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Modulation of Immunological, Biochemical, and Histopathological Changes of Airway Remodeling by Withania somnifera in an Experimental Model of Allergic Asthma in Rats

  • Nafaa Hasan Ali (Department of Pharmacology, Hamdard Institute of Medical Sciences and Research (HIMSR), Jamia Hamdard University) ;
  • Sana Rehman (Department of Pharmacology, Hamdard Institute of Medical Sciences and Research (HIMSR), Jamia Hamdard University) ;
  • Maaz Naqvi (Department of Pharmacology, Hamdard Institute of Medical Sciences and Research (HIMSR), Jamia Hamdard University) ;
  • Kavita Gulati (Department of Pharmacology, Vallabhbhai Patel Chest Institute, University of Delhi) ;
  • Arunabha Ray (Department of Pharmacology, Hamdard Institute of Medical Sciences and Research (HIMSR), Jamia Hamdard University)
  • Received : 2022.11.09
  • Accepted : 2023.02.27
  • Published : 2023.06.30

Abstract

Objectives: Airway remodeling in asthma involves chronic inflammation associated with structural changes, which result in severe airflow limitation and very few therapeutic options. Thus, the present study was designed to experimentally evaluate the ameliorative effects of Withania somnifera (WS) root extract against Ovalbumin (OVA)-induced airway remodeling in a rat model of asthma. Methods: Wistar rats were immunized (i.p) and challenged (aerosol) with ovalbumin (OVA), and the effects of WS extract were investigated on the development and progress of airway remodeling by assessing immunological, biochemical, and histological changes in these rats. Results: OVA-immunization and challenge in rats resulted in significant increases in the levels of IL-13, 8-OhdG, TGF-β, hydroxyproline, and periostin in bronchoalveolar lavage fluid (BALF) and serum/lung homogenate compared to normal control (saline only) rats, and these changes were attenuated after WS extract (200 and 400 mg/kg), as well as dexamethasone (DEX, 1 mg/kg) pretreatments. Further, WS extract attenuated histopathological changes and maintained lung integrity. In herb-drug interactions, sub-threshold doses of WS extract and DEX showed synergistic effects on all parameters studied as compared to either form of monotherapy. Conclusion: These results indicated that WS exerted significant protective effects against airway remodeling in the experimental model by modulating inflammatory and fibrotic cytokines, and could have the potential for developing a therapeutic alternative/adjunct for the treatment of airway remodeling of bronchial asthma.

Keywords

Acknowledgement

The authors thank the Indian Council of Medical Research (ICMR) for the financial support. The infrastructural support provided by HIMSR, New Delhi, is gratefully acknowledged.

References

  1. Chung F. Anti-inflammatory cytokines in asthma and allergy: interleukin-10, interleukin-12, interferon-gamma. Mediators Inflamm. 2001;10(2):51-9.  https://doi.org/10.1080/09629350120054518
  2. Fehrenbach H, Wagner C, Wegmann M. Airway remodeling in asthma: what really matters. Cell Tissue Res. 2017;367(3):551-69.  https://doi.org/10.1007/s00441-016-2566-8
  3. Chetta A, Zanini A, Foresi A, Del Donno M, Castagnaro A, D'Ippolito R, et al. Vascular component of airway remodeling in asthma is reduced by high dose of fluticasone. Am J Respir Crit Care Med. 2003;167(5):751-7.  https://doi.org/10.1164/rccm.200207-710OC
  4. Denis O, van den Brule S, Heymans J, Havaux X, Rochard C, Huaux F, et al. Chronic intranasal administration of mould spores or extracts to unsensitized mice leads to lung allergic inflammation, hyper-reactivity and remodelling. Immunology. 2007;122(2):268-78.  https://doi.org/10.1111/j.1365-2567.2007.02636.x
  5. Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med. 2012;18(5):716-25.  https://doi.org/10.1038/nm.2678
  6. Alzobaidi N, Rehman S, Naqvi M, Gulati K, Ray A. Periostin: a potential biomarker and therapeutic target in pulmonary diseases. J Pharm Pharm Sci. 2022;25:137-48.  https://doi.org/10.18433/jpps32306
  7. Gulati K, Rai N, Ray A. Status of research in respiratory pharmacology in India during the last five years (2012-2017). Proc Indian Natl Sci Acad. 2018;84(1):55-72.  https://doi.org/10.16943/ptinsa/2018/49304
  8. Ahmad M, Dar NJ. Withania somnifera: ethnobotany, pharmacology, and therapeutic functions. In: Bagchi D, editor. Sustained energy for enhanced human functions and activity. London: Academic Press; 2017. p. 137-54. 
  9. Rai N, Gulati K, Rahman RU, Ray A. Effects of a polyherbal agent on structural changes and biochemical markers during airway remodelling in experimental model of bronchial asthma. EC Pharmacol Toxicol. 2016;2(2):99-107. 
  10. Nair P, Prabhavalkar K. Anti-asthmatic effects of saffron extract and salbutamol in an ovalbumin-induced airway model of allergic asthma. Sinusitis. 2021;5(1):17-31.  https://doi.org/10.3390/sinusitis5010003
  11. Kim DI, Song MK, Lee K. Comparison of asthma phenotypes in OVA-induced mice challenged via inhaled and intranasal routes. BMC Pulm Med. 2019;19(1):241. 
  12. Mukherjee AA, Kandhare AD, Rojatkar SR, Bodhankar SL. Ameliorative effects of Artemisia pallens in a murine model of ovalbumin-induced allergic asthma via modulation of biochemical perturbations. Biomed Pharmacother. 2017;94:880-9.  https://doi.org/10.1016/j.biopha.2017.08.017
  13. Lambrecht BN, Hammad H, Fahy JV. The cytokines of asthma. Immunity. 2019;50(4):975-91. https://doi.org/10.1016/j.immuni.2019.03.018
  14. Yang G, Volk A, Petley T, Emmell E, Giles-Komar J, Shang X, et al. Anti-IL-13 monoclonal antibody inhibits airway hyperresponsiveness, inflammation and airway remodeling. Cytokine. 2004;28(6):224-32.  https://doi.org/10.1016/j.cyto.2004.08.007
  15. Oberholtzer HM, Pretorius E, Smir E, Ekpo OE, Humphries P, Auer RE, et al. Investigating the effect of Withania somnifera, selenium and hydrocortisone on blood count and bronchial lavage of experimental asthmatic BALB/c mice. Scand J Lab Anim Sci. 2008;35(4):239-48. 
  16. Zhao HM, Gao ZW, Xie SX, Han X, Sun QS. Withaferin A attenuates ovalbumin induced airway inflammation. Front Biosci (Landmark Ed). 2019;24(3):576-96.  https://doi.org/10.2741/4737
  17. Cho JY, Miller M, Baek KJ, Han JW, Nayar J, Lee SY, et al. Inhibition of airway remodeling in IL-5-deficient mice. J Clin Invest. 2004;113(4):551-60.  https://doi.org/10.1172/JCI19133
  18. Yan Y, Liu L, Dou Z, Xu Y, Yan X. Soufeng Yuchuan decoction mitigates the ovalbumin-induced lung damage in a rat model of asthma. Biomed Pharmacother. 2020;125:109933. 
  19. Singh P, Salman KA, Shameem M, Warsi MS. Withania somnifera (L.) dunal as add-on therapy for COPD patients: a randomized, placebo-controlled, double-blind study. Front Pharmacol. 2022;13:901710. 
  20. Eap R, Jacques E, Semlali A, Plante S, Chakir J. Cysteinyl leukotrienes regulate TGF-β(1) and collagen production by bronchial fibroblasts obtained from asthmatic subjects. Prostaglandins Leukot Essent Fatty Acids. 2012;86(3):127-33.  https://doi.org/10.1016/j.plefa.2011.11.001
  21. Chauhan PS, Dash D, Singh R. Intranasal curcumin inhibits pulmonary fibrosis by modulating matrix metalloproteinase-9 (MMP-9) in ovalbumin-induced chronic asthma. Inflammation. 2017;40(1):248-58.  https://doi.org/10.1007/s10753-016-0475-3
  22. Izuhara K, Matsumoto H, Ohta S, Ono J, Arima K, Ogawa M. Recent developments regarding periostin in bronchial asthma. Allergol Int. 2015;64 Suppl:S3-10.  https://doi.org/10.1016/j.alit.2015.04.012
  23. Scheerens H, Arron JR, Zheng Y, Putnam WS, Erickson RW, Choy DF, et al. The effects of lebrikizumab in patients with mild asthma following whole lung allergen challenge. Clin Exp Allergy. 2014;44(1):38-46. https://doi.org/10.1111/cea.12220