Vanillic acid attenuates H2O2-induced injury in H9c2 cells by regulating mitophagy via the PINK1/Parkin/Mfn2 signaling pathway

Abstract

Vanillic acid, a phenolic compound mainly obtained from the foot of Picrorhiza scrophulariiflora Pennell, has been demonstrated to possess a cardiovascular-protective effect in previous studies. However, there is lack of research on vanillic acid protecting cardiomyocytes from oxidative stress injury by mediating mitophagy. In the present study, oxidative stress injury in the H9c2 cell line was induced by H2O2. Our results confirmed that vanillic acid mitigated apoptosis and injury triggered by oxidative stress, evidenced by the decline in production of reactive oxygen species and malondialdehyde and level of lactate dehydrogenase and the increase of superoxide dismutase and glutathione. The use of vanillic acid could also improve the polarization of mitochondrial membrane potential and decrease the cellular calcium level. After treatment by vanillic acid, impaired autophagy flux and mitophagy were improved, and the length of mitochondria was restored. Vanillic acid increased the expression of PINK1, Parkin, Mfn2, and the ratio of LC3-II/LC3-I and decreased the expression of p62. But, under the intervention of mitophagy inhibitor 3-MA, vanillic acid could not change the expression of PINK1/Parkin/Mfn2 and downstream genes to affect cell autophagy, mitophagy, and mitochondrial function. Our findings suggested that vanillic acid activated mitophagy to improve mitochondrial function, in which the PINK1/Parkin/Mfn2 pathway could be the potential regulatory mechanism.

Vanillic acid protects mortality and toxicity induced by N-ethyl-N-nitrosourea in mice; in vivo model of chronic lymphocytic leukemia

“…In the current we observed the beneficial effects of vanillic acid on ENU-induced mitochondrial dysfunctions in mouse isolated lymphocytes. Our findings, consistent with previous studies [46] , [47] , [48] suggest that vanillic acid via its mitoprotective effects can protect mitochondrial dysfunction induced by different chemicals, which may finally lead to toxicity and cancer development induced.…”

Cyanidin-3-O-Glucoside Alleviates Alcoholic Liver Injury via Modulating Gut Microbiota and Metabolites in Mice

“…More than 20 kinds of C3G metabolites (C3G-Ms) in serum have been identified [ 64 ]. Among them, protocatechuic acid [ 65 , 66 , 67 ], vanillic acid [ 68 , 69 ] or their derivatives are the main bioactive metabolites, which have antioxidant and anti-inflammatory activities. The metabolites of C3G detected in this study were protocatechoic acid, methyl 3,4-dihydroxybenzoate, vanillic acid, 4-hydroxybenzeneacetic acid, et al, which may increase C3G bioavailability and contribute to the repair of gut mucosal barrier and intestinal microbiota disorder [ 70 , 71 ].…”

Anthocyanin Effects on Vascular and Endothelial Health: Evidence from Clinical Trials and Role of Gut Microbiota Metabolites

“…Concerning this last aspect, it has been observed that treatment with VA results in an upregulation of eNOS expression and a downregulation of endothelin-1 [ 116 ]. Furthermore, VA has been shown to exert its cardioprotective effects by modulating AMPK signaling pathways and upregulating endogenous antioxidant markers such as superoxide dismutase, catalase, glutathione peroxidase, and total antioxidant capacity [ 115 , 117 , 118 ], while an in vitro study conducted on H9c2 cell line showed that VA protection versus H 2 O 2 damage could be mediated via the regulation of PINK1/Parkin/Mfn2 signaling pathway [ 119 ]. Moreover, VA treatment showed anti-inflammatory properties by reducing proinflammatory cytokines, particularly IL-1β, IL-6, and TNF-α [ 117 ], and modifying microbiota composition, restoring the relative abundance of Lactobacillus and decreasing Bacteroides genera [ 120 ].…”