Five-Year Plan Support(No.2006BAI09B06-09), our study aimed at the traditional medicinal herb CSAO which is of affirmative clinical therapeutic effect focusing on the differences between the effects and clinical applications respectively before and after processing, expecting to elucidate the mechanism and active components for the anti-diarrhea effect, further interpreting the scientific connotation of the theory for the stir-heating with salt solution of CSAO, and then providing a new idea for investigations on drug processing by common techniques in stir-heating with salt solution.
Methods
The methods used in the research of the scientific connotation of the theory for the stir-heated CSAO with salt solution are philological, pharmacological and chemical means.
1. Systemically arrange the documents about the processing methods of the past and follow up the modern report timely by philological means in order to recognize the history and actuality of CSAO.
2. Study the pharmacodynamics and elucidate the possible mechanism by pharmacological means in order to recognize the effect of warming the spleen and anti-diarrhea.
3. The active fraction with the anti-diarrhea effect of CSAO was screened and prepared in order to recognize the active components of CSAO for anti-diarrhea. The initial investigations were carried out on the chemical means.
4. The differences that indicate in pharmacological effects and in the chemical compositions of CSAO and SSAO were focused.
Results
1. The results showed that CSAO could protect the mice from diarrhea induced by Folium Sennae, inhibit HCl/ethanol-induced gastric ulcers in rats, delay the gastric emptying and the small intestinal in mice, depress the contraction of duodenum of rabbits in vitro, and depress the content of GAS in serum, the content of VIP in plasm at the same time in rats of Spleen Deficiency.
2. The results showed that the active fraction of the anti-diarrhea effect of CSAO was volatile oil fraction or the extracted fraction of petroleum ether and chloroform. Nootkatone,β-sitosterol, Yakuchinone A, Oxyphyllol B and Daucosterol were isolated and identified from the active fraction. Nootkatone inhibited HCl/ethanol-induced gastric ulcer in rats, and Yakuchinone A depressed the contraction of duodenum of rabbits in vitro.
3. The results showed that CSAO and SSAO could also protect the mice from diarrhea induced by Folium Sennae, and depress the contraction of duodenum of rabbits in vitro, there is no distinctly difference between CSAO and SSAO, but the decoction of CSAO showed a stronger effect than the decoction of SSAO, at the same time, there is no distinctly change of content of volatile oil and Nootkatone between CSAO and SSAO, but the decoction of CSAO contain more volatile oil and Nootkatone than the decoction of SSAO.
4. After stir-heating with salt solution, the water in seeds fell, the texture became more crumble, the comminuted powder became small, at the same time, surface of the seeds was fragmented, the inner structure became more loosened, so active components can dissolve more into decoction in a shorter time. As a result, there is an increasing loss of the components in the decoction of SSAO.
Conclusions
1. CSAO has certain effect of warming the spleen and anti-diarrhea, the action mechanism lies in the depression of gastrointestinal movement and the depression of the content of gastrointestinal hormone.
2. The active fraction with the anti-diarrhea effect of CSAO was volatile oil fraction or the extracted fraction of petroleum ether and chloroform. Nootkatone and Yakuchinone A are both of the active components of CSAO for anti-diarrhea.
3. CSAO and SSAO could both protect the mice from diarrhea, but the decoction of CSAO showed a stronger effect than the decoction of SSAO. The result accorded with the TCM theory of'CSAO acts on spleen channel.'
Innovations
1. Elucidate the mechanisms of CSAO for anti-diarrhea initially, provide the pharmacological explanation for its effect of warming the spleen and anti-diarrhea, and provide a reasonable instruction of using CSAO afterwards.
2. Elucidate the active components of CSAO for anti-diarrhea initially, provide the reference for establishing a more reasonable quality standard of CSAO.
3. Elucidate the influence on CSAO by stir-heating with salt solution, provide the reference for further interpreting the scientific connotation of the theory for the stir-heating with salt solution of CSAO, and also provide a new idea for the investigations on the drug processing by common techniques in stir-heating with salt solution.
目的
在国家“十一五”科技支撑计划项目“盐炙法——炮制共性技术”(编号：2006BAI09B06-09)课题的支持下,本课题组以益智仁为代表药物,基于对其“生品入脾,盐炙入肾,生熟有别”的传统认识,开展文献和实验研究,进行盐炙原理的探讨。前期已经完成益智仁“盐炙缩尿”部分的研究,因此本文以“温脾止泻”功效为切入点,在阐明这一功效作用机制和药效物质的基础上,探讨盐炙对其的影响,进一步来揭示盐炙原理,并为解析盐炙共性技术的科学内涵提供参考。
方法
采用文献学、药理学和化学相结合的手段开展益智仁盐炙的炮制学研究。
1采用文献学方法,整理中药益智的炮制历史沿革和现代研究进展,搞清中药益智炮制的历史情况和研究现状。
2采用药理学方法,开展益智仁温脾止泻功效的药效学研究,并探讨其可能的作用机制,认识益智仁温脾止泻的功效。
3采用化学方法,以药效为导向,筛选益智仁止泻作用的有效部位,并对有效部位进行的成分分离,揭示益智仁止泻功效的药效物质基础。
4在上述研究的基础上,开展益智仁盐炙前后药理作用的比较研究和化学成分的比较研究,阐明盐炙对其的影响,探讨盐炙的原理。
结果
1药理实验表明：益智仁对番泻叶所致的小鼠腹泻有对抗作用,对盐酸乙醇所致的大鼠胃溃疡有抑制作用,并且能够抑制小鼠在体胃肠的运动和家兔离体肠肌的收缩,降低脾虚泄泻模型大鼠血清胃泌素和血浆血管活性肠肽的含量。
2化学实验表明：益智仁止泻作用的有效部位为挥发油部位或石油醚和三氯甲烷萃取部位,通过对石油醚和三氯甲烷萃取部位的成分分离,得到了圆柚酮、β-谷甾醇、益智酮甲、Oxyphyllol B和胡萝卜苷五种化合物。其中圆柚酮能抑制盐酸乙醇所致的大鼠胃溃疡,益智酮甲能抑制家兔离体肠肌的收缩。
3益智仁盐炙前后对番泻叶所致的小鼠腹泻和对家兔离体肠肌收缩均有抑制作用,生品与盐炙品的作用无明显差异,而在水煎液中,生品的作用均强于盐炙品。益智仁生品与盐炙品中挥发油和圆柚酮的含量无明显差异,而在水煎液中,生品的含量均高于盐炙品。原因是益智仁盐炙后,水分含量降低,质地变得松脆,更加易于粉碎,同时表皮破碎,组织结构变得疏松,所含成分易于溶出,导致在水煎过程中,盐炙品中的药效成分较之生品,溶出更快,挥散更多,损失更大。
结论
益智仁具有一定的温脾止泻作用,其作用机制可能与抑制动物胃肠运动和调节胃肠激素水平有关。益智仁温脾止泻功效的有效部位为挥发油部位或石油醚和三氯甲烷萃取部位,圆柚酮和益智酮甲均为其有效成分。益智仁盐炙前后均有止泻作用,生品水煎液的作用强于盐炙品水煎液,这与“生品入脾,温脾止泻见长”的传统经验一致。结合课题组前期对于“盐炙缩尿”研究的结果,证明了益智仁“生品入脾,盐炙入肾,生熟有别”传统认识的正确性,认为用于温脾止泻,益智仁无需盐炙,生用即可；用于暖肾缩尿,则需要盐炙,以炙品为佳。
创新点
本文在中医药理论指导下,运用现代科学技术和方法,开展益智仁盐炙前后温脾止泻作用的研究,其创新性如下：
1揭示益智仁温脾止泻作用的药效机制,为其治疗脾寒泄泻提供现代药理学的依据,也为临床上进一步的合理用药提供参考。
2明确益智仁温脾止泻作用的物质基础,为进一步制定合理的质量标准,更好地评价与控制其质量提供参考。
3阐明盐炙对益智仁温脾止泻作用的影响,为进一步揭示益智仁盐炙原理和解析盐炙共性技术的科学内涵提供参考。
Fructus Alpiniae Oxyphyllae(FAO) is recorded in 'Pharmacopoeia of the People's Republic of China'(2005 edition). It is the dry ripe fruit of Alpinia oxyphylla Miq., pungent in flavour, warm, acting on the spleen channel and the kidney channel, and good at warming the spleen and anti-diarrhea, astringing and preserving the droll-spittle, specializing in conserving essence and arresting polyuria, usually being used to treat abdominal pain, diarrhoea, uncontrollable drolling and emissions, premature ejaculation, frequent micturition and enuresis resulted from kidney qi deficiency cold. There are two kinds of processed forms, which are'The Crude Seed Alpiniae Oxyphyllae (CSAO)'and'The Stir-heated Seed Alpiniae Oxyphyllae (SSAO)', CSAO is processed by excluding impurity and hull of FAO, and SSAO is stir-heating the CSAO with salt solution.
Objective
Being a part of'Technical Commonness in the Processing Method of Stir-heating with Salt Solution' project which is under the State Ministry of Science and Technology 11th Five-Year Plan Support(No.2006BAI09B06-09), our study aimed at the traditional medicinal herb CSAO which is of affirmative clinical therapeutic effect focusing on the differences between the effects and clinical applications respectively before and after processing, expecting to elucidate the mechanism and active components for the anti-diarrhea effect, further interpreting the scientific connotation of the theory for the stir-heating with salt solution of CSAO, and then providing a new idea for investigations on drug processing by common techniques in stir-heating with salt solution.
Methods
The methods used in the research of the scientific connotation of the theory for the stir-heated CSAO with salt solution are philological, pharmacological and chemical means.
1. Systemically arrange the documents about the processing methods of the past and follow up the modern report timely by philological means in order to recognize the history and actuality of CSAO.
2. Study the pharmacodynamics and elucidate the possible mechanism by pharmacological means in order to recognize the effect of warming the spleen and anti-diarrhea.
3. The active fraction with the anti-diarrhea effect of CSAO was screened and prepared in order to recognize the active components of CSAO for anti-diarrhea. The initial investigations were carried out on the chemical means.
4. The differences that indicate in pharmacological effects and in the chemical compositions of CSAO and SSAO were focused.
Results
1. The results showed that CSAO could protect the mice from diarrhea induced by Folium Sennae, inhibit HCl/ethanol-induced gastric ulcers in rats, delay the gastric emptying and the small intestinal in mice, depress the contraction of duodenum of rabbits in vitro, and depress the content of GAS in serum, the content of VIP in plasm at the same time in rats of Spleen Deficiency.
2. The results showed that the active fraction of the anti-diarrhea effect of CSAO was volatile oil fraction or the extracted fraction of petroleum ether and chloroform. Nootkatone,β-sitosterol, Yakuchinone A, Oxyphyllol B and Daucosterol were isolated and identified from the active fraction. Nootkatone inhibited HCl/ethanol-induced gastric ulcer in rats, and Yakuchinone A depressed the contraction of duodenum of rabbits in vitro.
3. The results showed that CSAO and SSAO could also protect the mice from diarrhea induced by Folium Sennae, and depress the contraction of duodenum of rabbits in vitro, there is no distinctly difference between CSAO and SSAO, but the decoction of CSAO showed a stronger effect than the decoction of SSAO, at the same time, there is no distinctly change of content of volatile oil and Nootkatone between CSAO and SSAO, but the decoction of CSAO contain more volatile oil and Nootkatone than the decoction of SSAO.
4. After stir-heating with salt solution, the water in seeds fell, the texture became more crumble, the comminuted powder became small, at the same time, surface of the seeds was fragmented, the inner structure became more loosened, so active components can dissolve more into decoction in a shorter time. As a result, there is an increasing loss of the components in the decoction of SSAO.
Conclusions
1. CSAO has certain effect of warming the spleen and anti-diarrhea, the action mechanism lies in the depression of gastrointestinal movement and the depression of the content of gastrointestinal hormone.
2. The active fraction with the anti-diarrhea effect of CSAO was volatile oil fraction or the extracted fraction of petroleum ether and chloroform. Nootkatone and Yakuchinone A are both of the active components of CSAO for anti-diarrhea.
3. CSAO and SSAO could both protect the mice from diarrhea, but the decoction of CSAO showed a stronger effect than the decoction of SSAO. The result accorded with the TCM theory of'CSAO acts on spleen channel.'
Innovations
1. Elucidate the mechanisms of CSAO for anti-diarrhea initially, provide the pharmacological explanation for its effect of warming the spleen and anti-diarrhea, and provide a reasonable instruction of using CSAO afterwards.
2. Elucidate the active components of CSAO for anti-diarrhea initially, provide the reference for establishing a more reasonable quality standard of CSAO.
3. Elucidate the influence on CSAO by stir-heating with salt solution, provide the reference for further interpreting the scientific connotation of the theory for the stir-heating with salt solution of CSAO, and also provide a new idea for the investigations on the drug processing by common techniques in stir-heating with salt solution.
引文
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