# Tiliroside from Lagopsis supina Ameliorates Myocardial Ischemia Injury in Zebrafish by Activating the kdr-Mediated PI3K-Akt and MAPK Signaling Pathways

## TL;DR

Tiliroside, a compound from Lagopsis supina, reduces heart injury in zebrafish by activating key cell survival pathways.

## Contribution

Identifies tiliroside as a novel compound that activates kdr-mediated PI3K-Akt and MAPK pathways to treat myocardial ischemia.

## Key findings

- Tiliroside improves heart function in zebrafish with myocardial ischemia.
- Tiliroside binds to key proteins like KDR, PI3K, and Akt, activating protective signaling pathways.
- Tiliroside upregulates genes like kdr and bcl-2b while downregulating bax and caspase3.

## Abstract

Lagopsis supina (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 L. supina against MI and reveal their underlying mechanisms in zebrafish. LSD fraction was screened out for anti-MI active fraction from L. supina 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. 1–30) were isolated and identified from LSD by various chromatographic techniques and nuclear magnetic resonance spectroscopy. Among them, six compounds, including three lignin compounds (Nos. 15, 16, and 18) and three flavonoid glycosides (Nos. 14, 25, and 26), showed noticeable anti-MI activities, and tiliroside (No. 25) 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 kdr, pik3cb, akt2, mapk1, mapk11, mapk14, and bcl-2b and prominently downregulated expression levels of genes bax and caspase3. According to the above results, tiliroside activated the kdr-mediated PI3K-Akt and MAPK signaling pathways to exert the anti-MI activity. These discoveries give a scientific basis for applying L. supina in MI treatment and suggest new avenues for developing tiliroside as a candidate for MI therapy.