Bioassay-Guide Preparative Separation of Hypoglycemic Components from <i>Gynura divaricata</i> (L.) DC by Conventional and pH-Zone Refining Countercurrent Chromatography

<i>Gynura divaricata</i> (L.) DC is a long-used medicinal and edible plant in China folk. Its hyperglycemic effects have garnered increasing public attention in recent years. This study revealed that the ethyl acetate (EtOAc) and butanol (BuOH) partition fractions of <i>G. divarica...

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Main Authors: Zetao Shen, Jing Xu, Lijiao Wen, Lu Yin, Xueli Cao, Hairun Pei, Xi Zhao
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Foods
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Online Access:https://www.mdpi.com/2304-8158/14/4/578
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author Zetao Shen
Jing Xu
Lijiao Wen
Lu Yin
Xueli Cao
Hairun Pei
Xi Zhao
author_facet Zetao Shen
Jing Xu
Lijiao Wen
Lu Yin
Xueli Cao
Hairun Pei
Xi Zhao
author_sort Zetao Shen
collection DOAJ
description <i>Gynura divaricata</i> (L.) DC is a long-used medicinal and edible plant in China folk. Its hyperglycemic effects have garnered increasing public attention in recent years. This study revealed that the ethyl acetate (EtOAc) and butanol (BuOH) partition fractions of <i>G. divaricata</i> crude extract exhibited significantly higher α-glucosidase inhibition activity and enhanced glucose uptake ability compared to other fractions. Guided by the hypoglycemic bioassay, these two fractions were subjected to isolation of active compounds using high-speed countercurrent chromatography (HSCCC). A two-phase solvent system composed of hexane-methyl tert-butyl ether (MtBE)-methanol-0.1% TFA water was employed for the separation of the EtOAc fraction by conventional HSCCC through a gradient elution strategy. Five major compounds were obtained and identified as chlorogenic acid (1), 3,4-dicaffeoylquinic acid (2), 3,5-dicaffeoylquinic acid (3), 4,5-dicaffeoylquinic acid (4), and kaempferol-3-O-β-D-glucopyranoside (5) by ESI-MS, <sup>1</sup>HNMR, and <sup>13</sup>CNMR. The chlorogenic acid and the three dicaffeoylquinic acids were found to display higher inhibitory activities against α-glucosidase compared to the flavonoid. Considering their acidic nature, pH-zone-refining CCC (PHZCCC) was then applied for further scale-up separation using a solvent system MtBE: n-butanol: acetonitrile: water with trifluoroacetic acid (TFA) as a retainer and ammonium hydroxide (NH<sub>4</sub>OH) as an eluter. A significantly higher yield of chlorogenic acid was obtained from the BuOH fraction by PZRCCC. Molecular docking between the caffeoylquinic acids and α-glucosidase confirmed their hypoglycemic activities. This study demonstrates that CCC is a powerful tool for preparative separation of active constituents in natural products. This research presents a novel and effective method for the preparative isolation of hypoglycemic compounds from <i>Gynura divaricata.</i>
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spelling doaj-art-a86b41d5d76044eaa836f0b6ffa702af2025-08-20T03:12:02ZengMDPI AGFoods2304-81582025-02-0114457810.3390/foods14040578Bioassay-Guide Preparative Separation of Hypoglycemic Components from <i>Gynura divaricata</i> (L.) DC by Conventional and pH-Zone Refining Countercurrent ChromatographyZetao Shen0Jing Xu1Lijiao Wen2Lu Yin3Xueli Cao4Hairun Pei5Xi Zhao6Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, ChinaBeijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, ChinaBeijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, ChinaBeijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, ChinaBeijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, ChinaBeijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, ChinaBeijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China<i>Gynura divaricata</i> (L.) DC is a long-used medicinal and edible plant in China folk. Its hyperglycemic effects have garnered increasing public attention in recent years. This study revealed that the ethyl acetate (EtOAc) and butanol (BuOH) partition fractions of <i>G. divaricata</i> crude extract exhibited significantly higher α-glucosidase inhibition activity and enhanced glucose uptake ability compared to other fractions. Guided by the hypoglycemic bioassay, these two fractions were subjected to isolation of active compounds using high-speed countercurrent chromatography (HSCCC). A two-phase solvent system composed of hexane-methyl tert-butyl ether (MtBE)-methanol-0.1% TFA water was employed for the separation of the EtOAc fraction by conventional HSCCC through a gradient elution strategy. Five major compounds were obtained and identified as chlorogenic acid (1), 3,4-dicaffeoylquinic acid (2), 3,5-dicaffeoylquinic acid (3), 4,5-dicaffeoylquinic acid (4), and kaempferol-3-O-β-D-glucopyranoside (5) by ESI-MS, <sup>1</sup>HNMR, and <sup>13</sup>CNMR. The chlorogenic acid and the three dicaffeoylquinic acids were found to display higher inhibitory activities against α-glucosidase compared to the flavonoid. Considering their acidic nature, pH-zone-refining CCC (PHZCCC) was then applied for further scale-up separation using a solvent system MtBE: n-butanol: acetonitrile: water with trifluoroacetic acid (TFA) as a retainer and ammonium hydroxide (NH<sub>4</sub>OH) as an eluter. A significantly higher yield of chlorogenic acid was obtained from the BuOH fraction by PZRCCC. Molecular docking between the caffeoylquinic acids and α-glucosidase confirmed their hypoglycemic activities. This study demonstrates that CCC is a powerful tool for preparative separation of active constituents in natural products. This research presents a novel and effective method for the preparative isolation of hypoglycemic compounds from <i>Gynura divaricata.</i>https://www.mdpi.com/2304-8158/14/4/578<i>Gynura divaricata</i> (L.) DChigh-speed countercurrent chromatography (HSCCC)pH-zone refining CCCcaffeoylquinic acidshypoglycemic components
spellingShingle Zetao Shen
Jing Xu
Lijiao Wen
Lu Yin
Xueli Cao
Hairun Pei
Xi Zhao
Bioassay-Guide Preparative Separation of Hypoglycemic Components from <i>Gynura divaricata</i> (L.) DC by Conventional and pH-Zone Refining Countercurrent Chromatography
Foods
<i>Gynura divaricata</i> (L.) DC
high-speed countercurrent chromatography (HSCCC)
pH-zone refining CCC
caffeoylquinic acids
hypoglycemic components
title Bioassay-Guide Preparative Separation of Hypoglycemic Components from <i>Gynura divaricata</i> (L.) DC by Conventional and pH-Zone Refining Countercurrent Chromatography
title_full Bioassay-Guide Preparative Separation of Hypoglycemic Components from <i>Gynura divaricata</i> (L.) DC by Conventional and pH-Zone Refining Countercurrent Chromatography
title_fullStr Bioassay-Guide Preparative Separation of Hypoglycemic Components from <i>Gynura divaricata</i> (L.) DC by Conventional and pH-Zone Refining Countercurrent Chromatography
title_full_unstemmed Bioassay-Guide Preparative Separation of Hypoglycemic Components from <i>Gynura divaricata</i> (L.) DC by Conventional and pH-Zone Refining Countercurrent Chromatography
title_short Bioassay-Guide Preparative Separation of Hypoglycemic Components from <i>Gynura divaricata</i> (L.) DC by Conventional and pH-Zone Refining Countercurrent Chromatography
title_sort bioassay guide preparative separation of hypoglycemic components from i gynura divaricata i l dc by conventional and ph zone refining countercurrent chromatography
topic <i>Gynura divaricata</i> (L.) DC
high-speed countercurrent chromatography (HSCCC)
pH-zone refining CCC
caffeoylquinic acids
hypoglycemic components
url https://www.mdpi.com/2304-8158/14/4/578
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