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Ginsenoside Rb1 Protects Human Umbilical Vein Endothelial Cells against High Glucose-Induced Mitochondria-Related Apoptosis through Activating SIRT3 Signalling Pathway

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Abstract

Objective

To investigate whether ginsenoside Rb1 (Rb1) can protect human umbilical vein endothelial cells (HUVECs) against high glucose-induced apoptosis and examine the underlying mechanism.

Methods

HUVECs were divided into 5 groups: control group (5.5 mmol/L glucose), high glucose (HG, 40 mmol/L) treatment group, Rb1 (50 µ mol/L) treatment group, Rb1 plus HG treatment group, and Rb1 and 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP, 16 µ mol/L) plus HG treatment group. Cell viability was evaluated by cell counting kit-8 assay. Mitochondrial and intracellular reactive oxygen species were detected by MitoSox Red mitochondrial superoxide indicator and dichloro-dihydro-fluorescein diacetate assay, respectively. Annexin V/propidium iodide staining and fluorescent dye staining were used to measure the apoptosis and the mitochondrial membrane potential of HUVECs, respectively. The protein expressions of apoptosis-related proteins [Bcl-2, Bax, cleaved caspase-3 and cytochrome c (Cyt-c)], mitochondrial biogenesis-related proteins [proliferator-activated receptor gamma coactivator 1-alpha, nuclear respiratory factor-1 and mitochondrial transcription factor A)], acetylation levels of forkhead box O3a and SOD2, and sirtuin-3 (SIRT3) signalling pathway were measured by immunoblotting and immunoprecipitation.

Results

Rb1 ameliorated survival in cells in which apoptosis was induced by high glucose (P<0.05 or P<0.01). Upon the addition of Rb1, mitochondrial and intracellular reactive oxygen species generation and malondialdehyde levels were decreased (P<0.01), while the activities of antioxidant enzymes were increased (P<0.05 or P<0.01). Rb1 preserved the mitochondrial membrane potential and reduced the release of Cyt-c from the mitochondria into the cytosol (P<0.01). In addition, Rb1 upregulated mitochondrial biogenesis-associated proteins (P<0.01). Notably, the cytoprotective effects of Rb1 were correlated with SIRT3 signalling pathway activation (P<0.01). The effect of Rb1 against high glucose-induced mitochondria-related apoptosis was restrained by 3-TYP (P<0.05 or P<0.01).

Conclusion

Rb1 could protect HUVECs from high glucose-induced apoptosis by promoting mitochondrial function and suppressing oxidative stress through the SIRT3 signalling pathway.

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Authors and Affiliations

  1. Department of Cardiology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China

    Shi-ye Ke, Shu-jie Yu, Ding-hui Liu, Guang-yao Shi, Min Wang, Bin Zhou, Lin Wu, Jie-ming Zhu & Xiao-xian Qian

  2. Department of Cardiology, the Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong Province, 518033, China

    Shi-ye Ke

  3. Department of Cardiology, the First Affiliated Hospital of Henan University, Kaifeng, Henan Province, 475001, China

    Zhi-ming Song

  4. Department of Nutrition and Food Science, Texas A&M University, College Station, TX, 77843, United States of America

    Chao-dong Wu

  5. Institute of Integrated Traditional Chinese and Western Medicine, Sun Yat-Sen University, Guangzhou, 510630, China

    Xiao-xian Qian

Authors
  1. Shi-ye Ke
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  2. Shu-jie Yu
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  3. Ding-hui Liu
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  4. Guang-yao Shi
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  5. Min Wang
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  6. Bin Zhou
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  7. Lin Wu
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  8. Zhi-ming Song
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  9. Jie-ming Zhu
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  10. Chao-dong Wu
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Contributions

Ke SY, Yu SJ, Wu L and Qian XX contributed to the conception and design of this work. Liu DH, Shi GY, Wang M and Song ZM contributed to data analyses. Ke SY, Zhou B, Zhu JM and Wu CD wrote the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Xiao-xian Qian.

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Conflict of Interest

The authors declare that they have no conflict of interest.

Supported by the National Natural Science Foundation of China (No. 81370447), Science and Technology Planning Project of Guangdong Province, China (No. 2016A050502014), and the Ph.D. Start-up Fund of Natural Science Foundation of Guangdong Province, China (No. 2015A030310048, and 2016A030310203)

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Ke, Sy., Yu, Sj., Liu, Dh. et al. Ginsenoside Rb1 Protects Human Umbilical Vein Endothelial Cells against High Glucose-Induced Mitochondria-Related Apoptosis through Activating SIRT3 Signalling Pathway. Chin. J. Integr. Med. 27, 336–344 (2021). https://doi.org/10.1007/s11655-020-3478-8

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