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Panax Notoginseng Saponin Attenuates Gastric Mucosal Epithelial Cell Injury Induced by Dual Antiplatelet Drugs through COX and PI3K/Akt/ VEGF-GSK-3β-RhoA Network Pathway

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Abstract

Objective

To elucidate the underlying mechanism of Panax notoginseng saponin (PNS) on gastric epithelial cell injury and barrier dysfunction induced by dual antiplatelet (DA).

Methods

Human gastric mucosal epithelial cell (GES-1) was cultured and divided into 4 groups: a control, a DA, a PNS+DA and a LY294002+PNS+DA group. GES-1 apoptosis was detected by flow cytometry, cell permeability were detected using Transwell, level of prostaglandins E2 (PGE2), 6-keto-prostaglandin F1α (6-keto-PGF1α) and vascular endothelial growth factor (VEGF) in supernatant were measured by enzyme linked immunosorbent assay (ELISA), expression of phosphatidylinositide 3-kinase (PI3K), phosphorylated-PI3K (p-PI3K), Akt, phosphorylated-Akt (p-Akt), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), glycogen synthase kinase-3β (GSK-3β) and Ras homolog gene family member A (RhoA) were measured by Western-blot.

Results

DA induced apoptosis and hyper-permeability in GES-1, reduced supernatant level of PGE2, 6-keto-PGF1α and VEGF (P<0.05). Addition of PNS reduced the apoptosis of GES-1 caused by DA, restored the concentration of PGE2, 6-keto-PGF1α and VEGF (P<0.05). In addition, PNS attenuated the alteration of COX-1 and COX-2 expression induced by DA, up-regulated p-PI3K/p-Akt, down-regulated RhoA and GSK-3β. LY294002 mitigated the effects of PNS on cell apoptosis, cell permeability, VEGF concentration, and expression of RhoA and GSK-3β significantly.

Conclusions

PNS attenuates the suppression on COX/PG pathway from DA, alleviates DA-induced GES-1 apoptosis and barrier dysfunction through PI3K/Akt/ VEGF-GSK-3β-RhoA network pathway.

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Author information

Authors and Affiliations

  1. Beijing First Hospital of Integrated Chinese and Western Medicine, Beijing, 100039, China

    Ming-ming Wang, Yan-hui Wang, Rui-jie Li & Hong-yan Jiang

  2. Center for Cardiovascular Disease, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China

    Mei Xue & Da-zhuo Shi

  3. Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, 100102, China

    Zhong-hai Xin

Authors
  1. Ming-ming Wang
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  2. Mei Xue
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  4. Yan-hui Wang
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  5. Rui-jie Li
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  6. Hong-yan Jiang
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  7. Da-zhuo Shi
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Contributions

Prof. Shi DZ and Dr. Jiang HY have made substantial intellectual contributions to the conception and design of this study, with revising and final approve of the article. Wang MM has contributed to the experiment conduction and data analysis of this study, and the article drafting. Assoc. Prof. Xue M has contributed to the drug material supply and blood sampling and FACS procession. Dr. Xin ZH has contributed to the data analysis. Dr. Li RJ and Wang YH have made substantial contribution to the language revision. All the authors approve the submission and publication of the manuscript.

Corresponding author

Correspondence to Hong-yan Jiang.

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The authors declare no competing financial interests.

Additional information

Supported by the National Natural Science Foundation of China (No. 81273933 and 81102722), the Eleven Five-Year Plan of National Science and Technology Support Project (No. 2006BAI04A01-2), the Jilin Province Major Science and Technology Achievement Transforming Project (No. 11ZDZH005)

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Wang, Mm., Xue, M., Xin, Zh. et al. Panax Notoginseng Saponin Attenuates Gastric Mucosal Epithelial Cell Injury Induced by Dual Antiplatelet Drugs through COX and PI3K/Akt/ VEGF-GSK-3β-RhoA Network Pathway. Chin. J. Integr. Med. 27, 819–824 (2021). https://doi.org/10.1007/s11655-021-2854-3

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