Insight into the Hypoglycemic Effects of Pinus nigra Arn. Bark Extracts Through In Silico and In Vivo Analysis

Diabetes mellitus is a major global health burden, and plant-derived polyphenols are increasingly explored as adjuncts for metabolic control. Hence, the hypoglycaemic potential of Pinus nigra bark extract from Serbia was evaluated using complementary in silico and in vivo approaches. Major constituents reported for P. nigra bark (catechin, epicatechin, taxifolin, caffeic, ferulic, p-coumaric, protocatechuic, and syringic acids) were docked against selected metabolic targets (LXRα, LXRβ, PTP1B, and SUR1) as hypothesis-generating screening due to the frequent PAINS behaviour of small polyphenols. For in vivo assessment, normoglycaemic and alloxan-induced diabetic Wistar rats received a 7-day oral treatment with ethanol bark extract (100 mg/kg) alone or combined with metformin (100 mg/kg) or gliclazide (10 mg/kg), and fasting glycaemia, oral glucose tolerance, lipid profile, and body weight were assessed. The ethanol extract reduced glycaemia, improved glucose tolerance, and favourably modulated dyslipidaemia, with additive effects observed in combinations with metformin or gliclazide. These findings suggest activity relevant to hypoglycaemic-relevant activity of P. nigra bark extract in vivo; however, comprehensive chemical profiling, mechanistic confirmation, and safety evaluation are required before translational consideration.