Abstract
Functional gastrointestinal disorders (FGIDs) are characterized by abdominal pain, bloating and bowel disturbances. FGID therapy is primarily symptomatic, including treatment with herbal remedies. Flower extract of Tilia tomentosa Moench (TtM) is occasionally used as an anti-spasmodic in popular medicine. Since its effect on intestinal response is unknown, we evaluated the influence of TtM extract on small intestine contractility. Ileal preparations from C57BL/6J mice were mounted in organ baths to assess changes in muscle tension, following addition of TtM extract (0.5–36 μg/mL) or a vehicle (ethanol). Changes in contractile response to receptor- and non-receptor-mediated stimuli were assessed in ileal preparations pretreated with 12 μg/mL TtM. Alterations in the enteric nervous system neuroglial network were analyzed by confocal immunofluorescence. Increasing addition of TtM induced a marked relaxation in ileal specimens compared to the vehicle. Pretreatment with TtM affected cholinergic and tachykininergic neuromuscular contractions as well as K+-induced smooth muscle depolarization. Following incubation with TtM, a significant reduction in non-adrenergic non-cholinergic-mediated relaxation sensitive to Nω-Nitro-L-arginine methyl ester hydrochloride (pan-nitric oxide synthase inhibitor) was found. In vitro incubation of intestinal specimens with TtM did not affect the myenteric plexus neuroglial network. Our findings show that TtM-induced intestinal relaxation is mediated by nitric oxide pathways, providing a pharmacological basis for the use of TtM in FGIDs.
Highlights
Functional gastrointestinal disorders (FGIDs), such as irritable bowel syndrome (IBS), are characterized by abdominal pain, constipation, bloating, and diarrhea, and often arise following lifestyle disturbances, physical or/and emotional stress, or drug therapy, determining about a third of gastroenterology examinations [1]
Following identify quercetin and kaempferol as the dominant aglycones (Figure 1). Based on these the treatment with tomentosa Moench (TtM), the relaxed ileal tissues immediately recovered after washing with results, the quantitative analyses referred to quercetin and kaempferol derivatives
Overall, based on the present findings, it is plausible to hypothesize that TtM, antagonizing cholinergic and tachykininergic neurotransmission and enhancing nitric oxide (NO)-mediated response, could contribute to the modulation of the small intestinal motor abnormalities occurring in presence of several diseases, including FGDIs [46,47]. In this regard, considering that plants belonging to the Tilia genus produce compounds, such as flavonoids, that have been shown to exert anti-neuroinflammatory and antiproliferative activities in an in vitro model [48], we further focused our attention on testing the effect of TtM on the small intestine myenteric neuroglial network by whole-mount immunohistochemistry, which has a crucial role in the development of microinflammatory processes predisposing to neuroplastic adaptive changes [15]
Summary
Functional gastrointestinal disorders (FGIDs), such as irritable bowel syndrome (IBS), are characterized by abdominal pain, constipation, bloating, and diarrhea, and often arise following lifestyle disturbances, physical or/and emotional stress, or drug therapy, determining about a third of gastroenterology examinations [1]. One of the factors contributing to the pathogenesis of FGIDs appears to be a dysfunction of the autonomic nervous system i.e., the etiology is complex and multi-factorial. Antispasmodic agents and gutbrain neuromodulators are widely used for the treatment of FGIDs with no clear relative efficacy [2]. Ex DC.), commonly known as silver linden or silver lime, is a deciduous tree native of southeastern Europe and Asia that belongs to the Malvaceae family [3].
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