Dl-3-n-Butylphthalide Reduces Cognitive Deficits and Alleviates Neuropathology in P301S Tau Transgenic Mice

Abstract

Alzheimer’s disease (AD) is a destructive and burdensome neurodegenerative disease, one of the most common characteristics of which are neurofibrillary tangles (NFTs) that are composed of abnormal tau protein. Animal studies have suggested that dl-3-n-butylphthalide (dl-NBP) alleviates cognitive impairment in mouse models of APP/PS1 and SAMP8. However, the underlying mechanisms related to this remain unclear. In this study, we examined the effects of dl-NBP on learning and memory in P301S transgenic mice, which carry the human tau gene with the P301S mutation. We found that dl-NBP supplementation effectively improved behavioral deficits and rescued synaptic loss in P301S tau transgenic mice, compared with vehicle-treated P301S mice. Furthermore, we also found that it markedly inhibited the hyperphosphorylated tau at the Ser262 site and decreased the activity of MARK4, which was associated with tau at the Ser262 site. Finally, dl-NBP treatment exerted anti-inflammatory effects and reduced inflammatory responses in P301S mice. In conclusion, our results provide evidence that dl-NBP has a promising potential for the therapy of tauopathies, including AD.

Myelin repair in Alzheimer’s disease: a review of biological pathways and potential therapeutics

“…Dl-3-butylphtalide (dl-NBP) can ameliorate neuropathology related to AD [ 124 ] and may ameliorate myelin injury in vascular models. Specifically, dl-NBP has been shown to promote OPC proliferation through the neurite outgrowth inhibitor (Nogo-A) and brain-derived neurotrophic factor signaling pathways [ 125 ].…”

Efficacy and safety of 3‐n‐butylphthalide combined with endovascular treatment in acute ischemic stroke due to large vessel occlusion

“…Thus, NBP improves the cellular tolerance to ischemic stroke, leading to an overall improvement in postischemic neurological impairment. (3) Inhibiting inflammatory responses and antioxidant stress: first, NBP can exert its anti‐inflammatory effect by upregulating the expression of hepatocyte growth factor and downregulating the expression of Toll‐like receptor 4 19,20 . Second, NBP reduces oxidative stress by increasing superoxide dismutase activity in the cerebral ischemic area, reducing reactive oxygen species and malondialdehyde levels 21,22 .…”

“…A total of 1820 patients were included in this study. The median (interquartile range) age was 66 (57-74) years, the baseline NIHSS score was 17 (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24), and 1150 (63.5%) of the patients were women. The rate of IVT was 25.8%, and 84.1% (1524/1812) of patients achieved successful reperfusion (mTICI 2b-3).…”

“…There were 628 (37.5%) and 1138 (62.5%) patients in the NBP and non-NBP groups, respectively. Compared with the non-NBP group, patients in the NBP group had a lower baseline NIHSS score (16 [11][12][13][14][15][16][17][18][19][20][21][22] vs. 18 [13][14][15][16][17][18][19][20][21][22][23][24][25][26] 42.7% vs. 50.2%, p = 0.006). Other baseline characteristics did not differ significantly between the groups (p > 0.05) (Table 1).…”

(−)-Epicatechin Reduces Neuroinflammation, Protects Mitochondria Function, and Prevents Cognitive Impairment in Sepsis-Associated Encephalopathy

“…Use 0.1% glacial acetic acid to differentiate the sections until the Nissl body was dark blue, and the background was light blue or colorless. The slides were dried and coverslipped with Permount TM Mounting Medium [ 36 ].…”