Helichrysum stoechas (L.) Moench (H. stoechas) is a medicinal plant traditionally used in the Iberian Peninsula to treat different disorders such as arterial hypertension. The aim of this study was to investigate the vascular effects of a polyphenolic methanolic extract of H. stoechas, which has high antioxidant activity, and its mechanism of action. Isometric myography studies were performed in an organ bath with rat aortic rings with intact endothelium. The H. stoechas extract produced vasorelaxation in the aortic rings that were precontracted by phenylephrine or KCl. L-NAME and Rp-8-Br-PET-cGMPS but not indomethacin or H-89; it also reduced the relaxant response evoked by H. stoechas extract on the phenylephrine-induced contractions. H. stoechas extract reduced the response to CaCl₂ similar to verapamil and reduced the phenylephrine-induced contractions comparable with heparin. TRAM-34, apamin and glibenclamide reduced relaxation induced by the H. stoechas extract. The combination of L-NAME+TRAM-34+apamin almost completely inhibited the H. stoechas-induced effect. In conclusion, the relaxant effect of the H. stoechas extract is partially mediated by endothelium through the activation of the NO/PKG/cGMP pathway and the opening of Ca²⁺-activated K⁺ channels. Furthermore, the decrease in the cytosolic Ca²⁺ by the inhibition of Ca²⁺ influx through the L-type Ca²⁺ channels and by the reduction of Ca²⁺ release from the sarcoplasmic reticulum via the IP₃ pathway is also involved.

Functional gastrointestinal diseases (FGID) are worldwide prevalent conditions. Pharmacological treatments can be ineffective, leading the population to turn to herbal or traditional remedies. Helichrysum stoechas (L.) Moench is a medicinal plant traditionally used in the Iberian Peninsula to treat digestive disorders, but its effects on gastrointestinal motility have not been scientifically demonstrated. The aim of this work was to evaluate the antispasmodic effect of a polyphenolic extract of H. stoechas (HSM), its mechanism of action and its antioxidant activity. Isometric myography studies were performed in rat ileum, and malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) levels were measured in rat jejunum. HSM reduced the integrated mechanical activity of spontaneous contractions. In Ca²⁺-free medium, HSM reduced the concentration–response curve of CaCl₂ similarly to verapamil. Pre-incubation with the extract blocked the contraction induced by Bay K8644, KCl and carbachol. L-NAME, ODQ, Rp-8-Br-PET-cGMPS, KT-5823, apamin, TRAM-34 and charybdotoxin reduced the relaxant effect of the extract on spontaneous contractions. MDA+4-HDA levels in LPS-treated tissue were reduced by the extract, showing antioxidant activity. In conclusion, HSM showed antispasmodic activity through inhibition of Ca²⁺ influx, activation of the NO/PKG/cGMP pathway and opening of Ca²⁺-activated K⁺ channels. The results suggest that H. stoechas could help in the prevention or treatment of FGIDs.

Inflammatory bowel disease is a gut–brain axis disorder that comprises chronic inflammatory conditions affecting the gastrointestinal tract, where alterations in the mood of patients are common. Gut–brain axis is a bidirectional communication that link gut and brain. The close association between inflammatory bowel disease and neuroinflammation has far-reaching implications, as is increasingly recognized as a contributing factor to neuropsychiatric and neurodegenerative diseases. The increasing prevalence and high economic cost, together with the loss of life quality of people suffering from these diseases, point to the need to find alternatives to alleviate them. Exploring new therapeutic avenues prompts us to consider the potential benefits of milk fractions, taking advantage of the use of dairy by-products, such as whey and buttermilk. This study examines the impact of cow’s whey- and buttermilk-based formulas supplemented with bovine lactoferrin and milk fat globule membrane on the expression of cytokines, as well as on the components of immune and serotonergic system of the brain in a murine model of dextran sodium sulfate-induced colitis. Our results show the potential of these dairy by-products, especially whey, as functional foods in ameliorating neuroinflammation and safeguarding the central nervous system function amid the neurological complications induced or concomitant with intestinal inflammatory processes.

Bovine lactoferrin (bLf) is a multifunctional milk glycoprotein with diverse biological activities pivotal for gastrointestinal health. This study investigates the modulatory effects of bLf on the intestinal serotonergic system and its implications for intestinal inflammation and homeostasis. Intestinal serotonergic system plays a critical role in gut homeostasis, regulating various physiological processes via serotonin (5-HT) signaling. Dysregulation of this system contributes to inflammatory bowel diseases, characterized by chronic inflammation and disrupted intestinal function. We evaluated the impact of bLf on the intestinal serotonergic system in vitro and in vivo. In Caco-2/TC7 cells, bLf treatment enhanced serotonin transporter (SERT) activity and mRNA expression and modulated the mRNA levels of several serotonin receptors (5-HTRs). In mice, oral bLf administration upregulated SERT, tryptophan hydroxylase 2 (TPH2), and 5-HTRs mRNA expression in the ileum. Moreover, in a dextran sodium sulphate (DSS)-induced colitis model, bLf attenuated clinical signs of colonic inflammation, while normalizing the mRNA expression of SERT, TPH1, TPH2, and 5-HTRs in colon. These findings highlight the ability of bLf to modulate key components of the intestinal serotonergic system under both physiological and inflammatory conditions. Given the leading role of serotonin in gut-brain axis and immune regulation, bLf emerges as a promising functional food ingredient with potential for preventing or managing intestinal inflammation. Further exploration of its dietary applications may support the development of innovative nutritional strategies targeting gut-related disorders.