Evaluation of the safety, gastroprotective activity and mechanism of action of standardised leaves infusion extract of Copaifera malmei Harms
Journal of Ethnopharmacology
Área de Farmacologia, Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso (UFMT), Av.Fer- nando Correada Costa, no.2367-Boa Esperança, Cuiabá-MT, Brazil; Área de Histologia, Departamento de Ciências Básica
Ethnopharmacological relevance Copaifera malmei Harms (Fabaceae) is a plant that occurs in the central region of Brazil, where the plant's leaves infusion is popularly used to treat gastric ulcer and inflammatory diseases. This study was aimed to investigate the gastroprotective activity and mode of action of the plants' leaves infusion in order to establish the scientific basis for such usage, and to assess its potential as a source of an anti-ulcer agent. Materials and methods Leaves infusion extract of the plant (SIECm) was prepared, freeze dried and lyophilised. Its qualitative and quantitative phytochemical constituents were investigated using TLC and HPLC techniques. The safety profile was evaluated on CHO-k1 epithelial cells viability using the Alamar blue assay, and by acute toxicity test in mice. The gastroprotection and anti-ulcer efficacy of the SIECm (25, 100 and 400 mg/kg, p.o.) were tested using acute (acidified ethanol, piroxicam and water restrain stress), and chronic (acetic acid) experimental ulcer models. The plausible mode of action of the SIECm was assessed using gastric secretion, gastric barrier mucus, nitric oxide, and its antioxidant (myeloperoxidase and catalase) effects in mice and rats. The histopathological analyses of the ulcerated tissues as well as the extract's activity on Helicobacter pylori were also investigated. Results Phytochemical tests indicated the presence of mainly phytosterols, phenolics and flavonoids. The SIECm exhibited no cytotoxic effects on the CHO-k1 cells, and no oral acute toxicity in mice. It prevented against the acute induced ulcerations by enhancing gastroprotection through gastric mucus production, NO modulation, antioxidant, reduced gastric secretion and enhanced chronic ulcers healing process, as shown by reduction/prevention of epithelial and vascular damage, in addition to reduction in leucocyte infiltration. The SIECm however did not exhibit activity against H. pylori. Conclusion The SIECm is safe, contain useful phytochemicals and exhibited significant gastroprotective/anti-ulcer effects. The results justify its folkloric usage, and provided scientific evidence of its potential as a source of new phytodrug to treat gastric ulcers. © 2015 Elsevier Ireland Ltd. All rights reserved.
acetic acid; alcohol; antiulcer agent; carbenoxolone; catalase; catechin; copaifera malmei extract; ellagic acid; flavonoid; gallic acid; myeloperoxidase; nitric oxide; phenol derivative; phytosterol; piroxicam; plant extract; quercetin; rutoside; unclassified drug; water; acute toxicity; adult; analytic method; animal experiment; animal model; animal tissue; antioxidant activity; antiulcer activity; Article; blood vessel injury; cell viability; CHO cell line; clinical assessment; controlled study; Copaifera malmei; drug efficacy; drug mechanism; drug safety; drug screening; epithelium cell; experimental mouse; experimental rat; Fabaceae; freeze drying; Helicobacter pylori; high performance liquid chromatography; histopathology; immobilization stress; infusion; lymphocytic infiltration; lyophilisate; medicinal plant; mouse; nonhuman; plant leaf; qualitative analysis; quantitative analysis; rat; resazurin assay; single drug dose; stomach lesion; stomach mucus; stomach protection; stomach secretion; stomach ulcer; thin layer chromatography; ulcer healing; water restraint stress