Houttuynia cordata Improves Cognitive Deficits in Cholinergic Dysfunction Alzheimer’s Disease-Like Models

Abstract

Cognitive impairment is a result of dementia of diverse causes, such as cholinergic dysfunction and Alzheimer’s disease (AD). Houttuynia cordata Thunb. (Saururaceae) has long been used as a traditional herbal medicine. It has biological activities including protective effects against amyloid beta (Aβ) toxicity, via regulation of calcium homeostasis, in rat hippocampal cells. To extend previous reports, we investigated the effects of water extracts of H. cordata herb (HCW) on tauopathies, also involving calcium influx. We then confirmed the effects of HCW in improving memory impairment and neuronal damage in mice with Aβ-induced neurotoxicity. We also investigated the effects of HCW against scopolamine-induced cholinergic dysfunction in mice. In primary neuronal cells, HCW inhibited the phosphorylation of tau by regulating p25/p35 expression in Aβ-induced neurotoxicity. In mice with Aβ-induced neurotoxicity, HCW improved cognitive impairment, as assessed with behavioral tasks, such as novel object recognition, Y-maze, and passive avoidance tasks. HCW also inhibited the degeneration of neurons in the CA3 region of the hippocampus in Aβ-induced neurotoxicity. Moreover, HCW, which had an IC50 value of 79.7 μg/ml for acetylcholinesterase inhibition, ameliorated scopolamine-induced cognitive impairment significantly in Y-maze and passive avoidance tasks. These results indicate that HCW improved cognitive impairment, due to cholinergic dysfunction, with inhibitory effects against tauopathies and cholinergic antagonists, suggesting that HCW may be an interesting candidate to investigate for the treatment of AD.

Edaravone injection ameliorates cognitive deficits in rat model of Alzheimer’s disease

“…These data indicate that edaravone inhibits AChE and ChAT to modulate cholinergic dysfunction and improve cognitive deficits. Consistent with our results, recent studies suggested that the improvement of cognitive deficits was associated the inhibition of AChE in the mouse and rat models [15,16]. In addition, a recent study demonstrated that oxidative stress was involved in the cognitive impairment in AD [17].…”

Determination of dibutyl phthalate neurobehavioral toxicity in mice

“…The characteristics of the maze have been described previously (Huh et al, 2014). This test is based on willingness of rodents to explore new environments.…”

“…After each trial the arms were cleaned with 20% ethanol to remove any residual odors. The results were expressed as described below: (Huh et al, 2014 …”

Mori Fructus improves cognitive and neuronal dysfunction induced by beta-amyloid toxicity through the GSK-3β pathway in vitro and in vivo

“…Results were expressed as percentage of novel object recognition time: Novel object recognition index¼ [(time of exploring novel object)/(time of exploring novel objectþtime of the familiar object)]  100. Y-maze test was carried out in a black three-arms with equal angles between all arms (40 cm  3 cm  12 cm) as previously described (Huh et al, 2014). An actual alternation was defined as entries into all three arms consecutively (i.e., ABC, CAB, or BAC but not ABA).…”

“…Novel objective test (NORT) was carried out in a black open field box (45 cm  45 cm  50 cm) as previously described (Huh et al, 2014). Results were expressed as percentage of novel object recognition time: Novel object recognition index¼ [(time of exploring novel object)/(time of exploring novel objectþtime of the familiar object)]  100.…”