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

**Authors:** Manuel Adrian Picos-Salas, Erika Ortega-Hernández, Luis Angel Cabanillas-Bojórquez, Nayely Leyva-López, Josefina León-Félix, Miguel Angel Angulo-Escalante, José Basilio Heredia, Marilena Antunes-Ricardo, Erick Paul Gutiérrez-Grijalva

PMC · DOI: 10.3390/molecules31050876 · Molecules · 2026-03-06

## TL;DR

This study shows that a supercritical CO2 extract from Mexican oregano can help reduce diabetes-related issues like oxidative stress and insulin resistance.

## Contribution

The novel contribution is demonstrating the bioactivity of a supercritical CO2 extract from Lippia graveolens after simulated digestion.

## Key findings

- The supercritical extract showed over 80% antioxidant activity in Caco-2 cells.
- It increased glucose uptake in HepG2 cells by 29.9% and reduced NO production by 38.1%.
- Supercritical CO2 extraction yielded higher flavonoid content than methanolic extraction.

## Abstract

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.

## Linked entities

- **Chemicals:** naringenin (PubChem CID 932)
- **Diseases:** diabetes (MONDO:0005015)
- **Species:** Lippia graveolens (taxon 1986359)

## Full-text entities

- **Diseases:** Metabolic Disturbances (MESH:D024821), colorectal adenocarcinoma (MESH:D003110), Diabetes (MESH:D003920), hepatocellular carcinoma (MESH:D006528), insulin resistance (MESH:D007333)
- **Chemicals:** glucose (MESH:D005947), CO2 (MESH:D002245), flavonoid (MESH:D005419), Naringenin (MESH:C005273), Lippia graveolens (-), NO (MESH:D009569)
- **Species:** Lippia graveolens (species) [taxon 1986359], Origanum vulgare (oregano, species) [taxon 39352], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12985424/full.md

## References

60 references — full list in the complete paper: https://tomesphere.com/paper/PMC12985424/full.md

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Source: https://tomesphere.com/paper/PMC12985424