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Maslinic Acid Suppresses High Glucose-induced Inflammation by Epigenetically Inhibiting TXNIP Expression

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Abstract

Objective

Hyperglycemia-induced inflammation and subsequent endothelial injuries ultimately lead to the pathogenesis of cardiovascular diseases associated with high mortality, such as atherosclerosis. Maslinic acid (MA) is a phytochemical with anti-inflammatory activity. However, it remains unknown whether it can inhibit diabetes-associated cardiovascular inflammation. The present study aimed to determine the effect of MA on high glucose-induced endothelial inflammation and apoptosis in human umbilical vein endothelial cells (HUVECs) and to explore the underlying mechanism.

Methods

HUVECs were treated with high glucose to induce inflammation and apoptosis. Apoptosis was determined by flow cytometry. CCK-8 assay was used to examine cell viability. Production levels of cytokines were detected by quantitative realtime PCR (qPCR) and ELISA. Protein expression levels and signaling pathways activation were detected by Western blotting. RNA immunoprecipitation and qPCR were used to determine the N6-methyladenosine (m6A) levels of target mRNAs.

Results

MA promoted the recruitment of RNA demethylase ALKBH5 to TXNIP mRNA, and subsequently enhanced its m6A demethylation. By this means, MA decreased the stability of TXNIP mRNA and downregulated its expression level. Subsequently, reactive oxygen species (ROS) and production of pro-inflammatory cytokines, including TNF-α, IL-6 and IL-1β, were inhibited. And high glucose-induced apoptosis in HUVECs was inhibited by MA.

Conclusion

MA ameliorates high glucose-induced endothelial inflammation and injury, serving as a new potential therapeutic application for protecting against diabetes-associated atherosclerosis and other inflammatory diseases.

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Acknowledgements

We are grateful to Ming-yue WEN and Min-juan WU for their expert technical assistance.

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Authors and Affiliations

  1. Department of Traditional Chinese Medicine, Naval Medical University, Shanghai, 200433, China

    Lin Wang, Yi-fu Fan & Li-na Wang

  2. School of Basic Medicine, Naval Medical University, Shanghai, 200433, China

    Bing-rui Li & Wen-hui Sun

Authors
  1. Lin Wang
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  2. Yi-fu Fan
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  3. Bing-rui Li
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  4. Wen-hui Sun
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  5. Li-na Wang
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Correspondence to Lin Wang or Li-na Wang.

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The authors declare no conflict of interests.

Additional information

This work was supported by grants from the National Natural Science Foundation of China (No. 81804053), and the Natural Science Foundation of Shanghai Science and Technology Commission (No. 16ZR1401000).

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Wang, L., Fan, Yf., Li, Br. et al. Maslinic Acid Suppresses High Glucose-induced Inflammation by Epigenetically Inhibiting TXNIP Expression. CURR MED SCI 42, 1213–1219 (2022). https://doi.org/10.1007/s11596-022-2657-6

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  • DOI: https://doi.org/10.1007/s11596-022-2657-6

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