基于代谢框架和鲜药材的炮制“幼朴”与厚朴的等效性研究
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摘要
厚朴是我国传统药材,为木兰科植物厚朴(Magnolia offcinalis Rehd.et Wils.)或凹叶厚朴(Magnolia officinalis Rehd.et Wils.var.biloba Rehd.et Wils.)的干燥干皮、根皮和枝皮。由于木本药材生长周期太长,突发需求时,给资源安全将带来隐患。本论文主要以鲜药材为样本,基于植物代谢组学的技术创新性提出“代谢框架”的构想,通过研究厚朴不同部位中厚朴总酚代谢积累的数据表征,提出获取幼龄厚朴(简称“幼朴”)的根皮为资源的最佳利用方式,并对“幼朴”与传统厚朴进行化学、药效、毒理、临床等效性比较研究。在此基础上结合其他相关资源的研究,尝试性基于“代谢框架”和鲜药材初加工的中药资源高效利用观点。
本论文实验得到以下实验结果：
(1)以厚朴酚、和厚朴酚为指标成分,研究厚朴总酚(厚朴酚及和厚朴酚)在不同生长年份,在根、茎、枝皮中代谢积累的数据表征,确定使用2-5年生“幼朴”的根皮作为获取厚朴总酚的最佳原料来源方式。
(2)优选3年生“幼朴”的根皮代替10年以上生传统厚朴作为中药资源。
(3)用气相色谱法分离并经质谱扫描分析,证实“幼朴”、根朴,甚至包括筒朴在挥发性化学成分组成上没有明显差异。
(4)急性经口毒性实验表明,“幼朴”与厚朴的水提取物和醇提取物的最大耐受剂量为200 g·kg-1(以原药材计),毒性也无显著性差异。
(5)以“厚朴三物汤”为载体,小鼠胃肠功能药效实验证实,”幼朴”与传统厚朴入药对正常小鼠及便秘型小鼠的肠道功能作用相当。
(6)以“厚朴三物汤”为载体,临床观察对老年功能性便秘热结型的治疗作用,显示“幼朴”与传统厚朴入药治疗有效率相当,两组临床均无不良反应发生,表明“幼朴”与厚朴在临床上具有等效性。
(7)通过对博落回、小果博落回、黄芩、葡萄等植物中的目标成分在不同部位代谢积累数据表征的研究,进一步佐证了基于“代谢框架’和鲜药材初加工的中药资源高效利用思路的合理性。
Magnolia is a traditional Chinese herb medicine, which is the dried parts of stem bark, root bark and branch bark of Magnolia officinalis Rehd.et Wils. or Magnolia officinalis Rehd.et wils.var.biloba Rehd.et Wils.. The severe situation of resource scarcity gradually becomes worse and worse as its broad usage. This thesis is intended to study the process method and resource utilize method primarily basing on the fresh herbs and through the way of plant metabolomics technology to analyze the data which accumulated by metabolism of magnolol and Honokiol in Magnolia. This study brings forward the conception of "Metabolic framework" for the first time, and conduct a comparative research on chemical, pharmacological, toxicological and clinical equivalence of traditional Magnolia and "Young Magnolia", which is intented to explore the high efficiency on the basis of "Metabolic framework" and fresh herbs in conjunction with the research of related resources so as to make the best of Chinese medicine resources.
We got the following results from the experiments related to this thesis.
(1) We use the magnolol and honokiol as the marker compounds, and prove that the uses of 2 to 5 years old "Young Magnolia" to replace traditional Magnolia as alternative sources of raw materials is feasible.
(2) Comprehensively consideration of the technical feasibility of choosing 3-year-old "Young Magnolia" to replace 10 or more years of traditional Magnolia as alternative source of raw materials so as to obtain total magnolol and Honokiol quickly and efficiently.
(3) After the separation of gas chromatography and scan by mass spectrometry, we can draw the conclusion that there were very little difference in volatile chemical compositions between both root bark and stem bark of "Young Magnolia",.
(4) From the experiment we can draw the conclusion that "Young Magnolia" Sanwu Decotion and traditional Houpu Sanwu Decoction had equivalent medical effects.
(5) We found no toxicity in water extracts and alcohol extracts of "Young Magnolia" and traditional Magnolia in the experiment of acute oral toxicity, and the maximum tolerated dose is 200g·kg-1(the original ingredients of dollars).
(6) In the clinical observation of Magnolia Bark Sanwu Decotion's medical effects on hot functional constipation of the elder patients, we found similar clinical treatment efficiency for "Young Magnolia" Houpu Sanwu Decoction group and traditional Houpu Sanwu Decoction group and there were no adverse reactions occurred.
(7) Further experiments shall be conducted from every aspect on other representative plants such as Macleaya cordata, Macleaya microcarpa, Scutellaria, and Grape etc.. to explain in detail based on "metabolic framework" and fresh herbs of traditional Chinese medicine resources and use patterns of thinking.
本论文实验得到以下实验结果：
(1)以厚朴酚、和厚朴酚为指标成分,研究厚朴总酚(厚朴酚及和厚朴酚)在不同生长年份,在根、茎、枝皮中代谢积累的数据表征,确定使用2-5年生“幼朴”的根皮作为获取厚朴总酚的最佳原料来源方式。
(2)优选3年生“幼朴”的根皮代替10年以上生传统厚朴作为中药资源。
(3)用气相色谱法分离并经质谱扫描分析,证实“幼朴”、根朴,甚至包括筒朴在挥发性化学成分组成上没有明显差异。
(4)急性经口毒性实验表明,“幼朴”与厚朴的水提取物和醇提取物的最大耐受剂量为200 g·kg-1(以原药材计),毒性也无显著性差异。
(5)以“厚朴三物汤”为载体,小鼠胃肠功能药效实验证实,”幼朴”与传统厚朴入药对正常小鼠及便秘型小鼠的肠道功能作用相当。
(6)以“厚朴三物汤”为载体,临床观察对老年功能性便秘热结型的治疗作用,显示“幼朴”与传统厚朴入药治疗有效率相当,两组临床均无不良反应发生,表明“幼朴”与厚朴在临床上具有等效性。
(7)通过对博落回、小果博落回、黄芩、葡萄等植物中的目标成分在不同部位代谢积累数据表征的研究,进一步佐证了基于“代谢框架’和鲜药材初加工的中药资源高效利用思路的合理性。
Magnolia is a traditional Chinese herb medicine, which is the dried parts of stem bark, root bark and branch bark of Magnolia officinalis Rehd.et Wils. or Magnolia officinalis Rehd.et wils.var.biloba Rehd.et Wils.. The severe situation of resource scarcity gradually becomes worse and worse as its broad usage. This thesis is intended to study the process method and resource utilize method primarily basing on the fresh herbs and through the way of plant metabolomics technology to analyze the data which accumulated by metabolism of magnolol and Honokiol in Magnolia. This study brings forward the conception of "Metabolic framework" for the first time, and conduct a comparative research on chemical, pharmacological, toxicological and clinical equivalence of traditional Magnolia and "Young Magnolia", which is intented to explore the high efficiency on the basis of "Metabolic framework" and fresh herbs in conjunction with the research of related resources so as to make the best of Chinese medicine resources.
We got the following results from the experiments related to this thesis.
(1) We use the magnolol and honokiol as the marker compounds, and prove that the uses of 2 to 5 years old "Young Magnolia" to replace traditional Magnolia as alternative sources of raw materials is feasible.
(2) Comprehensively consideration of the technical feasibility of choosing 3-year-old "Young Magnolia" to replace 10 or more years of traditional Magnolia as alternative source of raw materials so as to obtain total magnolol and Honokiol quickly and efficiently.
(3) After the separation of gas chromatography and scan by mass spectrometry, we can draw the conclusion that there were very little difference in volatile chemical compositions between both root bark and stem bark of "Young Magnolia",.
(4) From the experiment we can draw the conclusion that "Young Magnolia" Sanwu Decotion and traditional Houpu Sanwu Decoction had equivalent medical effects.
(5) We found no toxicity in water extracts and alcohol extracts of "Young Magnolia" and traditional Magnolia in the experiment of acute oral toxicity, and the maximum tolerated dose is 200g·kg-1(the original ingredients of dollars).
(6) In the clinical observation of Magnolia Bark Sanwu Decotion's medical effects on hot functional constipation of the elder patients, we found similar clinical treatment efficiency for "Young Magnolia" Houpu Sanwu Decoction group and traditional Houpu Sanwu Decoction group and there were no adverse reactions occurred.
(7) Further experiments shall be conducted from every aspect on other representative plants such as Macleaya cordata, Macleaya microcarpa, Scutellaria, and Grape etc.. to explain in detail based on "metabolic framework" and fresh herbs of traditional Chinese medicine resources and use patterns of thinking.
引文
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