Anti-neuroinflammatory effect of 3,4-dihydroxybenzaldehyde in ischemic stroke

Increasing evidence from human and animal studies suggests that cerebral ischemic diseases are associated with nerve dysfunction and neuroinflammation. Therefore, alleviating neuroinflammation is a potential way to treat ischemic stroke. Gastrodia elata Blume (GEB) is a traditional Chinese medicine used to treat central nervous system diseases and related conditions, such as vertigo, headache, epilepsy. We have previously shown that GEB has a protective effect in ischemic stroke, and that the underlying mechanism is related to anti-neuroinflammation. 3,4-Dihydroxybenzaldehyde (DBD) is a phenolic component of GEB and may be responsible for the neuroprotective effect of GEB; however, the detailed molecular mechanisms underlying the effects of DBD are unknown. The anti-neuroinflammatory effect of DBD and the potential mechanisms underlying it were assessed. We using a rat model of middle cerebral artery occlusion/reperfusion and lipopolysaccharide-treated BV2 microglial cells. DBD (10 mg/kg) significantly decreased infarct volume. Additionally, it alleviated neurological deficits in the rats by inhibiting microglia activation. DBD (0.01, 0.1, and 1 μM) also significantly decreased the levels of inflammatory mediators and cytokines such as tumor necrosis factor-α, interleukin (IL)-1β, IL-6, prostaglandin E2. Furthermore, phenotypic analysis of the BV2 cells showed that DBD significantly down-regulated the expression of M1 marker but significantly up-regulated the expression of M2 marker. Moreover, it suppressed nuclear factor (NF)-κB activation and inhibited the phosphorylation of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase, and extracellular signal-regulated protein kinases 1/2. The neuroprotective and anti-inflammatory effects of DBD are associated with selective modulation of microglia polarization and reduction in the production of inflammatory mediators and cytokines through inhibition of MAPK and NF-κB activation. These findings suggest that DBD may be a potential treatment for ischemic stroke and other neuroinflammatory diseases.