References (3)

Title : Ursolic acid and its isomer oleanolic acid are responsible for the anti-dementia effects of Ocimum sanctum in olfactory bulbectomized mice - Nguyen_2022_J.Nat.Med__
Author(s) : Nguyen HT , Le XT , Van Nguyen T , Phung HN , Pham HTN , Nguyen KM , Matsumoto K
Ref : J Nat Med , : , 2022
Abstract : This study aims to clarify the bioactive constituents responsible for the anti-dementia effects of Ocimum sanctum Linn. ethanolic extract (OS) using olfactory bulbectomized (OBX) mice, an animal model of dementia. The effects of OS or its extract further fractionated with n-hexane (OS-H), ethyl acetate (OS-E), and n-butanol (OS-B) on the spatial cognitive deficits of OBX mice were elucidated by the modified Y-maze tests. The effects of the major constituents of the most active OS fraction were also elucidated using the reference drug donepezil. The administration of OS and OS-E ameliorated the spatial cognitive deficits caused by OBX, whereas OS-H or OS-B had no effect. Two major constituents, ursolic acid (URO) and oleanolic acid (OLE), and three minor constituents were isolated from OS-E. URO (6 and 12 mg/kg) and OLE (24 mg/kg) attenuated the OBX-induced cognitive deficits. URO (6 mg/kg) and donepezil reversed the OBX-induced down-regulation of vascular endothelial growth factor (VEGF) and choline acetyltransferase expression levels in the hippocampus. URO inhibited the ex vivo activity of acetylcholinesterase with similar efficacy to donepezil. URO inhibited the in vitro activity of acetylcholinesterase (IC(50) = 106.5 microM), while the effects of OS, OS-E, and other isolated compounds were negligible. These findings suggest that URO and OLE are responsible for the anti-dementia action of OS extract, whereas URO possesses a more potent anti-dementia effect than its isomer OLE. The effects of URO are, at least in part, mediated by normalizing the function of central cholinergic systems and VEGF protein expression.
ESTHER : Nguyen_2022_J.Nat.Med__
PubMedSearch : Nguyen_2022_J.Nat.Med__
PubMedID: 35218459

Title : Ocimum sanctum Linn. Extract Improves Cognitive Deficits in Olfactory Bulbectomized Mice via the Enhancement of Central Cholinergic Systems and VEGF Expression - Le_2021_Evid.Based.Complement.Alternat.Med_2021_6627648
Author(s) : Le XT , Nguyen HT , Nguyen TV , Pham HTN , Nguyen PT , Nguyen KM , Nguyen BV , Matsumoto K
Ref : Evid Based Complement Alternat Med , 2021 :6627648 , 2021
Abstract : This study aimed to clarify the antidementia effects of ethanolic extract of Ocimum sanctum Linn. (OS) and its underlying mechanisms using olfactory bulbectomized (OBX) mice. OBX mice were treated daily with OS or a reference drug, donepezil (DNP). Spatial and nonspatial working memory performance was measured using a modified Y maze test and a novel object recognition test, respectively. Brain tissues of the animals were subjected to histochemical and neurochemical analysis. OS treatment attenuated OBX-induced impairment of spatial and nonspatial working memories. OBX induced degeneration of septal cholinergic neurons, enlargement of the lateral ventricles, and suppression of hippocampal neurogenesis. OS and DNP treatment also depressed these histological damages. OS administration reduced ex vivo activity of acetylcholinesterase in the brain. OBX diminished the expression levels of genes coding vascular endothelial growth factor (VEGF) and VEGF receptor type 2 (VEGFR2). Treatment with OS and DNP reversed OBX-induced decrease in VEGF gene and protein expression levels without affecting the expression of the VEGFR2 gene. These results demonstrate that the administration of OS can lessen the cognitive deficits and neurohistological damages of OBX and that these actions are, at least in part, mediated by the enhancement of central cholinergic systems and VEGF expression.
ESTHER : Le_2021_Evid.Based.Complement.Alternat.Med_2021_6627648
PubMedSearch : Le_2021_Evid.Based.Complement.Alternat.Med_2021_6627648
PubMedID: 34306149

Title : Bacopa monnieri Ameliorates Memory Deficits in Olfactory Bulbectomized Mice: Possible Involvement of Glutamatergic and Cholinergic Systems - Le_2013_Neurochem.Res_38_2201
Author(s) : Le XT , Pham HT , Do PT , Fujiwara H , Tanaka K , Li F , Van Nguyen T , Nguyen KM , Matsumoto K
Ref : Neurochem Res , 38 :2201 , 2013
Abstract : This study investigated the effects of alcoholic extract of Bacopa monnieri (L.) Wettst. (BM) on cognitive deficits using olfactory bulbectomized (OBX) mice and the underlying molecular mechanisms of its action. OBX mice were treated daily with BM (50 mg/kg, p.o.) or a reference drug, tacrine (2.5 mg/kg, i.p.), 1 week before and continuously 3 days after OBX. Cognitive performance of the animals was analyzed by the novel object recognition test, modified Y maze test, and fear conditioning test. Brain tissues of OBX animals were used for neurochemical and immunohistochemical studies. OBX impaired non-spatial short-term memory, spatial working memory, and long-term fair memory. BM administration ameliorated these memory disturbances. The effect of BM on short-term memory deficits was abolished by a muscarinic receptor antagonist, scopolamine. OBX downregulated phosphorylation of synaptic plasticity-related signaling proteins: NR1 subunit of N-methyl-D-aspartate receptor, glutamate receptor 1 (GluR1), and calmodulin-dependent kinase II but not cyclic AMP-responsive element binding protein (CREB), and reduced brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus. OBX also reduced choline acetyltransferase in the hippocampus and cholinergic neurons in the medial septum, and enlarged the size of lateral ventricle. BM administration reversed these OBX-induced neurochemical and histological alterations, except the decrease of GluR1 phosphorylation, and enhanced CREB phosphorylation. Moreover, BM treatment inhibited ex vivo activity of acetylcholinesterase in the brain. These results indicate that BM treatment ameliorates OBX-induced cognition dysfunction via a mechanism involving enhancement of synaptic plasticity-related signaling and BDNF transcription and protection of cholinergic systems from OBX-induced neuronal damage.
ESTHER : Le_2013_Neurochem.Res_38_2201
PubMedSearch : Le_2013_Neurochem.Res_38_2201
PubMedID: 23949198