CZ2HF mitigates β-amyloid 25-35 fragment-induced learning and memory impairment through inhibition of neuroinflammation and apoptosis in rats

Abstract

cu-zhi-2-hao-fang (cZ2HF), a traditional chinese medicine, has been used clinically for the treatment of amnesia. However, whether cZ2HF is capable of alleviating learning and memory impairment in Alzheimer's disease (Ad) remains to be elucidated. The present study was designed to explore the effect and mechanism of cZ2HF on β-amyloid [25][26][27][28][29][30][31][32][33][34][35] )-induced impairment in the learning and memory of rats. Morris water maze test was used to determine spatial learning and memory ability in Aβ 25-35 -induced Ad rats and hippocampal neuronal damage and apoptosis were observed using hematoxylin and eosin staining, Nissl staining and terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) assays, respectively. The levels of β-amyloid 1-42 (Aβ 1-42 ), pro-inflammatory factors, such as cyclooxygenase-2 (cOX-2), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and apoptosis-associated genes including B cell leukemia/lymphoma 2 (Bcl-2), Bcl-2-associated X, apoptosis regulator (Bax), pro-caspase-3, inhibitor of κB (IκB-α) degradation and phosphorylated-nuclear factor-κB p65 (p-NF-κB p65) activation were analyzed using western blotting. The findings of the present study revealed that CZ2HF treatment significantly attenuated Aβ 25-35 -induced cognitive impairments in rats. Subsequently, cZ2HF treatment markedly inhibited neuronal damage and deletions. Furthermore, cZ2HF reduced TNF-α, IL-1β, cOX-2 protein expression levels, Bax/Bcl-2 ratio, and reduced Aβ 1-42 and active-caspase-3 levels. In addition, IκB-α degradation and p-NF-κB p65 activation were reduced by cZ2HF. These findings suggested that cZ2HF treatment improved Aβ 25-35 -induced learning and memory impairment and hippocampal neuronal injury, and its underlying mechanism may be due to the inhibition of neuroinflammation and neuronal apoptosis. cZ2HF may be a potential agent for the treatment of Ad. Abbreviations:Ad, Alzheimer's disease; cZ2HF, cu-zhi-2-hao-fang; Aβ 25-35 , β-amyloid 25-35; MWM, Morris water maze; H&E, hematoxylin and eosin; TUNEL, terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling; cOX-2, cyclooxygenase-2; TNF-α, tumor necrosis factor-α; IL-1β, interleukin-1β; NF-κB p65, nuclear factor-κB p65

A network pharmacological approach to investigate the pharmacological effects of CZ2HF decoction on Alzheimer's disease

“…Emerging evidence shows that TCM exerts excellent neuroprotective effects on AD due to its multiple active ingredients and targets. Although our previous study has revealed the therapeutic effects of CZ2HF formula on Aβ25‐35‐induced AD in rats (Zeng L et al, 2019), its therapeutic mechanisms remains still a mystery. Therefore, we applied a network pharmacology with large‐scale text‐mining, ADME screening, target predicting to decipher the active compounds, potential targets and possible mechanisms of CZ2HF formula for treatment of AD.…”

“…Its validity in AD treatment has been verified in clinic. Moreover, in our previous study, CZ2HF also showed an obvious beneficial effects on Aβ25‐35‐induced learning and memory impairment and hippocampal neuronal injury in rats (Zeng L, et al, 2019); however, its exact molecular mechanism remains still unclear. Network pharmacology approach provides a novel insight into the mechanism of anti‐AD formula and its active ingredients as the approach has superiority in the analysis of multi‐compounds, multi‐targets, and multi‐effects.…”

Protective effects of Forsythiae fructus and Cassiae semen water extract against memory deficits through the gut-microbiome-brain axis in an Alzheimer’s disease model

“… 2017a ; Zeng et al. 2019 ). In the present study, amyloid-β (25–35) infusion into the hippocampus induced amyloid-β deposition and short-term and spatial memory impairments, whereas amyloid-β (35–25) infusion did not elicit these effects.…”

Zuoguiwan Ameliorates Cognitive Deficits and Neuro-Inflammation in Streptozotocin-Induced Alzheimer’s Disease Rats

“…For instance, Kai-Xin-San, a classical Chinese traditional prescription, expedites the recovery of AD by regulating proinflammatory factors [25]. Another study conducted by Zeng et al [26] reveals that traditional Chinese medicine Cu-zhi-2-hao-fang markedly restricts the expression levels of TNF-α and IL-1β and may be an alternative agent for AD patients. In our experiment, we detected the mRNA expression levels of IL-1β, IL-6, and TNF-α by ELISA.…”