Neuroprotective effects of hawthorn leaf flavonoids in Aβ_25–35‐induced Alzheimer's disease model

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by β‐amyloid (Aβ) plaques, neurofibrillary tangles, neuronal cell loss, and oxidative stress. Further deposition of Aβ in the brain induces oxidative stress, neuroinflammation, and memory dysfunction. Hawthorn (Crataegus pinnatifida Bge.) leaf, a known traditional Chinese medicine, is commonly used for the treatment of hyperlipidemia, heart palpitations, forgetfulness, and tinnitus, and its main bioactive components are Hawthorn Leaf Flavonoids (HLF). In this study, we investigated the neuroprotective effects of the HLF on the Aβ25–35 (bilateral hippocampus injection) rat model of AD. The results showed that the oral administration of HLF at a dose of 50, 100, and 200 mg/kg for 30 days significantly ameliorated neuronal cell damage and memory deficits, and markedly increased the enzyme activities of superoxide dismutase and catalase, and the content of glutathione whereas it decreased the malondialdehyde content in the Aβ25–35 rat model of AD as well as suppressed the activation of astrocytes. In addition, HLF up‐regulated Nrf‐2, NQO‐1, and HO‐1 protein expressions. Also, it reduced neuroinflammation by inhibiting activation of astrocytes. In summary, these results indicated that HLF decreased the oxidative stress via activating Nrf‐2/antioxidant response element signaling pathways, and may suggest as a potential candidate for AD therapeutic agent.

Natural antioxidants that act against Alzheimer’s disease through modulation of the NRF2 pathway: a focus on their molecular mechanisms of action

“…HLF was administered at doses of 50, 100, and 200 mg/kg for a period of 30 days and showed a significant improvement in neuronal damage and memory deficits, an increase in the activity and levels of the antioxidant enzymes SOD, CAT, and GSH, and a decrease in MDA. HLF reduced oxidative stress specifically through activation of the NRF2/ARE signaling pathway ( 107 ).…”

Rapid determination of four flavonoids from hawthorn leaves in plasma by ultra‐high performance liquid chromatography‐tandem mass spectrometry and study on its pharmacokinetics

“…[1], with the effects of activating blood flow and removing blood stasis [2][3][4][5]. Hawthorn leaf extract is a liquid obtained by extracting hawthorn leaf powder with 50% ethanol and elution with D101 macroporous resin or extracted by ultrasonic extraction after adding 60% methanol [6][7][8]. It has been reported that hawthorn leaf extract can reduce blood plasma viscosity, promote hemoglobin degradation, and increase the number of platelets to possess therapeutic effects on the cardiovascular systems [9].…”

“…The extract is a complex multicomponent system including flavonoids, sterols, terpenes, organic acids, etc. ; flavonoids are the main active ingredients [4,7,8].…”