# Thymoquinone Protects Against Cardiac Hypertrophy via PPAR‐γ/PI3K/Akt Pathway

## TL;DR

Thymoquinone, a compound from black cumin, protects the heart from stress-induced enlargement by activating a specific biological pathway.

## Contribution

This study is the first to show that thymoquinone protects against cardiac hypertrophy via the PPAR-γ/PI3K/Akt pathway.

## Key findings

- Thymoquinone reduces stress-induced cardiac hypertrophy in mice and AngII-induced hypertrophy in H9c2 cells.
- Thymoquinone inhibits cardiomyocyte ferroptosis and apoptosis by modulating PTGS2, Bax, GPX4, and Bcl-2.
- PPAR-γ inhibition reverses the protective effects of thymoquinone, and TQ increases P-PI3K and P-Akt protein levels.

## Abstract

Thymoquinone (TQ), the principal active constituent of Nigella stativa, has demonstrated numerous biological properties and therapeutic effects on various diseases. However, its therapeutic potential against cardiac hypertrophy remains uncertain. This study aims to investigate the protective effects of TQ on stress‐induced cardiac hypertrophy and elucidate the underlying mechanisms. Our findings reveal that TQ mitigates stress‐induced cardiac hypertrophy in mice and AngII‐induced hypertrophy in H9c2 cells. Moreover, TQ inhibits cardiomyocyte ferroptosis and apoptosis by downregulating PTGS2, Bax, and upregulating GPX4, Bcl‐2, thereby alleviating cardiac hypertrophy and dysfunction. Mechanistically, the protective effects of TQ against ferroptosis and apoptosis in cardiac hypertrophy were reversed by the PPAR‐γ inhibitor (GW9662). In addition, TQ treatment led to increased protein expression levels of P‐PI3K and P‐AKt. Taken together, our findings suggest that TQ could attenuate cardiac hypertrophy through activation of the PPAR‐γ/PI3K/Akt signalling pathway.