Research ReportNobiletin promotes antioxidant and anti-inflammatory responses and elicits protection against ischemic stroke in vivo

- Rat middle cerebral artery occlusion model is used to analyze nobiletin׳s effect.
- Nobiletin ameliorates the neurological deficit, brain edema and infarct volume.
- Nobiletin increases Nrf2, HO-1, SOD1 and GSH expression.
- Nobiletin decreases NF-κB, MMP-9 and MDA expression.
- Nobiletin has protective effect in the acute phase of cerebral ischemia.

BackgroundPost-ischemic oxidative stress and inflammation play pivotal roles in the pathogenesis of ischemic stroke and may represent therapeutic targets. Nobiletin (NOB) has been reported to elicit a variety of biological effects through its anti-oxidant and anti-inflammatory properties. Our previous study has demonstrated the beneficial effect of NOB in ischemic stroke, but the underlying mechanisms remain poorly defined. We therefore further investigated the role of NOB in cerebral ischemia and its potential mechanisms.MethodsAdult male Sprague-Dawley rats were randomly assigned to five groups: Sham (sham-operated+0.05% Tween-80), permanent middle cerebral artery occlusion (pMCAO+0.9% saline), Vehicle (pMCAO+0.05% Tween-80), NOB-L (pMCAO+NOB 10 mg/kg) and NOB-H (pMCAO+NOB 25 mg/kg) groups. Rats were pre-administered intraperitoneally once daily for 3 days prior to ischemia and then received once again immediately after surgery. Neurological deficit, brain edema and infarct volume were evaluated at 24 h after stroke. Immunohistochemistry, western blot and RT-qPCR were used to detect the expression of Nrf2, HO-1, SOD1, NF-κB and MMP-9. SOD1, GSH and MDA were measured by spectrophotometer.ResultsCompared with Vehicle group, neurological deficits and brain edema were relieved in NOB-H group, infarct volume was lessened in both NOB-L and NOB-H groups (P<0.05). NOB significantly increased the expression of Nrf2, HO-1, SOD1 and GSH, while decreased the levels of NF-κB, MMP-9 and MDA (P<0.05).ConclusionNOB may have a neuroprotective effect on cerebral ischemia, and this protection may be through upregulating Nrf2, HO-1 and downregulating NF-κB expression.