Cellular and molecular mechanisms involved in the protective effects of Aerva Lanata Linn.on airways remodeling in experimental model of bronchial asthma in rats
DOI:
https://doi.org/10.22270/ajprd.v12i2.1367Abstract
Bronchial asthma is a chronic inflammatory respiratory disease characterized by bronchoconstriction and hyperresponsiveness of the bronchial airways. The treatment for bronchial asthma is mainly aimed at relieving symptoms by bronchodilators and controlling asthmatic attacks with anti-inflammatory agents. These therapeutic strategies are associated with several adverse drug effects and high cost that may negatively affect the compliance to therapy. Chronic asthma also results in structural remodeling of the airways which enhances the incidence of refractory asthma and increases morbidity/mortality. It is therefore important to explore adjuncts from alternative forms of therapy to compliment/supplement the conventional treatment. The study assessed the effects of Aerva Lanata Linn., a medicinal plant used in the traditional systems of medicine, on airway remodeling in an experimental model of asthma in rats. Wistar rats were immunized on day 0 with ovalbumin and Al(OH)3 and challenged with aerosolized ovalbumin from day 15 to 22. The rats were treated orally with various doses of standardized aqueous extract of whole plant of Aerva Lanata Linn. or prednisolone (10 mg/kg) for 22 days. After 24 hrs of last challenge, blood, bronchoalveolar lavage (BAL) fluid and lung tissue were collected and assayed for markers of structural remodeling viz, (a) cytokine levels (TGF-β and IL-13); (b) hydroxyproline content, and (c) histopathology. The results showed that Aerva Lanata Linn. markedly reduced the levels of TGF-β, IL-13 in both blood and BAL fluid and hydroxyproline content in lung homogenates. Histopathological examination of lung tissue confirmed the modulatory effects of Aerva Lanata Linn. on airway remodeling as evidenced by reductions in goblet cell hyperplasia, inflammatory cells infiltration and sub epithelial fibrosis, as compared to that in the experimental (disease control) group. The results showed that Aerva Lanata Linn. Attenuated the histopathological changes and biochemical markers of airway remodeling by altering the levels of IL-13 and TGFβ, and the study suggested that it could be beneficial in cases of chronic bronchial asthma.
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References
Homer RJ, Elias JA. Airway remodeling in asthma: therapeutic implications of mechanisms. Physiology (Bethesda). 2005; 20(1):28-35.
Roche WR, Beasley R,Williams JH, Holgate ST. Subepithelial fibrosis in the bronchi of asthmatics. Lancet. 1989; 1.8637:520-524.
Carroll N, Elliot J, Morton A, James A. The structure of large and small airways in nonfatal and fatal asthma. American Review of Respiratory Disease. 1993; 147(2):405-410.
Demoly P, Simony-Lafontaine J, Chanez P, Pujol J L, Lequeux N, Michel FB et. al.. Cell proliferation in the bronchial mucosa of asthmatics and chronic bronchitics. American Journal of Respiratory and Critical Care Medicine. 1994;150(1):214-217.
Tanaka H , Yamada G, Saikai T, Hashimoto M, Tanaka S, Suzuki K et. al. Increased airway vascularity in newly diagnosed asthma using a high-magnification bronchovideoscope. American Journal of Respiratory and Critical Care Medicine. 2003;168(12):1495-1499.
Johnson PR and Burgess JK. Airway smooth muscle and fibroblasts in the pathogenesis of asthma.Current Allergy and Asthma Reports. 2004;4(2):102-108.
Bergeron C, Tulic MK, Hamid Q. Tools used to measure airway remodeling in research. European Respiratory Journal. 2007;29(3):596-604.
Sing S, Salvi S, Mangal DK. Singh M, Awasthi S, Mahesh PA et al. Prevalence, time trends and treatment practices of asthma in India. The Global Asthma Network Study. ERJ open research. 2022;8:00528-2021
Barnes PJ. Corticosteroid resistance in airway disease.Proceedings of the American Thoracic Society. 2004;1(3):264-268.
Wenzel SE, Covar R. Update in asthma 2005.American Journal of Respiratory and Critical Care Medicine. 2006;173(7):698-706.
Verma P, Gulati K, Ray A. Evaluation of anti-inflammatory and immunomodulatory potential of a traditional herbal drug in experimental model of bronchial asthma. EC Pharmacology and Toxicology. 2021;9(4): 130-138.
Kumar D, Prasad DN, Parkash J, Bhatnagar SP, Kumar D. Aantiasthmatic activity of ethanolic extract of Aervalanata Linn. Pharmacology online. 2009;2:1075-1081.
Nagaratna A, Hegde PL, Harini A. A Pharmacological review on gorkha ganja (Aervalanata (Linn.) juss. Ex. Schult), Journal of Pharmacognosy and Phytochemistry. 2014; 3(4):253-257.
Athira P, Nair SN. A pharmacognostic review of medicinal plant AervalanataLinn.. Journal of Pharmaceutical Science and Research. 2017; 9:1420-1423.
Bitasta M, Madan S. Aervalanata: A Blessing of Mother Nature. Journal of pharmacognosy and phytochemistry. 2016; 5(1):92-101.
ICMR. Indian Medicinal Plants. 2004; 1:338-340.
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 Pharmacology and Toxicology. 2016;2(2):99-107.
Stagemann H, Schearze J. Determination of hydroxyproline. Clinica Chimica Acta. 1967; 18:267.
Wynn TA. Type 2 cytokines: mechanisms and therapeutic strategies. Nature Reviews Immunology. 2015;15:271–82.
Dong L, Wang SJ, Camoretti-Mercado B, Li HJ, Chen M, Bi WX. FIZZ1 plays a crucial role in early stage airway remodeling of OVA-induced asthma. Journal of Asthma. 2008; 45(8):648-653.
Ali NS, Rehman S, Naqvi M, Gulati K, Ray A. Modulation of immunological, biomedical, and histopathological changes of airway remodeling by withaniasomnifera in an experimental model of allergic asthma in rats. Journal of Pharmacopuncture. 2023; 26(2):158-166.
Ying DX, Hua J, Mui A, O'Connor R, Grotendorst G, Khalil N. Release of biologically active TGF-beta1 by alveolar epithelial cells results in pulmonary fibrosis.American Journal of Physiology Lung Cellular and Molecular Physiology. 2003;285(3):L527-L539.
Makinde T, Murphy RF, Agrawal DK. The regulatory role of TGF-beta in airway remodeling in asthma.Immunology and Cell Biology. 2007;85(5):348- 356.
Minshall EM, Donald Y, Leung M, Richard JM, Song YL, Cameron L et. al. Eosinophil-associated TGF-beta1 mRNA expression and airways fibrosis in bronchial asthma.American Journal of Respiratory Cell and Molecular Biology. 1997; 17(3):326-333.
Redington AE, Madden J, Frew A J, Djukanovic R, Roche W R, Holgate S T et. al. Redington AE. Transforming growth factor-β1 in asthma. Measurement in bronchoalveolar lavage fluid”.American Journal of Respiratory and Critical Care Medicine. 1997; 156(2):642-647.
Kenyon NJ, Ward RW, McGrew G, Last J A. TGF-beta1 causes airway fibrosis and increased collagen I and III mRNA in mice. Thorax. 2003;58(9):772-777
Blease K, Jakubzick C, Westwick J, Lukacs N, Kunkel S L, Hogaboam C M. Therapeutic effect of IL-13 immunoneutralization during chronic experimental fungal asthma. Journal of Immunology. 2001; 166(8):5219-5224.
Kumar RK,, Herbert C, Yang M, Koskinen A M L, McKenzie A N J, Foster P S. “Role of interleukin-13 in eosinophil accumulation and airway remodeling in a mouse model of chronic asthma”.Clinical and Experimental Allergy. (2002); 32(7):1104-1111.
Wynn TA. IL-13 effector functions.Annual Review of Immunology. 2003; 21:425-456.
Wills-Karp M, Chiaramonte M. Interleukin-13 in asthma. Current Opinion in Pulmonary Medicine. 2003; 9(1): 21-27.
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;2 8(6):224-232.
Lee CG, Homer R J, Zhu Z, Lanone S, Wang X, Koteliansky V et. al. Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor β1. Journal of Experimental Medicine. 2001; 194(6):809-821.
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