Mumefural Ameliorates Cognitive Impairment in Chronic Cerebral Hypoperfusion via Regulating the Septohippocampal Cholinergic System and Neuroinflammation

Abstract

Chronic cerebral hypoperfusion (CCH) causes cognitive impairment and neurogenic inflammation by reducing blood flow. We previously showed that Fructus mume (F. mume) improves cognitive impairment and inhibits neuroinflammation in a CCH rat model. One of the components of F. mume, Mumefural (MF), is known to improve blood flow and inhibit platelet aggregation. Whether MF affects cerebral and cognitive function remains unclear. We investigated the effects of MF on cognitive impairment and neurological function-related protein expression in the rat CCH model, established by bilateral common carotid arterial occlusion (BCCAo). Three weeks after BCCAo, MF (20, 40, or 80 mg/kg) was orally administrated once a day for 42 days. Using Morris water maze assessment, MF treatment significantly improved cognitive impairment. MF treatment also inhibited cholinergic system dysfunction, attenuated choline acetyltransferase-positive cholinergic neuron loss, and regulated cholinergic system-related protein expressions in the basal forebrain and hippocampus. MF also inhibited myelin basic protein degradation and increased the hippocampal expression of synaptic markers and cognition-related proteins. Moreover, MF reduced neuroinflammation, inhibited gliosis, and attenuated the activation of P2X7 receptor, TLR4/MyD88, NLRP3, and NF-κB. This study indicates that MF ameliorates cognitive impairment in BCCAo rats by enhancing neurological function and inhibiting neuroinflammation.

Mumefural Improves Blood Flow in a Rat Model of FeCl3-Induced Arterial Thrombosis

“…MF, a component of Japanese apricot juice concentrate PMFE [ 17 , 23 , 24 ], is well known to inhibit platelet aggregation [ 18 ], improve cognitive impairment [ 21 ], and have various beneficial effects [ 20 , 25 , 26 , 27 ]. In this study, we showed the anti-thrombotic efficacy and anti-inflammatory effects of MF in an FeCl 3 -induced thrombosis model.…”

“…P. mume fruit containing MF is widely used as a health food, especially in Japan [ 18 , 19 , 20 ]. We have previously shown that MF ameliorates cognitive impairment resulting from reduced cerebral blood flow by modulating the cholinergic system and neuroinflammation [ 21 ]. Although there are few studies on the efficacy of MF to date, it is expected to have an excellent effect on inhibiting platelet activity and suppressing inflammation.…”

Memory Impairment Related to NLRP3 Inflammasome Activation and TRPC5 Decrease in Hippocampal Excitatory Synapses in Microglia Knockout IL-10 Mice

“…Neuroin ammation can trigger cognitive impairment, and the role of in ammasome NLRP3 processes involved in recognition impairment in a variety of nervous system diseases, has been supported by experimental evidence, especially in recent years. Several studies have shown that NLRP3 can be a target for improving memory impairment in diabetes [28][29][30][31], sepsis-associated encephalopathy [32], hypoxemia [33], epilepsy [34,35], AD [36,37], intracerebral hemorrhage [38], cerebral ischemia [39], and aged [40]. Baicalin increases the performance of APP/PS1 transgenic mice in MWM by suppressing NLRP3 in ammasomes to alleviate microglia-mediated neuroin ammation [41].…”

Impaired Cognitive Flexibility Induced by Chronic Cerebral Hypoperfusion in the 5XFAD Transgenic Mouse Model of Mixed Dementia

“…Western blot analysis was performed as previously described ( 30 ). Tissues were homogenized on ice in radio-immunoprecipitation assay (RIPA) buffer, and equivalent amounts of samples were fractionated by sodium dodecyl sulfate (SDS)–gel electrophoresis, transferred onto polyvinylidene difluoride membranes, and blocked with 5% nonfat milk in phosphate-buffered saline containing Tween-20.…”