The Aqueous Extract of Humulus japonicus Ameliorates Cognitive Dysfunction in Alzheimer's Disease Models via Modulating the Cholinergic System.

Humulus japonicus (HJ) is an herbal medicine, which has been reported as being antioxidative and anti-inflammatory. The present study aimed to investigate the effect of oral administration of HJ water extract (HJW) on cognitive function through the cholinergic system in Alzheimer's disease (AD) mouse models. Institute of Cancer Research mice injected with beta-amyloid (Aß) (1-42) (i.c.v.) and APP/PS1 transgenic (TG) mice were orally administered with HJW at 500 mg/kg/day for 3 weeks. Aß-injected mice and APP/PS1 TG mice showed cognitive dysfunction, which was evaluated by various behavioral tests. HJW treatment significantly attenuated memory impairments in Aß-injected mice and APP/PS1 TG mice. Aß injection decreased acetylcholine (ACh) concentrations and choline acetyltransferase (ChAT) activity, and increased acetylcholinesterase (AChE) activity. These cholinergic impairments were also found in APP/PS1 TG mice. HJW significantly attenuated cholinergic alterations in Aß-injected mice and TG mice. In addition, HJW significantly decreased Aß plaque deposition in the cerebral cortex and hippocampus of TG mice. Therefore, the present study demonstrated that HJW protected against AD-related memory impairments via enhancing the cholinergic system and inhibiting Aß plaque deposition.

Korean Red Pine (Pinus densiflora) Bark Extract Attenuates Aß-Induced Cognitive Impairment by Regulating Cholinergic Dysfunction and Neuroinflammation.

In this study, we investigated the anti-amnesic effect of Korean red pine (Pinus densiflora) bark extract (KRPBE) against amyloid beta1-42 (Aß1-42)-induced neurotoxicity. We found that treatment with KRPBE improved the behavioral function in Aß-induced mice, and also boosted the antioxidant system in mice by decreasing malondialdehyde (MDA) content, increasing superoxide dismutase (SOD) activities, and reducing glutathione (GSH) levels. In addition, KRPBE improved the cholinergic system by suppressing reduced acetylcholine (ACh) content while also activating acetylcholinesterase (AChE), regulating the expression of choline acetyltransferase (ChAT), postsynaptic density protein-95 (PSD-95), and synaptophysin. KRPBE also showed an ameliorating effect on cerebral mitochondrial deficit by regulating reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and ATP levels. Moreover, KRPBE modulated the expression levels of neurotoxicity indicators Aß and phosphorylated tau (p-tau) and inflammatory cytokines TNF-α, p-IκB-α, and IL-1ß. Furthermore, we found that KRPBE improved the expression levels of neuronal apoptosis-related markers BAX and BCl-2 and increased the expression levels of BDNF and p-CREB. Therefore, this study suggests that KRPBE treatment has an anti-amnestic effect by modulating cholinergic system dysfunction and neuroinflammation in Aß1-42-induced cognitive impairment in mice.

Effect of natural products on diabetes associated neurological disorders.

Diabetes mellitus, a metabolic disorder, is associated with neurological complications such as depression, anxiety, hypolocomotion, cognitive dysfunction, phobias, anorexia, stroke, pain, etc. Traditional system of medicine is long known for its efficient management of diabetes. The current review discusses the scope of some common medicinal herbs as well as secondary metabolites with a special focus on diabetes-mediated central nervous system complications. Literatures suggest that natural products reduce diabetes-mediated neurological complications partly by reducing oxidative stress and/or inflammation or apoptosis in certain brain regions. Natural products are known to modulate diabetes-mediated alterations in the level of acetylcholinesterase, choline acetyltransferase, monoamine oxidase, serotonin receptors, muscarinic receptors, insulin receptor, nerve growth factor, brain-derived neurotrophic factor, and neuropeptide in brain. Further, there are several natural products reported to manage diabetic complications with unknown mechanism. In conclusion, medicinal plants or their secondary metabolites have a wide scope and possess therapeutic potential to effectively manage neurological complications associated with chronic diabetes.

Complementary remedy of aged-related learning and memory deficits via exogenous choline acetyltransferase.

The present study aimed to examine whether the aged mice with naturally occurring cognitive deficits in learning and memory would benefit from supplementation of choline acetyltransferase (ChAT), the biosynthetic enzyme for neurotransmitter acetylcholine. Delivered by protein transduction domain (PTD), ChAT could pass through the blood-brain barrier, enter the neurons, interact with heat shock protein 70kDa, and retain enzyme activity. In behavior tests, PTD-ChAT given to the aged and memory-deficient mice almost completely reversed the behavioral changes, such as impairment of memory retention in the step-through test (an index of long-term memory) and prolonged swimming time in water maze test (an index of spatial recognition memory). The results suggest a novel and potential therapeutic use of PTD-ChAT in the age-related cognitive deficits.