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Abstract Title:

Chrysin protects cardiac H9c2 cells against HO-induced endoplasmic reticulum stress by up-regulating the Nrf2/PERK pathway.

Abstract Source:

Mol Cell Biochem. 2022 Aug 9. Epub 2022 Aug 9. PMID: 35943656

Abstract Author(s):

Subramani Yuvaraj, Arumugam Kalaiselvi Ajeeth, Shanavas Syed Mohamed Puhari, Albert Abhishek, Tharmarajan Ramprasath, Varadaraj Vasudevan, Narasimman Vignesh, Govindan Sadasivam Selvam

Article Affiliation:

Subramani Yuvaraj

Abstract:

Oxidative and endoplasmic reticulum (ER) stress-mediated cardiac apoptosis is an essential pathological process in cardiovascular diseases (CVDs). Chrysin (Chy) is a natural flavonoid that exerts several health benefits, particularly anti-oxidative and anti-apoptotic effects. However, its protective effect against CVDs and its mechanism of action at a molecular level remains unclear. Therefore, the present study aimed to investigate the interaction of ER stress response protein with Chy by computational analysis and molecular action in HO-induced oxidative and ER stress in cardiomyoblast cells. H9c2 cells were pre-treated with 50 μM of Chy for 24 h and exposed to HOfor 1 h. Explore the Chy-mediated Nrf2 signalling on ER stress reduction, H9c2 cell lines were transfected with Nrf2 siRNA for 48 h and further treated with Chy for 24 h and subjected to HOfor 1 h. Chy pre-treatment increased the Nrf2-regulated gene expression, reduced the ER stress signalling genes such as CHOP and GRP78, and increased the PERK and AFT6 expression compared to HO-treated cells. Chy preincubation down-regulated the expression of PI3K, NF-κB, and caspase-3. Fluorescence staining revealed that Chy reduced intracellular ROS generation, ER stress, apoptosis, and increased MMP. This beneficial effect of Chy was abolished when silencing Nrf2 in H9c2 cells. Overall, the present study confirmed that Chy showed the cardioprotective effect by attenuating ER stress via the activation of Nrf2 signalling. Therefore, the study concluded that improving Nrf2 signalling by Chy supplementation could provide a promising therapeutic target in oxidative and ER stress-mediated CVDs complications.

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