Polyphenol-rich infusions from Serra da Estrela Natural Park: Therapeutic potential for the management of inflammation and oxidative stress in diabetes mellitus

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Diabetes affects over one-tenth of adults worldwide, and oxidative stress and inflammation contribute to disease progression and complications. This study evaluated whether aqueous infusions of ethnopharmacologically selected plants from Portugal’s Serra da Estrela Natural Park can provide multi-target activities relevant to diabetes. Thirty-eight species were prepared as dried-plant infusions and screened for alpha-glucosidase inhibition by spectrophotometry; the most active infusions were defined by a half-maximal inhibitory concentration (IC 50 ). Fourteen lead infusions from 10 species were then assessed for total phenolic compounds (gallic acid equivalents) and radical-scavenging against 2,2-diphenyl-1-picrylhydrazyl (DPPH ● ), nitric oxide (NO ● ) and superoxide (O 2 ●− ). Cytotoxicity was evaluated in normal human dermal fibroblasts and HepG2 hepatocytes, and anti-inflammatory activity was assessed in lipopolysaccharide-stimulated RAW264.7 macrophages by measuring NO ● production. All 10 lead species produced infusions that met the threshold for α-glucosidase activity. Total phenolics ranged from 116.966 ± 1.326 to 336.393 ± 10.222 mg gallic acid equivalents/g dry weight and were accompanied by strong radical-scavenging (IC 50 < 50 μg/mL) across DPPH ● , NO ● and O 2 ●− assays. Sanguisorba minor and Viburnum tinus were non-cytotoxic up to 200 μg/mL, whereas Cistus salviifolius showed dose-dependent toxicity; notably, Viburnum tinus reduced macrophage NO ● production by >70% at 50 μg/mL. These findings identify Serra da Estrela infusions with combined enzyme-inhibitory, antioxidant and anti-inflammatory actions and support further standardisation and mechanistic validation for diabetes-oriented applications.