1.β-Amyrin Ameliorates Alzheimer’s Disease-Like Aberrant Synaptic Plasticity in the Mouse Hippocampus
Hye Jin PARK ; Huiyoung KWON ; Ji Hye LEE ; Eunbi CHO ; Young Choon LEE ; Minho MOON ; Mira JUN ; Dong Hyun KIM ; Ji Wook JUNG
Biomolecules & Therapeutics 2020;28(1):74-82
Alzheimer’s disease (AD) is a progressive and most frequently diagnosed neurodegenerative disorder. However, there is still no drug preventing the progress of this disorder. β-Amyrin, an ingredient of the surface wax of tomato fruit and dandelion coffee, is previously reported to ameliorate memory impairment induced by cholinergic dysfunction. Therefore, we tested whether β-amyrin can prevent AD-like pathology. β-Amyrin blocked amyloid β (Aβ)-induced long-term potentiation (LTP) impairment in the hippocampal slices. Moreover, β-amyrin improved Aβ-induced suppression of phosphatidylinositol-3-kinase (PI3K)/Akt signaling.LY294002, a PI3K inhibitor, blocked the effect of β-amyrin on Aβ-induced LTP impairment. In in vivo experiments, we observed that β-amyrin ameliorated object recognition memory deficit in Aβ-injected AD mice model. Moreover, neurogenesis impairments induced by Aβ was improved by β-amyrin treatment. Taken together, β-amyrin might be a good candidate of treatment or supplement for AD patients.
2.Spinosin Attenuates Alzheimer’s Disease-Associated Synaptic Dysfunction via Regulation of Plasmin Activity
Mudan CAI ; Inho JUNG ; Huiyoung KWON ; Eunbi CHO ; Jieun JEON ; Jeanho YUN ; Young Choon LEE ; Dong Hyun KIM ; Jong Hoon RYU
Biomolecules & Therapeutics 2020;28(2):131-136
Hippocampal synaptic dysfunction is a hallmark of Alzheimer’s disease (AD). Many agents regulating hippocampal synaptic plasticity show an ameliorative effect on AD pathology, making them potential candidates for AD therapy. In the present study, we investigated spinosin as a regulating agent of synaptic plasticity in AD. Spinosin attenuated amyloid β (Aβ)-induced long-term potentiation (LTP) impairment, and improved plasmin activity and protein level in the hippocampi of 5XFAD mice, a transgenic AD mouse model. Moreover, the effect of spinosin on hippocampal LTP in 5XFAD mice was prevented by 6-aminocaproic acid, a plasmin inhibitor. These results suggest that spinosin improves synaptic function in the AD hippocampus by regulating plasmin activity.
3.Neuroprotective effect of the ethanol extract of Artemisia capillaris on transient forebrain ischemia in mice via nicotinic cholinergic receptor.
Huiyoung KWON ; Ji Wook JUNG ; Young Choon LEE ; Jong Hoon RYU ; Dong Hyun KIM
Chinese Journal of Natural Medicines (English Ed.) 2018;16(6):428-435
Artemisia capillaris Thunberg is a medicinal plant used as a traditional medicine in many cultures. It is an effective remedy for liver problems including hepatitis. Recent pharmacological reports have indicated that Artemisia species can exert various neurological effects. Previously, we reported a memory-enhancing effect of Artemisia species. However, the mechanisms underlying the neuroprotective effect of A. capillaris (AC) are still unknown. In the present study, we investigated the effect of an ethanol extract of AC on ischemic brain injury in a mouse model of transient forebrain ischemia. The mice were treated with AC for seven days, beginning one day before induction of transient forebrain ischemia. Behavioral deficits were investigated using the Y-maze. Nissl and Fluoro-jade B staining were used to indicate the site of injury. To determine the underlying mechanisms for the drug, we measured acetylcholinesterase activity. AC (200 mg·kg) treatment reduced transient forebrain ischemia-induced neuronal cell death in the hippocampal CA1 region. The AC-treated group also showed significant amelioration in the spontaneous alternation of the Y-maze test performance, compared to that in the untreated transient forebrain ischemia group. Moreover, AC treatment showed a concentration-dependent inhibitory effect on acetylcholinesterase activity in vitro. Finally, the effect of AC on forebrain ischemia was blocked by mecamylamine, a nonselective nicotinic acetylcholine receptor antagonist. Our results suggested that in a model of forebrain ischemia, AC protected against neuronal death through the activation of nicotinic acetylcholine receptors.
Acetylcholinesterase
;
metabolism
;
Animals
;
Artemisia
;
Cell Death
;
drug effects
;
Cholinergic Antagonists
;
pharmacology
;
Disease Models, Animal
;
Ethanol
;
chemistry
;
Hippocampus
;
pathology
;
physiopathology
;
Ischemic Attack, Transient
;
drug therapy
;
pathology
;
physiopathology
;
Male
;
Mecamylamine
;
pharmacology
;
Memory
;
drug effects
;
Mice
;
Mice, Inbred C57BL
;
Models, Neurological
;
Neuroprotective Agents
;
administration & dosage
;
pharmacology
;
Phytotherapy
;
Plant Components, Aerial
;
chemistry
;
Plant Extracts
;
administration & dosage
;
pharmacology
;
Receptors, Cholinergic
;
metabolism