苦木的化学成分及药理活性研究
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摘要
苦木为苦木科(Simaroubaceae)苦树属(Picrasma B1.)植物苦木Picrasma quassioides (D.Don) Benn.的干燥枝和叶。据2010版《中国药典》记载：苦木味苦,性寒,归肺和大肠经,具有清热、祛湿、解毒的功效,用于治疗咽喉肿痛、风热感冒、湿热泻痢、毒蛇咬伤、疥疮,湿疹等症。研究发现苦木中的化学成分主要为生物碱类和苦味素类,其次为挥发油、三萜、皂苷、甾醇、香豆素、醌类等。现代药理学研究表明,苦木还具有解热、降压、抗菌消炎、降低转氨酶、抗疟、抗蛇毒、抗癌、健胃等作用。本课题对苦木的化学成分、药理活性进行了研究,为苦木药材进一步应用提供了实验依据。
1苦木的化学成分研究
本实验将苦木药材粉碎后用80%的乙醇回流提取后,再采用传统柱色谱分离方法对其进行系统的分离,共得到7个化合物,通过薄层色谱、MS、UV、IR、H1NMR及C13NMR等方法鉴定了其结构,分别为：4-甲氧基-5-羟基-铁屎米酮,4,5-二甲氧基-铁屎米酮,5-甲氧基-铁屎米酮,1-甲氧-甲酰基-p-咔巴啉,3-甲基-铁屎米-2,6-二酮,胡萝卜苷和p-谷甾醇。此外,对其脂溶性生物总碱进行了HSCCC分离,得到了三个化合物,分别为4-甲氧基-5-羟基-铁屎米酮,1-甲氧-甲酰基-p-咔巴啉及3-甲基-铁屎米-2,6-二酮。最后,利用HPLC法对苦木中主要化学成分进行了定量分析,发现苦木中含量最高的生物碱为4-甲氧基-5-羟基-铁屎米酮,且大别山区的含量最高,本研究为苦木的药材质量控制提供了科学依据。
2苦木生物碱的生物活性研究
采用苦木总生物碱对SHR大鼠连续灌胃六周,通过无创血压测量分析系统定期测量大鼠血压发现,苦木总生物碱对SHR大鼠具有显著的降压作用,能降低大鼠的收缩压、舒张压及平均压,对心率没有显著影响。此外,通过血清药理学、组织病理学及免疫组化学实验发现苦木的降压机理可能是：通过升高eNOS的蛋白表达,促进内皮细胞合成释放血管舒张因子NO,使血管扩张,血压下降,同时减少AngⅡ的生成；通过提高抗氧化酶SOD的活性,减少脂质过氧化反应,在一定程度上保护内皮细胞。
采用苦木总生物碱对TNBS-乙醇溶液诱导的小鼠炎症性肠病进行治疗,通过检测细胞因子及结肠组织中MPO活性及COX-2、iNOS的表达,发现苦木具有降低血清中TNF-α、IL-8活性及结肠组织中MPO的活性,此外,还可抑制结肠中COX-2和iNOS的蛋白的表达,说明苦木通过发挥抗炎及免疫调节作用,对IBD小鼠组织损伤进行修复,本实验为进一步开发治疗IBD的新药提供研究基础。
Ku-mu is the dried branches and leaves of tree of Picrasma quassioides (D.Don) Benn., genus Picrasma B1., family Simaroubaceae. According to the2010edition of Chinese Pharmacopoeia, it has been used for the treatment of sore throat, cold, snakebite, scabies, eczema and so on. Studies find that alkaloids and picrasins are the major components of Picrasma quassioides (D.Don) Benn., following by volatile oil, triterpenes, saponins, sterols, coumarins and quinones. The modern pharmacology studies have shown that it also has antipyretic, antihypertensive, anti-bacterial, anti-inflammatory, anti-snake anti-malarial, anti-cancer activities as well as reducing transaminase. In our present study, we made research on the chemical components and pharmacological activities of Picrasma quassioides (D.Don) Benn., what we do may provide some references for the further studies and utilization of Picrasma quassioides (D.Don) Benn.
Part1Studies on the chemical components of PQB
Picrasma quassioides (D.Don) Benn was firstly extracted with80%ethanol by reflux, after evaporated the solvent, the dryness of the extracts were subjected to conventional column chromatography to separate the components, a total of seven compounds was separated and identified by TLC, MS, UV, IR, H1NMR and C13NMR methods, they are:4-methoxy-5-hydroxy-canthin,4,5-dimethoxy-canthin,5-methoxy-canthin,1-methoxy-formyl-P-carboline,3-methyl-canthin-2,6-dione, daucosterol and β-sitosterol. In addition, the total alkaloids of Picrasma quassioides (D.Don) Benn was then subjected to HSCCC to obtained three major compounds with high purities:4-methoxy-5-canthin,1-methoxy-formyl-β-carboline and3-methyl-canthin-2,6-dione. What's more, the HPLC method was used for quantitative analysis of the main chemical ingredient of Picrasma quassioides (D.Don) Benn, the result showed that4-methoxy-5-hydroxy-canthin had the highest concentrations in PQB and it was higher producing from Dabieshan, what we have done can offer scientific references for the quality control of the herbs.
Part2Studies on the biological activities of alkaloids from PQB
Extract from Picrasma quassiodes (D. Don) Benn. was administrated to SHR rats by gavage for six consecutive weeks, the blood pressures of the rats were measured with non-invasive blood pressure measurement system. Results showed that PQB had significant antihypertensive effect on SHR, it can reduce the systolic, diastolic, and mean pressure, but have no significant effect on heart rate of SHR. In addition, serum pharmacology, histopathology and immunohistochemistry experiment revealed that the mechanism of its antihypertensive effect may be:increasing expression of important proteins in NO pathway namely eNOS and improving NO availability which infers relaxation of the vessel wall to control blood pressure as well as reducing the Ang II activty; attenuating vascular oxidative stress via enhancing serum SOD activity and protecting endothelial cells to some extent.
PQB extract was administrated to mice with inflammatory bowel disease induced by TNBS-ethanol solution, the results from detection of serum cytokines> colonic tissue MPO activity and COX-2, iNOS expression showed that PQB could inhibited the pro-inflammatory mediator production such as IL-8and TNF-a as well as the reduced colonnic tissue levels of MPO activity. In addition, PQB may also restrain the protein expression of colonic COX-2and iNOS. All above experiment results suggested that PQB treatment could repair the IBD mice colon tissue injury through it anti-inflammatory and immunomodulatory effects, our experimental research provide evidence for the further study and therapeutic of IBD.
1苦木的化学成分研究
本实验将苦木药材粉碎后用80%的乙醇回流提取后,再采用传统柱色谱分离方法对其进行系统的分离,共得到7个化合物,通过薄层色谱、MS、UV、IR、H1NMR及C13NMR等方法鉴定了其结构,分别为：4-甲氧基-5-羟基-铁屎米酮,4,5-二甲氧基-铁屎米酮,5-甲氧基-铁屎米酮,1-甲氧-甲酰基-p-咔巴啉,3-甲基-铁屎米-2,6-二酮,胡萝卜苷和p-谷甾醇。此外,对其脂溶性生物总碱进行了HSCCC分离,得到了三个化合物,分别为4-甲氧基-5-羟基-铁屎米酮,1-甲氧-甲酰基-p-咔巴啉及3-甲基-铁屎米-2,6-二酮。最后,利用HPLC法对苦木中主要化学成分进行了定量分析,发现苦木中含量最高的生物碱为4-甲氧基-5-羟基-铁屎米酮,且大别山区的含量最高,本研究为苦木的药材质量控制提供了科学依据。
2苦木生物碱的生物活性研究
采用苦木总生物碱对SHR大鼠连续灌胃六周,通过无创血压测量分析系统定期测量大鼠血压发现,苦木总生物碱对SHR大鼠具有显著的降压作用,能降低大鼠的收缩压、舒张压及平均压,对心率没有显著影响。此外,通过血清药理学、组织病理学及免疫组化学实验发现苦木的降压机理可能是：通过升高eNOS的蛋白表达,促进内皮细胞合成释放血管舒张因子NO,使血管扩张,血压下降,同时减少AngⅡ的生成；通过提高抗氧化酶SOD的活性,减少脂质过氧化反应,在一定程度上保护内皮细胞。
采用苦木总生物碱对TNBS-乙醇溶液诱导的小鼠炎症性肠病进行治疗,通过检测细胞因子及结肠组织中MPO活性及COX-2、iNOS的表达,发现苦木具有降低血清中TNF-α、IL-8活性及结肠组织中MPO的活性,此外,还可抑制结肠中COX-2和iNOS的蛋白的表达,说明苦木通过发挥抗炎及免疫调节作用,对IBD小鼠组织损伤进行修复,本实验为进一步开发治疗IBD的新药提供研究基础。
Ku-mu is the dried branches and leaves of tree of Picrasma quassioides (D.Don) Benn., genus Picrasma B1., family Simaroubaceae. According to the2010edition of Chinese Pharmacopoeia, it has been used for the treatment of sore throat, cold, snakebite, scabies, eczema and so on. Studies find that alkaloids and picrasins are the major components of Picrasma quassioides (D.Don) Benn., following by volatile oil, triterpenes, saponins, sterols, coumarins and quinones. The modern pharmacology studies have shown that it also has antipyretic, antihypertensive, anti-bacterial, anti-inflammatory, anti-snake anti-malarial, anti-cancer activities as well as reducing transaminase. In our present study, we made research on the chemical components and pharmacological activities of Picrasma quassioides (D.Don) Benn., what we do may provide some references for the further studies and utilization of Picrasma quassioides (D.Don) Benn.
Part1Studies on the chemical components of PQB
Picrasma quassioides (D.Don) Benn was firstly extracted with80%ethanol by reflux, after evaporated the solvent, the dryness of the extracts were subjected to conventional column chromatography to separate the components, a total of seven compounds was separated and identified by TLC, MS, UV, IR, H1NMR and C13NMR methods, they are:4-methoxy-5-hydroxy-canthin,4,5-dimethoxy-canthin,5-methoxy-canthin,1-methoxy-formyl-P-carboline,3-methyl-canthin-2,6-dione, daucosterol and β-sitosterol. In addition, the total alkaloids of Picrasma quassioides (D.Don) Benn was then subjected to HSCCC to obtained three major compounds with high purities:4-methoxy-5-canthin,1-methoxy-formyl-β-carboline and3-methyl-canthin-2,6-dione. What's more, the HPLC method was used for quantitative analysis of the main chemical ingredient of Picrasma quassioides (D.Don) Benn, the result showed that4-methoxy-5-hydroxy-canthin had the highest concentrations in PQB and it was higher producing from Dabieshan, what we have done can offer scientific references for the quality control of the herbs.
Part2Studies on the biological activities of alkaloids from PQB
Extract from Picrasma quassiodes (D. Don) Benn. was administrated to SHR rats by gavage for six consecutive weeks, the blood pressures of the rats were measured with non-invasive blood pressure measurement system. Results showed that PQB had significant antihypertensive effect on SHR, it can reduce the systolic, diastolic, and mean pressure, but have no significant effect on heart rate of SHR. In addition, serum pharmacology, histopathology and immunohistochemistry experiment revealed that the mechanism of its antihypertensive effect may be:increasing expression of important proteins in NO pathway namely eNOS and improving NO availability which infers relaxation of the vessel wall to control blood pressure as well as reducing the Ang II activty; attenuating vascular oxidative stress via enhancing serum SOD activity and protecting endothelial cells to some extent.
PQB extract was administrated to mice with inflammatory bowel disease induced by TNBS-ethanol solution, the results from detection of serum cytokines> colonic tissue MPO activity and COX-2, iNOS expression showed that PQB could inhibited the pro-inflammatory mediator production such as IL-8and TNF-a as well as the reduced colonnic tissue levels of MPO activity. In addition, PQB may also restrain the protein expression of colonic COX-2and iNOS. All above experiment results suggested that PQB treatment could repair the IBD mice colon tissue injury through it anti-inflammatory and immunomodulatory effects, our experimental research provide evidence for the further study and therapeutic of IBD.
引文
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