The gastroprotective effect of nobiletin against ethanol-induced acute gastric lesions in mice: impact on oxidative stress and inflammation.

CONTEXT: Gastric ulcer is a common gastrointestinal disorder with increasing incidence and prevalence attributed to loss of balance between aggressive and protective factors. Nobiletin (NOB), a major component of polymethoxyflavones in citrus fruits, has a broad spectrum of health beneficial properties including anti-inflammatory and anti-tumor activities. Although NOB was originally shown to possess anti-inflammatory activity, its effects on gastric ulcer were rarely explored previously.

OBJECTIVE

The aim of the present study was to investigate the anti-ulcerogenic activity of NOB on ethanol-induced gastric ulcer in mice and to elucidate the underlying mechanisms.

METHODS

Seventy-two male Kunming mice administered with absolute ethanol (0.2 ml/animal) were pretreated with NOB (5, 10 or 20 mg/kg), cimetidine (100 mg/kg), or vehicles by intragastric administration in different experimental groups for three days, and animals were euthanized 3 h after ethanol ingestion. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration.

RESULTS

The results showed that ethanol induced gastric injury, increased malondialdehyde (MDA) levels, decreased glutathione (GSH) content, superoxide dismutase (SOD) activity, and prostaglandin E2 (PGE2) levels, increased pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels and myeloperoxidase (MPO) activity, as well as the expression MAPK signaling pathway. Pretreatment with NOB significantly attenuated the gastric lesions as compared to the ethanol group.

CONCLUSIONS

These findings suggest that the gastroprotective activity is attribute to the improvement of antioxidant activities, the stimulation of PGE2, and the reduction of pro-inflammatory cytokines through the MAPK pathway.