Study on the Neuroprotective Effects of Eight Iridoid Components Using Cell Metabolomics
Iridoid components have been reported to have significant neuroprotective effects. However, it is not yet clear whether the efficacy and mechanisms of iridoid components with similar structures are also similar. This study aimed to compare the neuroprotective effects and mechanisms of eight iridoid...
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MDPI AG
2024-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/29/7/1497 |
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| author | Bingxian Zhang Ning Zhou Zhenkai Zhang Ruifeng Wang Long Chen Xiaoke Zheng Weisheng Feng |
| author_facet | Bingxian Zhang Ning Zhou Zhenkai Zhang Ruifeng Wang Long Chen Xiaoke Zheng Weisheng Feng |
| author_sort | Bingxian Zhang |
| collection | DOAJ |
| description | Iridoid components have been reported to have significant neuroprotective effects. However, it is not yet clear whether the efficacy and mechanisms of iridoid components with similar structures are also similar. This study aimed to compare the neuroprotective effects and mechanisms of eight iridoid components (catalpol (CAT), genipin (GE), geniposide (GEN), geniposidic acid (GPA), aucubin (AU), ajugol (AJU), rehmannioside C (RC), and rehmannioside D (RD)) based on corticosterone (CORT)-induced injury in PC12 cells. PC12 cells were randomly divided into a normal control group (NC), model group (M), positive drug group (FLX), and eight iridoid administration groups. Firstly, PC12 cells were induced with CORT to simulate neuronal injury. Then, the MTT method and flow cytometry were applied to evaluate the protective effects of eight iridoid components on PC12 cell damage. Thirdly, a cell metabolomics study based on ultra-performance liquid chromatography–quadrupole–time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was performed to explore changes in relevant biomarkers and metabolic pathways following the intervention of administration. The MTT assay and flow cytometry analysis showed that the eight iridoid components can improve cell viability, inhibit cell apoptosis, reduce intracellular ROS levels, and elevate MMP levels. In the PCA score plots, the sample points of the treatment groups showed a trend towards approaching the NC group. Among them, AU, AJU, and RC had a weaker effect. There were 38 metabolites (19 metabolites each in positive and negative ion modes, respectively) identified as potential biomarkers during the experiment, among which 23 metabolites were common biomarkers of the eight iridoid groups. Pathway enrichment analysis revealed that the eight iridoid components regulated the metabolism mainly in relation to D-glutamine and D-glutamate metabolism, arginine biosynthesis, the TCA cycle, purine metabolism, and glutathione metabolism. In conclusion, the eight iridoid components could reverse an imbalanced metabolic state by regulating amino acid neurotransmitters, interfering with amino acid metabolism and energy metabolism, and harmonizing the level of oxidized substances to exhibit neuroprotective effects. |
| first_indexed | 2024-04-24T10:39:22Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-24T10:39:22Z |
| publishDate | 2024-03-01 |
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| spelling | doaj.art-a89343612b2a4b4383e9a3095f4027802024-04-12T13:23:13ZengMDPI AGMolecules1420-30492024-03-01297149710.3390/molecules29071497Study on the Neuroprotective Effects of Eight Iridoid Components Using Cell MetabolomicsBingxian Zhang0Ning Zhou1Zhenkai Zhang2Ruifeng Wang3Long Chen4Xiaoke Zheng5Weisheng Feng6College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, ChinaCollege of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, ChinaCollege of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, ChinaCollege of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, ChinaCollege of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, ChinaCollege of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, ChinaCollege of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, ChinaIridoid components have been reported to have significant neuroprotective effects. However, it is not yet clear whether the efficacy and mechanisms of iridoid components with similar structures are also similar. This study aimed to compare the neuroprotective effects and mechanisms of eight iridoid components (catalpol (CAT), genipin (GE), geniposide (GEN), geniposidic acid (GPA), aucubin (AU), ajugol (AJU), rehmannioside C (RC), and rehmannioside D (RD)) based on corticosterone (CORT)-induced injury in PC12 cells. PC12 cells were randomly divided into a normal control group (NC), model group (M), positive drug group (FLX), and eight iridoid administration groups. Firstly, PC12 cells were induced with CORT to simulate neuronal injury. Then, the MTT method and flow cytometry were applied to evaluate the protective effects of eight iridoid components on PC12 cell damage. Thirdly, a cell metabolomics study based on ultra-performance liquid chromatography–quadrupole–time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was performed to explore changes in relevant biomarkers and metabolic pathways following the intervention of administration. The MTT assay and flow cytometry analysis showed that the eight iridoid components can improve cell viability, inhibit cell apoptosis, reduce intracellular ROS levels, and elevate MMP levels. In the PCA score plots, the sample points of the treatment groups showed a trend towards approaching the NC group. Among them, AU, AJU, and RC had a weaker effect. There were 38 metabolites (19 metabolites each in positive and negative ion modes, respectively) identified as potential biomarkers during the experiment, among which 23 metabolites were common biomarkers of the eight iridoid groups. Pathway enrichment analysis revealed that the eight iridoid components regulated the metabolism mainly in relation to D-glutamine and D-glutamate metabolism, arginine biosynthesis, the TCA cycle, purine metabolism, and glutathione metabolism. In conclusion, the eight iridoid components could reverse an imbalanced metabolic state by regulating amino acid neurotransmitters, interfering with amino acid metabolism and energy metabolism, and harmonizing the level of oxidized substances to exhibit neuroprotective effects.https://www.mdpi.com/1420-3049/29/7/1497iridoidPC12 cellneuronal injurycell metabolomicsUPLC-Q/TOF-MS |
| spellingShingle | Bingxian Zhang Ning Zhou Zhenkai Zhang Ruifeng Wang Long Chen Xiaoke Zheng Weisheng Feng Study on the Neuroprotective Effects of Eight Iridoid Components Using Cell Metabolomics Molecules iridoid PC12 cell neuronal injury cell metabolomics UPLC-Q/TOF-MS |
| title | Study on the Neuroprotective Effects of Eight Iridoid Components Using Cell Metabolomics |
| title_full | Study on the Neuroprotective Effects of Eight Iridoid Components Using Cell Metabolomics |
| title_fullStr | Study on the Neuroprotective Effects of Eight Iridoid Components Using Cell Metabolomics |
| title_full_unstemmed | Study on the Neuroprotective Effects of Eight Iridoid Components Using Cell Metabolomics |
| title_short | Study on the Neuroprotective Effects of Eight Iridoid Components Using Cell Metabolomics |
| title_sort | study on the neuroprotective effects of eight iridoid components using cell metabolomics |
| topic | iridoid PC12 cell neuronal injury cell metabolomics UPLC-Q/TOF-MS |
| url | https://www.mdpi.com/1420-3049/29/7/1497 |
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