Neuroprotective effects of delavatine A on LPS-induced activation of microglia in vitro and in a rat model of ischemia-reperfusion injury

Abstract

Purpose: To investigate the neuroprotective effects of deloratine A on liposaccharide (LPS)-induced microglia activation in vitro and in a rat model of ischemia-reperfusion injury. Methods: LPS-induced microglial activation was successfully established in mouse microglia BV2 cell line. Then, the cells were randomly divided into model group, 2.5 μM delavatine A group, 5 μM delavatine A group, and 10 μM delavatine A group. The effect of delavatine A on the release of NO, TNF-α, IL-1β and IL-6 in BV2 cells was determined. In the vivo studies, 21 male Sprague Dawley (SD) rats were used to establish a rat model of ischemia-reperfusion injury, and effect of delavatine A on neural function and cerebral infarction area was determined. Results: The NO content was significantly higher in LPS-induced microglial activation model than in blank control, but it was significantly lower in the 3 delavatine A groups than in model group (p < 0.05). The expression levels of TNF-α, IL-1β, and IL-6 were significantly higher in model group than in blank control group, but they were significantly and dose-dependently lower in delavatine A groups than in model group (p < 0.05). In the in vivo rat studies, neural function score and cerebral infarction area in the model group were significantly higher than those in the sham group, while cerebral infarction area in delavatine A groups were significantly lower than that in the model group (p < 0.05). Conclusion: Delavatine A significantly reduces the inflammation associated with LPS-induced microglial activation, mitigates loss of neural function, and reduces cerebral infarction area in rats with ischemia-reperfusion injury. These findings may lead to the development of new neuroprotective drugs. Keywords: Delavatine A; LPS; Microglia activation; Ischemia-reperfusion injury; Neural function; Cerebral infarction area