Chrysin reduces heart endoplasmic reticulum stress-induced apoptosis by inhibiting PERK and Caspase 3–7 in high-fat diet-fed rats

• Published in: Molecular biology reports 2024-12, Vol.51 (1), p.678-678, Article 678
• Main Authors: Yuvaraj, Subramani, Vasudevan, Varadaraj, Puhari, Shanavas Syed Mohamed, Sasikumar, Sunderasan, Ramprasath, Tharmarajan, Selvi, Mariaraj Sivakumar, Selvam, Govindan Sadasivam
• Format: Article
• Language: English
• Subjects: Animal Anatomy; Animal Biochemistry; Animals; Apoptosis; Apoptosis - drug effects; Atorvastatin; Biomedical and Life Sciences; Caspase 3 - metabolism; Caspase-3; Diet, High-Fat - adverse effects; eIF-2 Kinase - genetics; eIF-2 Kinase - metabolism; Endoplasmic reticulum; Endoplasmic Reticulum Stress - drug effects; Enzymes; Flavonoids; Flavonoids - pharmacology; High fat diet; Histology; Immunohistochemistry; Inflammation; Life Sciences; Lipid peroxidation; Lipids; Lipoproteins (very low density); Low density lipoprotein; Male; Medicinal plants; Morphology; Myocardium; Myocardium - metabolism; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; Original Article; Plant extracts; Rats; Rats, Wistar; Signal transduction; Signal Transduction - drug effects; Therapeutic targets
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-024-09612-4

Background Chrysin (Chy) is a naturally occurring flavonoid found in fruits, vegetables, honey, propolis, and many plant extracts that has shown notable medicinal value. Chy exhibits diverse pharmacological properties, including anti-oxidative, anti-inflammatory, anti-apoptotic, anti-cholesteremic, and cardioprotective. However, the influence of Chy in mitigating high-fat diet (HFD)-induced ER stress of rat myocardium remains unknown. Purpose The current work intended to determine the therapeutic potential of Chy against HFD-induced endoplasmic stress-mediated apoptosis. Methods To evaluate the therapeutic value of Chy in HFD-induced endoplasmic stress-mediated apoptosis in the myocardium; The male wistar rats were divided into different groups; control, HFD control, HFD fed followed by Chy-treated and HFD fed followed by atorvastatin (Atv) treated rats. Results When compared to the control group, the HFD-fed rats had significantly higher levels of marker enzymes such as CK-NAC and ALP, as well as lipid peroxidation and lipid profile (TC, TG, LDL, and VLDL). Chy therapy greatly reversed these marker enzymes and the lipid profile. qRT-PCR Studies showed that Chy supplementation considerably improved Nrf2 and its target genes. In addition, Chy lowered the expression of PERK, CHOP, ATF6, GRP78, and Caspase-3 genes in the heart tissue of HFD-fed rats. Immunohistochemistry results demonstrated that Chy substantially enhanced the Nrf2 and reduced PERK and Caspase3-7 protein expression in HFD-fed rats. Conclusion The current study concluded that Chy may mediate the cardioprotective effect by activating Nrf2 and inhibiting PERK signaling pathway against ER stress-mediated apoptosis induced by HFD. Therefore, supplementation with Chy could serve as a promising therapeutic target against HFD-induced ER stress-mediated cardiac complication. Graphical abstract