Revealing the potential hypoglycaemic ingredients of Terminalia chebula Retz. by spectrum–effect relationship combining molecular docking and experimental validation

• Published in: Journal of functional foods Vol. 121; p. 106402
• Main Authors: Yan, Yahui, Abdulla, Rahima, Xin, Xuelei, Akber Aisa, Haji
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.10.2024; Elsevier
• Subjects: Hypoglycemic activity; Molecular docking; Spectrum–effect relationship; Terminalia chebula Retz; UHPLC-Q-Orbitrap-HRMS; Hypoglycemic activity; UHPLC-Q-Orbitrap-HRMS; Terminalia chebula Retz; Spectrum–effect relationship; Molecular docking
• ISSN: 1756-4646
• DOI: 10.1016/j.jff.2024.106402

[Display omitted] •The hypoglycemic chemical fingprints of T. chebula was characterized by LC–MS.•Six compounds are considered to be the potential quality markers of antidiabetic by spectrum–effect relationship.•Molecular docking revealed antidiabetic mechanism of chebulagic acid, punicalagin and chebulinic acid.•Punicalagin had potent andiabetes ability by inhibiting the activating the PI3K/AKT signaling pathway. Terminalia chebula Retz. is commonly used in the treatment of diabetes, but its specific ingredients and hypoglycaemic mechanisms remain unclear. In this study, spectrum-effect relationships between common peaks of fingerprint and DPPH, ABTS, PTP1B, α-glucosidase, were used to screen six compounds as the potential hypoglycemic ingredients. Molecular docking studies were conducted on chebulagic acid, chebulinic acid and punicalagin, which were identified by reference standard, revealing the potent in teractions between these bioactive substances and the PTP1B, α-glucosidase protein. Additionally, the cellular level results showed that punicalagin displayed stronger inhibition of PTP1B and α-glucosidase, with IC50 values of 0.0236 and 0.335 μg/mL, respectively, while improving glucose consumption and intracellular glycogen content of insult-resistant L6 muscle cell, and the hypoglycemic effect was achieved by activating the PI3K/AKT signaling pathway. This study demonstrated that T. chebula has the potential to become a hypoglycemic functional food, and offers a strategy for characterization hypoglycemic ingredients.