桑白皮化学成分的研究
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摘要
中药材桑白皮为桑科植物桑Morus alba L.除去栓皮的干燥根皮。别称桑皮，桑根皮，桑根白皮等。是一种常用的中药，味甘，苦，性寒，主治肺热喘咳、水肿、腹胀、尿少等症。
桑白皮的化学成分以Diels-Alder型加合物及黄酮类化合物为主，此外还有萜类、香豆素类、糖类、甾醇类、挥发油类等。
本实验以桑白皮为原料，利用85%乙醇加热回流提取，提取物经柱层析（硅胶，ODS，葡聚糖凝胶，聚酰胺）分离和重结晶等手段，得到6个单体化合物。结合它们的理化性质，并利用各种波谱学手段（核磁共振，质谱等），鉴定了这6个化合物的结构，分别是桑呋喃G（mulberrofuran G），环桑黄酮（cyclomorusin），α-香树脂醇（α-amyranol），熊果酸（Ursolic acid），β-谷甾醇（sitosterol）和2,6,8,10-四甲基-6,10-环氧-[3.2.2]三环十一烷（2,6,8,10-butamethyl-6,10-epoxy-[3.2.2]tricycloundecane）。其中2,6,8,10-四甲基-6,10-环氧-[3.2.2]三环十一烷为首次从桑白皮中分得。
本实验还建立了桑白皮中桑呋喃G的HPLC测定方法。
本实验深入研究了桑白皮中主要的化学成分，建立了桑白皮特征成分的HPLC测定方法，为桑白皮质量标准的完善提供了含量测定指标，也为桑白皮的开发应用提供了新的科学依据。
Cortex Mori radicis is a traditional Chinese medicine, which is the dry roots ofMorus alba L.. A series of chemical investigations revealed that Diels-Alder typeadduct compounds and flavonoid were the major compositions of Morus alba L.. Inaddition, there are coumarins and terpenoid as well as sterols in it. It clinically usedin the treatment of edema, pleuritis, trachitis, pertussis and diabetes mellitus etc.
In this research, six compounds were seperated from the roots of Morus alba L..Various spectral methods, such as NMR, MS, IR and UV, were used to identify theirstructures, and they were elucidated as mulberrofuran G (S1), cyclomorusin (S2),α-amyranol(S3), Ursolic acidl (S4), sitosterol (S5)and (2,6,8,10-butamethyl-6,10-epoxy-[3.2.2]tricycloundecane.
In this paper, the quantification analytical method of Diels-Alder type adduct (S1)using HPLC were also investigated in order to improve the quality standards for theroots of Cortex Mori radicis.Extraction, separation and identification
20kilograms of dried roots of Morus alba L. were crushed and extracted by heatreflux in85%ethanol (the volume fraction,160L) three times (1.5h,1.0h and0.5hrespectively). The combined extracted soluion was evaporated to dryness, then it wasdiluted with water and flowed through the anion-exchange column andcation-exchange column. After that, the efflux was concentrated and extracted byn-butanol and the solvent was recovered,900g of extraction was obtained. By usingsilica gel, polyamide and ODS column chromatography repeatedly, six compoundspreviously described were separated. The mobile phase was made of methanol,petroleum ether, ethyl acetate, chloroform and so on in certain ratio. Combine theirphysical and chemical properties, IR, UV, MS and NMR were used to identifystructures of the compounds isolated after comparing with the literature reports.
Structures of the six isolated compounds were identified, they aremulberrofuran G (S1), cyclomorusin (S2), α-amyranol(S3), Ursolic acidl (S4),sitosterol (S5) and2,6,8,10-butamethyl-6,10-epoxy-[3.2.2] tricycloundecane (S6).Contents determination of mulberrofuran G
The research was performed on Agilent1200HPLC instrument and EclipseXDB-C18coloum (4.6×250mm,5μm), using a mixture of methanol-0.1%Aceticacid in ratio of55:45as the mobile phase. The flow rate was1.0mL.min-1at35℃,the wavelength of VWD detector was set at220nm.
Results
Ⅰ Theoretical plate number and Resolution
The Theoretical plate number of mulberrofuran G was16373；The Resolution ofmulberrofuran G was1.61.
Ⅱ Precision test
Solution of mulberrofuran G was injected into HPLC for six times in one day, theRSD of peak area and retention time for mulberrofuran G were0.15%and0.37%.
Ⅲ The standard curve
The linearity was in the range of0.1～10μg for mulberrofuran G, and thecorrelation coefficients was1.0000. The regression equations wasY=3548.9X+44.596.
Ⅳ Repeatability
Six copies of the sample solution were injected into HPLC, the RSD of peak areaand content for mulberrofuran G was1.77%and2.50%respectively.
Ⅴ Stability test
The same sample solution was injected into HPLC in2h,4h,6h,8h,10h and12h,the RSD of peak area and retention time for mulberrofuran G were0.22%and0.20%respectively.
Ⅵ LOD and LOQ
For mulberrofuran G，the experiment gave their detection limi（tLOD）in0.02ng and quantification limit(LOQ) in0.06ng.
Ⅶ Recovries
The average recovery for mulberrofuran G was100.93%and the RSD (n=6) was2.11%.
Ⅷ Contents determination of samples
Five batches of samples of the roots of Morus alba L. were determined, and theresults showed that the average content of mulberrofuran G was0.018%、0.022%、0.014%、0.024%、0.024%, respectively.
In this paper, the chemical constituents of Cortex Mori radicis was furtherlystudied, and new index of content determination was offered to perfect qualitystandard of the roots of Morus alba L.. The results of this paper provided atheoretical support for further study and a scientific basis for development andutilization of Cortex Mori radicis.
桑白皮的化学成分以Diels-Alder型加合物及黄酮类化合物为主，此外还有萜类、香豆素类、糖类、甾醇类、挥发油类等。
本实验以桑白皮为原料，利用85%乙醇加热回流提取，提取物经柱层析（硅胶，ODS，葡聚糖凝胶，聚酰胺）分离和重结晶等手段，得到6个单体化合物。结合它们的理化性质，并利用各种波谱学手段（核磁共振，质谱等），鉴定了这6个化合物的结构，分别是桑呋喃G（mulberrofuran G），环桑黄酮（cyclomorusin），α-香树脂醇（α-amyranol），熊果酸（Ursolic acid），β-谷甾醇（sitosterol）和2,6,8,10-四甲基-6,10-环氧-[3.2.2]三环十一烷（2,6,8,10-butamethyl-6,10-epoxy-[3.2.2]tricycloundecane）。其中2,6,8,10-四甲基-6,10-环氧-[3.2.2]三环十一烷为首次从桑白皮中分得。
本实验还建立了桑白皮中桑呋喃G的HPLC测定方法。
本实验深入研究了桑白皮中主要的化学成分，建立了桑白皮特征成分的HPLC测定方法，为桑白皮质量标准的完善提供了含量测定指标，也为桑白皮的开发应用提供了新的科学依据。
Cortex Mori radicis is a traditional Chinese medicine, which is the dry roots ofMorus alba L.. A series of chemical investigations revealed that Diels-Alder typeadduct compounds and flavonoid were the major compositions of Morus alba L.. Inaddition, there are coumarins and terpenoid as well as sterols in it. It clinically usedin the treatment of edema, pleuritis, trachitis, pertussis and diabetes mellitus etc.
In this research, six compounds were seperated from the roots of Morus alba L..Various spectral methods, such as NMR, MS, IR and UV, were used to identify theirstructures, and they were elucidated as mulberrofuran G (S1), cyclomorusin (S2),α-amyranol(S3), Ursolic acidl (S4), sitosterol (S5)and (2,6,8,10-butamethyl-6,10-epoxy-[3.2.2]tricycloundecane.
In this paper, the quantification analytical method of Diels-Alder type adduct (S1)using HPLC were also investigated in order to improve the quality standards for theroots of Cortex Mori radicis.Extraction, separation and identification
20kilograms of dried roots of Morus alba L. were crushed and extracted by heatreflux in85%ethanol (the volume fraction,160L) three times (1.5h,1.0h and0.5hrespectively). The combined extracted soluion was evaporated to dryness, then it wasdiluted with water and flowed through the anion-exchange column andcation-exchange column. After that, the efflux was concentrated and extracted byn-butanol and the solvent was recovered,900g of extraction was obtained. By usingsilica gel, polyamide and ODS column chromatography repeatedly, six compoundspreviously described were separated. The mobile phase was made of methanol,petroleum ether, ethyl acetate, chloroform and so on in certain ratio. Combine theirphysical and chemical properties, IR, UV, MS and NMR were used to identifystructures of the compounds isolated after comparing with the literature reports.
Structures of the six isolated compounds were identified, they aremulberrofuran G (S1), cyclomorusin (S2), α-amyranol(S3), Ursolic acidl (S4),sitosterol (S5) and2,6,8,10-butamethyl-6,10-epoxy-[3.2.2] tricycloundecane (S6).Contents determination of mulberrofuran G
The research was performed on Agilent1200HPLC instrument and EclipseXDB-C18coloum (4.6×250mm,5μm), using a mixture of methanol-0.1%Aceticacid in ratio of55:45as the mobile phase. The flow rate was1.0mL.min-1at35℃,the wavelength of VWD detector was set at220nm.
Results
Ⅰ Theoretical plate number and Resolution
The Theoretical plate number of mulberrofuran G was16373；The Resolution ofmulberrofuran G was1.61.
Ⅱ Precision test
Solution of mulberrofuran G was injected into HPLC for six times in one day, theRSD of peak area and retention time for mulberrofuran G were0.15%and0.37%.
Ⅲ The standard curve
The linearity was in the range of0.1～10μg for mulberrofuran G, and thecorrelation coefficients was1.0000. The regression equations wasY=3548.9X+44.596.
Ⅳ Repeatability
Six copies of the sample solution were injected into HPLC, the RSD of peak areaand content for mulberrofuran G was1.77%and2.50%respectively.
Ⅴ Stability test
The same sample solution was injected into HPLC in2h,4h,6h,8h,10h and12h,the RSD of peak area and retention time for mulberrofuran G were0.22%and0.20%respectively.
Ⅵ LOD and LOQ
For mulberrofuran G，the experiment gave their detection limi（tLOD）in0.02ng and quantification limit(LOQ) in0.06ng.
Ⅶ Recovries
The average recovery for mulberrofuran G was100.93%and the RSD (n=6) was2.11%.
Ⅷ Contents determination of samples
Five batches of samples of the roots of Morus alba L. were determined, and theresults showed that the average content of mulberrofuran G was0.018%、0.022%、0.014%、0.024%、0.024%, respectively.
In this paper, the chemical constituents of Cortex Mori radicis was furtherlystudied, and new index of content determination was offered to perfect qualitystandard of the roots of Morus alba L.. The results of this paper provided atheoretical support for further study and a scientific basis for development andutilization of Cortex Mori radicis.
引文
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