Anti-Inflammatory and Immunomodulatory Effects of Withania Somnifera In. an Experimental Model of Bronchial Asthma in Normal and Stressed Rats
Creators
- 1. Department of Pharmacology, Hamdard Institute of Medical Sciences & Research & Associated HAHC Hospital, Hamdard Nagar, New Delhi, India
- 2. Department of Pharmacology, Department of Pharmacology, Hamdard Institute of Medical Sciences & Research & Associated HAHC Hospital, Hamdard Nagar, New Delhi, India
- 3. Department of Pharmacology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India
Description
Introduction: Airway inflammation and hyperresponsiveness are distinctive features of bronchial asthma and chronic inflammation may lead to structural changes known as airway remodelling. Complex and interacting mechanisms regulate the pathophysiology of asthma and confounding factors like emotional stress have been implicated. Withania somnifera (WS) is a potent anti-stress and immunomodulator in view of which it could be considered as possible therapeutic agent for asthma. Objective: The present study examined the anti-inflammatory and immunomodulatory effects of s WS root extract on markers of airway inflammation and immunity in normal as well as stressed rats in experimentally induced bronchial asthma. Methods: Wistar rats (200-225 g) were immunized with ovalbumin (OVA) + aluminium hydroxide on day 1 and challenged with OVA on day 14. The rats were divided into stressed (RS x 15 days) and non-stressed groups and were administered WS extract (200 and 400 mg/kg). Following this, the animals were sacrificed, and Broncho alveolar lavage fluid (BALF) and blood were collected for assay of immune and inflammatory markers of the airways. Results: WS extract significantly decreased OVA-induced elevations in IgE, IL-4, TNF-α and IL-13 levels in both blood and BALF in RS exposed and non-RS rats with the higher dose of WS. These WS effects were comparable to those seen after dexamethasone treatment. Further, the OVA-induced responses in RS-exposed rats and their modulation by WS were of greater magnitude as compared to their non-RS groups. Conclusion: Our study findings indicate that WS extract effectively attenuated markers of immunity and airway inflammation in stressed and non-stressed rats, in the OVA model of asthma and suggests that anti-inflammatory, immunomodulatory and anti-stress effects could contribute to these responses.
Abstract (English)
Introduction: Airway inflammation and hyperresponsiveness are distinctive features of bronchial asthma and chronic inflammation may lead to structural changes known as airway remodelling. Complex and interacting mechanisms regulate the pathophysiology of asthma and confounding factors like emotional stress have been implicated. Withania somnifera (WS) is a potent anti-stress and immunomodulator in view of which it could be considered as possible therapeutic agent for asthma. Objective: The present study examined the anti-inflammatory and immunomodulatory effects of s WS root extract on markers of airway inflammation and immunity in normal as well as stressed rats in experimentally induced bronchial asthma. Methods: Wistar rats (200-225 g) were immunized with ovalbumin (OVA) + aluminium hydroxide on day 1 and challenged with OVA on day 14. The rats were divided into stressed (RS x 15 days) and non-stressed groups and were administered WS extract (200 and 400 mg/kg). Following this, the animals were sacrificed, and Broncho alveolar lavage fluid (BALF) and blood were collected for assay of immune and inflammatory markers of the airways. Results: WS extract significantly decreased OVA-induced elevations in IgE, IL-4, TNF-α and IL-13 levels in both blood and BALF in RS exposed and non-RS rats with the higher dose of WS. These WS effects were comparable to those seen after dexamethasone treatment. Further, the OVA-induced responses in RS-exposed rats and their modulation by WS were of greater magnitude as compared to their non-RS groups. Conclusion: Our study findings indicate that WS extract effectively attenuated markers of immunity and airway inflammation in stressed and non-stressed rats, in the OVA model of asthma and suggests that anti-inflammatory, immunomodulatory and anti-stress effects could contribute to these responses.
Files
IJTPR,Vol12,Issue9,Article49.pdf
Files
(717.2 kB)
| Name | Size | Download all |
|---|---|---|
|
md5:4266f581267d6afae58a155407a63196
|
717.2 kB | Preview Download |
Additional details
Dates
- Accepted
-
2022-09-26
Software
References
- 1. Olin JT, Wechsler ME. Asthma: Pathogenesis and novel drugs for treatment. Br Med J. 2014;349:5517. 2. Ware L, Matthay M. The Acute Respiratory Distress Syndrome. N Engl J Med. 2000; 342(18): 1334–49. 3. Wong H R, Wispe J R. The stress response and the lung. Am J Physiol 1997;273: 1-9. 4. Birben E, Sahiner U, Sackesen C, Erzurum S, Kalayci O. Oxidative Stress and Antioxidant Defense Mechanism in. Science. 1997;22(96): 161–8. 5. Huntley A, Edzard E. Herbal medicines for asthma: A systematic review. Thorax. 2000; 55:925-9. 6. Mukherjee PK, anerjee S, Biswas S , DasB, Kar A , Katiyar CK. Withania somnifera (L.) Dunal - Modern perspectives of an ancient Rasayana from Ayurveda. J Ethnopharmacol. 2021. 7. Kwasniewski FH, Tavares De Lima W, Bakhle YS, Jancar S. Impairment in connective tissue mast cells degranulation in spontaneously hypertensive rats: Stimulus dependent resistance. Br J Pharmacol. 1998;124(4):772–8. 8. Singh P, Daniels M, Winsett DW, Richards J, Doerfler D, Hatch G, et al. Phenotypic comparison of allergic airway responses to house dust mite in three rat strains. Am J Physiol - Lung Cell Mol Physiol. 2003;284: 588–98. 9. Kanemitsu Y, Matsumoto H, Izuhara K, Tohda Y, Kita H, Horiguchi T, et al. Increased periostin associates with greater airflow limitation in patients receiving inhaled corticosteroids. J Allergy ClinImmunol. 2013;132(2):305-312.e3. 10. Pare W. P., Glavin G. B. Restraint stress in biomedical research: a review. Neurosci. Biobehav. Rev. 1986; 10:339- 370 11. Kandhare AD, Patil MVK, Bodhankar SL. Ameliorative Effect of Alkaloidal Fraction of Leaves of Alstoniascholaris Against Acetic Acid Induced Colitis via Modulation of Oxido-nitrosative and Proinflammatory Cytokines. Pharmacologia. 2016; 7(4):170–81. 12. Rosalind J Wright, Mario Rodriguez, Sheldon Cohen. Review of psychosocial stress and asthma: an integrated biopsychosocial approach. Thorax 1998; 53:1066–1074. 13. Scichilone N, Ventura MT, Bonini M, Braido F, Bucca C, Caminati M, et al. Choosing wisely: Practical considerations on treatment efficacy and safety of asthma in the elderly. ClinMol Allergy. 2015; 13(1):1–14. 14. Wilson DR, Merrett TG, Varga EM, Smurthwaite L, Gould HJ, Kemp M, et al. Increases in allergen-specific IgE in BAL after segmental allergen challenge in atopic asthmatics. Am J Respir Crit Care Med. 2002;165(1):22–6. 15. Matucci A, Vultaggio A, Maggi E, Kasujee I. Is IgE or eosinophils the key player in allergic asthma pathogenesis? Are we asking the right question? Respir Res. 2018;19(1):1–10. 16. Barnes PJ. The cytokine network in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol. 2009;41(6): 631–8. 17. Singh DK, Gulati K, Ray A. Effects of chelidonic acid, a secondary plant metabolite, on mast cell degranulation and adaptive immunity in rats. Int Immunopharmacol. 2016;40: 229–34. 18. R Archana, A Namasivayam, Antistressor effect of Withania somnifera. J Ethnopharmacol, 1998;64:91-93. 19. Cazzola M, Polosa R. Anti-TNF-α and Th1 cytokine-directed therapies for the treatment of asthma. Curr Opin Allergy Clin Immunol. 2006; 6(1):43–50. 20. Yilmaz O, Karaman M, Bagriyanik HA, Firinci F, Kiray M, Turkeli A, et al. Comparison of TNF antagonism by etanercept and dexamethasone on airway epithelium and remodeling in an experimental model of asthma. Int Immunopharmacol. 2013; 17(3): 768–73. 21. Kate Blease, Claudia Jakubzick, John Westwick, Nicholas Lukacs, Steven L. Kunkel and Cory M. Hogaboam. Therapeutic Effect of IL-13 Immunoneutralization during chronic experimental fungal Asthma. J Immunol 2001; 166(8):5219-5224.