Scopoletin inhibits PDGF-BB-induced proliferation and migration of airway smooth muscle cells by regulating NF-κB signaling pathway

Main Article Content

Zhongxiang Fan
Dan Tang
Qiang Wu
Qun Huang
Jie Song
Qiping Long

Keywords

asthma, airway smooth, muscle cells (ASMCs), migration, NF-KB signaling, pathway, PDGF-BB

Abstract

Background: Asthma is a common chronic inflammatory disease of the airway, and airway remodeling and the proliferation mechanism of airway smooth muscle cells (ASMCs) is of great significance to combat this disease.


Objective: To assess possible effects of scopoletin on asthma and the potential signaling pathway.


Materials and methods: ASMCs were treated PDGF-BB and scopoletin and subjected to cell viability detection by CCK-8 assay. Cell migration of ASMCs was determined by a wound closure assay and transwell assay. The protein level of MMP2, MMP9, calponin and α-SMA were measured using western blot. The levels of NF-κB signaling pathway were detected by Western blotting.


Results: Scopoletin inhibited proliferation of PDGF-BB - induced ASMCs. Also it suppressed the migration and invasion of PDGF-BB - induced ASMCs. We further showed that Scopoletin regulated phenotypic transition of ASMCs. Mechanically, Scopoletin inhibited proliferation and invasion of ASMCs by regulating NF-κB signaling pathway.


Conclusions: We therefore thought Scopoletin could serve as a promising drug for the treatment of asthma.

Abstract 68 | PDF Downloads 50 HTML Downloads 4 XML Downloads 0

References

1. Nasab EM, Athari SM, Ghafarzade S, Nasab A-RM, Athari SS. Immunomodulatory effects of two silymarin isomers in a Balb/c mouse model of allergic asthma. Allergologia et Immunopathol. 2020;48(6):646–53. 10.1016/j.aller.2020.01.003

2. Gao S, Wang J, Zhang Q, Shu J, Li C, Li H, et al. Cytokine antibody array-based analysis of IL-37 treatment effects in asthma. Aging. 2021 Sep;13;13(17):21729–42 (undefined). 10.18632/aging.203515

3. Luan Y, Luan Y, Yuan RX, Feng Q, Chen X, Yang Y. Structure and function of mitochondria-associated endoplasmic reticulum membranes (MAMs) and their role in cardiovascular diseases. Oxid Med Cell Longev. 2021;2021:4578809. 10.1155/2021/4578809

4. Dorosz A, Urbankowski T, Zielinski K, Michnikowski M, Krenke R, Moskal A. Modeling of inhalation profiles through dry powder inhaler in healthy adults and asthma patients as a prerequisite for further in vitro and in silico studies. J Aerosol Med Pulm Drug Deliv. 2021, Sep. Online ahead of print. 10.1089/jamp.2021.0021

5. Jang JH, Park JE, Han JS. Scopoletin inhibits alpha-glucosidase in vitro and alleviates postprandial hyperglycemia in mice with diabetes. Eur J Pharmacol. 2018;834:152–6. 10.1016/j.ejphar.2018.07.032

6. Li B, Lu M, Chu Z, Lei S, Sun P, Xiong S, et al. Evaluation of pharmacokinetics, bioavailability and urinary excretion of scopolin and its metabolite scopoletin in Sprague–Dawley rats by liquid chromatography-tandem mass spectrometry. Biomed Chromatogr (BMC). 2019;33(12):e4678. 10.1002/bmc.4678

7. Sakthivel KM, Vishnupriya S, Priya Dharshini LC, Rasmi RR, Ramesh B. Modulation of multiple cellular signalling pathways as targets for anti-inflammatory and anti-tumorigenesis action of Scopoletin. J Pharm Pharmacol. 2021 Apr;rgab047. Online ahead of print. 10.1093/jpp/rgab047

8. Lee EJ, Na W, Kang MK, Kim YH, Kim DY, Oh H, et al. Hydroxycoumarin scopoletin inhibits bone loss through enhancing induction of bone turnover markers in a mouse model of type 2 diabetes. Biomedicines. 2021, Jun;9(6):648. 10.3390/biomedicines9060648

9. Narasimhan KKS, Jayakumar D, Velusamy P, Srinivasan A, Mohan T, Ravi DB, et al. Morinda citrifolia and its active principle scopoletin mitigate protein aggregation and neuronal apoptosis through augmenting the DJ-1/Nrf2/ARE signaling pathway. Oxid Med Cell Longev. 2019;2019:2761041. 10.1155/2019/2761041

10. Kiris I, Skalicka-Wozniak K, Basar MK, Sahin B, Gurel B, Baykal AT. Molecular effects of pteryxin and scopoletin in the 5xFAD Alzheimer’s disease mouse model. Curr Med Chem. 2021. Online ahead of print. 10.2174/0929867328666210827152914

11. Wang X, Chen T, Deng Z, Gao W, Liang T, Qiu X, et al. Melatonin promotes bone marrow mesenchymal stem cell osteogenic differentiation and prevents osteoporosis development through modulating circ_0003865 that sponges miR-3653-3p. Stem Cell Res Ther. 2021;12(1):150. 10.1186/s13287-021-02224-w

12. Kang H, Davis-Dusenbery BN, Nguyen PH, Lal A, Lieberman J, Van Aelst L, et al. Bone morphogenetic protein 4 promotes vascular smooth muscle contractility by activating microRNA-21 (miR-21), which down-regulates expression of family of dedicator of cytokinesis (DOCK) proteins. J Biol Chem. 2012;287(6):3976–86. 10.1074/jbc.M111.303156

13. Jang JE, Kim HP, Han SW, Jang H, Lee SH, Song SH, et al. NFATC3-PLA2G15 fusion transcript identified by RNA sequencing promotes tumor invasion and proliferation in colorectal cancer cell lines. Cancer Res Treat. 2019;51(1):391–401. 10.4143/crt.2018.103

14. Wang T, Zhang C, Xie H, Jiang M, Tian H, Lu L, et al. Anti-VEGF therapy prevents Muller intracellular edema by decreasing VEGF-A in diabetic retinopathy. Eye Vision. 2021;8(1):13. 10.1186/s40662-021-00237-3

15. Spadaro G, Lagnese G, Punziano A, Poto R, Varricchi G, Detoraki A. The immunology of switching biologics in severe eosinophilic asthma patients. J Allergy Clin Immunol Pract. 2021;9(9):3528–9. 10.1016/j.jaip.2021.05.044

16. Kosloski MP, Kalliolias GD, Xu CR, Harel S, Lai CH, Zheng W, et al. Pharmacokinetics and pharmacodynamics of Itepekimab in healthy adults and patients with asthma: Phase I first-in-human and first-in-patient trials. Clin Transl Sci. 2021, Sep 15. Online ahead of print. 10.1111/cts.13157

17. Liang L, Gu X, Shen HJ, Shi YH, Li Y, Zhang J, et al. Chronic intermittent hypoxia reduces the effects of glucosteroid in asthma via activating the p38 MAPK signaling pathway. Front Physiol. 2021;12:703281. 10.3389/fphys.2021.703281

18. Andersen H, Ilmarinen P, Honkamaki J, Tuomisto LE, Hisinger-Molkanen H, Backman H, et al. Influence of childhood exposure to a farming environment on age at asthma diagnosis in a population-based study. J Asthma Allergy. 2021;14:1081–91. 10.2147/JAA.S323504

19. D’Urzo AD, Price D, Kardos P, Maleki-Yazdi MR. Importance of distinguishing between asthma and chronic obstructive pulmonary disease in primary care. Can Fam Physician Med de Fam Can. 2021;67(9):661–7.

20. Luo L, Sun T, Yang L, Liu A, Liu QQ, Tian QQ, et al. Scopoletin ameliorates anxiety-like behaviors in complete Freund’s adjuvant-induced mouse model. Mol Brain. 2020;13(1):15. 10.1186/s13041-020-0560-2

21. Ahmadi N, Mohamed S, Sulaiman Rahman H, Rosli R. Epicatechin and scopoletin-rich Morinda citrifolia leaf ameliorated leukemia via anti-inflammatory, anti-angiogenesis, and apoptosis pathways in vitro and in vivo. J Food Biochem. 2019;43(7):e12868. 10.1111/jfbc.12868

22. Yuan C, Wang MH, Wang F, Chen PY, Ke XG, Yu B, et al. Network pharmacology and molecular docking reveal the mechanism of Scopoletin against non-small cell lung cancer. Life Sci. 2021;270:119105. 10.1016/j.lfs.2021.119105

23. Pradhan P, Majhi O, Biswas A, Joshi VK, Sinha D. Enhanced accumulation of reduced glutathione by Scopoletin improves survivability of dopaminergic neurons in Parkinson’s model. Cell Death Dis. 2020;11(9):739. 10.1038/s41419-020-02942-8

24. Long H, Ruan J, Zhang M, Wang C, Huang Y. Gastrodin alleviates Tourette syndrome via Nrf-2/HO-1/HMGB1/NF-small ka, Cyrillic-B pathway. J Biochem Mol Toxicol. 2019;33(10):e22389. 10.1002/jbt.22389

25. Liang Y, Zeng X, Guo J, Liu H, He B, Lai R, et al. Scopoletin and umbelliferone from Cortex Mori as protective agents in high glucose-induced mesangial cell as in vitro model of diabetic glomerulosclerosis. Chin J Physiol. 2021;64(3):150–8. 10.4103/cjp.cjp_9_21

26. Leema G, Tamizhselvi R. Protective effect of Scopoletin against cerulein-induced acute pancreatitis and associated lung injury in mice. Pancreas. 2018;47(5):577–85. 10.1097/MPA.0000000000001034

27. Zhang F, Zhang Y, Yang T, Ye ZQ, Tian J, Fang HR, et al. Scopoletin suppresses activation of dendritic cells and pathogenesis of experimental autoimmune encephalomyelitis by inhibiting NF-kappa-B Signaling. Front Pharmacol. 2019;10:863. 10.3389/fphar.2019.00863; 10.3389/fphar.2019.01037

28. Lee S, Shin S, Kim H, Han S, Kim K, Kwon J, et al. Anti-inflammatory function of arctiin by inhibiting COX-2 expression via NF-kappaB pathways. J Inflamm. 2011;8(1):16. 10.1186/1476-9255-8-16

29. Yang Y, Luan Y, Yuan RX, Luan Y. Histone methylation related therapeutic challenge in cardiovascular diseases. Front Cardiovasc Med. 2021;8(710053). 10.3389/fcvm.2021.710053