Integrated transcriptomics and metabolomics analysis reveals that C3 and C5 are vital targets of DuZhi Wan in protecting against cerebral ischemic injury
Background/Aims: Duzhi Wan (DZW) has been extensively used in the prevention and treatment of ischemic stroke, but the mechanisms underlying its effects remain unclear. In this study, a combination of transcriptomics, metabolomics and network analysis was applied to identify the preventive mechanism...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222010927 |
| _version_ | 1811237658190413824 |
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| author | Jing-yi Hou Guang-zhao Cao Liang-liang Tian Rui Zhou Yi Zhang He Xu Hong-wei Wu Li-fang Wang Hong-jun Yang Jing-jing Zhang |
| author_facet | Jing-yi Hou Guang-zhao Cao Liang-liang Tian Rui Zhou Yi Zhang He Xu Hong-wei Wu Li-fang Wang Hong-jun Yang Jing-jing Zhang |
| author_sort | Jing-yi Hou |
| collection | DOAJ |
| description | Background/Aims: Duzhi Wan (DZW) has been extensively used in the prevention and treatment of ischemic stroke, but the mechanisms underlying its effects remain unclear. In this study, a combination of transcriptomics, metabolomics and network analysis was applied to identify the preventive mechanism of DZW in middle cerebral artery occlusion (MCAO)-induced ischemia/reperfusion (I/R) injury. Methods: The mice were divided into five groups: the sham group, I/R group, I/R + Ginaton group, I/R+DZW-L group, and I/R+DZW-H group. Neurological deficit scores and regional cerebral blood flow (rCBF), hematoxylin and eosin (H&E) and Nissl staining results were evaluated. Transcriptomics analysis and metabolomics analysis were applied to identify the key genes and metabolites, and qRT-PCR, ELISA, and immunofluorescence were applied to verify the key targets. Results: DZW significantly decreased the infarction size and neurological deficit scores, increased the rCBF percentage and neuronal number and improved neuronal morphology after MCAO. Transcriptomics and metabolomics analysis revealed that C3 and C5ar1 were core targets of DZW and indirectly regulated downstream purine metabolism, the pentose phosphate pathway, and glycerophospholipid metabolism-associated pathways via inflammatory cells. Moreover, ELISA, qRT-PCR, and immunofluorescence further confirmed that DZW significantly decreased the expression of C3, C5ar1, C5 and downstream inflammatory cytokines, including IL-6, IL-1β and MMP-9, at the gene and protein levels, suggesting that DZW decreased neuroinflammation and inhibited related metabolic pathways. Conclusion: C3 and C5 play important roles in the neuroprotective and antineuroinflammatory effects of DZW in protecting against cerebral I/R. This study provides novel insights into the neuroprotective effects of DZW and its clinical application. |
| first_indexed | 2024-04-12T12:27:03Z |
| format | Article |
| id | doaj.art-f13cc1c174244a75a1811d466e7cfc45 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-12T12:27:03Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-f13cc1c174244a75a1811d466e7cfc452022-12-22T03:33:08ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-11-01155113703Integrated transcriptomics and metabolomics analysis reveals that C3 and C5 are vital targets of DuZhi Wan in protecting against cerebral ischemic injuryJing-yi Hou0Guang-zhao Cao1Liang-liang Tian2Rui Zhou3Yi Zhang4He Xu5Hong-wei Wu6Li-fang Wang7Hong-jun Yang8Jing-jing Zhang9Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China; Corresponding authors at: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; Chinese Institute for Brain Research, Beijing 102206, China; Corresponding authors at: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaBackground/Aims: Duzhi Wan (DZW) has been extensively used in the prevention and treatment of ischemic stroke, but the mechanisms underlying its effects remain unclear. In this study, a combination of transcriptomics, metabolomics and network analysis was applied to identify the preventive mechanism of DZW in middle cerebral artery occlusion (MCAO)-induced ischemia/reperfusion (I/R) injury. Methods: The mice were divided into five groups: the sham group, I/R group, I/R + Ginaton group, I/R+DZW-L group, and I/R+DZW-H group. Neurological deficit scores and regional cerebral blood flow (rCBF), hematoxylin and eosin (H&E) and Nissl staining results were evaluated. Transcriptomics analysis and metabolomics analysis were applied to identify the key genes and metabolites, and qRT-PCR, ELISA, and immunofluorescence were applied to verify the key targets. Results: DZW significantly decreased the infarction size and neurological deficit scores, increased the rCBF percentage and neuronal number and improved neuronal morphology after MCAO. Transcriptomics and metabolomics analysis revealed that C3 and C5ar1 were core targets of DZW and indirectly regulated downstream purine metabolism, the pentose phosphate pathway, and glycerophospholipid metabolism-associated pathways via inflammatory cells. Moreover, ELISA, qRT-PCR, and immunofluorescence further confirmed that DZW significantly decreased the expression of C3, C5ar1, C5 and downstream inflammatory cytokines, including IL-6, IL-1β and MMP-9, at the gene and protein levels, suggesting that DZW decreased neuroinflammation and inhibited related metabolic pathways. Conclusion: C3 and C5 play important roles in the neuroprotective and antineuroinflammatory effects of DZW in protecting against cerebral I/R. This study provides novel insights into the neuroprotective effects of DZW and its clinical application.http://www.sciencedirect.com/science/article/pii/S0753332222010927Cerebral ischemia/reperfusion injuryDuzhi Wan (DZW)C3C5NeuroprotectionAntineuroinflammation |
| spellingShingle | Jing-yi Hou Guang-zhao Cao Liang-liang Tian Rui Zhou Yi Zhang He Xu Hong-wei Wu Li-fang Wang Hong-jun Yang Jing-jing Zhang Integrated transcriptomics and metabolomics analysis reveals that C3 and C5 are vital targets of DuZhi Wan in protecting against cerebral ischemic injury Biomedicine & Pharmacotherapy Cerebral ischemia/reperfusion injury Duzhi Wan (DZW) C3 C5 Neuroprotection Antineuroinflammation |
| title | Integrated transcriptomics and metabolomics analysis reveals that C3 and C5 are vital targets of DuZhi Wan in protecting against cerebral ischemic injury |
| title_full | Integrated transcriptomics and metabolomics analysis reveals that C3 and C5 are vital targets of DuZhi Wan in protecting against cerebral ischemic injury |
| title_fullStr | Integrated transcriptomics and metabolomics analysis reveals that C3 and C5 are vital targets of DuZhi Wan in protecting against cerebral ischemic injury |
| title_full_unstemmed | Integrated transcriptomics and metabolomics analysis reveals that C3 and C5 are vital targets of DuZhi Wan in protecting against cerebral ischemic injury |
| title_short | Integrated transcriptomics and metabolomics analysis reveals that C3 and C5 are vital targets of DuZhi Wan in protecting against cerebral ischemic injury |
| title_sort | integrated transcriptomics and metabolomics analysis reveals that c3 and c5 are vital targets of duzhi wan in protecting against cerebral ischemic injury |
| topic | Cerebral ischemia/reperfusion injury Duzhi Wan (DZW) C3 C5 Neuroprotection Antineuroinflammation |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222010927 |
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