Gastroprotective effect of the alkaloid boldine: Involvement of non-protein sulfhydryl groups, prostanoids and reduction on oxidative stress. (25th August 2020)

• Record Type: Journal Article
• Authors: Boeing, Thaise; Mariano, Luisa Natália Bolda; dos Santos, Ana Caroline; Tolentino, Bianca; Vargas, Angela Cadorin; de Souza, Priscila; Nesello, Luciane Angela Nottar; da Silva, Luísa Mota
• Is Part Of: Chemico-biological interactions. Volume 327(2020)
• Publication Date: 2020-08-25
• Subjects: Boldine -- Boldo -- Gastric ulcer -- Ethanol -- Indomethacin -- H+/K+-ATPase; CAT catalase -- CBX carbenoxolone -- GSH reduced glutathione -- GST Glutathione-S-transferase -- HE hematoxylin and eosin -- LOOH lipid hydroperoxides -- MPO myeloperoxidase -- NO nitric oxide -- NP-SH non-protein endogenous sulfhydryl compounds -- NSAIDs non-steroidal anti-inflammatory drugs -- PAS periodic acid of Schiff -- PGE prostaglandin -- SOD superoxide dismutase -- TNF tumor necrosis factor -- VEH vehicle; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2020.109166
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Boldine is the main alkaloid of Peumus boldus Molina, widely used in the traditional medicine for the treatment of digestive disorders. It is a compound with excellent antioxidant and anti-inflammatory properties already described. Despite the widespread use of P. boldus for digestive disorders treatment, the gastroprotective effect of Boldine remains unknown. Considering the need for new approaches to treat gastric ulcers with fewer side effects than current therapy, this study aimed to investigate the gastroprotective effect of Boldine in mice, as well as the mechanisms underlying this effect. The gastroprotective effect of Boldine was evaluated on gastric ulcer induced by 60% ethanol/0.3 M HCl or indomethacin (100 mg/kg) in mice. Histological analysis and the mucin-like glycoprotein content were evaluated in ethanol-ulcerated tissue, as well as, oxidative stress and inflammatory parameters. The mechanisms involved in the effect of Boldine were evaluated by pretreating mice with NEM (a sulfhydryl group chelator, 10 mg/kg, i.p.), l -NAME (a non-selective nitric oxide synthase inhibitor, 70 mg/kg, i.p.), yohimbine (an alpha-adrenergic receptor antagonist, 2 mg/kg, i.p.) and indomethacin (a cyclooxygenase inhibitor, 10 mg/kg, i.p.). In addition, the in vitro effect of Boldine on H + /K + -ATPase activity was determined. Boldine was able to protect gastric mucosa against the damage induced by ethanol/HCl and indomethacin, as evidenced by reduced lesion area and histological analysis. Moreover, the alkaloid reduced oxidative stress and inflammatory mediators in ethanol-ulcerated tissue, beyond has increased mucin-like glycoprotein amount. Finally, Boldine effect is dependent on non-protein sulfhydryl groups and prostanoids but does not involve the inhibition of H+/K + -ATPase activity, being a promising natural resource for gastric ulcer treatment. Graphical abstract: Image 1 Highlights: Boldine protects gastric mucosa against damage induced by ethanol and indomethacin. Boldine reduces oxidative stress and inflammatory mediators. Boldine increases mucin-like glycoprotein in the gastric mucosa. Boldine's effect is dependent on non-protein sulfhydryl groups and prostanoids.