Luteolin downregulates TLR4, TLR5, NF-κB and p-p38MAPK expression, upregulates the p-ERK expression, and protects rat brains against focal ischemia.

BACKGROUND: Inflammatory damage is known to be involved in ischemic stroke. Luteolin has been proved to elicit a series of biologic effects through its anti-inflammatory property in multiple sclerosis and rheumatoid arthritis. Whether this protective effect applies to ischemic injury in brain is still unknown, we therefore investigate the potential neuroprotective role of luteolin in ischemic stroke and the underlying mechanisms.

METHODS: Male Sprague-Dawley rats were subjected to pMCAO and luteolin was administered intraperitoneally immediately after surgery, then once daily thereafter. Neurological deficit, infarct volume, and brain water content were measured at 24 h and 72 h after stroke. The expression of TLR4, TLR5, and NF-κB were measured by real-time PCR, immunohistochemical staining (IHC), and Western blot. P38MAPK and extracellular signal-regulated kinase (ERK) were detected by IHC, and Western blot.

RESULTS: Compared with pMCAO group, luteolin significantly alleviated neurological deficit, decreased infarct volume and suppressed edema after ischemic stroke, which were accompanied with decreased expression of TLR4, TLR5, NF-κB and p-p38MAPK. Meanwhile, luteolin activated the expression of p-ERK1/2 (P<0.05).

CONCLUSIONS: Luteolin protected the brain from the damage caused by pMCAO, and this effect may be through downregulation of TLR4, TLR5, NF-κB, p38MAPK and upregulation of ERK expression.