The protective effects of moscatilin against methylglyoxal-induced neurotoxicity via the regulation of p38/JNK MAPK pathways in PC12 neuron-like cells

Lai, Mei Chou; Liu, Wayne Young; Liou, Shorong‐Shii; Liu, I-Min

doi:10.1016/j.fct.2020.111369

Cited by 22 publications

(12 citation statements)

References 36 publications

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“…MGO is a reactive cytotoxic dicarbonyl compound formed during the metabolism of glucose and fructose, and its reactive activity is 20,000 times higher than that of glucose [8–10] . Lipid peroxidation, DNA degradation, and the absorption from food are the other sources of MGO [11] .…”

Section: Introductionmentioning

confidence: 99%

Potential Mechanisms of Methylglyoxal‐Induced Human Embryonic Kidney Cells Damage: Regulation of Oxidative Stress, DNA Damage, and Apoptosis

Liú

Cheng

Tang

et al. 2022

Chemistry & Biodiversity

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Methylglyoxal (MGO) is a reactive carbonyl species that can cause cellular damage and is closely related to kidney disease, especially diabetic nephropathy. The toxic effect of MGO (0.5, 1, and 2 mM) on human embryonic kidney (HEK293) cells and its underlying mechanisms were explored in this study. Cell viability, apoptosis and the signaling pathways were measured with MTT, fluorescent staining and western blot experiments, the results showed that MGO could induce oxidative stress and cell inflammation, the level of reactive oxygen species (ROS) increased, and p38MAPK, JNK and NF‐κB signaling pathways were activated. Meanwhile, MGO also induced DNA damage. The expression of DNA oxidative damage marker 8‐hydroxy‐2’‐deoxyguanosine (8‐OHdG) increased, the expression of double‐strand break marker γH2AX increased significantly, and ATM/Chk2/p53 DNA damage response signaling pathway was activated. Furthermore, the expression of the receptor for advanced glycation end products (RAGE) also increased. Finally, mitochondrial membrane potential (MMP) decreased, fluorescence intensity of Hoechst33258 increased, and the protein expression ratio of Bax/Bcl‐2 increased significantly after the treatment of MGO. These results demonstrated that MGO might induce HEK293 cells damage by regulating oxidative stress, inflammation, DNA damage, and cell apoptosis, which revealed the specific mechanisms of MGO‐induced damage to HEK293 cells.

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Section: Introductionmentioning

confidence: 99%

Potential Mechanisms of Methylglyoxal‐Induced Human Embryonic Kidney Cells Damage: Regulation of Oxidative Stress, DNA Damage, and Apoptosis

Liú

Cheng

Tang

et al. 2022

Chemistry & Biodiversity

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“…It can respond rapidly to genotoxic stresses caused by DNA damage and induce caspase-9 activation and BCL-2 expression, leading to accelerated cell apoptosis [30]. MAPK signaling pathway, including P38 and JNK, mediates cell apoptosis through combining a complex with a proapoptotic factor of p53 [31]. In addition, it can motivate the expression of in ammatory factors mediated through NF-κB signaling pathways and accelerate the kidney pathological changes [32].…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology Study Reveals the Mechanism of Astragali Radix in Treatment of Diabetic Nephropathy

Tian¹,

Chen²,

Chen³

et al. 2020

Preprint

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Background Diabetic nephropathy (DN), a unique complication of diabetes, could contribute to an increase in mortality. In this study, we predicted and proved the molecular pharmacological mechanism concerning the protective effects of Astragali Radix on DN. Methods The same potential target genes from Astragali Radix and DN were analyzed and constructed the protein interaction network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment-related major targets and signal pathways were performed. The drug-ingredients-target-disease network was visually built using Cytoscape 3.6.1. The beneficial pharmacological activities of quercetin from Astragali Radix were confirmed by CCK-8 assay, determination of antioxidant parameters and Western blotting analysis. Results There are 12 bioactive components from Astragali Radix and 56 same targets between Astragali Radix and DN. The GO analysis results showed that the biological processes mainly included protein homodimerization activity. KEGG analysis indicate that the screened targets were most closely linked to the mitogen-activated protein kinase (MAPK) signaling pathway. The drug-ingredients-target-disease network results revealed that the therapeutic effects of Astragali Radix mainly included oxidative stress, inflammatory reaction and apoptosis. During the verification process, quercetin from Astragali Radix could attenuate cytotoxicity, enhance catalase (CAT) and superoxide dismutase (SOD) activities and suppress MAPK signaling pathway. Conclusions In the current study, network pharmacology with experimental analysis predicted and proved the therapeutic function of Astragali Radix by improving antioxidant capacity and suppressing MAPK signaling pathway, these investigations could provide a new perspective for further exploration of Astragali Radix on DN treatment.

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“…In addition to evaluating the effects of R. rosea root extract and fraction layers on AchE inhibition, we further investigated their neuroprotective effects on MG-induced cellular damage. Neuroprotection studies were performed on different cell lines, including SH-SY5Y human neuroblastoma cells [20], N2A mouse neuroblastoma cells [21,22], murine BV2 microglia cells [19,23], and PC-12 neuro-like cells [24]. The N2A cell line was applied extensively to screen compounds for neurotoxic/neuroprotective properties [21,25,26].…”

Section: Neuroprotective Activitymentioning

confidence: 99%

Protective Evaluation of Compounds Extracted from Root of Rhodiola rosea L. against Methylglyoxal-Induced Toxicity in a Neuronal Cell Line

et al. 2020

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Rhodiola rosea L. (R. rosea) is one of the most beneficial medicinal plants and it is studied as an adaptogen. This study aims to evaluate the neuroprotective activity of compounds extracted from the root of R. rosea against methylglyoxal (MG)-induced apoptosis in neuro-2A (N2A) cells. The root of R. rosea was extracted with ethanol and partitioned with water, ethyl acetate, and n-butanol fractions to evaluate acetylcholinesterase (AChE) inhibitory activity and neuroprotective activity. The ethyl acetate fraction exhibited the highest values of AChE inhibitory activity (49.2% ± 3%) and cell viability (50.7% ± 4.8%) for neuroprotection. The structure identification of the most potential fraction (ethyl acetate fraction) revealed 15 compounds, consisting of three tannins, five flavonoids, and seven phenolics by infrared spectroscopy, nuclear magnetic resonance, and mass spectroscopy. All compounds were evaluated for their neuroprotective activity. Salidroside had the most potential neuroprotective activity. Gallic acid and methyl gallate had potential cytotoxicity in N2A cells. This study showed that R. rosea might have potential neuroprotective activities.

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The protective effects of moscatilin against methylglyoxal-induced neurotoxicity via the regulation of p38/JNK MAPK pathways in PC12 neuron-like cells

Cited by 22 publications

References 36 publications

Potential Mechanisms of Methylglyoxal‐Induced Human Embryonic Kidney Cells Damage: Regulation of Oxidative Stress, DNA Damage, and Apoptosis

Potential Mechanisms of Methylglyoxal‐Induced Human Embryonic Kidney Cells Damage: Regulation of Oxidative Stress, DNA Damage, and Apoptosis

Network Pharmacology Study Reveals the Mechanism of Astragali Radix in Treatment of Diabetic Nephropathy

Protective Evaluation of Compounds Extracted from Root of Rhodiola rosea L. against Methylglyoxal-Induced Toxicity in a Neuronal Cell Line

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