Tiliroside from Ameliorates Myocardial Ischemia Injury in Zebrafish by Activating the -Mediated PI3K-Akt and MAPK Signaling Pathways.

(Steph. ex. Willd.) Ikonn.-Gal., an ancient Chinese herbal medicine, is traditionally used to treat blood stasis diseases such as myocardial ischemia (MI). However, its pharmacodynamics substances of the anti-MI effect and their potential mechanisms remain unclear. This study aims to elucidate the pharmacodynamics effects of against MI and reveal their underlying mechanisms in zebrafish. LSD fraction was screened out for anti-MI active fraction from by isoprenaline hydrochloride (ISO)-induced zebrafish. It could increase the stroke volume, ejection fraction, and ventricular short-axis systolic rate in the zebrafish model. A total of 30 compounds (Nos. -) were isolated and identified from LSD by various chromatographic techniques and nuclear magnetic resonance spectroscopy. Among them, six compounds, including three lignin compounds (Nos. , , and ) and three flavonoid glycosides (Nos. , , and ), showed noticeable anti-MI activities, and tiliroside (No. ) was more active. Molecular docking indicated that tiliroside has a strong binding ability with the proteins KDR, PI3K, Akt, Erk, p38, Bcl-2, Bax, and Caspase3. In the end, the results of RT-qPCR manifested that tiliroside markedly upregulated expression levels of genes , , , , , , and and prominently downregulated expression levels of genes and . According to the above results, tiliroside activated the -mediated PI3K-Akt and MAPK signaling pathways to exert the anti-MI activity. These discoveries give a scientific basis for applying in MI treatment and suggest new avenues for developing tiliroside as a candidate for MI therapy.