Berberine Promotes Cardiac Function by Upregulating PINK1/Parkin-Mediated Mitophagy in Heart Failure

Abstract

Berberine has been verified to protect cardiac function in patients with heart failure (HF). However, the mechanism(s) involved in berberine-mediated cardioprotective effects has not been clearly elucidated. The aim of this study was to further investigate the mechanism(s) involved in the beneficial effects of berberine on transverse aortic contraction (TAC)-induced chronic HF. Mice were randomly divided into four groups. Berberine was administered at a dose of 50 mg/kg/day for 4 weeks via oral gavage. Our findings showed that TAC-induced pressure overload (PO) prompted cardiac dysfunction, cardiac hypertrophy, interstitial fibrosis, cardiomyocyte apoptosis and mitochondrial injury, accompanied with suppressed mitophagy, the effects of which were attenuated by berberine. Furthermore, mitophagy regulators PINK1 and mito-Parkin were downregulated in TAC-induced HF, while berberine upregulated PINK1/Parkinmediated mitophagy. Notably, knockdown of PINK1 by small interfering RNA significantly suppressed Parkin-mediated mitochondrial ubiquitination and nullified the beneficial actions on HF exerted by berberine. Taken together, our results indicated that berberine plays a critical role in attenuating cardiac hypertrophy and preserving cardiac function from PO induced HF. The potential underlying mechanism is the activation of mitochondrial autophagy via PINK1/Parkin/Ubiquitination pathway.

RETRACTED: Molecular Perspectives of Mitophagy in Myocardial Stress: Pathophysiology and Therapeutic Targets

“…In acute alcohol intake-induced cardiomyopathy, deficient Parkin-induced mitophagy was found to exacerbate alcohol-evoked cardiotoxicity, while Parkin overexpression abolished this effect ( Le Cras et al, 2020 ; Yang et al, 2021a ). In transverse aortic contraction-induced heart failure, the activation of Parkin-induced mitophagy using the berberine was reported to improve cardiac function, reduce interstitial fibrosis, inhibit cardiac hypertrophy, and suppress cardiomyocyte apoptosis ( Abudureyimu et al, 2020 ).…”

[Retracted] Alleviation of Inflammation and Oxidative Stress in Pressure Overload‐Induced Cardiac Remodeling and Heart Failure via IL‐6/STAT3 Inhibition by Raloxifene

“…Meanwhile, the expression of Bnip3, which plays a critical role in the mitophagy receptor-dependent pathway, was also increased after IL-6 stimulation. Excessive activation of autophagy elicited by pathological stimuli, such as pressure overload, is maladaptive and promotes cell apoptosis, which was reported to aggravate cardiac hypertrophy and speed up the process of HF [ 44 ]. Mitophagy, as a selective autophagy, is activated in the early stage of cardiac hypertrophy during HF, which ultimately promotes cell apoptosis [ 45 ].…”

The Physiological Functionality of PGR5/PGRL1-Dependent Cyclic Electron Transport in Sustaining Photosynthesis

“…Plants lacking PGRL1 showed a decrease in CET rate and exhibiting a similar performance to the pgr5 mutant ( Dalcorso et al, 2008 ; Yadav et al, 2020 ). The regulatory role of PGR5/PGRL1-dependent CET under environmental perturbations has been studied ( Wang et al, 2014 ; Yamori et al, 2016 ; Wolf et al, 2020 ). PGR5 is a small thylakoid protein without any known motifs that suggest its function ( Munekage et al, 2002 ), while PGRL1 is a transmembrane protein with two transmembrane domains, and its two cysteine residues are involved in an iron cofactor binding ( Hertle et al, 2013 ).…”