RESUMO
Peptic ulcers are lesions that affect the gastrointestinal tract and that can be triggered by external factors such as alcohol use. This study investigated the gastroprotective role of two anthocyanidins, malvidin and cyanidin chloride, in an ethanol-induced gastric ulcer model in male and female mice (ovariectomized and supplemented with 17ß-estradiol or not) and aimed to evaluate the effectiveness of anthocyanidins in preventing the formation of lesions and to identify the underlying mechanisms, while considering hormonal differences. Moreover, in silico comparative analysis was performed to predict the properties and biological behaviors of the molecules. We observed that the hormonal status did not interfere with the gastroprotective action of malvidin, although antioxidant mechanisms were modulated differently depending on sex. On the other hand, cyanidin showed gastroprotective activity at different doses, demonstrating that, for the same experimental model, there is a need to adjust the effective dose depending on sex. In silico analysis showed that, despite being structurally similar, the interaction with receptors and target proteins in this study (myeloperoxidase, superoxide dismutase, catalase, and reduced glutathione) differed between the two molecules, which explains the difference observed in in vivo treatments.
RESUMO
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.
Assuntos
Antocianinas/uso terapêutico , Inflamação/complicações , Inflamação/tratamento farmacológico , Estresse Oxidativo , Úlcera Péptica/complicações , Úlcera Péptica/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Ácido Acético , Animais , Antocianinas/farmacologia , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Ciclo-Oxigenase 1/genética , Ciclo-Oxigenase 1/metabolismo , Modelos Animais de Doenças , Duodeno/efeitos dos fármacos , Duodeno/patologia , Fator de Crescimento Epidérmico/genética , Fator de Crescimento Epidérmico/metabolismo , Etanol , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Indometacina , Inflamação/genética , Masculino , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Úlcera Péptica/genética , Úlcera Péptica/imunologia , Polimedicação , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/genética , Úlcera Gástrica/imunologia , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Cicatrização/efeitos dos fármacosRESUMO
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.