title: Boswellia serrata Preserves Intestinal Epithelial Barrier from Oxidative and Inflammatory Damage.
abstract: Aminosalicylates, corticosteroids and immunosuppressants are currently the therapeutic choices in inflammatory bowel diseases (IBD), however, with limited remission and often serious side effects. Meanwhile complementary and alternative medicine (CAM) use is increasing, particularly herbal medicine. Boswellia serrata is a traditional Ayurvedic remedy with anti-inflammatory properties, of interest for its usefulness in IBDs. The mechanism of this pharmacological potential of Boswellia serrata was investigated in colonic epithelial cell monolayers exposed to H2O2 or INF-γ+TNF-α, chosen as in vitro experimental model of intestinal inflammation. The barrier function was evaluated by the transepithelial electrical resistance (TEER) and paracellular permeability assay, and by the tight junction proteins (zonula occludens-1, ZO-1 and occludin) immunofluorescence. The expression of phosphorylated NF-κB and reactive oxygen species (ROS) generation were determined by immunoblot and cytofluorimetric assay, respectively. Boswellia serrata oleo-gum extract (BSE) and its pure derivative acetyl-11-keto-β-boswellic acid (AKBA), were tested at 0.1-10 μg/ml and 0.027 μg/ml, respectively. BSE and AKBA safety was demonstrated by no alteration of intestinal cell viability and barrier function and integrity biomarkers. H2O2 or INF-γ+TNF-α treatment of Caco-2 cell monolayers significantly reduced TEER, increased paracellular permeability and caused the disassembly of tight junction proteins occludin and ZO-1. BSE and AKBA pretreatment significantly prevented functional and morphological alterations and also the NF-κB phosphorylation induced by the inflammatory stimuli. At the same concentrations BSE and AKBA counteracted the increase of ROS caused by H2O2 exposure. Data showed the positive correlation of the antioxidant activity with the mechanism involved in the physiologic maintenance of the integrity and function of the intestinal epithelium. This study elucidates the pharmacological mechanisms mediated by BSE, in protecting intestinal epithelial barrier from inflammatory damage and supports its use as safe adjuvant in patients affected by IBD.
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Largo E. Meneghetti 2, 35131, Padova, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Catanzaro
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Largo E. Meneghetti 2, 35131, Padova, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Rancan
authors.affiliation: IRCCS "E. Medea," Conegliano, Italy.
authors.forename: Genny
authors.initials: G
authors.lastname: Orso
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Largo E. Meneghetti 2, 35131, Padova, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Dall'Acqua
authors.affiliation: Department of Molecular Medicine, University of Padova, via Gabelli 63, 35121, Padova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Brun
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Largo E. Meneghetti 2, 35131, Padova, Italy.
authors.forename: Maria Cecilia
authors.initials: MC
authors.lastname: Giron
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Largo E. Meneghetti 2, 35131, Padova, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Carrara
authors.affiliation: Department of Molecular Medicine, University of Padova, via Gabelli 63, 35121, Padova, Italy.
authors.forename: Ignazio
authors.initials: I
authors.lastname: Castagliuolo
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Largo E. Meneghetti 2, 35131, Padova, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Ragazzi
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Largo E. Meneghetti 2, 35131, Padova, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Caparrotta
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Largo E. Meneghetti 2, 35131, Padova, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Montopoli
mesh_terms: D000975:Antioxidants / Q000008:administration & dosage* / Q000737:chemistry; D029743:Boswellia / Q000737:chemistry; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry; D062725:Tight Junction Proteins / Q000378:metabolism; D014315:Triterpenes / Q000008:administration & dosage*
chemical_list: D000975:Antioxidants; D016328:NF-kappa B; D010936:Plant Extracts; D062725:Tight Junction Proteins; D014315:Triterpenes; C094432:acetyl-11-ketoboswellic acid; D006861:Hydrogen Peroxide