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<p><i>Salvia hispanica</i> L. (<i>chia</i>) seeds are recognized as a functional food rich in phenolic compounds, yet the mechanistic basis linking their chemical profile with antidiabetic activity remains insufficiently defined. To evaluate the antioxidant properties, α-glucosidase inhibition, antihyperglycemic and hypoglycemic responses of <i>chia</i> seed extracts of increasing polarity, and to characterize their major phenolics using UPLC-DAD-ESI-MS and molecular docking. <i>n</i>-hexane, dichloromethane, and methanolic extracts were assessed in normoglycemic Wistar rats using an oral sucrose tolerance test and an acute hypoglycemia model. In vitro inhibition of maltase, sucrase, and starch-degrading enzymes was quantified. Total phenolic content and antioxidant activity were determined by Folin–Ciocalteu, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. UPLC-DAD-ESI-MS tentatively identified phenolic constituents, and molecular docking was performed against α-glucosidase catalytic domains. The methanolic extract (<i>MESh</i>) exhibited the highest phenolic content and antioxidant activity, a phenolic profile dominated by rosmarinic acid, caffeic acid, and their hexosides, and the strongest antihyperglycemic effect, producing a glycemic curve comparable to acarbose. <i>MESh</i> moderately inhibited sucrase (61.5%), while the dichloromethane extracts moderately inhibited maltase (62.9%). Docking analyses revealed that rosmarinic acid and its hexoside displayed high binding affinities (–7.7 to − 8.1 kcal/mol) toward α-glucosidase targets, closely approaching those of acarbose (–7.9 to − 9.1 kcal/mol) and exceeding those of caffeic-acid derivatives, supporting their potential contribution to the in vitro and in vivo responses. <i>Chia</i> seed extracts exhibit complementary antidiabetic-related activities involving antioxidant effects, modulation of intestinal α-glucosidases, and attenuation of postprandial glycemic excursions. Rosmarinic-acid derivatives emerge as key contributors to these effects. These findings reinforce <i>S. hispanica</i> as a promising functional food for glycemic regulation.</p>

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Unlocking the Role of Chia (Salvia hispanica L.) Seed Phenolic Metabolites in Postprandial Glucose Modulation: in vitro, in vivo, and Antioxidant Evidence Supported by Molecular Docking

  • 期刊论文

  • 发表日期：

    2026年6月18日

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  • Luis Alfredo Herbert-Doctor,
  • Jesús Alfredo Araujo-León,
  • Rolffy Ortiz-Andrade,
  • Maricarmen Bleis-Uc,
  • Itzell A. Gallardo-Ortiz,
  • Julio E. Oney-Montalvo,
  • Sergio Hidalgo-Figueroa,
  • Zhelmy Martín-Quintal,
  • Emanuel Herrera-Pool,
  • Neith Pacheco,
  • Luis Manuel Peña-Rodríguez

摘要

Salvia hispanica L. (chia) seeds are recognized as a functional food rich in phenolic compounds, yet the mechanistic basis linking their chemical profile with antidiabetic activity remains insufficiently defined. To evaluate the antioxidant properties, α-glucosidase inhibition, antihyperglycemic and hypoglycemic responses of chia seed extracts of increasing polarity, and to characterize their major phenolics using UPLC-DAD-ESI-MS and molecular docking. n-hexane, dichloromethane, and methanolic extracts were assessed in normoglycemic Wistar rats using an oral sucrose tolerance test and an acute hypoglycemia model. In vitro inhibition of maltase, sucrase, and starch-degrading enzymes was quantified. Total phenolic content and antioxidant activity were determined by Folin–Ciocalteu, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. UPLC-DAD-ESI-MS tentatively identified phenolic constituents, and molecular docking was performed against α-glucosidase catalytic domains. The methanolic extract (MESh) exhibited the highest phenolic content and antioxidant activity, a phenolic profile dominated by rosmarinic acid, caffeic acid, and their hexosides, and the strongest antihyperglycemic effect, producing a glycemic curve comparable to acarbose. MESh moderately inhibited sucrase (61.5%), while the dichloromethane extracts moderately inhibited maltase (62.9%). Docking analyses revealed that rosmarinic acid and its hexoside displayed high binding affinities (–7.7 to − 8.1 kcal/mol) toward α-glucosidase targets, closely approaching those of acarbose (–7.9 to − 9.1 kcal/mol) and exceeding those of caffeic-acid derivatives, supporting their potential contribution to the in vitro and in vivo responses. Chia seed extracts exhibit complementary antidiabetic-related activities involving antioxidant effects, modulation of intestinal α-glucosidases, and attenuation of postprandial glycemic excursions. Rosmarinic-acid derivatives emerge as key contributors to these effects. These findings reinforce S. hispanica as a promising functional food for glycemic regulation.