Therapeutic Effect of Shikimic Acid on Heat Stress-Induced Myocardial Damage: Assessment via Network Pharmacology,...

Background: Rising global temperatures have been linked to an increased incidence of heat stress (HS)-induced myocardial damage.

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.

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.

These findings offer evidence for the therapeutic potential of SA in HS-induced myocardial damage.