Therapeutic Effect of Shikimic Acid on Heat Stress-Induced Myocardial Damage: Assessment via Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation, and In Vitro Experiments
<b>Abstract:</b> Background: Rising global temperatures have been linked to an increased incidence of heat stress (HS)-induced myocardial damage. Methods: This study aimed to investigate the therapeutic potential of shikimic acid (SA) on HS-induced myocardial damage using network pharmac...
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MDPI AG
2024-11-01
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| Series: | Pharmaceuticals |
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| author | Yan Gu Jingyi Zhang Haohong Zheng Yuyang Qin Min Zheng Yanchun Hu Jialiang Xin |
| author_facet | Yan Gu Jingyi Zhang Haohong Zheng Yuyang Qin Min Zheng Yanchun Hu Jialiang Xin |
| author_sort | Yan Gu |
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| description | <b>Abstract:</b> Background: Rising global temperatures have been linked to an increased incidence of heat stress (HS)-induced myocardial damage. Methods: This study aimed to investigate the therapeutic potential of shikimic acid (SA) on HS-induced myocardial damage using network pharmacology, molecular docking, molecular dynamics (MD) simulations, and in vitro experiments. Results: Network pharmacology analysis indicated that SA significantly attenuates the inflammatory response to HS by modulating 60 targets, including TNF, IL-6, and STAT3, which are enriched in the PI3K/AKT signaling pathway. Molecular docking and MD simulation analyses demonstrated that SA forms stable complexes with TNF (−6.642 kcal/mol) and IL-6 (−7.261 kcal/mol), with no significant conformational changes over a 100 ns simulation period. In vitro experiments demonstrated that SA, within the concentration range of 250 μM to 31.25 μM, significantly promoted the proliferation of normal HL-1 cells by an average of 31.0%. Moreover, it enhanced the survival rate of HL-1 cells exposed to 43 °C for 3 h by approximately 59.9% and downregulated the expression of Hsp90 and Hsp70. Additionally, this concentration range of SA reduced the expression of TNF-α, IL-6, TLR2, and COL1A1. Conclusions: These findings offer evidence for the therapeutic potential of SA in HS-induced myocardial damage. |
| format | Article |
| id | doaj-art-3fe4be372c354bf18a5f51670d28d5ad |
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| issn | 1424-8247 |
| language | English |
| publishDate | 2024-11-01 |
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| spelling | doaj-art-3fe4be372c354bf18a5f51670d28d5ad2025-08-20T01:53:57ZengMDPI AGPharmaceuticals1424-82472024-11-011711148510.3390/ph17111485Therapeutic Effect of Shikimic Acid on Heat Stress-Induced Myocardial Damage: Assessment via Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation, and In Vitro ExperimentsYan Gu0Jingyi Zhang1Haohong Zheng2Yuyang Qin3Min Zheng4Yanchun Hu5Jialiang Xin6Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaGuangxi Center for Animal Disease Control and Prevention, Nanning 530001, ChinaKey Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China<b>Abstract:</b> Background: Rising global temperatures have been linked to an increased incidence of heat stress (HS)-induced myocardial damage. Methods: This study aimed to investigate the therapeutic potential of shikimic acid (SA) on HS-induced myocardial damage using network pharmacology, molecular docking, molecular dynamics (MD) simulations, and in vitro experiments. Results: Network pharmacology analysis indicated that SA significantly attenuates the inflammatory response to HS by modulating 60 targets, including TNF, IL-6, and STAT3, which are enriched in the PI3K/AKT signaling pathway. Molecular docking and MD simulation analyses demonstrated that SA forms stable complexes with TNF (−6.642 kcal/mol) and IL-6 (−7.261 kcal/mol), with no significant conformational changes over a 100 ns simulation period. In vitro experiments demonstrated that SA, within the concentration range of 250 μM to 31.25 μM, significantly promoted the proliferation of normal HL-1 cells by an average of 31.0%. Moreover, it enhanced the survival rate of HL-1 cells exposed to 43 °C for 3 h by approximately 59.9% and downregulated the expression of Hsp90 and Hsp70. Additionally, this concentration range of SA reduced the expression of TNF-α, IL-6, TLR2, and COL1A1. Conclusions: These findings offer evidence for the therapeutic potential of SA in HS-induced myocardial damage.https://www.mdpi.com/1424-8247/17/11/1485network pharmacologyheat stressmyocardial damageshikimic acidmolecular dockingmolecular dynamics simulation |
| spellingShingle | Yan Gu Jingyi Zhang Haohong Zheng Yuyang Qin Min Zheng Yanchun Hu Jialiang Xin Therapeutic Effect of Shikimic Acid on Heat Stress-Induced Myocardial Damage: Assessment via Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation, and In Vitro Experiments Pharmaceuticals network pharmacology heat stress myocardial damage shikimic acid molecular docking molecular dynamics simulation |
| title | Therapeutic Effect of Shikimic Acid on Heat Stress-Induced Myocardial Damage: Assessment via Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation, and In Vitro Experiments |
| title_full | Therapeutic Effect of Shikimic Acid on Heat Stress-Induced Myocardial Damage: Assessment via Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation, and In Vitro Experiments |
| title_fullStr | Therapeutic Effect of Shikimic Acid on Heat Stress-Induced Myocardial Damage: Assessment via Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation, and In Vitro Experiments |
| title_full_unstemmed | Therapeutic Effect of Shikimic Acid on Heat Stress-Induced Myocardial Damage: Assessment via Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation, and In Vitro Experiments |
| title_short | Therapeutic Effect of Shikimic Acid on Heat Stress-Induced Myocardial Damage: Assessment via Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation, and In Vitro Experiments |
| title_sort | therapeutic effect of shikimic acid on heat stress induced myocardial damage assessment via network pharmacology molecular docking molecular dynamics simulation and in vitro experiments |
| topic | network pharmacology heat stress myocardial damage shikimic acid molecular docking molecular dynamics simulation |
| url | https://www.mdpi.com/1424-8247/17/11/1485 |
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