Salvianolic acid A promotes mitochondrial biogenesis and function via regulating the AMPK/PGC‑1α signaling pathway in HUVECs

Wang,Xuelian; Zhang,Mi; Zhang,Mengyao; Han,Yantao; Chen,Xuehong; Zhao,Wenwen; Han,Zhiwu; Sun,Jialin

doi:10.3892/etm.2022.11412

Salvianolic acid A promotes mitochondrial biogenesis and function via regulating the AMPK/PGC‑1α signaling pathway in HUVECs

Authors:
- Xuelian Wang
- Mi Zhang
- Mengyao Zhang
- Yantao Han
- Xuehong Chen
- Wenwen Zhao
- Zhiwu Han
- Jialin Sun
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Affiliations: School of Basic Medicine, Qingdao University, Qingdao, Shandong 266071, P.R. China, Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
Published online on: June 1, 2022 https://doi.org/10.3892/etm.2022.11412
Article Number: 485
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Mitochondrial dysregulation is an important pathology that leads to endothelial dysfunction, and the occurrence and development of cardiovascular diseases. Salvianolic acid A (SAA) has been demonstrated to be effective in the treatment of vascular complications of type 2 diabetes mellitus. Limited information has been reported on the effects of SAA on mitochondrial function in endothelial cells. In the present study, the effects of SAA on mitochondrial biogenesis and the related underlying mechanisms were investigated in human umbilical vein endothelial cells (HUVECs). Mitotracker red staining and transmission electron microscopy were used to evaluate the effect of SAA on mitochondrial quality. The effect of SAA treatment on mitochondrial DNA/nuclear DNA ratio of HUVECs was detected by real‑time quantitative PCR. Western blot was used to determine the protein expression levels of complex III and Complex IV of mitochondrial oxidative phosphorylation subunit, and ATP production was determined by ATP test kit. Real‑time quantitative PCR and Western blot were used to determine the effects of SAA on the expression of peroxisome proliferator‑activated receptor γ coactivator (PGC‑1α) and its target genes nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) proteins and genes. Finally, in the presence of 5'AMP‑activated protein kinase (AMPK) specific inhibitors, the expression of PGC‑1α, NRF1 and TFAM proteins and the phosphorylation levels of AMPK and Acetyl CoA Carboxylase (ACC) were detected by Western blot or real‑time quantitative PCR. The results showed that SAA treatment significantly promoted mitochondrial biogenesis and enhanced mitochondrial function of HUVECs. SAA significantly increased the expression levels of PGC‑1α and its target genes NRF1 and (TFAM), a key regulator of mitochondrial biogenesis in HUVECs. These enhancements were accompanied by significantly increased phosphorylation of AMPK and ACC, and were significantly inhibited by specific AMPK inhibitors. These results suggest that SAA may promote mitochondrial biogenesis in endothelial cells by activating the AMPK‑mediated PGC‑1α/TFAM signaling pathway. These data provide new insights into the mechanism of action of SAA in treating diabetic vascular complications.

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