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<p>Type 2 diabetes is characterized by postprandial hyperglycemia resulting from carbohydrate hydrolysis by α-glucosidase. However, the gradual decline in efficacy and the side effects of conventional α-glucosidase inhibitors have driven continued research into naturally occurring plant-derived alternatives. Within this context, unsaponifiable lipids have attracted increasing interest because of their health benefits and widespread use in dietary supplements and functional foods. Accordingly, this study evaluated the anti-α-glucosidase activity of unsaponifiable lipids from cold-pressed plum (<i>Prunus domestica</i> L) seed oil (UFPO) and elucidated their mechanism of action. Three subfractions 4-desmethyl sterols, 4-methylsterols, and policosanols were isolated from UFPO using TLC and characterized by GC/MS, leading to the identification of 13 compounds. The α-glucosidase inhibitory activity of the tested extracts, presented as the IC<sub>50</sub> values, ranged from 0.35 to 0.44&#xa0;mg/mL. Notably, total UFPO exhibited stronger inhibition than its individual subfractions, indicating a synergistic effect among unsaponifiable components. Among the subfractions, 4-desmethyl sterols showed the highest inhibitory activity (IC<sub>50</sub> = 0.38&#xa0;mg/mL), likely due to the predominance of β-sitosterol. Moreover, the combined UFPO–acarbose solution (1:1, v/v) produced the strongest inhibition (IC<sub>50</sub> = 0.24&#xa0;mg/mL), suggesting complementary effects. In silico analysis further demonstrated that the identified compounds form hydrogen and hydrophobic interactions within the enzyme active site, supporting their role as competitive inhibitors. In particular, policosanols established hydrogen bonding with key catalytic residues (Asp542 and Asp443). Accordingly, for the first time, this study evaluated the anti-α-glucosidase activity of unsaponifiable lipids from cold-pressed plum seed oil (UFPO) and elucidated their mechanism of action.</p> Graphical Abstract <p></p>

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Metabolomic profiling and evaluation of the in vitro and in silico antidiabetic potential of unsaponifiable matter isolated from cold-pressed plum seed oil

  • 期刊论文

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  • 发表日期：

    2026年5月8日

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  • Hamza Sakhri,
  • Cyrine Landolsi,
  • Moncef Feki,
  • Farah Hosseinian,
  • Saoussem Harrabi

摘要

Type 2 diabetes is characterized by postprandial hyperglycemia resulting from carbohydrate hydrolysis by α-glucosidase. However, the gradual decline in efficacy and the side effects of conventional α-glucosidase inhibitors have driven continued research into naturally occurring plant-derived alternatives. Within this context, unsaponifiable lipids have attracted increasing interest because of their health benefits and widespread use in dietary supplements and functional foods. Accordingly, this study evaluated the anti-α-glucosidase activity of unsaponifiable lipids from cold-pressed plum (Prunus domestica L) seed oil (UFPO) and elucidated their mechanism of action. Three subfractions 4-desmethyl sterols, 4-methylsterols, and policosanols were isolated from UFPO using TLC and characterized by GC/MS, leading to the identification of 13 compounds. The α-glucosidase inhibitory activity of the tested extracts, presented as the IC50 values, ranged from 0.35 to 0.44 mg/mL. Notably, total UFPO exhibited stronger inhibition than its individual subfractions, indicating a synergistic effect among unsaponifiable components. Among the subfractions, 4-desmethyl sterols showed the highest inhibitory activity (IC50 = 0.38 mg/mL), likely due to the predominance of β-sitosterol. Moreover, the combined UFPO–acarbose solution (1:1, v/v) produced the strongest inhibition (IC50 = 0.24 mg/mL), suggesting complementary effects. In silico analysis further demonstrated that the identified compounds form hydrogen and hydrophobic interactions within the enzyme active site, supporting their role as competitive inhibitors. In particular, policosanols established hydrogen bonding with key catalytic residues (Asp542 and Asp443). Accordingly, for the first time, this study evaluated the anti-α-glucosidase activity of unsaponifiable lipids from cold-pressed plum seed oil (UFPO) and elucidated their mechanism of action.

Graphical Abstract