Beneficial properties of Minthostachys veticillata on experimental colitis

[Speaker] Susana Gorzalczany:1
[Co-author] Angeles Rodriguez Basso:1, Andrea Carranza:2, Hernan Bach:1
1:Universidad de Buenos Aires, School of Pharmacy and Biochemistry, Argentina, 2:ININCA, CONICET, Universidad de Buenos Aires, Argentina

Inflammatory bowel disease is a chronic disorder characterized by pain, cramps and inflammation of the gastrointestinal tract. To date, no complete response has been achieved with conventional therapies. Therefore, the development of new strategies to treat it is a relevant goal. Minthostachysveticillata, known as Peperina (PP), is an argentinian medicinal plant with a traditional use as a digestive, antispasmodic and antidiarrheic properties but up to now there was no scientific evaluation of its aqueous extract on gastrointestinal tract. PP (250 and 500 mg/Kg, po) and reference drug mesalazine (MZ: 300 mg/kg, po), were tested in colitis model induced by intracolonic instillation of a acetic acid solution (2 mL, 4% v/v). PP induced a reduction in the colon weight/length ratio, expressed in g/2cm (control: 0.14±0.02 colitis: 0.53±0.06, PP 250 mg/K: 0.36±0.03, PP 500 mg/Kg: 0.36±0.05, MZ: 0.31±0.02) and biomarker of oxidative stress such as GSSG/GSH ratio (control: 0.03±0.01, colitis: 0.96±0.11, PP 250 mg/Kg: 0.30±0.05, PP 500 mg/Kg: 0.17±0.10, MZ: 0.06±0.03). Histological examination of the colonic sections showed that acetic acid caused severe injury in the colon mucosa with crypt distortion, leukocytes infiltration, massive hemorrhage (HE) and reduced the number of goblet cells (Alcian Blue). But, the treatment with PP and MZ reduced the severity of tissue damage induced by acetic acid. Immunoblot analysis regarding to the expression of COX2, IL-6 and TNFalfa was up-regulated in experimental colitis, but this effect was reduced by PP and mesalazine. PP significantly reduced the intestinal motility induced by ricin oil (125 mg/Kg: 70.6±4.4, 250 mg/Kg: 63.7±6.9 and 500 mg/Kg: 58.7±11.2) as well as reference drug atropine (0.1 mg/kg: 31.4±5.3). Furthermore, in isolated jejunum PP significantly reduced the response in a concentration-dependent manner induced by Ach (Emax 1 mg/mL: 79.6%, 3 mg/mL: 54.9%), by CaCl2 (E max 0.1 mg/mL: 85.3%, 0.3 mg/mL: 49.6%, 1 mg/mL: 27.1 %, 3 mg/mL: 5.4%) and inhibited both low (25mM) and high (80 mM) potassium induced contractions, suggesting that antispasmodic activity of PP could be related to antagonistic activity on calcium channels. Therefore, this study could demonstrate that PP possesses beneficial properties in preclinical models related to gastrointestinal diseases.
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