Hopeahainol A attenuates memory deficits by targeting β‐amyloid in APP/PS1 transgenic mice

Abstract

SummaryIncreasing evidence demonstrates that amyloid beta (Ab) elicits mitochondrial dysfunction and oxidative stress, which contributes to the pathogenesis of Alzheimer's disease (AD). Identification of the molecules targeting Ab is thus of particular significance in the treatment of AD. Hopeahainol A (HopA), a polyphenol with a novel skeleton obtained from Hopea hainanensis, is potentially acetylcholinesterase-inhibitory and anti-oxidative in H 2 O 2 -treated PC12 cells. In this study, we reported that HopA might bind to Ab 1-42 directly and inhibit the Ab 1-42 aggregation using a combination of molecular dynamics simulation, binding assay, transmission electron microscopic analysis and staining technique. We also demonstrated that HopA decreased the interaction between Ab 1-42 and Ab-binding alcohol dehydrogenase, which in turn reduced mitochondrial dysfunction and oxidative stress in vivo and in vitro. In addition, HopA was able to rescue the long-term potentiation induction by protecting synaptic function and attenuate memory deficits in APP/PS1 mice. Our data suggest that HopA might be a promising drug for therapeutic intervention in AD.

Oridonin Attenuates Synaptic Loss and Cognitive Deficits in an Aβ1–42-Induced Mouse Model of Alzheimer’s Disease

“…Aβ 1–42 was prepared with 1% NH 3 xH 2 O at a concentration of 1 mg/ml and incubated at 37°C for 5 days to allow for oligomerization as described previously[ 20 ]. Ori was dissolved in DMSO at a concentration of 20 mg/ml and diluted to the desired concentration in saline as described previously[ 19 ].…”

CART treatment improves memory and synaptic structure in APP/PS1 mice

“…Intracellular 4-hydroxy-2-nonenal (4-HNE) and 8-hydroxydeoxyguanosine (8-OHdG) levels in the hippocampus and cortex (n = 3 per group) were measured as previously described 36 . Briefly, the samples were added into the microplate pre-coated with mouse 4-HNE or 8-OHdG antibody.…”

Pictet–Spengler reaction-based biosynthetic machinery in fungi

“…In this sense, the investigation strengthens the access to novel biocatalysts organized cryptically in the microbial biosynthetic machineries. As a result of complicated microbial interactions with external chemicals such as 1-methyltryptophan used here, more potentially bioactive unnatural natural products can be generated as exemplified by the characterization of chaetoglines A−H (1-8), of which 2 and 6 are potently antibacterial to pathogens as health risks (43), with the latter being additionally inhibitory on AChE as a proven target for treating Alzheimer's disease (21,22).…”

“…Chaetoglines B (2) and F (6) have been found to be more antibacterial than tinidazole (a coassayed drug prescribed in clinic for bacterial infections) against pathogenic anaerobes Veillonella parvula, Bacteroides vulgatus, Streptococcus sp., and Peptostreptococcus sp. Moreover, alkaloid 6 is potently inhibitory on acetylcholinesterase (AChE), an effective target enzyme exploited for the treatment of Alzheimer's disease (21,22).…”