Inflammatory bowel disease, which encompasses ulcerative colitis and Crohn’s disease, affects millions of people worldwide and is characterized by chronic, relapsing inflammation of the gastrointestinal tract. Current therapies, including corticosteroids, immunosuppressants, and biologics targeting tumor necrosis factor alpha, can be effective but often carry substantial side effects, high costs, and loss of efficacy over time. This therapeutic gap has driven intense interest in natural products, particularly polyphenol-rich plant extracts, that might modulate inflammation with fewer adverse consequences. Grapevine leaves have been used in traditional medicine across the Mediterranean for centuries, valued for their astringent and anti-inflammatory properties, but their potential in intestinal inflammation had remained largely unexplored in rigorous preclinical models.

The research team, led by Houssam Shaib with collaborators including Laura Dosh, Lara Diab, Rana Bou Khalil, and Abdo Jurjus, began by characterizing the phytochemical profile of grapevine leaves collected from Mount Lebanon. Using hydroethanolic extraction, a method that efficiently captures both water-soluble and alcohol-soluble compounds, they quantified the extract’s total phenolic content, condensed tannin levels, and antioxidant reducing power. The results were striking: the extract contained 63.3 milligrams of gallic acid equivalents per gram for total phenolics and 60.8 milligrams of catechin equivalents per gram for condensed tannins, both indicating a densely polyphenol-rich preparation. Reducing power activity, a measure of the extract’s capacity to donate electrons and neutralize reactive species, yielded an EC50 of 121.4 micrograms per milliliter, confirming substantial antioxidant capacity.

These measurements matter because oxidative stress is a central driver of intestinal inflammation. In colitis, infiltrating immune cells generate reactive oxygen species that damage epithelial cells lining the colon, breach the mucosal barrier, and allow luminal bacteria to trigger further immune activation. Polyphenols and condensed tannins can interrupt this cascade at multiple points, scavenging free radicals, chelating pro-oxidant metal ions, and modulating intracellular signaling pathways such as nuclear factor kappa B and mitogen-activated protein kinase, which orchestrate the transcription of inflammatory genes. The chemical profile of the Lebanese grapevine leaf extract therefore suggested it was well equipped to counter the oxidative and inflammatory damage characteristic of colitis.

To test this hypothesis, the researchers induced acute colitis in BALB/c mice using intrarectal administration of 2,4,6-trinitrobenzenesulfonic acid, or TNBS, a widely used haptenizing agent that provokes a T helper cell type 1 and type 17 driven inflammatory response closely mimicking aspects of human Crohn’s disease. TNBS damages the colonic epithelium and renders it immunogenic, unleashing a wave of inflammatory cytokines that recruit immune cells into the gut wall. Following induction, the mice received oral doses of the grapevine leaf extract at different concentrations, allowing the team to assess both efficacy and dose-response relationships.

The disease model performed as expected. TNBS-treated mice displayed marked intestinal inflammation, with increased colon weight reflecting edema and tissue thickening, dense infiltration of inflammatory cells, and visible epithelial damage. At the molecular level, the researchers observed significant upregulation of the genes encoding interleukin-17, interleukin-23, interferon gamma, and transforming growth factor beta, a cytokine signature that maps directly onto the IL-23/IL-17 axis now recognized as a pivotal pathway in inflammatory bowel disease. Biologic drugs targeting IL-17 and IL-23 have shown clinical benefit in patients, underscoring the relevance of this signaling axis as a therapeutic target.

Treatment with the grapevine leaf extract changed the picture dramatically. Mice receiving the extract showed significantly improved clinical signs and attenuated histopathological lesions, with reduced inflammatory cell infiltration and less epithelial injury compared with untreated colitic animals. Most notably, the 300 milligram per kilogram body weight dose demonstrated the strongest immunomodulatory effect, restoring inflammatory cytokine gene expression toward basal levels comparable to those of healthy control mice. This dose-dependent normalization of the IL-17, IL-23, IFN-gamma, and TGF-beta signature suggests that the extract does not merely mask symptoms but actively recalibrates the immune signaling underlying the disease process.

The authors analyzed parametric data using one-way analysis of variance with Tukey’s post hoc test, while non-parametric data such as disease scores and gene expression were evaluated with the Kruskal-Wallis test, providing statistical rigor appropriate to the mixed data types. All animal procedures were approved by the Institutional Animal Care and Use Committee of the American University of Beirut, and plant samples were collected from private land with the landowner’s explicit permission. The work was funded by the Farouk Jabre Grant at the American University of Beirut, and the authors declare no competing interests.

The implications extend beyond the laboratory. Grapevine leaves are an abundant agricultural residue generated in enormous quantities by the wine industry each pruning season, which means a therapeutic extract could be sourced sustainably and inexpensively from material that would otherwise be discarded. This aligns with growing interest in circular economy approaches to nutraceutical and pharmaceutical development, particularly in Mediterranean countries where both viticulture and inflammatory bowel disease intersect. A standardized grapevine leaf extract could, in principle, be developed as a complementary therapy for maintaining remission in inflammatory bowel disease patients or as a preventive agent in at-risk populations, though considerable work remains before such applications.

Important caveats temper the excitement. The study was conducted in an acute mouse model of chemically induced colitis, which, while valuable for dissecting inflammatory mechanisms, does not fully recapitulate the chronic, relapsing nature of human inflammatory bowel disease. Bioavailability of polyphenols and tannins in humans is often limited by poor absorption and rapid metabolism, and effective doses in mice do not translate directly to human dosing. Human clinical trials, chronic disease models, and detailed mechanistic studies identifying the specific active compounds within the extract will all be necessary. Nevertheless, the demonstration that a simple, traditionally used plant extract can restore a disease-driving cytokine profile to healthy baseline levels in vivo is a compelling proof of concept, and it adds grapevine leaves to the expanding pharmacopoeia of natural products under investigation for inflammatory disorders.

Subject of Research: Anti-inflammatory effects of grapevine leaf extract in a mouse model of TNBS-induced colitis

Article Title: Protective anti-inflammatory effects of Vitis vinifera leaf extract against TNBS-induced colitis in mice

Article References: Protective anti-inflammatory effects of Vitis vinifera leaf extract against TNBS-induced colitis in mice. (n.d.). https://doi.org/10.1186/s12906-026-05639-1

Image Credits: AI Generated

DOI: 10.1186/s12906-026-05639-1

Keywords: Vitis vinifera, grapevine leaf extract, colitis, TNBS, inflammatory bowel disease, cytokines, IL-17, IL-23, antioxidants, polyphenols, natural products, mouse model