Gypenosides Inhibit Inflammatory Response and Apoptosis of Endothelial and Epithelial Cells in LPS-Induced ALI: A Study Based on Bioinformatic Analysis and in Vivo/vitro Experiments

Overview

Journal Drug Des Devel Ther

Specialty Pharmacology

Date 2021 Feb 3

PMID 33531796

Citations 13

Authors

Qing Tu

Yabing Zhu

Yuan Yuan

Long Guo

Lu Liu

Liangfang Yao

Yun Zou

Jinbao Li

Feng Chen

Affiliations

Soon will be listed here.

Abstract

Introduction: Severe inflammatory response leads to poor prognosis of acute lung injury (ALI), the role of gypenosides (GPs) on ALI is not fully clear. The study aimed at investigating the effects of GPs on ALI.

Methods: We firstly established LPS-induced ALI mice model. Then, we tested whether GPs contributed to alleviate inflammatory response and lung injury of ALI in vivo. In order to identify specific mechanisms of the phenomenon, we conducted a bioinformatic analysis of LPS-induced ALI mice based on GEO database to identify hub differentially expressed genes (DEGs). PPI network of the DEGs was used to find hub-genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted based on the DAVID database to identify which pathways the genes enriched. Then, we tested whether GPs inhibited lung injury and inflammatory response via the enriched pathways. We also tested whether GPs inhibited the apoptosis of endothelial and epithelial cells secondary to severe inflammation.

Results: We found GPs significantly alleviated lung injury and improved the survival rate of LPS-induced ALI mice in vivo. Bioinformatic analysis identified 20 hub-genes from DEGs, they were mainly enriched in NF-κB and TNF-α pathways. GPs could reduce the lung injury and inflammatory response via inhibiting NF-κB and TNF-α pathways in vivo. Our results indicated that GPs also inhibited inflammatory response of epithelial and endothelial cells via NF-κB and TNF-α pathways in vitro. Severe inflammatory response could also lead to apoptosis of endothelial and epithelial cells. Our results indicated that GPs effectively inhibited the apoptosis of endothelial and epithelial cells.

Conclusion: Our study suggested GPs contributed to alleviated lung injury in vivo and inhibited inflammation and apoptosis of endothelial and epithelial cells in vitro, providing novel strategies for the prevention and therapy for ALI.

Citing Articles

Cinnamaldehyde Alleviates Alveolar Epithelial Cell Injury in ALI by Inhibiting the CaMKII Pathway.

Liu L, Zhang H, Chen S, Dian W, Zheng Z Cell Biochem Biophys. 2024; 83(1):1097-1104.

PMID: 39316262 DOI: 10.1007/s12013-024-01544-x.

3-methyladenine ameliorates acute lung injury by inhibiting oxidative damage and apoptosis.

Lei X, Liu X, Yu J, Li K, Xia L, Su S Heliyon. 2024; 10(13):e33996.

PMID: 39055838 PMC: 11269838. DOI: 10.1016/j.heliyon.2024.e33996.

Gypenosides exert cardioprotective effects by promoting mitophagy and activating PI3K/Akt/GSK-3/Mcl-1 signaling.

Zheng Y, Wei W, Wang Y, Li T, Wei Y, Gao S PeerJ. 2024; 12:e17538.

PMID: 38912051 PMC: 11193969. DOI: 10.7717/peerj.17538.

Global research progress of endothelial cells and ALI/ARDS: a bibliometric analysis.

Zhou T, Long K, Chen J, Zhi L, Zhou X, Gao P Front Physiol. 2024; 15:1326392.

PMID: 38774649 PMC: 11107300. DOI: 10.3389/fphys.2024.1326392.

Gypenosides ameliorate high-fat diet-induced nonalcoholic fatty liver disease in mice by regulating lipid metabolism.

Zhou T, Cao L, Du Y, Qin L, Lu Y, Zhang Q PeerJ. 2023; 11:e15225.

PMID: 37065701 PMC: 10103699. DOI: 10.7717/peerj.15225.

References

Wang X, Yang L, Yang L, Xing F, Yang H, Qin L . Gypenoside IX Suppresses p38 MAPK/Akt/NFκB Signaling Pathway Activation and Inflammatory Responses in Astrocytes Stimulated by Proinflammatory Mediators. Inflammation. 2017; 40(6):2137-2150. DOI: 10.1007/s10753-017-0654-x. View

Liu H, Yu X, Yu S, Kou J . Molecular mechanisms in lipopolysaccharide-induced pulmonary endothelial barrier dysfunction. Int Immunopharmacol. 2015; 29(2):937-946. DOI: 10.1016/j.intimp.2015.10.010. View

Cline M, Smoot M, Cerami E, Kuchinsky A, Landys N, Workman C . Integration of biological networks and gene expression data using Cytoscape. Nat Protoc. 2007; 2(10):2366-82. PMC: 3685583. DOI: 10.1038/nprot.2007.324. View

Kawasaki M, Kuwano K, Hagimoto N, Matsuba T, Kunitake R, Tanaka T . Protection from lethal apoptosis in lipopolysaccharide-induced acute lung injury in mice by a caspase inhibitor. Am J Pathol. 2000; 157(2):597-603. PMC: 1850133. DOI: 10.1016/S0002-9440(10)64570-1. View

Matthay M, Ware L, Zimmerman G . The acute respiratory distress syndrome. J Clin Invest. 2012; 122(8):2731-40. PMC: 3408735. DOI: 10.1172/JCI60331. View

Dhaliwal K, Scholefield E, Ferenbach D, Gibbons M, Duffin R, Dorward D . Monocytes control second-phase neutrophil emigration in established lipopolysaccharide-induced murine lung injury. Am J Respir Crit Care Med. 2012; 186(6):514-24. PMC: 3480527. DOI: 10.1164/rccm.201112-2132OC. View

Shen W, Gan J, Xu S, Jiang G, Wu H . Penehyclidine hydrochloride attenuates LPS-induced acute lung injury involvement of NF-kappaB pathway. Pharmacol Res. 2009; 60(4):296-302. DOI: 10.1016/j.phrs.2009.04.007. View

Dong P, Yu B, Pan L, Tian X, Liu F . Identification of Key Genes and Pathways in Triple-Negative Breast Cancer by Integrated Bioinformatics Analysis. Biomed Res Int. 2018; 2018:2760918. PMC: 6098886. DOI: 10.1155/2018/2760918. View

Dong S, Zhang Q, Zhu J, Chen M, Li C, Liu Q . Gypenosides reverses depressive behavior via inhibiting hippocampal neuroinflammation. Biomed Pharmacother. 2018; 106:1153-1160. DOI: 10.1016/j.biopha.2018.07.040. View

10.

Cai H, Liang Q, Ge G . Gypenoside Attenuates β Amyloid-Induced Inflammation in N9 Microglial Cells via SOCS1 Signaling. Neural Plast. 2016; 2016:6362707. PMC: 4861811. DOI: 10.1155/2016/6362707. View

11.

Zhang H, Ye Y, Li K, Zhao Z, He J . Gypenosides Prevent HO-Induced Retinal Ganglion Cell Apoptosis by Concurrently Suppressing the Neuronal Oxidative Stress and Inflammatory Response. J Mol Neurosci. 2020; 70(4):618-630. PMC: 7066284. DOI: 10.1007/s12031-019-01468-9. View

12.

Ji Q, Sun Z, Yang Z, Zhang W, Ren Y, Chen W . Protective effect of ginsenoside Rg1 on LPS-induced apoptosis of lung epithelial cells. Mol Immunol. 2018; 136:168-174. DOI: 10.1016/j.molimm.2018.11.003. View

13.

Crosby L, Waters C . Epithelial repair mechanisms in the lung. Am J Physiol Lung Cell Mol Physiol. 2010; 298(6):L715-31. PMC: 2886606. DOI: 10.1152/ajplung.00361.2009. View

14.

Peng X, Li X, Li Y, Huang X, Luo Z . The protective effect of oleanolic acid on NMDA-induced MLE-12 cells apoptosis and lung injury in mice by activating SIRT1 and reducing NF-κB acetylation. Int Immunopharmacol. 2019; 70:520-529. DOI: 10.1016/j.intimp.2019.03.018. View

15.

Shen Y, Wang L, Zhang B, Hu Q, Wang P, He B . Ethyl Rosmarinate Protects High Glucose-Induced Injury in Human Endothelial Cells. Molecules. 2018; 23(12). PMC: 6321336. DOI: 10.3390/molecules23123372. View

16.

Kitamura Y, Hashimoto S, Mizuta N, Kobayashi A, Kooguchi K, Fujiwara I . Fas/FasL-dependent apoptosis of alveolar cells after lipopolysaccharide-induced lung injury in mice. Am J Respir Crit Care Med. 2001; 163(3 Pt 1):762-9. DOI: 10.1164/ajrccm.163.3.2003065. View

17.

Chang L, Shi R, Wang X, Bao Y . Gypenoside A protects ischemia/reperfusion injuries by suppressing miR-143-3p level via the activation of AMPK/Foxo1 pathway. Biofactors. 2020; 46(3):432-440. DOI: 10.1002/biof.1601. View

18.

Zhang H, Ye Y, Zhao Z, Li K, Du Y, Hu Q . Neuroprotective effects of gypenosides in experimental autoimmune optic neuritis. Int J Ophthalmol. 2017; 10(4):541-549. PMC: 5406630. DOI: 10.18240/ijo.2017.04.07. View

19.

Yao Y, Jia H, Wang G, Ma Y, Sun W, Li P . miR-297 Protects Human Umbilical Vein Endothelial Cells against LPS-Induced Inflammatory Response and Apoptosis. Cell Physiol Biochem. 2019; 52(4):696-707. DOI: 10.33594/000000049. View

20.

Miyoshi K, Yanagi S, Kawahara K, Nishio M, Tsubouchi H, Imazu Y . Epithelial Pten controls acute lung injury and fibrosis by regulating alveolar epithelial cell integrity. Am J Respir Crit Care Med. 2012; 187(3):262-75. DOI: 10.1164/rccm.201205-0851OC. View