Detecting Key Functional Components Group and Speculating the Potential Mechanism of Xiao-Xu-Ming Decoction in Treating Stroke
Stroke is a cerebrovascular event with cerebral blood flow interruption which is caused by occlusion or bursting of cerebral vessels. At present, the main methods in treating stroke are surgical treatment, statins, and recombinant tissue-type plasminogen activator (rt-PA). Relatively, traditional Ch...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.753425/full |
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| author | Yu-peng Chen Yu-peng Chen Ke-xin Wang Jie-qi Cai Jie-qi Cai Yi Li Hai-lang Yu Hai-lang Yu Qi Wu Wei Meng Wei Meng Handuo Wang Handuo Wang Chuan-hui Yin Chuan-hui Yin Jie Wu Jie Wu Mian-bo Huang Rong Li Dao-gang Guan Dao-gang Guan |
| author_facet | Yu-peng Chen Yu-peng Chen Ke-xin Wang Jie-qi Cai Jie-qi Cai Yi Li Hai-lang Yu Hai-lang Yu Qi Wu Wei Meng Wei Meng Handuo Wang Handuo Wang Chuan-hui Yin Chuan-hui Yin Jie Wu Jie Wu Mian-bo Huang Rong Li Dao-gang Guan Dao-gang Guan |
| author_sort | Yu-peng Chen |
| collection | DOAJ |
| description | Stroke is a cerebrovascular event with cerebral blood flow interruption which is caused by occlusion or bursting of cerebral vessels. At present, the main methods in treating stroke are surgical treatment, statins, and recombinant tissue-type plasminogen activator (rt-PA). Relatively, traditional Chinese medicine (TCM) has widely been used at clinical level in China and some countries in Asia. Xiao-Xu-Ming decoction (XXMD) is a classical and widely used prescription in treating stroke in China. However, the material basis of effect and the action principle of XXMD are still not clear. To solve this issue, we designed a new system pharmacology strategy that combined targets of XXMD and the pathogenetic genes of stroke to construct a functional response space (FRS). The effective proteins from this space were determined by using a novel node importance calculation method, and then the key functional components group (KFCG) that could mediate the effective proteins was selected based on the dynamic programming strategy. The results showed that enriched pathways of effective proteins selected from FRS could cover 99.10% of enriched pathways of reference targets, which were defined by overlapping of component targets and pathogenetic genes. Targets of optimized KFCG with 56 components can be enriched into 166 pathways that covered 80.43% of 138 pathways of 1,012 pathogenetic genes. A component potential effect score (PES) calculation model was constructed to calculate the comprehensive effective score of components in the components-targets-pathways (C-T-P) network of KFCGs, and showed that ferulic acid, zingerone, and vanillic acid had the highest PESs. Prediction and docking simulations show that these components can affect stroke synergistically through genes such as MEK, NFκB, and PI3K in PI3K-Akt, cAMP, and MAPK cascade signals. Finally, ferulic acid, zingerone, and vanillic acid were tested to be protective for PC12 cells and HT22 cells in increasing cell viabilities after oxygen and glucose deprivation (OGD). Our proposed strategy could improve the accuracy on decoding KFCGs of XXMD and provide a methodologic reference for the optimization, mechanism analysis, and secondary development of the formula in TCM. |
| first_indexed | 2024-04-10T21:14:23Z |
| format | Article |
| id | doaj.art-90353939eec14f53abf402e956e59816 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-10T21:14:23Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-90353939eec14f53abf402e956e598162023-01-20T12:46:05ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-05-011010.3389/fcell.2022.753425753425Detecting Key Functional Components Group and Speculating the Potential Mechanism of Xiao-Xu-Ming Decoction in Treating StrokeYu-peng Chen0Yu-peng Chen1Ke-xin Wang2Jie-qi Cai3Jie-qi Cai4Yi Li5Hai-lang Yu6Hai-lang Yu7Qi Wu8Wei Meng9Wei Meng10Handuo Wang11Handuo Wang12Chuan-hui Yin13Chuan-hui Yin14Jie Wu15Jie Wu16Mian-bo Huang17Rong Li18Dao-gang Guan19Dao-gang Guan20Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, National Key Clinical Specialty/Engineering Technology Research Center of Education Ministry of China, Neurosurgery Institute, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, Guangzhou, ChinaDepartment of Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, Guangzhou, ChinaDepartment of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, Guangzhou, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, Guangzhou, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, Guangzhou, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, Guangzhou, ChinaDepartment of Histology and Embryology, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Cardiovascular Disease, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, Guangzhou, ChinaStroke is a cerebrovascular event with cerebral blood flow interruption which is caused by occlusion or bursting of cerebral vessels. At present, the main methods in treating stroke are surgical treatment, statins, and recombinant tissue-type plasminogen activator (rt-PA). Relatively, traditional Chinese medicine (TCM) has widely been used at clinical level in China and some countries in Asia. Xiao-Xu-Ming decoction (XXMD) is a classical and widely used prescription in treating stroke in China. However, the material basis of effect and the action principle of XXMD are still not clear. To solve this issue, we designed a new system pharmacology strategy that combined targets of XXMD and the pathogenetic genes of stroke to construct a functional response space (FRS). The effective proteins from this space were determined by using a novel node importance calculation method, and then the key functional components group (KFCG) that could mediate the effective proteins was selected based on the dynamic programming strategy. The results showed that enriched pathways of effective proteins selected from FRS could cover 99.10% of enriched pathways of reference targets, which were defined by overlapping of component targets and pathogenetic genes. Targets of optimized KFCG with 56 components can be enriched into 166 pathways that covered 80.43% of 138 pathways of 1,012 pathogenetic genes. A component potential effect score (PES) calculation model was constructed to calculate the comprehensive effective score of components in the components-targets-pathways (C-T-P) network of KFCGs, and showed that ferulic acid, zingerone, and vanillic acid had the highest PESs. Prediction and docking simulations show that these components can affect stroke synergistically through genes such as MEK, NFκB, and PI3K in PI3K-Akt, cAMP, and MAPK cascade signals. Finally, ferulic acid, zingerone, and vanillic acid were tested to be protective for PC12 cells and HT22 cells in increasing cell viabilities after oxygen and glucose deprivation (OGD). Our proposed strategy could improve the accuracy on decoding KFCGs of XXMD and provide a methodologic reference for the optimization, mechanism analysis, and secondary development of the formula in TCM.https://www.frontiersin.org/articles/10.3389/fcell.2022.753425/fullXXMDKFCGnetwork pharmacologyfunctional response spaceeffective proteinsPC12 cells |
| spellingShingle | Yu-peng Chen Yu-peng Chen Ke-xin Wang Jie-qi Cai Jie-qi Cai Yi Li Hai-lang Yu Hai-lang Yu Qi Wu Wei Meng Wei Meng Handuo Wang Handuo Wang Chuan-hui Yin Chuan-hui Yin Jie Wu Jie Wu Mian-bo Huang Rong Li Dao-gang Guan Dao-gang Guan Detecting Key Functional Components Group and Speculating the Potential Mechanism of Xiao-Xu-Ming Decoction in Treating Stroke Frontiers in Cell and Developmental Biology XXMD KFCG network pharmacology functional response space effective proteins PC12 cells |
| title | Detecting Key Functional Components Group and Speculating the Potential Mechanism of Xiao-Xu-Ming Decoction in Treating Stroke |
| title_full | Detecting Key Functional Components Group and Speculating the Potential Mechanism of Xiao-Xu-Ming Decoction in Treating Stroke |
| title_fullStr | Detecting Key Functional Components Group and Speculating the Potential Mechanism of Xiao-Xu-Ming Decoction in Treating Stroke |
| title_full_unstemmed | Detecting Key Functional Components Group and Speculating the Potential Mechanism of Xiao-Xu-Ming Decoction in Treating Stroke |
| title_short | Detecting Key Functional Components Group and Speculating the Potential Mechanism of Xiao-Xu-Ming Decoction in Treating Stroke |
| title_sort | detecting key functional components group and speculating the potential mechanism of xiao xu ming decoction in treating stroke |
| topic | XXMD KFCG network pharmacology functional response space effective proteins PC12 cells |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.753425/full |
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