ABSTRACT
Solidago chilensis Meyenmost (Asteraceae), popularly known as "Brazilian arnica" or "arnica-do-campo," is widely used in the folk medicine to treat gastric disorders. Based on this, the gastroprotective activity of S. chilensis methanolic extract was investigated. Besides, a phytochemical study allowed isolation of two flavonoids (quercitrin and afzelin). The gastroprotective effects were investigated in acute gastric ulcer models, and the antisecretory activity was assessed in vivo and in vitro. The adhered mucus levels, reduced glutathione (GSH) content and myeloperoxidase (MPO) activity were quantified in ulcerated tissues. The contribution of isolated compounds in extract effects was evaluated, and its doses were calculated according to its yield. To evaluate the in vivo healing properties of S. chilensis methanolic extract, a chronic gastric ulcer was induced in mice by 10 % acetic acid. Evaluation of tumor necrosis factor (TNF) levels was also performed at the site of the acetic acid-induced gastric ulcer. In parallel, effects on cell viability and cell proliferation of fibroblasts (L929 cells) were determined by in vitro trials. Firstly, the S. chilensis methanolic extract (100 or 300 mg/kg) reduced the ulcer area induced by ethanol/HCl in mice when compared to the vehicle group. Moreover, the S. chilensis extract (300 mg/kg) prevented the mucus depletion, the increase in MPO activity and the decrease in the GSH levels in the ulcerated gastric tissue. The S. chilensis extract also was able to decrease the indomethacin-induced gastric ulcer in rats at a dose of 100 mg/kg. The antisecretory effect of the extract (100 mg/kg, intraduodenal (i.d.)) was confirmed by the reduction in the volume and acidity in parallel to an increase in the pH of gastric content. In addition, quercitrin (1.38 mg/kg, but not 0.46 mg/kg) and afzelin (0.026 and 0.078 mg/kg) decreased the ethanol/HCl-induced gastric ulcer. In this model, quercitrin (1.38 mg/kg) prevented the depletion of gastric GSH content and both quercitrin (1.38 mg/kg) and afzelin (0.078 mg/kg) reduced the MPO activity. These compounds also inhibited the H(+),K(+)-ATPase activity at a concentration of 1-100 µg/ml. In addition, the participation of quercitrin and afzelin in these effects also was confirmed. Furthermore, after 4 days of the treatment, an oral administration of S. chilensis methanolic extract (100 mg/kg) reduced the area of the gastric ulcer induced by acetic acid and the regeneration of the gastric mucosa was accompanied by a reduction in gastric TNF levels. The healing properties of the extract also were confirmed by enhancement of proliferation and coverage of scratched wounds in a fibroblast monolayer. Together, our results confirmed the gastroprotective effect of S. chilensis methanolic extract as well as its gastric healing potential and provided some support to the traditional use of S. chilensis for prevention and treatment of gastric lesions in complementation to its known anti-inflammatory properties.
Subject(s)
Anti-Ulcer Agents/pharmacology , Gastric Mucosa/drug effects , Mannosides/pharmacology , Methanol/chemistry , Plant Extracts/pharmacology , Proanthocyanidins/pharmacology , Quercetin/analogs & derivatives , Solidago/chemistry , Solvents/chemistry , Stomach Ulcer/prevention & control , Wound Healing/drug effects , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Ulcer Agents/chemistry , Anti-Ulcer Agents/isolation & purification , Cell Line , Cell Proliferation/drug effects , Disease Models, Animal , Dose-Response Relationship, Drug , Female , Fibroblasts/drug effects , Fibroblasts/metabolism , Fibroblasts/pathology , Gastric Mucosa/metabolism , Gastric Mucosa/pathology , Glutathione/metabolism , H(+)-K(+)-Exchanging ATPase/metabolism , Hydrogen-Ion Concentration , Mannosides/chemistry , Mannosides/isolation & purification , Mice , Phytotherapy , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Leaves , Plants, Medicinal , Proanthocyanidins/chemistry , Proanthocyanidins/isolation & purification , Proton Pump Inhibitors/pharmacology , Quercetin/chemistry , Quercetin/isolation & purification , Quercetin/pharmacology , Rabbits , Rats, Wistar , Stomach Ulcer/chemically induced , Stomach Ulcer/metabolism , Stomach Ulcer/pathology , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Mimusops spp. is used as plant-based antiulcer drugs in Indian traditional medicine. In this study, a bio-guiding study of methanolic extracts of Mimusops balata edible fruits was performed to identify an antiulcer gastric compound. The gastric lesions induced by HCl/ethanol in mice were significantly improved by methanolic extract from seed (MESe, 300 mg/kg), but not by methanolic extract from peel (MEPe, 300 mg/kg) or pulp (MEPu, 300 mg/kg), when compared to the vehicle group. Treatment with MESe also decreased gastric ulceration induced by indomethacin. The antiulcerogenic activity of MESe appears to involve the maintainance of GSH levels, reduction of LPO content, inhibition of neutrophil migration (as evidenced by a decrease in the MPO activity) and a potent free radical scavenger activity (IC50 = 3.4 µg/ml). Moreover, MESe decrease the gastric volume, pH, total acidity, and pepsin activity in the gastric juice. Exceptionally, MESe showed a high content of phenolic compound, identified by layer chromatography and Folin-Ciocalteu reagent. Considering the better pharmacological and phytochemical profile, MESe was successively partitioned and resulted in isolation and identification of a constituent, the flavonoid taxifolin, identified by spectroscopic methods ((1)H, (13)C NMR, and HPLC). Taxifolin also inhibited the ulcerogenic effect of HCl/ethanol at a low dose of 1.14 mg/kg and inhibited in vitro H+/K(+)-ATPase activity by 41% at a concentration of 100 µg/ml. Taken together, these results evidenced the gastroprotective potential of fruits from M. balata and showed that this effect is exclusive to the seeds.
