niga-ichigoside-f1 and Stomach-Ulcer

Previous phytochemical studies carried out with Rubus imperialis Chum. Schl. (Rosaceae) have demonstrated the presence of triterpenes (niga-ichigoside F1 and 2β,3β,19α-trihydroxyursolic acid) in this species. The literature indicates that triterpenes are closely related to some pharmacological activities, including antiulcer activity. Therefore, in view of the previous promising results with this species, this work extends the phytochemical studies, as well as investigates its gastroprotective action in different models using rodents. The hydroalcoholic extract was tested using the following protocols in mice: ethanol/HCl and nonsteroidal anti-inflammatory drug (NSAID)-induced ulcer, acetic acid-induced chronic ulcer, ligature pylorus model, and free mucus quantification in mucosa. Isolated triterpenes were investigated in the ethanol/HCl-induced ulcer model. The results of this study show that R. imperialis extract (100, 250, or 500 mg) displays gastroprotective activity in the ethanol-induced ulcer model with a percentage of inhibition of gastric lesions of 70, 71, and 86 %, respectively. The extract also significantly reduced the ulcerative lesions in the indomethacin-induced ulcer. In this model, the percentage of inhibition of ulcer was 41, 44, and 70 %, respectively. Regarding the model of gastric secretion, a reduction of gastric juice volume and total acidity was observed, as well as an increase in gastric pH; however, gastric mucus production was not altered by treatment with the extract. It was also observed that the ethyl acetate fraction presented higher activity, leading to the isolation of niga-ichigoside F1 and 2β,3β-19-α-trihydroxyursolic acid, which presented antiulcer activity comparable to that of omeprazole, with an inhibition percentage of 98 and 99 %, respectively. These results demonstrate that R. imperialis extract and isolated compounds (niga-ichigoside F1 and 2β,3β-19-α-trihydroxyursolic acid) produce gastroprotective effects, and this activity seems, at least in part, to be related to antisecretory effects.

Topics: Acetic Acid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Ethanol; Indomethacin; Male; Mice; Mucus; Phytotherapy; Plant Components, Aerial; Plant Extracts; Rats; Rats, Wistar; Rosaceae; Saponins; Stomach Ulcer; Triterpenes

This study was undertaken to produce the clinical merits of two natural antinociceptive anti-inflammatory triterpenoids which synthetic anti-inflammatory drugs do not have. The triterpenoid glycoside niga-ichigoside F1 (NIF1) and its aglycone 23-hydroxytormentic acid (23-HTA), which were isolated from the unripe fruits of Rubus coreanus (Rosaceae), reduced rheumatoid arthritis (RA) factor and C-reactive protein (CRP) factor in Freund's complete adjuvant reagent-induced rats, suggesting that these two triterpenoids had an anti-rheumatic effect. It was also shown that treatment with NIF1 or 23-HTA reduced gastric lesion extent, acidity and total gastric acid output induced by EtOH plus sodium salicylate in a gastric secretion test. Moreover, 23-HTA had a greater effect than the glycoside, NIF1. To clarify the anti-gastropathic mechanism of these two compounds, their free radical scavenging activities in the gastric mucosa were examined in a rat EtOH-sodium salicylate-induced gastropathy model. The two compounds significantly increased superoxide dismutase and glutathione peroxidase activities, indicating that the healing effects of NIF1 and 23-HTA against gastropathy are associated with free radical scavenging enzyme activities. These results support the notion that the long-term administration of NIF1 or 23-HTA should overcome the adverse effects of synthetic anti-inflammatory drugs.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Antirheumatic Agents; Arthritis, Experimental; C-Reactive Protein; Free Radical Scavengers; Freund's Adjuvant; Fruit; Gastric Juice; Gastric Mucosa; Glutathione Peroxidase; Indicators and Reagents; Male; Rats; Rats, Sprague-Dawley; Rosaceae; Saponins; Sodium Salicylate; Stomach Ulcer; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Triterpenes