Protective effects of aloin on asthmatic mice by activating Nrf2/HO-1 pathway and inhibiting TGF-β/Smad2/3 pathway
Main Article Content
Keywords
aloin, asthma, inflammation, Nrf2/HO-1, oxidative stress, TGF-β/Smad
Abstract
Background: Asthma is a severe chronic respiratory disease affecting all age groups with increasing prevalence. Anti-inflammatory strategies are promising options for the treatment of asthma. Although the inhibitory effect of aloin on inflammation has been demonstrated in various diseases, its effect on asthma remains unknown.
Methods: A mice asthma model was established by treating with ovalbumin (OVA). The effects and mechanism of aloin on the OVA-treated mice were determined by enzyme-linked--immunosorbent serologic assay, biochemical examination, hematoxylin and eosin and Masson's staining, and Western blot assay.
Results: OVA treatment in mice significantly increased the number of total cells, neutrophils, eosinophils, and macrophages and the concentration of interleukin (IL)-4, IL-5, and IL-13, which were attenuated with the administration of aloin. The content of malondialdehyde was enhanced in OVA-treated mice, with the decreased levels of superoxide dismutase and glutathione, which were reversed with aloin treatment. Aloin treatment reduced the airway resistance of OVA-induced mice. The inflammatory cell infiltration around small airways was accompanied by the thickening and contraction of bronchial walls and pulmonary collagen deposition in OVA-treated mice; however, these conditions were ameliorated with aloin treatment. Mechanically, aloin upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)—heme oxygenase 1 (HO-1) pathway but inhibited the level of transforming growth factor beta–SMAD2/3 genes (TGF-β/Smad2/3) axis in OVA-induced mice.
Conclusion: Aloin treatment lessened airway hyperresponsiveness, airway remodeling, inflammation, and oxidative stress in OVA-treated mice, and was closely related to the activation of Nrf2/HO-1 pathway and the weakening of TGF-β/Smad2/3 pathway.
References
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2. Chen ZH, Wang PL, Shen HH. Asthma research in China: A five-year review. Respirology. 2013;18 Suppl 3:10–9. 10.1111/resp.12196
3. Shen W, Ming Y, Zhu T, Luo L. The association between air pollutants and hospitalizations for asthma: An evidence from Chengdu, China. Ann Transl Med. 2023;11(2):65. 10.21037/atm-22-6265
4. Sears MR. Trends in the prevalence of asthma. Chest. 2014;145(2):219–25. 10.1378/chest.13-2059
5. Zhang J, Dai J, Yan L, Fu W, Yi J, Chen Y, et al. Air pollutants, climate, and the prevalence of pediatric asthma in urban areas of China. Biomed Res Int. 2016;2016:2935163. 10.1155/2016/2935163
6. Zhou X, Hong J. Pediatric asthma management in China: Current and future challenges. Paed Drugs. 2018;20(2):105–10. 10.1007/s40272-017-0276-7
7. Willis-Owen SAG, Cookson WOC, Moffatt MF. The genetics and genomics of asthma. Ann Rev Genomics Hum Genet. 2018;19:223–46. 10.1146/annurev-genom-083117-021651
8. Licari A, Marseglia GL, Ciprandi G. The relevance of symptom perception in the management of severe asthma in adolescents. Allergol Immunopathol (Madr). 2020;48(6):810–3. 10.1016/j.aller.2019.10.004
9. Nie Y, Yang B, Hu J, Zhang L, Ma Z. Bruceine D ameliorates the balance of Th1/Th2 in a mouse model of ovalbumin-induced allergic asthma via inhibiting the NOTCH pathway. Allergol Immunopathol (Madr). 2021;49(6):73–9. 10.15586/aei.v49i6.499
10. Poddighe D, Brambilla I, Licari A, Marseglia GL. Omalizumab in the therapy of pediatric asthma. Recent Pat Inflamm Allergy Drug Discov. 2018;12(2):103–9. 10.2174/1872213X12666180430161351
11. Dahl R. Systemic side effects of inhaled corticosteroids in patients with asthma. Respir Med. 2006;100(8):1307–17. 10.1016/j.rmed.2005.11.020
12. Roland NJ, Bhalla RK, Earis J. The local side effects of inhaled corticosteroids: Current understanding and review of the literature. Chest. 2004;126(1):213–9. 10.1378/chest.126.1.213
13. Jangra A, Sharma G, Sihag S, Chhokar V. The dark side of miracle plant Aloe vera: A review. Mol Biol Rep. 2022;49(6):5029–40. 10.1007/s11033-022-07176-9
14. Shida T, Yagi A, Nishimura H, Nishioka I. Effect of Aloe extract on peripheral phagocytosis in adult bronchial asthma. Planta Med. 1985(3):273–5. 10.1055/s-2007-969480
15. Yang Y, Wu JJ, Xia J, Wan Y, Xu JF, Zhang L, et al. Can aloin develop to medicines or healthcare products? Biomed Pharmacother. 2022;153:113421. 10.1016/j.biopha.2022.113421
16. Lee IC, Bae JS. Inhibitory effects of aloin on lipopolysaccharide--induced severe inflammatory responses. J Asian Nat Prod Res. 2022;24(10):987–99. 10.1080/10286020.2022.2026932
17. Sun W, Wang Z, Sun M, Huang W, Wang Y, Wang Y. Aloin antagonizes stimulated ischemia/reperfusion-induced damage and inflammatory response in cardiomyocytes by activating the Nrf2/HO-1 defense pathway. Cell Tissue Res. 2021;384(3):735–44. 10.1007/s00441-020-03345-z
18. Xu Q, Fan Y, Loor JJ, Liang Y, Lv H, Sun X, et al. Aloin protects mice from diet-induced non-alcoholic steatohepatitis via activation of Nrf2/HO-1 signaling. Food Funct. 2021;12(2):696–705. 10.1039/D0FO02684K
19. Dong H, Wang H, Zhang X. Inhibition of NOX2 contributes to the therapeutic effect of aloin on traumatic brain injury. Folia Neuropathol. 2020;58(3):265–74. 10.5114/fn.2020.100069
20. Birari L, Wagh S, Patil KR, Mahajan UB, Unger B, Belemkar S, et al. Aloin alleviates doxorubicin-induced cardiotoxicity in rats by abrogating oxidative stress and pro-inflammatory cytokines. Cancer Chemother Pharmacol. 2020;86(3):419–26. 10.1007/s00280-020-04125-w
21. Lee IC, Bae JS. Inhibitory effects of aloin on TGFBIp-mediated septic responses. J Asian Nat Prod Res. 2021;23(2):189–203. 10.1080/10286020.2019.1711066
22. National Research Council (US) Committee for the Update of the Guide for the Care, Use of Laboratory A. Guide for the Care and Use of Laboratory Animals. Washington, DC: National Academy of Sciences, National Academies Press (US); 2011. Reports funded by National Institutes of Health. PMid: 21595115.
23. Lu C, Zhang B, Xu T, Zhang W, Bai B, Xiao Z, et al. Piperlongumine reduces ovalbumin-induced asthma and airway inflammation by regulating nuclear factor-κB activation. Int J Mol Med. 2019;44(5):1855–65. 10.3892/ijmm.2019.4322
24. Jia S, Guo P, Lu J, Huang X, Deng L, Jin Y, et al. Curcumol ameliorates lung inflammation and airway remodeling via inhibiting the abnormal activation of the Wnt/β-catenin pathway in chronic asthmatic mice. Drug Des Devel Ther. 2021;15:2641–51. 10.2147/DDDT.S292642
25. Bostani M, Rahmati M, Mard SA. The effect of endurance training on levels of LINC complex proteins in skeletal muscle fibers of STZ-induced diabetic rats. Sci Rep. 2020;10(1):8738. 10.1038/s41598-020-65793-5
26. Rahmati M, Rashno A. Automated image segmentation method to analyse skeletal muscle cross section in exercise-induced regenerating myofibers. Sci Rep. 2021;11(1):21327. 10.1038/s41598-021-00886-3
27. Liu L, Ji X, Huang X. Dexmedetomidine improves myocardial ischemia-reperfusion injury by increasing autophagy via PINK1/PRKN pathway. Signa Vitae. 2022;18(5):125–32.
28. Yu C, Yu Q, Lu J, Zhou J. KRT17 enhances carboplatin resistance in ovarian cancer through the AKT/mTOR pathway. Eur J Gynaecol Oncol. 2022;43(4):49–57.
29. Rahmati M, Shariatzadeh Joneydi M, Koyanagi A, Yang G, Ji B, Won Lee S, et al. Resistance training restores skeletal muscle atrophy and satellite cell content in an animal model of Alzheimer's disease. Sci Rep. 2023;13(1):2535. 10.1038/s41598-023-29406-1
30. Rahmati M, Taherabadi SJ. The effects of exercise training on Kinesin and GAP-43 expression in skeletal muscle fibers of STZ-induced diabetic rats. Sci Rep. 2021;11(1):9535. 10.1038/s41598-021-89106-6
31. Huang CW, Zhao Q, Zhong LT, Zhong XY, Tong JZ, Huang YM. Comparative study of three animal models of asthma in mice. J Qiqihar Med Coll. 2019;40(11):1321–3. (In Chinese)
32. Poddighe D, Mathias CB, Brambilla I, Marseglia GL, Oettgen HC. Importance of basophils in eosinophilic asthma: The murine counterpart. J Biol Regul Homeost Agents. 2018;32(2):335–9.
33. Poddighe D, Mathias CB, Freyschmidt EJ, Kombe D, Caplan B, Marseglia GL, et al. Basophils are rapidly mobilized following initial aeroallergen encounter in naïve mice and provide a priming source of IL-4 in adaptive immune responses. J Biol Regul Homeost Agents. 2014;28(1):91–103.
34. Lambrecht BN, Hammad H, Fahy JV. The cytokines of asthma. Immunity. 2019;50(4):975–91. 10.1016/j.immuni.2019.03.018
35. Pritam P, Manna S, Sahu A, Swain SS, Ramchandani S, Bissoyi S, et al. Eosinophil: A central player in modulating pathological complexity in asthma. Allergol Immunopathol (Madr). 2021;49(2):191–207. 10.15586/aei.v49i2.50
36. Kidd P. Th1/Th2 balance: The hypothesis, its limitations, and implications for health and disease. Altern Med Rev. 2003;8(3):223–46.
37. Steinke JW, Borish L. Th2 cytokines and asthma. Interleukin-4: Its role in the pathogenesis of asthma, and targeting it for asthma treatment with interleukin-4 receptor antagonists. Respir Res. 2001;2(2):66–70. 10.1186/rr40
38. Foster PS, Hogan SP, Ramsay AJ, Matthaei KI, Young IG. Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model. J Exp Med. 1996;183(1):195–201. 10.1084/jem.183.1.195
39. Wills-Karp M, Luyimbazi J, Xu X, Schofield B, Neben TY, Karp CL, et al. Interleukin-13: Central mediator of allergic asthma. Science. 1998;282(5397):2258–61. 10.1126/science.282.5397.2258
40. Truyen E, Coteur L, Dilissen E, Overbergh L, Dupont LJ, Ceuppens JL, et al. Evaluation of airway inflammation by quantitative Th1/Th2 cytokine mRNA measurement in sputum of asthma patients. Thorax. 2006;61(3):202–8. 10.1136/thx.2005.052399
41. Ezzat DA, Morgan DS, Mohamed RA, Mohamed AF. Genetic association of interleukin 18 (-607C/A, rs1946518) single nucleotide polymorphism with asthmatic children, disease severity and total IgE serum level. Cent Eur J Immunol. 2019;44(3):285–91. 10.5114/ceji.2019.89603
42. Zhang N, Lu HT, Zhang RJ, Sun XJ. Protective effects of methane-rich saline on mice with allergic asthma by inhibiting inflammatory response, oxidative stress and apoptosis. J Zhejiang Univ Sci B. 2019;20(10):828–37. 10.1631/jzus.B1900195
43. Gon Y, Hashimoto S. Role of airway epithelial barrier dysfunction in pathogenesis of asthma. Allergol Int. 2018;67(1):12–7. 10.1016/j.alit.2017.08.011
44. Chen YF, Huang G, Wang YM, Cheng M, Zhu FF, Zhong JN, et al. Exchange protein directly activated by cAMP (Epac) protects against airway inflammation and airway remodeling in asthmatic mice. Respir Res. 2019;20(1):285. 10.1186/s12931-019-1260-2
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Jul 1, 2023
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Wu, S., Xia, Y., Yang, C., & Li, M. (2023). Protective effects of aloin on asthmatic mice by activating Nrf2/HO-1 pathway and inhibiting TGF-β/Smad2/3 pathway. Allergologia Et Immunopathologia, 51(4), 10-18. https://doi.org/10.15586/aei.v51i4.863
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How to Cite
Wu, S., Xia, Y., Yang, C., & Li, M. (2023). Protective effects of aloin on asthmatic mice by activating Nrf2/HO-1 pathway and inhibiting TGF-β/Smad2/3 pathway. Allergologia Et Immunopathologia, 51(4), 10-18. https://doi.org/10.15586/aei.v51i4.863