In Vitro Bioactivity of a Supercritical CO₂ Naringenin-Rich Lippia graveolens Extract on Diabetes-Related Metabolic...

A naringenin-rich extract was obtained from Mexican oregano (Lippia graveolens Kunth) by supercritical CO₂ extraction and subjected to simulated gastrointestinal digestion to evaluate its potential to mitigate oxidative stress, reduce nitric oxide (NO) production, and enhance glucose uptake, an indicator of insulin resistance. Even after the simulated digestion, the extracts still showed activity, as the digested supercritical extract showed cellular antioxidant activity in colorectal adenocarcinoma (Caco-2) cells higher than 80%, increased glucose uptake in hepatocellular carcinoma HepG2 cells with insulin resistance by 29.9% and decreased NO production in 38.1% in murine macrophages (RAW 264.7). The methanolic extract showed similar results but led to higher NO production. In general, supercritical CO₂ extraction yields higher flavonoid content in oregano extract than conventional methanolic extraction, as reflected in the biological activities; moreover, the green nature of the process supports the development of functional ingredients.