L-3-n-Butylphthalide reduces ischemic stroke injury and increases M2 microglial polarization

Abstract

Overwhelming evidence suggests that microglia play an important role in ischemic injury and they polarize into two different phenotypes with distinct functions after ischemic stroke. We performed the present study to investigate whether L-3-n butylphthalide (NBP) has an effect on microglial polarization. Mice were subjected to transient middle cerebral artery occlusion (MCAO) for 45 min, and then immediately after reperfusion were treated with NBP or vehicle via the caudal vein for 7 consecutive days. 2,3,5-Triphenyltetrazolium chloride (TTC) staining showed that NBP treatment resulted in a tendency to decrease cerebral infarct volume at 1 day after MCAO, and significant decreased infarct volume at 3 days after MCAO. Sensorimotor function was evaluated by the adhesive removal test and balance beam test, which were superior in NBP-treated mice compared with vehicle-treated mice at 1 and 3 days after MCAO. Immunofluorescent staining further indicated that NBP treatment significantly increased the number of CD206+/Iba1+ M2 microglia/macrophages and reduced the number of CD16+/Iba1+ M1 cells at 3 and 7 days after MCAO reperfusion. Western blot also showed an elevation of M2 marker (arginase-1) in NBP-treated brains at 7 days after MCAO. In conclusion, our results clearly show that NBP treatment significantly mitigates ischemic brain damage and promotes recovery of neurological function in early phase after ischemic stroke, probably by skewing M1 microglia/macrophages polarization towards M2 phenotype. Thus, our study provides new evidence that NBP might be a promising candidate for ameliorating injury caused by ischemic stroke.

Effects of dl‐3‐n‐butylphthalide on serum lipoprotein‐associated phospholipase A2 and hypersensitive C‐reactive protein levels in acute cerebral infarction

“…Some Chinese scholars (Wang, Ma, et al, ) have summarized the research progress of NBP in the treatment of ischemic stroke in the past 20 years, and it was considered as a promising drug for ischemic stroke. A large number of experiments at home and abroad have revealed that NBP can regulate brain energy metabolism (Yan, Wang, Yao, Liu, & Xiao, ), protect the mitochondria (Min et al, ), promote normal blood flow in the ischemic area (Xu et al, ), inhibit oxidative stress and platelet aggregation (Li et al, ; Zhao, Li, Zhang, Chen, & Li, ), and prevent the vigorous apoptosis of cells (Min et al, ). In addition, Chinese scholars found that NBP plays a neuroprotective role by acting on multiple active targets (Wang et al, ; Zhao et al, ).…”

Immune modulation of macrophage response by Cordyceps militaris extracts

“…2). Various compounds in phytoextracts such as melatonin and L-3-nbutylphthalide from celery and polyphenols from cocoa have been shown to activate the M2 polarization of macrophages [22][23][24]. Flow-cytometry and qPCR analysis showed that the extracts signi cantly inhibited TNF-α and IL-1β by suppression of M1 polarization in the macrophages.…”

<p>The Efficacy of N-Butylphthalide and Dexamethasone Combined with Hyperbaric Oxygen on Delayed Encephalopathy After Acute Carbon Monoxide Poisoning</p>

“…In animal models of cerebral apoplexy, NBP was mainly used for inhibiting platelet aggregation, reducing thrombosis, improving microcirculation, reducing the volume of cerebral infarction, resisting oxidative stress, protecting mitochondrial function, reducing neuronal apoptosis, alleviating inflammatory reaction, mediating autophagy of nerve cells, promoting neurogenesis and targeting in several pathophysiological mechanisms, which are mainly reflected in its obvious neuroprotective effect. [16][17][18][19][20][21][22][23][24][25][26] After further studies on its application, it was found that the beneficial effects of NBP are beyond those of apoplexy. Especially in neurodegenerative disease fields, it was found that NBP and its ramifications have unique function and effects in AD, vascular dementia (VaD), PD, ALS and DEACMP treatment.…”