Inhibitory role of ginsenoside Rb2 in endothelial senescence and inflammation mediated by microRNA‑216a

Chen,Yutong; Wang,Shuting; Yang,Shujun; Li,Rongxia; Yang,Yunyun; Chen,Yu; Zhang,Weili

doi:10.3892/mmr.2021.12054

Inhibitory role of ginsenoside Rb2 in endothelial senescence and inflammation mediated by microRNA‑216a

Authors:
- Yutong Chen
- Shuting Wang
- Shujun Yang
- Rongxia Li
- Yunyun Yang
- Yu Chen
- Weili Zhang
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Affiliations: Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing 100069, P.R. China, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100037, P.R. China
Published online on: March 30, 2021 https://doi.org/10.3892/mmr.2021.12054
Article Number: 415
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Targeting microRNAs (miRs) using small chemical molecules has become a promising strategy for disease treatment. miR‑216a has been reported to be a potential therapeutic target in endothelial senescence and atherosclerosis via the Smad3/NF‑κB signaling pathway. Ginsenoside Rb2 (Rb2) is the main bioactive component extracted from the plant Panax ginseng, and is a widely used traditional Chinese medicine. In the present study, Rb2 was identified to have a high score for miR‑216a via bioinformatics analysis based on its sequence and structural features. The microscale thermophoresis experiment further demonstrated that Rb2 had a specific binding affinity for miR‑216a and the dissociation constant was 17.6 µM. In both young and senescent human umbilical vein endothelial cells (HUVECs), as well as human aortic endothelial cells, Rb2 decreased the expression of endogenous miR‑216a. Next, a replicative endothelial senescence model of HUVECs was established by infection with pre‑miR‑216a recombinant lentiviruses (Lv‑miR‑216a) and the number of population‑doubling level (PDL) was calculated. Stable overexpression of miR‑216a induced a premature senescent‑like phenotype, whereas the senescent features and increased activity of senescence‑associated β‑galactosidase (SA‑β‑gal) were reversed after Rb2 treatment. The percentage of SA‑β‑gal‑positive cells in senescent PDL25 cells transfected with Lv‑miR‑216a was decreased 76% by Rb2 treatment compared with the Lv‑miR‑216a group without Rb2 treatment (P=0.01). Mechanistically, miR‑216a inhibited Smad3 protein expression, promoted IκBα degradation and activated NF‑κB‑responsive genes, such as vascular cell adhesion molecule 1 (VCAM1), which promoted the adhesiveness of endothelial cells to monocytes. These pro‑inflammatory effects of miR‑216a were significantly suppressed by Rb2 treatment. When Smad3 was suppressed by small interfering RNA, the elevated expression levels of intercellular adhesion molecule 1 and VCAM1 induced by miR‑216a were significantly reversed. Collectively, to the best of our knowledge, the present study demonstrated for the first time that Rb2 exerted an anti‑inflammation effect on the process of endothelial cell senescence and could be a potential therapeutic drug by targeting miR‑216a.

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