ABSTRACT
Cerebral ischemia/reperfusion (I/R) injury is a common cerebrovascular disease with high mortality. Bakuchiol (BAK), extracted from the seeds of psoralea corylifolia, exhibits anti-inflammatory effects on lung, kidney and heart injuries. However, the effect of BAK on brain I/R injury remains elusive. In our study, a cerebral I/R model in mice was established by 1-h middle cerebral artery occlusion and 24-h reperfusion (1-h MCAO/24-h R). Prior to it, mice were gavaged with BAK (2.5 or 5 mg/kg) per day for 5 days. BAK pre-treatment improved neurological deficit, and reduced infarct volume, cerebral edema and neuronal injury in MCAO/R-injured mice. BAK decreased the number of Iba1-immunoreactive cells in the brain, indicating a reduction of microglial activation. BAK also reduced the expressions of NLRP3, ASC, cleaved-caspase-1, IL-1ß and IL-18. BAK triggered Nrf2 nuclear accumulation and elevated HO-1 level. Further, the role of BAK was explored in BV-2 microglia with 3-h oxygen-glucose deprivation/24-h reperfusion (3-h OGD/24-h R). It was found that the functions of BAK in vitro were consistent with those in vivo, as manifested by reduced NLRP3 inflammasome and activated Nrf2 signaling. In addition, BV-2 cells were treated with Brusatol, an Nrf2 inhibitor. Results showed that Brusatol partially reversed the protective effect of BAK on OGD/R-injured BV-2 cells, further confirming that BAK might exhibit its anti-inflammatory property via activating Nrf2 signaling. In short, BAK is more meaningful in improving cerebral ischemic injury through suppressing NLRP3-mediated inflammatory response and activating the Nrf2 signaling pathway.
Subject(s)
Brain Ischemia/drug therapy , Inflammasomes/drug effects , NF-E2-Related Factor 2/drug effects , NLR Family, Pyrin Domain-Containing 3 Protein/drug effects , Neuroinflammatory Diseases/drug therapy , Phenols/pharmacology , Reperfusion Injury/drug therapy , Animals , Brain Edema/drug therapy , Brain Edema/immunology , Brain Edema/metabolism , Brain Ischemia/immunology , Brain Ischemia/metabolism , Disease Models, Animal , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/immunology , Infarction, Middle Cerebral Artery/metabolism , Inflammasomes/immunology , Inflammasomes/metabolism , Male , Mice , Mice, Inbred C57BL , Neuroinflammatory Diseases/immunology , Neuroinflammatory Diseases/metabolism , Phenols/administration & dosage , Reperfusion Injury/immunology , Reperfusion Injury/metabolism , Signal Transduction/drug effectsABSTRACT
Objective: This research aims to analyze the application regularity of Chinese patent medicine during the COVID-19 epidemic by collecting the names of the top three Chinese patent medicines used by 24 hospitals in 14 provinces of China in four time periods (January 20-22, February 16-18, March 01-03, April 01-03, 2020), and explore its contribution to combating the disease. Methods: 1) We built a database of the top three Chinese patent medicines used by 24 hospitals. 2) The frequency and efficacy distribution of Chinese patent medicine were analyzed with risk areas, regions, and hospitals of different properties as three factors. 3) Finally, we analyzed the differences in the use of heat-clearing and non-heat-clearing medicines among the three factors (χ2 test) and the correlation between the Chinese patent medicine and COVID-19 epidemic (correlation analysis) with SPSS 23.0 statistical software. Results: 1) The heat-clearing medicine was the main use category nationwide during January 20-22, 2020. Meanwhile, there was a significant difference in the utilization rate of heat-clearing and non-heat-clearing medicine in different risk areas (p < 0.01). 2) The variety of Chinese patent medicine was increased nationwide during February 16-18, 2020, mainly including tonics, blood-activating and resolving-stasis, and heat-clearing medicines. Meanwhile, there was a significant difference in the utilization rate of heat-clearing and non-heat-clearing medicine in the southern and northern regions (p < 0.05). 3) Tonics, and blood-activating and resolving-stasis medicines became the primary use categories nationwide during March 01-03, 2020. 4) The tonics class, and blood-activating and resolving-stasis medicine were still the primary categories nationwide during April 01-03, 2020. Meanwhile, there was a significant difference in the utilization rate of heat-clearing and non-heat-clearing medicine in different risk areas (p < 0.01). Conclusion: Chinese patent medicine has a certain degree of participation in fighting against the COVID-19. The efficacy distribution is related to the risk area, region, and hospital of different properties, among which the risk area is the main influencing factor. It is hoped that future research can further collect the application amount of Chinese patent medicine used in hospitals all over the country, so as to perfectly reflect the relationship between Chinese patent medicine and the epidemic situation.
