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

Area of Science:

• Cardiovascular Biology
• Pharmacology
• Molecular Medicine

Background:

• Thymoquinone (TQ), derived from Nigella sativa, exhibits diverse biological activities.
• The role of TQ in mitigating cardiac hypertrophy, a significant cardiovascular condition, requires further investigation.
• Cardiac hypertrophy involves complex cellular mechanisms including ferroptosis and apoptosis.

Purpose of the Study:

• To evaluate the protective effects of Thymoquinone (TQ) against experimentally induced cardiac hypertrophy.
• To elucidate the molecular mechanisms underlying TQ's action, focusing on cell death pathways and signaling cascades.
• To explore the potential of TQ as a therapeutic agent for cardiac hypertrophy.

Main Methods:

• Cardiac hypertrophy was induced in mice and H9c2 cells using stress and Angiotensin II (AngII), respectively.
• The effects of TQ on cardiomyocyte ferroptosis and apoptosis were assessed by analyzing key protein markers (PTGS2, Bax, GPX4, Bcl-2).
• The involvement of Peroxisome Proliferator-Activated Receptor gamma (PPAR-γ) was investigated using a specific inhibitor (GW9662).
• Activation of the PI3K/Akt signaling pathway was examined by measuring phosphorylated levels of PI3K and Akt (P-PI3K, P-AKt).

Main Results:

• Thymoquinone (TQ) significantly mitigated cardiac hypertrophy in both mouse models and H9c2 cell cultures.
• TQ treatment suppressed cardiomyocyte ferroptosis and apoptosis, evidenced by altered expression of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) proteins, and ferroptosis regulators (PTGS2, GPX4).
• The protective effects of TQ were dependent on PPAR-γ activation, as demonstrated by reversal with GW9662.
• TQ administration upregulated the phosphorylation of PI3K and Akt, indicating activation of the PI3K/Akt pathway.

Conclusions:

• Thymoquinone (TQ) demonstrates significant protective effects against cardiac hypertrophy by inhibiting cardiomyocyte ferroptosis and apoptosis.
• The underlying mechanism involves the activation of the PPAR-γ/PI3K/Akt signaling pathway.
• TQ represents a promising therapeutic candidate for managing cardiac hypertrophy and related cardiac dysfunction.