Rosmarinic acid improves intestinal barrier integrity through PI3K/AKT/Nrf2-mediated regulation of tight junction protein expression.
Level 5 - mechanism / opinion, no new human data
Preclinical animal and in vitro mechanism study with no human clinical data
PubMed 40834531 · doi:10.1016/j.intimp.2025.115380
What was done
Researchers evaluated the therapeutic effects and mechanism of rosmarinic acid (RA) in ulcerative colitis models. In vivo, RA was administered to mice with dextran sulfate sodium (DSS)-induced colitis to measure weight loss, colon length, histological inflammation, and tight junction protein levels (ZO-1, occludin, claudin-1). In vitro, lipopolysaccharide (LPS)-stimulated NCM460 human colonic epithelial cells were treated with RA with or without the pharmacological PI3K inhibitor LY294002 to assess PI3K/AKT signaling, AKT phosphorylation, and Nrf2 expression.
What was found
The abstract reports directional findings without numerical values. In mice with DSS-induced colitis, RA attenuated disease severity by mitigating weight loss, preventing colon shortening, and reducing histopathological inflammatory infiltration while upregulating tight junction proteins (ZO-1, occludin, claudin-1). In LPS-stimulated NCM460 cells, RA decreased AKT phosphorylation and enhanced Nrf2 expression. Pharmacological PI3K inhibition with LY294002 abolished RA-induced upregulation of Nrf2 and tight junction proteins.
Why it matters
This study delineates a specific mechanism (PI3K/AKT/Nrf2 modulation) by which rosmarinic acid preserves intestinal barrier integrity. It provides a preclinical rationale for exploring rosmarinic acid or downstream pathway targets in mucosal barrier disorders such as ulcerative colitis.
Limits
Findings are entirely derived from animal and cell culture models, which do not replicate the full complexity and chronicity of human ulcerative colitis. The abstract reports no numerical values, effect sizes, statistical confidence intervals, sample sizes (n), or dosing regimens. Clinical efficacy, pharmacokinetics, bioavailability, and human safety remain unstudied.
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