Chrysin protects cardiac H9c2 cells against H2O2-induced endoplasmic reticulum stress by up-regulating the Nrf2/PERK pathway

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...

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Published in:Molecular and cellular biochemistry 2023-03, Vol.478 (3), p.539-553
Main Authors: Yuvaraj, Subramani, Ajeeth, Arumugam Kalaiselvi, Puhari, Shanavas Syed Mohamed, Abhishek, Albert, Ramprasath, Tharmarajan, Vasudevan, Varadaraj, Vignesh, Narasimman, Selvam, Govindan Sadasivam
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
Apoptosis
Biochemistry
Biomedical and Life Sciences
Cancer Research
Cardiology
Cardiovascular diseases
Caspase-3
Cell lines
Computer applications
Endoplasmic reticulum
Flavonoids
Gene expression
Hydrogen peroxide
Life Sciences
Medical Biochemistry
NF-κB protein
NRF2 protein
Oxidative stress
Signal transduction
Signaling
siRNA
Therapeutic targets
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Summary: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 H 2 O 2 -induced oxidative and ER stress in cardiomyoblast cells. H9c2 cells were pre-treated with 50 μM of Chy for 24 h and exposed to H 2 O 2 for 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 H 2 O 2 for 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 H 2 O 2 -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. Graphical abstract
ISSN:0300-8177
1573-4919
DOI:10.1007/s11010-022-04531-z