Catalpol preserves neural function and attenuates the pathology of Alzheimer's disease in mice

Abstract

Alzheimer's disease (AD) is the most common form of dementia and there currently are no effective treatment strategies available. Catalpol is an iridoid glucoside, and large quantities can be isolated from the genus Rehmannia (Orobanchaceae). The present study assessed whether catalpol had any protective effects against Alzheimer's disease using a murine model. Reactive oxygen species (ROS)-associated enzymes as well as soluble Aβ40 and Aβ42 were detected using kits. Thioflavin‑S staining was performed to detect senile plaques and reverse-transcription quantitative polymerase chain reaction was used to assess iroquois homeobox protein 3 (IRX3) and obesity‑associated genes, while western blot analysis was used for β‑secretase 1 (BACE1), insulin‑degrading enzyme (IDE) and neprilysin (NEP) detection. The Morris water maze was used to detect the learning ability and spatial memory. The results revealed that catalpol was able to reduce the oxidative stress in the cerebral cortex by regulating the activities and concentration of ROS‑associated enzymes superoxide dismutase, glutathione peroxidase and catalase, however not malondialdehyde. Catalpol was also identified to be able to reduce the levels of soluble Aβ40 and Aβ42 in the cerebral cortex and thus inhibit the formation of senile plaques. These effects were observed to be regulated by IDE, however not by BACE1 or NEP. It is suggested that catalpol is not capable of directly regulating the expression of IRX3 and obesity‑associated genes. Subsequent to the treatment with catalpol, impairments in learning and memory were also observed to be relieved using the Morris water maze test. The results of the present study indicate that catalpol may be a potential drug for the treatment of neurodegenerative diseases such as AD.

Antioxidant activity against H 2 O 2 -induced cytotoxicity of the ethanol extract and compounds from Pyrola decorate leaves

“…For example, evidence implied that the anti-aging effects of catalpol, an iridoid glycoside from Rehmannia, were achieved by promoting endogenous antioxidant enzyme activities and normalizing energy disturbance (Huang et al. 2016 ). However, the effect of iridoids in P. decorate targeting in the treatment of oxidative stress related neurological diseases has not been reported before.…”

Catalpol Inhibits Amyloid-β Generation Through Promoting α-Cleavage of APP in Swedish Mutant APP Overexpressed N2a Cells

“…It has been shown that catalpol plays a role in protecting primary cultured neurons against Aβ toxicity via inhibiting mitochondrion dysfunction and neuroinflammation (Jiang et al, 2008a ; Liang et al, 2009 ). Catalpol can reduce the oxidative stress, decrease the levels of soluble Aβ, and thus inhibit the plaque formation in a mouse model of AD (Huang et al, 2016 ). The present study, for the first time, has revealed the underlying mechanism of catalpol on inhibiting Aβ production: catalpol reduces Aβ generation through promoting α-cleavage of APP processing.…”

“…Advancements have been made in the use of natural products to prevent AD. Catalpol, one of the iridoid glycoside compounds extracted from Rehmannia glutinosa , has shown beneficial effects on neurodegenerative diseases, such as Parkinson’s disease (PD) and AD (Mao et al, 2007 ; Bi et al, 2008 ; Huang et al, 2016 ). Catapol has a wide range of biological activities, includinganti-oxidation, anti-inflammation, anti-aging, anti-tumor and anti-apoptosis properties (Pungitore et al, 2004 ; Bi et al, 2013 ; Chen C. et al, 2013 ; Chen W. et al, 2013 ; Wei et al, 2014 ; Yang et al, 2016 ).…”

“…In vivo studies have demonstrated that catalpol protects synaptic proteins from Aβ-induced neuronal damage and improves cognitive abilities in aged rats (Xia et al, 2017 ). By using D-(+)-galactose intraperitoneal injected mouse as an AD model, catalpol is able to reduce soluble Aβ levels in the brain and relieve learning and memory impairments, through increasing the expression level of insulin degrading enzyme (IDE) and inhibiting oxidative stress (Huang et al, 2016 ). However, whether catalpol plays a role in mediating the activity of proteolytic enzymes, such as BACE-1 and ADAM 10, has not been fully understood.…”

Human-Induced Pluripotent Stem Cells and Herbal Small-Molecule Drugs for Treatment of Alzheimer’s Disease

“…Catalpol can improve memory and reduce neurodegeneration by increasing BDNF expression [97]. In vitro, catalpol has been able to reduce the levels of soluble Aβ40 and Aβ42 in the cerebral cortex, and thus, inhibit the formation of senile plaques [98].…”