莽草酸对热应激诱导的心肌损伤的治疗作用：通过网络药理学、分子对接、分子动力学模拟和体外实验进行评估
Therapeutic Effect of Shikimic Acid on Heat Stress-Induced Myocardial Damage: Assessment via Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation, and In Vitro Experiments.
作者信息
Gu Yan, Zhang Jingyi, Zheng Haohong, Qin Yuyang, Zheng Min, Hu Yanchun, Xin Jialiang
机构信息
Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.
Guangxi Center for Animal Disease Control and Prevention, Nanning 530001, China.
出版信息
Pharmaceuticals (Basel). 2024 Nov 5;17(11):1485. doi: 10.3390/ph17111485.
UNLABELLED
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.
未标注
背景：全球气温上升与热应激（HS）诱导的心肌损伤发病率增加有关。
方法
本研究旨在利用网络药理学、分子对接、分子动力学（MD）模拟和体外实验，研究莽草酸（SA）对HS诱导的心肌损伤的治疗潜力。
结果
网络药理学分析表明，SA通过调节60个靶点（包括TNF、IL-6和STAT3）显著减轻对HS的炎症反应，这些靶点在PI3K/AKT信号通路中富集。分子对接和MD模拟分析表明，SA与TNF（-6.642千卡/摩尔）和IL-6（-7.261千卡/摩尔）形成稳定复合物，在100纳秒模拟期内无明显构象变化。体外实验表明，在250微摩尔至31.25微摩尔浓度范围内，SA显著促进正常HL-1细胞增殖，平均增殖31.0%。此外，它将暴露于43°C 3小时的HL-1细胞存活率提高约59.9%，并下调Hsp90和Hsp70的表达。此外，该浓度范围的SA降低了TNF-α、IL-6、TLR2和COL1A1的表达。
结论
这些发现为SA在HS诱导的心肌损伤中的治疗潜力提供了证据。
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