Abstract
Ribes diacanthum Pall, a native Mongolian medicinal plant, has been reported to show antioxidant activities due to its polyphenol and flavonoid content, and is especially rich in the ethyl acetate fraction from an 80% methanol extraction (RDP). We assessed the cytoprotective effect of RDP on glutamate-caused oxidative stress and apoptosis in mouse hippocampal neuronal cells (HT-22 cells). Cell viability was significantly recovered by RDP treatment. Also, RDP effectively decreased the glutamate-induced production of intracellular reactive oxygen species (ROS). In flow cytometric analysis, apoptotic cells and the mitochondrial membrane potential were suppressed by RDP. In the Western blotting analysis, we found that RDP not only decreased the release of apoptotic proteins but also recovered anti-apoptotic protein. Additionally, RDP enhanced the antioxidant defense system by regulating the expression of antioxidant enzymes. Furthermore, treatment with RDP activated the BDNF/TrkB pathway. In accordance with the in vitro results, RDP meliorated memory deficit by defending hippocampal neuronal cells against oxidative damage in scopolamine-injected mice. Taken together, our present study showed that RDP exerted antioxidant and neuroprotective actions against oxidative stress. Therefore, RDP might facilitate the development of candidates for functional health foods for neurodegenerative disorders.
Highlights
Neurodegenerative disorders, like Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), and prion diseases, are characterized by the fatal loss of neuronal cells, accompanying functional regression of the nervous system in the brain [1,2]
Treatment with Ribes diacanthum Pall (RDP) at 50 significantly recovered the expression of these proteins compared to glutamate-alone-treated HT-22 μg/mL significantly recovered the expression of these proteins compared to glutamate-alone-treated cells. These results suggest that RDP exerted neuroprotective effects via the activation of both the HT-22 cells
RDP contains diverse polyphenols, including protocatechuic acid, epicatechin, catechol, syringic acid, gallic acid, and 4-methyl catechol, which have previously been reported to protect against neurodegenerative diseases [26,43,44]. These results suggest that RDP exerts neuroprotective effects by activating both the Akt/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) and extracellular signal-regulated kinase (ERK)/tyrosine receptor kinase B (TrkB)/calcium response element-binding protein (CREB) pathways, which are related to the expression of antioxidant enzymes and BDNF, respectively
Summary
Neurodegenerative disorders, like Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), and prion diseases, are characterized by the fatal loss of neuronal cells, accompanying functional regression of the nervous system in the brain [1,2]. Oxidative stress has been reported to be the main factor in progress of these neurodegenerative disorders [3]. Many associations between neuropathological processes and oxidative stress lead to neuronal damage and death [4]. Oxidative stress causes the accumulation of polyglutamate aggregates, protein misfolding, changes in intracellular mechanisms, membrane damage, mitochondrial dysfunction, and programmed cell death such as apoptosis and autophagy [5,6]. Various mechanisms suppress oxidative stress in the brain, many previous studies have reported momentous roles for the nuclear factor E2-related factor 2 (Nrf2)- signaling pathway and the expression of brain-derived neurotrophic factor (BDNF) in neuroprotective action [9,10,11,12]. The Nrf, as a transcription factor, regulates the expression of the antioxidant enzymes including NAD(P)H) quinone oxidoreductase 1 (NQO-1), glutamate-cysteine ligase catalytic subunit (GCLC), heme oxygenase 1
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