A trisaccharide phenylethanoid glycoside from Scrophularia flava Grau with potential anti-type 2 diabetic properties by inhibiting α-glucosidase enzyme and decreasing oxidative stress

Abstract

The Scrophularia genus is a rich source of phenylethanoid glycosides, with diverse biological activities including anti-diabetic properties. This study investigated anti-type 2 diabetic potential and active component of Scrophularia flava Grau. A new phenylethanoid glycoside was isolated from aerial parts of the plant and identified as 2-(4-hydroxy-3-methoxyphenyl) ethyl 6-deoxy-3-O-[(2E)-3-(3 hydroxy-4-methoxyphenyl) prop-2-enoyl]-α-rhamnopyranosyl-(1 → 3)-[α-rhamnopyranosyl-(1 → 6)]-4-O-[(2E)-3-(4-hydroxy-3-methoxyphenyl) prop-2-enoyl]-β-glucopyranoside. It was named flavaioside. The structure of flavaioside was identified based on ¹H NMR, ¹³C NMR, DEPT-HSQC, COSY, HMBC, NOESY and LC-ESI-MS-MS. Total methanol extract, fractions (A-F) and specific main phenylethanoid glycoside (flavaioside), were assessed for inhibitory effects against the α-glucosidase enzyme (in vitro anti-type 2 diabetic assay). The antioxidant activities of methanol extracts, all fractions and isolated flavaioside were identified based on 2, 2'-diphenyl-1-picrylhydrazyl radical (DPPH) scavenging activity, 2, 2'-azino-bis (3-ethylbenzothiazoline)-6-sulphonic acid radical cation (ABTS⁺) scavenging activity, phosphomolybdenum method, and metal chelating activity. In comparison to the other fractions, the best antioxidant result was observed in fraction E and its main compound, flavaioside, in DPPH (IC₅₀ = 4.26, 2.57 µg/mL) and ABTS⁺ (EC₅₀ = 55.45, 6.34 µg/mL) scavenging activities. Flavaioside showed significantly stronger activities than α-tocopherol and ascorbic acid in DPPH and ABTS⁺ assays. Furthermore, flavaioside showed a potent inhibitory activity on the α-glucosidase enzyme which was comparable with the known anti-type 2 diabetic drug, acarbose (91.85%, and 92.87%, respectively). Fraction E and flavaioside showed α-glucosidase inhibitory activities with IC₅₀ values, 65.05 and 6.50 µg/mL. The plant and its isolated flavaioside can possess acceptable anti-type 2 diabetic potential and anti-oxidant activity.

Keywords: Anti-diabetic; Antioxidant activity; Medicinal plant; Phenylethanoid glycoside; Phytochemical compound; Scrophulariaceae; Traditional medicine; α-glucosidase.