Abstract
Euonymus alatus is considered to elicit various beneficial effects against cancer, hyperglycemia, menstrual discomfort, diabetic complications, and detoxification. The young leaves of this plant are exploited as food and also utilized for traditional medicine in East Asian countries, including Korea and China. Our preliminary study demonstrated that ethanolic extract from the Euonymus alatus leaf (EAE) exhibited the strongest antioxidant enzyme-inducing activity among more than 100 kinds of edible tree leaf extracts. This study investigated whether EAE could attenuate the cognitive deficits caused by oxidative stress in mice. Oral intubation of EAE at 100 mg/kg bw or higher resulted in significant improvements to the memory and behavioral impairment induced via i.p. injection of scopolamine. Furthermore, EAE enhanced the expression levels of hippocampal neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor in mice, activated the Nrf2, and the downstream heme oxygenase-1 (HO-1) a quintessential antioxidant enzyme. As rutin (quercetin-3-O-rutinose) was abundantly present in EAE and free quercetin was able to induce defensive antioxidant enzymes in an Nrf2-dependent manner, our findings suggested that quercetin derived from rutin via the intestinal microflora played a significant role in the protection of the mouse hippocampus from scopolamine-induced damage through BDNF-mediated Nrf2 activation, thereby dampening cognitive decline.
Highlights
As rutin was abundantly present in Euonymus alatus leaf (EAE) and free quercetin was able to induce defensive antioxidant enzymes in an Nrf2-dependent manner, our findings suggested that quercetin derived from rutin via the intestinal microflora played a significant role in the protection of the mouse hippocampus from scopolamine-induced damage through brain-derived neurotrophic factor (BDNF)-mediated Nrf2 activation, thereby dampening cognitive decline
Nuclear factor erythroid-derived 2-related factor 2 (NRF2) is one of the transcription factors that stimulate the expression of a variety of detoxifying and/or antioxidant enzymes via interaction with the antioxidant response elements (AREs) [1,2]
We hypothesized that plant extract might be able to strongly activate the Nrf2 signaling pathway, which could attenuate memory impairment caused by scopolamine, a muscarinic cholinergic receptor antagonist that alters brain oxidative stress status [5]
Summary
Nuclear factor erythroid-derived 2-related factor 2 (NRF2) is one of the transcription factors that stimulate the expression of a variety of detoxifying and/or antioxidant enzymes via interaction with the antioxidant response elements (AREs) [1,2]. Nrf signaling pathway could ameliorate cognitive defects in Alzheimer’s disease model mice [2,3,4]. The main features of Alzheimer’s disease (AD) include neuronal loss and synaptic dysfunction, which is attributable to oxidative stress mainly produced by amyloid-β(Aβ)-peptide. Numerous compounds reportedly activate the Nrf signaling pathway, a few studies examined the potential of using a plant extract or other plant constituents to improve the cognitive function of mice in an AD animal model. We hypothesized that plant extract might be able to strongly activate the Nrf signaling pathway, which could attenuate memory impairment caused by scopolamine, a muscarinic cholinergic receptor antagonist that alters brain oxidative stress status [5]. Screening of more than 100 types of plant extracts for efficacy in the stimulation of the Nrf signaling pathway using mouse
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