Potential usefulness of methyl gallate in the treatment of experimental colitis
- 81 Downloads
Methyl gallate is a gallotannin widely distributed in nature. Previous studies have demonstrated its antioxidant, anti-inflammatory, antimicrobial and anti-tumor activities. In the present study, the activity of methyl gallate on experimental models of inflammatory bowel disease has been investigated. Experimental colitis was induced in Sprague–Dawley rats through the intracolonic instillation of an acetic acid solution (2 mL, 4% v/v). Methyl gallate (100 and 300 mg/kg, p.o.) and the reference drug mesalazine (100 mg/kg, p.o.) were tested. Methyl gallate induced a significant reduction in the colon weight/length ratio and macroscopic lesion score. Besides, the malondialdehyde content and the GSSG/GSH ratio were remarkably decreased. Furthermore, the administration of methyl gallate reduced the expression of COX2, IL-6, TNFα and the severity of microscopic tissue damage induced by acetic acid, while the mean goblet cell density was significantly higher in both the group treated with methyl gallate and the one treated with mesalazine, in comparison with untreated animals. The Na+K+ATPase pump activity was recovered in treated groups (control: 827.2 ± 59.6, colitis: 311.6 ± 54.8, methyl gallate 100 mg/kg: 642.2 ± 175.0, methyl gallate 300 mg/kg: 809.7 ± 100.6, mesalazine: 525.3 ± 81.7). Methyl gallate was also found to induce a significant reduction in the castor oil-induced intestinal motility in Swiss mice, decreasing the peristalsis by 74.5 and 58.82% at 100 and 300 mg/kg p.o., respectively. This compound also antagonized the jejunum contractions induced by Ach and CaCl2. This study demonstrates that methyl gallate exerts beneficial effects in a preclinical model of intestinal disorders.
KeywordsMethyl gallate Experimental colitis Intestinal motility Antispasmodic effect
This work was supported by Grants from Universidad de Buenos Aires, UBACYT 20020130200265BA. We extend our thanks to Bárbara Piotrkowski PhD, Universidad de Buenos Aires, IBIMOL CONICET for her assistance for GSH/GSSG quantification.
- Algieri F, Zorrilla P, Rodriguez-Nogales A, Garrido-Mesa N, Bañuelos O, Reyes González-Tejero M, Casares-Porcel M, Molero-Mesa J, Zarzuelo A, Utrilla MP, Rodriguez-Cabezas ME, Galvez J (2013) Intestinal anti-inflammatory activity of hydroalcoholic extracts of Phlomis purpurea L. and Phlomis lychnitis L. in the trinitrobenzenesulphonic acid model of rat colitis. J Ethnopharmacol 146:750–759CrossRefPubMedGoogle Scholar
- Calvo TR, Pinheiro Lima Z, Scaramelo Silva J, Rodrigues Ballesteros KV, Pellizzon CH, Akiko Hiruma-Lima C, Tamashiro J, Monteiro Souza Brito AR, Kiomi Takahira R, Villegas W (2007) Constituents and antiulcer effect of Alchornea glandulosa: activation of cell proliferation in gastric mucosa during the healing process. Biol Pharm Bull 30:451–459CrossRefPubMedGoogle Scholar
- Cavalher-Machado SC, Rosas EC, Brito F, Heringe AP, de Oliveira RR, Kaplan MA, Figueiredo MR, Henriques M (2008) The anti-allergic activity of the acetate fraction of Schinus terebinthifolius leaves in IgE induced mice paw edema and pleurisy. Int Immunopharmacol 8:1552–1560CrossRefPubMedGoogle Scholar
- Correa LB, Padua TA, Seito LN, Costa TE, Silva MA, Candea AL, Rosas EC, Henriques MG (2016) Anti-inflammatory effect of methyl gallate on experimental arthritis: inhibition of neutrophil recruitment. Production of inflammatory mediators, and activation of macrophages. J Nat Prod 79:1554–1566CrossRefPubMedGoogle Scholar
- Garrido-Mesa N, Camuesco D, Arribas B, Comalada M, Bailón E, Cueto-Sola M, Utrilla P, Nieto A, Zarzuelo A, Rodríguez-Cabezas ME, Gálvez J (2011) The intestinal anti-inflammatory effect of minocycline in experimental colitis involves both its immunomodulatory and antimicrobial properties. Pharmacol Res 63:308–319CrossRefPubMedGoogle Scholar
- Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Che 193:263–275Google Scholar
- Mariotto S, Esposito E, Di Paola R, Ciampa A, Mazzon E, Carcereri de Prati A, Darra E, Vincenzi S, Cucinotta G, Caminiti R, Suzuki H, Cuzzocrea S (2008) Protective effect of Arbutus unedo aqueous extract in carrageenan-induced lung inflammation in mice. Pharmacol Res 57:110–124CrossRefPubMedGoogle Scholar
- Mazzolin LP, de Almeida Kiguti LR, Oliveira da Maia E, Luchesi Fernandes LT, Machado da Rocha LR, Vilegas W, Sampaio Pupo A, Di Stasi LC, Hiruma-Lima CA (2013) Antidiarrheal and intestinal anti-inflammatory activities of a methanolic extract of Qualea parviflora Mart in experimental models. J Ethnopharmacol 150:1016–1023CrossRefPubMedGoogle Scholar
- Mehmood MH, Munir S, Khalid UA, Asrar M, Gilani AH (2015) Antidiarrhoeal, antisecretory and antispasmodic activities of Matricaria chamomilla are mediated predominantly through K(+)-channels activation. BMC Complement Altern Med 75:1–9Google Scholar