Notoginsenoside R1 ameliorates mitochondrial dysfunction to circumvent neuronal energy failure in acute phase of focal cerebral ischemia

Abstract

Due to sudden loss of cerebral blood circulation, acute ischemic stroke (IS) causes neuronal energy attenuation or even exhaustion by mitochondrial dysfunction resulting in aggravation of neurological injury. In this study, we investigated if Notoginsenoside R1 ameliorated cerebral energy metabolism by limiting neuronal mitochondrial dysfunction in acute IS. Male Sprague–Dawley rats (260–280 g) were selected and performed by permanent middle cerebral artery occlusion model. In vitro, the oxygen glucose deprivation (OGD) model of Neuro2a (N2a) cells was established. We found Notoginsenoside R1 treatment reduced rats' cerebral infarct volume and neurological deficits, with increased Adenosine triphosphate (ATP) level together with upregulated expression of glucose transporter 1/3, monocarboxylate transporter 1 and citrate synthase in brain peri‐ischemic tissue. In vitro, OGD‐induced N2a cell death was inhibited, cell mitochondrial morphology was improved. Mitochondrial amount, mitochondrial membrane potential, and mitochondrial DNA copy number were increased by Notoginsenoside R1 administration. Furthermore, mitochondrial energy metabolism‐related mRNA array found Atp12a and Atp6v1g3 gene expression were upregulated more than twofold, which were also verified in rat ischemic tissue by quantitative polymerase chain reaction (qPCR) assay. Therefore, Notoginsenoside R1 administration increases cerebral glucose and lactate transportation and ATP levels, ameliorates neuronal mitochondrial function after IS. Notoginsenoside R1 may be a novel protective agent for neuronal mitochondria poststroke.

Improving the developmental competences of porcine parthenogenetic embryos by Notoginsenoside R1‐induced enhancement of mitochondrial activity and alleviation of proapoptotic events

“…NGR1 has expressed capabilities such as antioxidant generation (Li et al, 2021; Luo et al, 2022; Zhao et al, 2020), apoptosis inhibition (Liu et al, 2021; Zhu et al, 2020), autophagy attenuation (Cao et al, 2021), mitochondrial function protection (Liu et al, 2021, 2022; Wang, Tang, et al, 2021; Wang, Wu, et al, 2021), and lipid metabolism regulation (Lei et al, 2022; Tian et al, 2022). However, its effect on early porcine embryos has so far remained unclear.…”

“…As a traditional Panax ginseng medicinal extract, NGR1 is recognized and commonly used in Chinese herbal medicine. Several studies have observed that specific NGR1 doses can enhance early embryonic development by protecting mitochondria function and thereby reducing oxidative stress (Liu et al, 2022; Luo et al, 2022; Meng et al, 2014; Sun et al, 2013). However, NGR1's effect on preimplantation porcine embryonic development has remained unclear.…”

Traditional Chinese medicine in treating ischemic stroke by modulating mitochondria: A comprehensive overview of experimental studies

“…However, these mitochondrial abnormalities were prevented by piperine pretreatment ( Kaushik et al, 2021 ). In vitro , OGD/R induced mitochondrial fragmentation, mitochondrial enlargement, mitochondrial number reduction, and mitochondrial swelling, which could be alleviated by pretreatment with notoginsenoside R1 ( Zhu et al, 2021 ; Liu et al, 2022 ), hydroxysafflor yellow A ( Huang et al, 2021 ), and calenduloside E ( Li et al, 2022b ). Ginsenoside Rd and piperine pretreatment improved mitochondrial energy metabolism after cerebral I/R injury ( Ye et al, 2011 ; Kaushik et al, 2021 ) whereas notoginsenoside R1 and notoginseng leaf triterpene pretreatment improved mitochondrial energy metabolism after OGD/R injury ( Xie et al, 2020 ; Zhu et al, 2021 ; Liu et al, 2022 ).…”

“…In vitro , OGD/R induced mitochondrial fragmentation, mitochondrial enlargement, mitochondrial number reduction, and mitochondrial swelling, which could be alleviated by pretreatment with notoginsenoside R1 ( Zhu et al, 2021 ; Liu et al, 2022 ), hydroxysafflor yellow A ( Huang et al, 2021 ), and calenduloside E ( Li et al, 2022b ). Ginsenoside Rd and piperine pretreatment improved mitochondrial energy metabolism after cerebral I/R injury ( Ye et al, 2011 ; Kaushik et al, 2021 ) whereas notoginsenoside R1 and notoginseng leaf triterpene pretreatment improved mitochondrial energy metabolism after OGD/R injury ( Xie et al, 2020 ; Zhu et al, 2021 ; Liu et al, 2022 ). In vivo ( Ye et al, 2011 ; Mukherjee et al, 2019 ; Zhang et al, 2019 ; Huang et al, 2021 ; Kaushik et al, 2021 ) and in vitro ( Li et al, 2017 ; Wu et al, 2017 ; Zhou et al, 2017 ; Huang et al, 2020 ; Xie et al, 2020 ; Li et al, 2021 ; Huang et al, 2021 ; Li et al, 2022b ; Ni et al, 2022 ; Peng et al, 2022 ) studies have reported that TCM compounds (e.g., piperine, ginsenoside Rd, hydroxysafflor yellow A, β-patchoulene, curcumin, ginsenoside Rb1, artemether, notoginseng leaf triterpenes, ginkgolide k, ginsenoside monomer compound k, tanshinone IIA, artemisinin, and kaempferol) inhibited oxidative stress and mPTP and upregulated MMP levels.…”

“…Mitochondria are highly dynamic cellular organelles that can change the shape, size, position, and integrity of mitochondrial DNA (mtDNA) through highly coordinated fission, fusion, and transport to tactical locations. The imbalance of mitochondrial fission and fusion after stroke may increase mitochondrial fragmentation, cause aberrant mitochondrial morphology, and disrupt mitochondrial homeostasis, leading to mitochondrial dysfunction and ultimately triggering neuronal death (Li et al, 2022). Additionally, mutation of gene-encoded subunits in mtDNA results in increased ROS generation, which makes mtDNA more susceptible to mutations than nuclear DNA .…”