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Journal of Traditional Chinese Medicine >

2022 , Vol. 42 >Issue 2: 296 - 303

DOI: https://doi.org/10.19852/j.cnki.jtcm.20220225.003

Research Articles

Anti-inflammatory mechanism of rhein in treating asthma based on network pharmacology

  • Junfang FENG ,
  • Ou CHEN ,
  • Yibiao WANG
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  • 1 Department of Pediatrics, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, China
    2 School of Nursing, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Prof. CHEN Ou, School of Nursing, Cheeloo College of Medicine, Shandong University, Jinan 250012, China. chenou@sdu.edu.cn, Telephone: +8653185875005; +86-531-82942003
Prof. WANG Yibiao, Department of Pediatrics, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, China. Wangyibiao@sdu.edu.cn;

Received date: 2021-06-23

  Accepted date: 2021-09-24

  Online published: 2022-02-25

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Abstract

OBJECTIVE: To predict the anti-inflammatory targets and related pathways of rhein in the treatment of asthma by using network pharmacology, and to further explore its potential mechanism in asthma.

METHODS: The corresponding targets of rhein were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the rhein-target network was constructed with Cytoscape 3.7.1 software. The Genbank and Drugbank databases were used to collect and screen asthma targets, and the rhein-target-disease interaction network was constructed. A target protein-protein interaction (PPI) network was constructed using the STRING database to screen key targets. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to identify biological processes and signaling pathways. The anti-asthmatic effects of rhein were tested in vitro, and the expression levels of proteins in the mitogen-activated protein kinase/nuclear factor kappa-B (MAPK/ NF-κB) signaling pathway were assessed by western blot analysis.

RESULTS: Altogether, 83 targets of rhein were screened in the relevant databases, 989 targets of asthma were obtained in the National Center for Biotechnology Information (NCBI) GENE Database. PPI network analysis and KEGG pathway enrichment analysis predicted that rhein could regulate the epidermal active growth factor receptor (EGFR), mitogen-activated protein kinase 14 (MAPK14), tumour necrosis factor receptor superfamily member 1A (TNFRSF1A), receptor tyrosine-protein kinase erbB-2 (ERBB2), and other signaling pathways. Furthermore, we selected the MAPK signaling pathway to determine the anti-inflammatory effects of rhein. Consistently, further in vitro experiments demonstrated that rhein was shown to inhibit HBE cells inflammation.

CONCLUSION: The anti-inflammatory mechanism of rhein in the treatment of asthma may be related to EGFR, MAPK14, TNFRSF1A and ERBB2 as well as their signaling pathways. To prevent the exacerbation of asthma, instead of targeting a single pathway or a single target, all these targets and their signaling pathways should be controlled holistically. Rhein may alleviate the inflammation of asthma by inhibiting the MAPK/NF-κB pathway.

Key words： asthma; rhein; anti-inflammatory agents; pharmacology; drug development

Cite this article

Junfang FENG , Ou CHEN , Yibiao WANG . Anti-inflammatory mechanism of rhein in treating asthma based on network pharmacology[J]. Journal of Traditional Chinese Medicine, 2022 , 42(2) : 296 -303 . DOI: 10.19852/j.cnki.jtcm.20220225.003

References

1. Papi A, Brightling C, Pedersen SE, Reddel HK. Asthma. Lancet 2018; 391: 783-800.
2. Peng TY, Yang QJ. The application of rhein in treatise on cold pathogenic and miscellaneous diseases. Henan Traditional Chinese Medicine 2018; 38: 336-8.
3. Chen QH, Pi RB, Chen JK. Rhein and its derivatives: progress in synthesis and pharmacological research. Yao Xue Yan Jiu 2018; 35: 161-7.
4. Wang BL. Study on active component-target-pathway of Zhizhu decoction based on network pharmacology. Zhong Yao Xin Yao Yu Lin Chuang Yao Li 2018; 29: 759-67.
5. Liu ZQ, Wang BL. Research progress on screening and target prediction of network pharmacology. Zhong Cheng Yao 2019; 41(01):171-8.
6. Chen O, Liu GY, Liu AH, et al. Network pharmacology predicts the anti-inflammatory mechanism of ephedra in the treatment of asthma. Shan Dong Da Xue Xue Bao (Yixue Ban) 2019; 57: 55-61.
7. Kuleshov MV, Diaz JEL, Flamholz ZN, et al. ModEnrichr: a suite of gene set enrichment analysis tools for model organisms. Nucleic Acids Res 2019: pii: gkz347.
8. Kun-Yi H, Yukiko M, Yoshiyuki A, et al. Systemsdock: a web server of network pharmacology-based prediction and analysis. J Nucleic Acids Res 2016; 44: 507-13.
9. Lei QL, Huang YL, Zhong Q, et al. Research on the anti-inflammatory mechanism of Scutellaria baicalensis Georgi based on network pharmacology. Zhong Cao Yao 2018; 49: 3523-30.
10. Liu J, Liu L, Sun J, et al. Icariin protects hippocampal neurons from endoplasmic reticulum stress and NF-kB mediated apoptosis in fetal rat hippocampal neurons and asthma rats. Front Pharmacol 2020; 10: 1660.
11. Cao F, Li HT, Wang MM. Therapeutic effect of rhein on rats with acute lung injury induced by oleic acid and its effect on pulmonary microvascular barrier and inflammatory response. Gui Zhou Yi Yao 2018; 42: 917-21.
12. Xu YD, Zhang Y, Meng XL. Anti-inflammatory effect of rhein based on reverse docking molecular mechanism research. Sichuan Sheng Li Ke Xue Za Zhi 2016; 38: 1-4.
13. Chang WC, Chu MT, Hsu CY, et al. Rhein, an anthraquinone drug, suppresses the NLRP3 inflammasome and macrophage activation in urate crystal-induced gouty inflammation. Am J Chin Med 2019; 47: 135-51.
14. Ge H, Tang H, Liang Y, et al. Rhein attenuates inflammation through inhibition of NF-kB and NALP3 inflammation in vivo and in vitro. Drug Des Devel Ther 2017; 11: 1663-71.
15. Ei-Hashim AZ, Khajah MA, Renno WM, et al. Src-dependent EGFR transactivation regulates lung inflammation via downstream signaling involving ERK1/2, P13Kδ/Akt and NFκB induction in murine asthma model. Sci Rep 2017; 7: 9919.
16. EI-Hashim AZ, Khajah MA, Babyson RS, et al. Ang-(1-7)/MAS1 receptor axis inhibits allergic airway inflammation via blockade of Src-mediated EGFR transactivation in a murine model of asthma. PLoS One 2019; 14: e0224163.
17. Jia CZ, Guan WC, Bing Li, et al. Effect of epidermal growth factor receptor inhibitor on acute respiratory inflammation induced by exogenous zinc ion in rats. Zheng Zhou Da Xue Xue Bao (Yixue Ban) 2011; 46: 349-51.
18. Pan HH, Hsiao YP, Chen PJ, et al. Epithelial growth factor receptor tyrosine kinase inhibitors alleviate house dust mite allergen Der p2-induced IL-6 and IL-8. Environ Toxicol 2019; 34: 476-85.
19. Xie J, Wang RL. Effect of emodin on lung tissue inflammation and p38 MAPK expression in mice with pneumococcal pneumonia. Shandong Yi Yao 2018; 58: 44-7.
20. Li X, Zhou X, Li Y, et al. Lyn cooperating with lipid rafts regulates inflammatory responses in Klebsiella pneumoniae infection thr-ough the p38 / NF-κB pathway. J Eur J Immunol 2014; 44: 763-73.
21. Choi YH, Jin GY, Piao HM, et al. Silibinin attenuates allergic airway inflammation in mice. Biochem Biophys Res Commun 2012; 427: 450-5.
22. Zhao SC, Chen HW, Wu GL, Zhao C. The association of NLRP3 and TNFRSF1A polymorphisms with risk of ankylosing spondylitis and treatment efficacy of etanercept. J Clin Lab Anal 2017; 31: e22138.
23. Hartman ZC, Yang XY, Glass O, et al. HER2 overexpression elicits a pro-inflammatory IL-6 autocrine signaling loop that is critical for tumorigenesis. Cancer Res 2011; 71: 4380-91.
24. Korkaya H, Kim GI, Davis A, et al. Activation of an IL-6 inflammatory loop mediates trastuzumab resistance in HER2+ breast cancer by expanding the cancer stem cell ell. J Molcel 2012; 47: 570-84.
25. Rodriguez-Barrueco R, Yu J, Saucedo-Cuevas LP, et al. Inhibition of the autocrine IL-6-JAK2-STAT3-calprotectin axis as targeted therapy for HR-/HER2+ breast cancers. Genes Dev 2015; 29: 1631-48.
26. Lin LP Niu GH; Zhang XQ. Influence of lncRNA MALAT1 on septic lung injury in mice through p38 MAPK/p65 NF-κB pathway. Eur Rev Med Pharmacol Sci 2019; 23: 1296-304.
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