Flavonoids and iridoids in the aerial parts of Vaccinium secundiflorum Hook. (Ericaceae): Insights into their antioxidant and antidiabetic activities

• Aerial parts of Vaccinium secundiflorum are traditionally used to treat diabetes. • Quercetin, isoquercetin, hyperoside, and rutin are main antioxidants in the extract. • Vaccinoside & 10- O-trans-p -coumaroyl-6α-hydroxydihydromonotropein are DPP-4 inhibitors. • Twenty-nine compounds were identified in the methanol extract by UHPLC-UV-HRMS-MS/MS. The aerial parts of Vaccinium secundiflorum Hook. (Ericaceae) are traditionally used by communities living near the Tapia forests of Madagascar to treat diabetes, diarrhoea, and stomach aches. Our previous research demonstrated that the methanolic extract this plant possesses both antioxidant and hypoglycaemic activities. To further investigate these preliminary findings, the present study aimed to isolate and identify the major bioactive compounds responsible for these pharmacological effects. Six compounds were isolated, including four flavonoids – quercetin ( A ), isoquercetin ( B ), hyperoside ( C ) and rutin ( D ) – and two iridoids – vaccinoside ( E ) and 10- O-trans-p -coumaroyl-6 α -hydroxydihydromonotropein ( F ). Their chemical structures were elucidated by spectroscopic techniques (UV, HRMS and NMR). Flavonoids A - D exhibited notable antioxidant activity against DPPH free radical, with IC 50 values of 34.37 ± 0.79, 50.47 ± 0.32, 49.48 ± 0.54, and 56.43 ± 0.52 µM, respectively. In contrast, iridoids E and F showed significant inhibitory activity against dipeptidyl peptidase-4 (DPP-4), a key enzyme involved in incretin degradation and established therapeutic target in diabetes, with IC 50 values of 52.24 ± 4.03 and 43.17 ± 1.19 µM, respectively. Additionally, phytochemical profiling of the methanolic extract using UHPLC-UV-HRMS-MS/MS tentatively identified twenty-nine compounds, including A - F , belonging to various chemical classes such as flavonoids, iridoids, tannins, lignans, organic acids, and other phenolic compounds. This study reports for the first time the DPP-4 inhibitory activity of vaccinoside ( E) and 10- O-trans-p -coumaroyl-6 α -hydroxydihydromonotropein ( F ), highlighting the therapeutic potential of V. secundiflorum as a natural source of antidiabetic agents.