Abstract
Notoginsenoside R1 (NGR1) is an active compound isolated from Panax notoginseng. Despite the NGR1 having been used as a traditional medicine, little is known about the neuroprotective effects. In this study, we investigate the protective effects of NGR1 against glutamate-induced cytotoxicity in HT22 cells and its possible molecular mechanism. We assessed the toxicity of NGR1 and the protective activity by MTT assay. The levels of oxidative stress indices superoxide dismutase (SOD), glutathione (GSH), and mitochondrial membrane potential (MMP) were measured by the kits. The levels of reactive oxygen species (ROS) and Ca2+ concentration were measured by flow cytometry. Furthermore, we determined the expression of mitochondrial dysfunction related protein PINK1, Parkin, silent mating type information regulation 2 homolog-1 (sirtuin 1; SIRT1), and Wnt/β-catenin by Western blotting. Here, we discovered that glutamate treatment led to cell viability loss, apoptosis facilitation, Ca2+ upregulation, MMP fluorescence intensity downregulation, and ROS generation of HT22 cells. In parallel, expression of Parkin was declined by glutamate. While, NGR1 treatment alleviated all the above phenomena. We further clarified that NGR1 alleviated glutamate-induced oxidative stress, apoptosis, and mitochondrial dysfunction by upregulating SIRT1 to activate Wnt/β-catenin pathways. These findings demonstrate that NGR1 alleviated glutamate-induced cell damage, and NGR1 may play a protective role in neurological complications.
Highlights
Oxidative stress caused by the accumulation of reactive oxygen species (ROS) is related to the development of many neurological complications [1, 2]
Oxidative stress caused by the accumulation of reactive oxygen species (ROS) in nerve cells is associated with neurological complications, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and neuropathic pain [15,16,17]. e antioxidants are the first defense to detoxify ROS [14]
We provide evidence that Notoginsenoside R1 (NGR1) alleviates glutamate-induced apoptosis, oxidative stress, and mitochondrial dysfunction, simultaneously restoring Ca2+ back to near normal
Summary
Oxidative stress caused by the accumulation of reactive oxygen species (ROS) is related to the development of many neurological complications [1, 2]. Excessive ROS induces oxidative stress and apoptosis in neuronal cells [3]. Extracting compounds with antioxidant activity and neuroprotective effects from plants is a potential alternative therapy for neurological complications [4], erefore, the identification of compounds of plants that inhibit oxidative stress in neuronal cells is crucial to protect the nervous system complications. Notoginsenoside R1 (NGR1) is an active compound isolated from Panax notoginseng [5, 6]. It has antioxidant, anti-inflammatory, antiapoptotic, and antitumor effects [7]. We found that NGR1 alleviated glutamate-induced oxidative stress and apoptosis by upregulating SIRT1 to activate the Wnt/β-catenin pathway
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