Mechanism of Bazi Bushen capsule in delaying the senescence of mesenchymal stem cells based on network pharmacology and experimental validation
Ageing is becoming an increasingly serious problem; therefore, there is an urgent need to find safe and effective anti-ageing drugs. Aims: To investigate the effects of Bazi Bushen capsule (BZBS) on the senescence of mesenchymal stem cells (MSCs) and explore its mechanism of action. Methods: Network...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024036776 |
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| author | Yaping Zhang Tongxing Wang Yanfei Song Meng Chen Bin Hou Bing Yao Kun Ma Yahui Song Siwei Wang Dan Zhang Junqing Liang Cong Wei |
| author_facet | Yaping Zhang Tongxing Wang Yanfei Song Meng Chen Bin Hou Bing Yao Kun Ma Yahui Song Siwei Wang Dan Zhang Junqing Liang Cong Wei |
| author_sort | Yaping Zhang |
| collection | DOAJ |
| description | Ageing is becoming an increasingly serious problem; therefore, there is an urgent need to find safe and effective anti-ageing drugs. Aims: To investigate the effects of Bazi Bushen capsule (BZBS) on the senescence of mesenchymal stem cells (MSCs) and explore its mechanism of action. Methods: Network pharmacology was used to predict the targets of BZBS in delaying senescence in MSCs. For in vitro studies, MSCs were treated with D-gal, BZBS, and NMN, and cell viability, cell senescence, stemness-related genes, and cell cycle were studied using cell counting kit-8 (CCK-8) assay, SA-β-galactosidase (SA-β-gal) staining, Quantitative Real-Time PCR (qPCR) and flow cytometry (FCM), respectively. Alkaline phosphatase (ALP), alizarin red, and oil red staining were used to determine the osteogenic and lipid differentiation abilities of MSCs. Finally, the expression of senescence-related genes and cyclin-related factors was detected by qPCR and western blotting. Results: Network pharmacological analysis suggested that BZBS delayed cell senescence by interfering in the cell cycle. Our in vitro studies suggested that BZBS could significantly increase cell viability (P < 0.01), decrease the quantity of β-galactosidase+ cells (P < 0.01), downregulate p16 and p21 (P < 0.05, P < 0.01), improve adipogenic and osteogenic differentiation, and upregulate Nanog, OCT4 and SOX2 genes (P < 0.05, P < 0.01) in senescent MSCs. Moreover, BZBS significantly reduced the proportion of senescent MSCs in the G0/G1 phase (P < 0.01) and enhanced the expression of CDK4, Cyclin D1, and E2F1 (P < 0.05, P < 0.01, respectively). Upon treatment with HY-50767A, a CDK4 inhibitor, the upregulation of E2F1 was no longer observed in the BZBS group. Conclusions: BZBS can protect MSCs against D-gal-induced senescence, which may be associated with cell cycle regulation via the Cyclin D1/CDK4/E2F1 signalling pathway. |
| first_indexed | 2024-04-24T13:49:13Z |
| format | Article |
| id | doaj.art-42fb0c3a147b4ee8b8a06cb8fc782754 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-24T13:49:13Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
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| spelling | doaj.art-42fb0c3a147b4ee8b8a06cb8fc7827542024-04-04T05:05:23ZengElsevierHeliyon2405-84402024-03-01106e27646Mechanism of Bazi Bushen capsule in delaying the senescence of mesenchymal stem cells based on network pharmacology and experimental validationYaping Zhang0Tongxing Wang1Yanfei Song2Meng Chen3Bin Hou4Bing Yao5Kun Ma6Yahui Song7Siwei Wang8Dan Zhang9Junqing Liang10Cong Wei11Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, 050091, ChinaNational Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, 050035, China; High-level TCM Key Disciplines of National Administration of Traditional Chinese Medicine—Luobing Theory, Hebei Province, Shijiazhuang, 050035, China; Key Laboratory of State Administration of TCM (Cardio-Cerebral Vessel Collateral Disease), Shijiazhuang, 050035, ChinaNational Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, 050035, China; High-level TCM Key Disciplines of National Administration of Traditional Chinese Medicine—Luobing Theory, Hebei Province, Shijiazhuang, 050035, China; Shijiazhuang Compound Traditional Chinese Medicine Technology Innovation Center, Shijiazhuang, 050035, ChinaNational Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, 050035, China; High-level TCM Key Disciplines of National Administration of Traditional Chinese Medicine—Luobing Theory, Hebei Province, Shijiazhuang, 050035, China; Shijiazhuang Compound Traditional Chinese Medicine Technology Innovation Center, Shijiazhuang, 050035, ChinaNational Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, 050035, China; High-level TCM Key Disciplines of National Administration of Traditional Chinese Medicine—Luobing Theory, Hebei Province, Shijiazhuang, 050035, ChinaNational Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, 050035, China; High-level TCM Key Disciplines of National Administration of Traditional Chinese Medicine—Luobing Theory, Hebei Province, Shijiazhuang, 050035, China; Shijiazhuang Compound Traditional Chinese Medicine Technology Innovation Center, Shijiazhuang, 050035, ChinaNational Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, 050035, China; High-level TCM Key Disciplines of National Administration of Traditional Chinese Medicine—Luobing Theory, Hebei Province, Shijiazhuang, 050035, China; Hebei Clinical Research Center of Cardiovascular Disease of Traditional Chinese Medicine, Shijiazhuang, 050035, ChinaNational Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, 050035, China; High-level TCM Key Disciplines of National Administration of Traditional Chinese Medicine—Luobing Theory, Hebei Province, Shijiazhuang, 050035, ChinaGraduate School, Hebei University of Chinese Medicine, Shijiazhuang, 050091, China; National Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, 050035, China; High-level TCM Key Disciplines of National Administration of Traditional Chinese Medicine—Luobing Theory, Hebei Province, Shijiazhuang, 050035, ChinaGraduate School, Hebei University of Chinese Medicine, Shijiazhuang, 050091, China; National Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, 050035, China; High-level TCM Key Disciplines of National Administration of Traditional Chinese Medicine—Luobing Theory, Hebei Province, Shijiazhuang, 050035, ChinaNational Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, 050035, China; High-level TCM Key Disciplines of National Administration of Traditional Chinese Medicine—Luobing Theory, Hebei Province, Shijiazhuang, 050035, China; Corresponding author. National Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, 050035, China.Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, 050091, China; National Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, 050035, China; High-level TCM Key Disciplines of National Administration of Traditional Chinese Medicine—Luobing Theory, Hebei Province, Shijiazhuang, 050035, China; Corresponding author. Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, 050091, China.Ageing is becoming an increasingly serious problem; therefore, there is an urgent need to find safe and effective anti-ageing drugs. Aims: To investigate the effects of Bazi Bushen capsule (BZBS) on the senescence of mesenchymal stem cells (MSCs) and explore its mechanism of action. Methods: Network pharmacology was used to predict the targets of BZBS in delaying senescence in MSCs. For in vitro studies, MSCs were treated with D-gal, BZBS, and NMN, and cell viability, cell senescence, stemness-related genes, and cell cycle were studied using cell counting kit-8 (CCK-8) assay, SA-β-galactosidase (SA-β-gal) staining, Quantitative Real-Time PCR (qPCR) and flow cytometry (FCM), respectively. Alkaline phosphatase (ALP), alizarin red, and oil red staining were used to determine the osteogenic and lipid differentiation abilities of MSCs. Finally, the expression of senescence-related genes and cyclin-related factors was detected by qPCR and western blotting. Results: Network pharmacological analysis suggested that BZBS delayed cell senescence by interfering in the cell cycle. Our in vitro studies suggested that BZBS could significantly increase cell viability (P < 0.01), decrease the quantity of β-galactosidase+ cells (P < 0.01), downregulate p16 and p21 (P < 0.05, P < 0.01), improve adipogenic and osteogenic differentiation, and upregulate Nanog, OCT4 and SOX2 genes (P < 0.05, P < 0.01) in senescent MSCs. Moreover, BZBS significantly reduced the proportion of senescent MSCs in the G0/G1 phase (P < 0.01) and enhanced the expression of CDK4, Cyclin D1, and E2F1 (P < 0.05, P < 0.01, respectively). Upon treatment with HY-50767A, a CDK4 inhibitor, the upregulation of E2F1 was no longer observed in the BZBS group. Conclusions: BZBS can protect MSCs against D-gal-induced senescence, which may be associated with cell cycle regulation via the Cyclin D1/CDK4/E2F1 signalling pathway.http://www.sciencedirect.com/science/article/pii/S2405844024036776Mesenchymal stem cellsCell senescenceBazi bushen capsuleCell cycleNetwork pharmacology |
| spellingShingle | Yaping Zhang Tongxing Wang Yanfei Song Meng Chen Bin Hou Bing Yao Kun Ma Yahui Song Siwei Wang Dan Zhang Junqing Liang Cong Wei Mechanism of Bazi Bushen capsule in delaying the senescence of mesenchymal stem cells based on network pharmacology and experimental validation Heliyon Mesenchymal stem cells Cell senescence Bazi bushen capsule Cell cycle Network pharmacology |
| title | Mechanism of Bazi Bushen capsule in delaying the senescence of mesenchymal stem cells based on network pharmacology and experimental validation |
| title_full | Mechanism of Bazi Bushen capsule in delaying the senescence of mesenchymal stem cells based on network pharmacology and experimental validation |
| title_fullStr | Mechanism of Bazi Bushen capsule in delaying the senescence of mesenchymal stem cells based on network pharmacology and experimental validation |
| title_full_unstemmed | Mechanism of Bazi Bushen capsule in delaying the senescence of mesenchymal stem cells based on network pharmacology and experimental validation |
| title_short | Mechanism of Bazi Bushen capsule in delaying the senescence of mesenchymal stem cells based on network pharmacology and experimental validation |
| title_sort | mechanism of bazi bushen capsule in delaying the senescence of mesenchymal stem cells based on network pharmacology and experimental validation |
| topic | Mesenchymal stem cells Cell senescence Bazi bushen capsule Cell cycle Network pharmacology |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024036776 |
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