Minthostachys verticillata aqueous extract ameliorates intestinal and systemic alterations induced by a model of...

Minthostachys verticillata (Griseb.) Epling (Lamiaceae), popularly known as Peperina (Mv), is a native plant widely used in traditional medicine as a digestive, sedative, antispasmodic, antidiarrheal, antiemetic, and carminative agent. However, its potential beneficial effects on intestinal and systemic changes induced by acute stress have not been fully elucidated.

To assess the effects of its aqueous extract on the gastrointestinal system in a rat model of acute restraint stress related to inflammatory intestinal pathologies.

Animals were treated for four consecutive days (n=6 per group) with Mv extract (250 and 500 mg/Kg p.o), clonazepam (1 mg/Kg p.o) or water. The acute stress model was induced by restraint for 6 hours in plastic cones adapted to the animal one hour after the last dose of the treatments. Control animals were not subjected to stress. Following the restraint period, animals were removed from the plastic cone and weighed. Glycemia and corticosterone were determined in plasma. Histological analysis and inflammatory and permeability markers were measured in colon and ileum samples.

Stressed animals exhibited elevated corticosterone levels and intestinal damage, including villous rupture, goblet cell depletion, and increased biogenic amines levels. Treatment with Mv extract prevented these alterations in the ileum and colon and improved short-chain fatty acid profiles, especially butyrate and acetate in the colon. Stress also increased the glutathione redox ratio, upregulated inflammatory markers (TNFα, IL-1β, IL-6, TGFβ) and PI3K/AKT pathway proteins in the colon, effects that were attenuated by the extract. Furthermore, markers associated with cytoskeletal uncoupling (pVASP) and extracellular matrix remodeling (MMP-2) were reduced by Mv, suggesting a protective effect against stress-induced mucosal structural and molecular alterations. No changes were observed in myeloperoxidase activity, indicating that neutrophils were likely not involved in the observed inflammatory response.

This study demonstrates, for the first time, the ability of Mv to reduce the imbalance induced by acute restraint stress. Mitigation of inflammatory cascades, preservation of goblet cell lineage, attenuation of markers associated with cytoskeletal uncoupling (pVASP) and extracellular matrix remodeling (MMP-2) markers, and maintenance of colonic short-chain fatty acids represent key protective mechanisms. These findings suggest that Mv could exert beneficial effects in stress-related intestinal disorders.