Gallic Acid Protects Against LPS‐Induced Cardiac Dysfunction by Modulating Inflammatory Responses and Notch Signaling in Zebrafish Embryo Larvae

ABSTRACT Cardiovascular diseases are a threat to human health and are associated with increased mortality. Gallic acid (GA) (3,4,5‐trihydroxybenzoic acid) is a naturally occurring polyphenolic compound with cardiovascular preventive properties. However, the precise mechanism underlying its cardioprotective effect is not fully understood. The Notch signaling system is essential in heart injury/repair mechanisms, and clarifying this mechanism in a Lipopolysaccharide (LPS) stimulated zebrafish embryo larvae (ZFEL) model for cardioprotective function. This study aimed to elucidate the cardioprotective activity of GA in LPS stimulated ZFEL via Notch signaling pathway. In this study, an in vivo cardiac injury model was developed in ZFEL using LPS induction. The GA cardioprotective property was investigated by LC 50, survival analysis, morphological assessment, heart rate assessment, cell death, and nitric oxide determination. Expression of Notch signaling and the cardiac biomarker protein were done by immunoblotting and in addition whole mount immunohistochemistry was performed for NICD, MMP 9, and MMP 13. GA protects LPS‐induced ZFEL by increasing survival rates, normalizing morphological anomalies, restoring abnormal heart rate, preventing cell death, and inhibiting NO generation. It suppressed the Notch signaling pathway (Notch1, Delta1, Hey1, and Hes1) and cardiac biomarker proteins (MPO, MMP‐9, MMP‐13, and NO) in LPS‐stimulated ZFEL, indicating cardioprotective property. Our findings showed that GA suppressed both molecular and cellular events during LPS‐induced heart damage via the Notch signaling pathway.