Study on the Anti-demyelination Mechanism of Bu-Shen-Yi-Sui Capsule in the Central Nervous System Based on Network Pharmacology and Experimental Verification
Background/Aims. Multiple sclerosis (MS) and neuromyelitis optica (NMO) are the most common autoimmune demyelinating diseases of the central nervous system (CNS), with some similar pathological and clinical features. Bu-Shen-Yi-Sui (BSYS) Capsule, a Chinese herbal prescription, has been shown to be...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2022/9241261 |
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| author | Zheng Zha Yi-Jiang Liu Si-Si Liu Nan Zhang Jun-Ling Li Fang Qi Liang-Yun Jin Bing Xue Tao Yang Yong-Ping Fan Hui Zhao Lei Wang |
| author_facet | Zheng Zha Yi-Jiang Liu Si-Si Liu Nan Zhang Jun-Ling Li Fang Qi Liang-Yun Jin Bing Xue Tao Yang Yong-Ping Fan Hui Zhao Lei Wang |
| author_sort | Zheng Zha |
| collection | DOAJ |
| description | Background/Aims. Multiple sclerosis (MS) and neuromyelitis optica (NMO) are the most common autoimmune demyelinating diseases of the central nervous system (CNS), with some similar pathological and clinical features. Bu-Shen-Yi-Sui (BSYS) Capsule, a Chinese herbal prescription, has been shown to be a potential therapeutic agent for MS and NMO. However, its antidemyelination mechanism in inflammatory demyelinating diseases of the CNS has not been fully clarified. This study is aimed at exploring the key components and potential mechanism of BSYS in the treatment of CNS demyelinating disease (CNSD) based on network pharmacology. Methods. The potential active ingredients and corresponding potential targets of BSYS Capsule were obtained from the TCMSP, BATMAN-TCM, Swiss Target Prediction platform, and literature research. Disease targets of CNSD were explored through the GeneCards and the DisGeNET databases. The matching targets of BSYS in CNSD were identified from a Venn diagram. The protein-protein interaction (PPI) network was constructed using bioinformatics methods. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict the mechanisms of BSYS. Furthermore, the neuroprotective effects of BSYS were evaluated using a cell model of hydrogen peroxide- (H2O2-) induced cell death in OLN-93 cells. Results. A total of 59 potential bioactive components of BSYS Capsule and 227 intersection targets were obtained. Topological analysis showed that AKT had the highest connectivity degrees in the PPI network. Enrichment analysis revealed that the targets of BSYS in the treatment of CNSD were the PI3K-Akt and MAPK signaling pathway, among other pathways. GO analysis results showed that the targets were associated with various biological processes, including apoptosis, reactive oxygen species metabolic process, and response to oxidative stress, among others. The experimental results demonstrated that BSYS drug-containing serum alleviated the H2O2-induced increase in LDH, MDA, and ROS levels and reversed the decrease in SOD and mitochondrial membrane potential induced by H2O2. BSYS treatment also decreased the number of TUNEL (+) cells, downregulated Bcl-2 expression, and upregulated Bax and c-caspase-3 expression by promoting Akt phosphorylation. Conclusion. BSYS Capsule alleviated H2O2-induced OLN-93 cell injury by increasing Akt phosphorylation to suppress oxidative stress and cell apoptosis. Therefore, BSYS can be potentially used for CNSD treatment. However, the results of this study are only derived from in vitro experiments, lacking the validation of in vivo animal models, which is a limitation of our study. We will further verify the underlying mechanisms of BSYS in animal experiments in the future. |
| format | Article |
| id | doaj-art-88041e51527a4a5ebafbd264a7d949f0 |
| institution | OA Journals |
| issn | 1466-1861 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
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| series | Mediators of Inflammation |
| spelling | doaj-art-88041e51527a4a5ebafbd264a7d949f02025-08-20T02:09:24ZengWileyMediators of Inflammation1466-18612022-01-01202210.1155/2022/9241261Study on the Anti-demyelination Mechanism of Bu-Shen-Yi-Sui Capsule in the Central Nervous System Based on Network Pharmacology and Experimental VerificationZheng Zha0Yi-Jiang Liu1Si-Si Liu2Nan Zhang3Jun-Ling Li4Fang Qi5Liang-Yun Jin6Bing Xue7Tao Yang8Yong-Ping Fan9Hui Zhao10Lei Wang11School of Traditional Chinese MedicineSchool of Traditional Chinese MedicineSchool of Traditional Chinese MedicineSchool of Traditional Chinese MedicineSchool of Traditional Chinese MedicineSchool of Traditional Chinese MedicineCore Facility CenterCore Facility CenterBeijing Tian Tan HospitalBeijing Tian Tan HospitalSchool of Traditional Chinese MedicineSchool of Traditional Chinese MedicineBackground/Aims. Multiple sclerosis (MS) and neuromyelitis optica (NMO) are the most common autoimmune demyelinating diseases of the central nervous system (CNS), with some similar pathological and clinical features. Bu-Shen-Yi-Sui (BSYS) Capsule, a Chinese herbal prescription, has been shown to be a potential therapeutic agent for MS and NMO. However, its antidemyelination mechanism in inflammatory demyelinating diseases of the CNS has not been fully clarified. This study is aimed at exploring the key components and potential mechanism of BSYS in the treatment of CNS demyelinating disease (CNSD) based on network pharmacology. Methods. The potential active ingredients and corresponding potential targets of BSYS Capsule were obtained from the TCMSP, BATMAN-TCM, Swiss Target Prediction platform, and literature research. Disease targets of CNSD were explored through the GeneCards and the DisGeNET databases. The matching targets of BSYS in CNSD were identified from a Venn diagram. The protein-protein interaction (PPI) network was constructed using bioinformatics methods. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict the mechanisms of BSYS. Furthermore, the neuroprotective effects of BSYS were evaluated using a cell model of hydrogen peroxide- (H2O2-) induced cell death in OLN-93 cells. Results. A total of 59 potential bioactive components of BSYS Capsule and 227 intersection targets were obtained. Topological analysis showed that AKT had the highest connectivity degrees in the PPI network. Enrichment analysis revealed that the targets of BSYS in the treatment of CNSD were the PI3K-Akt and MAPK signaling pathway, among other pathways. GO analysis results showed that the targets were associated with various biological processes, including apoptosis, reactive oxygen species metabolic process, and response to oxidative stress, among others. The experimental results demonstrated that BSYS drug-containing serum alleviated the H2O2-induced increase in LDH, MDA, and ROS levels and reversed the decrease in SOD and mitochondrial membrane potential induced by H2O2. BSYS treatment also decreased the number of TUNEL (+) cells, downregulated Bcl-2 expression, and upregulated Bax and c-caspase-3 expression by promoting Akt phosphorylation. Conclusion. BSYS Capsule alleviated H2O2-induced OLN-93 cell injury by increasing Akt phosphorylation to suppress oxidative stress and cell apoptosis. Therefore, BSYS can be potentially used for CNSD treatment. However, the results of this study are only derived from in vitro experiments, lacking the validation of in vivo animal models, which is a limitation of our study. We will further verify the underlying mechanisms of BSYS in animal experiments in the future.http://dx.doi.org/10.1155/2022/9241261 |
| spellingShingle | Zheng Zha Yi-Jiang Liu Si-Si Liu Nan Zhang Jun-Ling Li Fang Qi Liang-Yun Jin Bing Xue Tao Yang Yong-Ping Fan Hui Zhao Lei Wang Study on the Anti-demyelination Mechanism of Bu-Shen-Yi-Sui Capsule in the Central Nervous System Based on Network Pharmacology and Experimental Verification Mediators of Inflammation |
| title | Study on the Anti-demyelination Mechanism of Bu-Shen-Yi-Sui Capsule in the Central Nervous System Based on Network Pharmacology and Experimental Verification |
| title_full | Study on the Anti-demyelination Mechanism of Bu-Shen-Yi-Sui Capsule in the Central Nervous System Based on Network Pharmacology and Experimental Verification |
| title_fullStr | Study on the Anti-demyelination Mechanism of Bu-Shen-Yi-Sui Capsule in the Central Nervous System Based on Network Pharmacology and Experimental Verification |
| title_full_unstemmed | Study on the Anti-demyelination Mechanism of Bu-Shen-Yi-Sui Capsule in the Central Nervous System Based on Network Pharmacology and Experimental Verification |
| title_short | Study on the Anti-demyelination Mechanism of Bu-Shen-Yi-Sui Capsule in the Central Nervous System Based on Network Pharmacology and Experimental Verification |
| title_sort | study on the anti demyelination mechanism of bu shen yi sui capsule in the central nervous system based on network pharmacology and experimental verification |
| url | http://dx.doi.org/10.1155/2022/9241261 |
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