ABSTRACT
Peptic ulcer episodes cause damage to the stomach and intestine, with inflammatory cell infiltration and oxidative stress as the main players. In this study, we investigated the potential of anthocyanidin malvidin for preventive and curative peptic ulcer treatment. The anthocyanidin effects were examined in gastric ulcer mouse models induced by ethanol, non-steroidal anti-inflammatory drugs (NSAIDs), ischemia-reperfusion (IR), acetic acid and duodenal ulcer induced by polypharmacy. Expression levels of oxidative and inflammatory genes were measured to investigate the mechanism of anthocyanin activity. At a dose of 5 mg·kg-1, Malvidin prevented gastric ulcer induction by ethanol, NSAID and repaired the tissue after 6 days of IR. Moreover, the anthocyanidin accelerated the healing of acetic acid-induced ulcer, increased the gene expression of EGF and COX-1, and downregulated MMP-9. Anthocyanin treatment mitigated the effect of polypharmacy on inflammation and oxidative stress observed in the intestine. Additionally, the compound downregulated cytokine expression and TLR4 and upregulated HMOX-1 and IL-10, exhibiting protective activity in the mouse gut. Malvidin thus prevented gastric and duodenal ulcers due to prominent anti-inflammatory and antioxidative effects on the gastrointestinal tract that were related to gene expression modulation and an increase in endogenous defense mechanisms.
Subject(s)
Anthocyanins/therapeutic use , Inflammation/complications , Inflammation/drug therapy , Oxidative Stress , Peptic Ulcer/complications , Peptic Ulcer/drug therapy , Protective Agents/therapeutic use , Acetic Acid , Animals , Anthocyanins/pharmacology , Antioxidants/metabolism , Biomarkers/metabolism , Cyclooxygenase 1/genetics , Cyclooxygenase 1/metabolism , Disease Models, Animal , Duodenum/drug effects , Duodenum/pathology , Epidermal Growth Factor/genetics , Epidermal Growth Factor/metabolism , Ethanol , Gastric Mucosa/drug effects , Gastric Mucosa/pathology , Gene Expression Regulation/drug effects , Indomethacin , Inflammation/genetics , Male , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Mice , Oxidative Stress/drug effects , Oxidative Stress/genetics , Peptic Ulcer/genetics , Peptic Ulcer/immunology , Polypharmacy , Protective Agents/pharmacology , Reperfusion Injury/complications , Reperfusion Injury/drug therapy , Reperfusion Injury/pathology , Stomach Ulcer/chemically induced , Stomach Ulcer/drug therapy , Stomach Ulcer/genetics , Stomach Ulcer/immunology , Tight Junctions/drug effects , Tight Junctions/metabolism , Wound Healing/drug effectsABSTRACT
Chrysin exhibits anti-inflammatory and antioxidant activities. Here, the gastroprotective effect of chrysin was investigated in mouse models of gastric ulcer induced by absolute ethanol, acetic acid, and ischemia-reperfusion injury. The gastric-healing effect was evaluated at 7 and 14 days after treatment; the mechanism of action was verified using the expression of metalloproteinase 2 (MMP-2) and 9 (MMP-9), caspase-3, cyclooxygenase 1 (COX-1) and 2 (COX-2), epidermal growth factor (EGF), and interleukin-10. Chrysin (10 mg/kg) inhibited macroscopic lesions and increased catalase activity in the mouse model established using absolute ethanol. It ameliorated the gastric ulcer caused by acetic acid by improving the expression of inflammatory genes such as COX-2, inhibiting negative remodeling promoted by MMP-9, increasing cell proliferation effect via EGF, and reducing cellular apoptosis by modulating caspase-3. A faster healing effect was evident in the first 7 days of treatment compared to 14 days of treatment, indicating the pharmacological potential of chrysin. Overall, these results demonstrate the potent effect of chrysin in the gastrointestinal tract and elucidate the genes involved in the healing of gastric ulcers. Moreover, an increase in the levels of gastric mucosa defensive factors is involved in the activity of chrysin in the gastric mucosa.
Subject(s)
Anti-Ulcer Agents/therapeutic use , Cell Proliferation/drug effects , Flavonoids/therapeutic use , Gene Expression Regulation/drug effects , Stomach Ulcer/drug therapy , Wound Healing/drug effects , Acetic Acid/toxicity , Animals , Anti-Ulcer Agents/pharmacology , Apoptosis/genetics , Caspase 3/metabolism , Catalase/metabolism , Cyclooxygenase 1/metabolism , Cyclooxygenase 2/metabolism , Epidermal Growth Factor/metabolism , Ethanol/toxicity , Flavonoids/pharmacokinetics , Flavonoids/pharmacology , Gastric Mucosa/drug effects , Gastric Mucosa/metabolism , Inflammation , Interleukin-10/metabolism , Male , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Membrane Proteins/metabolism , Mice , Oxidation-Reduction/drug effects , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Reperfusion Injury/drug therapy , Stomach Ulcer/chemically induced , Stomach Ulcer/enzymologyABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Ethnopharmacological survey indicated leaves of Byrsonima fagifolia Nied. (Malpighiaceae) against gastrointestinal disorders. AIM OF THE STUDY: The methanolic extract from the leaves of Byrsonima fagifolia (denominated BF) was evaluated for toxic, mutagenic, gastroprotective, antidiarrheal, antibacterial and immunomodulatory activities. MATERIALS AND METHODS: The preventive and healing action of BF against gastric ulcer was evaluated in experimental models in rodents. We evaluated immunomodulatory (by murine peritoneal macrophages), antidiarrheal (by induced diarrhea with castor oil and intestinal motility) and antibacterial action of BF against standard strain of Escherichia coli, Staphylococcus aureus and Helicobacter pylori. The safety of use of BF was also evaluated by mutagenic (Ames assay) and by analyses of toxicity parameters. RESULTS: Phytochemical BF profile indicated the presence of phenolic compounds with antioxidant and radical-scavenging properties. BF significantly inhibited gastric lesions induced by ethanol and HCl/ethanol and endogenous mucosal sulphydryl groups (SHs) participated efficaciously in BF gastroprotection. BF blocked development of inflammation process and also has antidiarrheal actions. This extract accelerated the healing of the gastric ulcerated mucosa by stimulating proliferative factors and by increasing production of gastric mucus with no toxic action. The substances responsible for the protective action are concentrated in the ethyl acetate fraction that demonstrated no mutagenic action in vitro. CONCLUSIONS: Byrsonima fagifolia presents gastroprotective, healing and antidiarrheal activities supporting previous claims that its traditional use by Brazilians can treat these gastrointestinal ailments.