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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

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          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.

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          Most cited references23

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          Asthma phenotypes: the evolution from clinical to molecular approaches.

          Although asthma has been considered as a single disease for years, recent studies have increasingly focused on its heterogeneity. The characterization of this heterogeneity has promoted the concept that asthma consists of multiple phenotypes or consistent groupings of characteristics. Asthma phenotypes were initially focused on combinations of clinical characteristics, but they are now evolving to link biology to phenotype, often through a statistically based process. Ongoing studies of large-scale, molecularly and genetically focused and extensively clinically characterized cohorts of asthma should enhance our ability to molecularly understand these phenotypes and lead to more targeted and personalized approaches to asthma therapy.
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            The Cytokines of Asthma

            Asthma is a chronic inflammatory airway disease associated with type 2 cytokines interleukin-4 (IL-4), IL-5, and IL-13, which promote airway eosinophilia, mucus overproduction, bronchial hyperresponsiveness (BHR), and immunogloubulin E (IgE) synthesis. However, only half of asthma patients exhibit signs of an exacerbated Type 2 response. "Type 2-low" asthma has different immune features: airway neutrophilia, obesity-related systemic inflammation, or in some cases, few signs of immune activation. Here, we review the cytokine networks driving asthma, placing these in cellular context and incorporating insights from cytokine-targeting therapies in the clinic. We discuss established and emerging paradigms in the context of the growing appreciation of disease heterogeneity and argue that the development of new and improved therapeutics will require understanding the diverse mechanisms underlying the spectrum of asthma pathologies.
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              Airway remodeling in asthma: what really matters

              Airway remodeling is generally quite broadly defined as any change in composition, distribution, thickness, mass or volume and/or number of structural components observed in the airway wall of patients relative to healthy individuals. However, two types of airway remodeling should be distinguished more clearly: (1) physiological airway remodeling, which encompasses structural changes that occur regularly during normal lung development and growth leading to a normal mature airway wall or as an acute and transient response to injury and/or inflammation, which ultimately results in restoration of a normal airway structures; and (2) pathological airway remodeling, which comprises those structural alterations that occur as a result of either disturbed lung development or as a response to chronic injury and/or inflammation leading to persistently altered airway wall structures and function. This review will address a few major aspects: (1) what are reliable quantitative approaches to assess airway remodeling? (2) Are there any indications supporting the notion that airway remodeling can occur as a primary event, i.e., before any inflammatory process was initiated? (3) What is known about airway remodeling being a secondary event to inflammation? And (4), what can we learn from the different animal models ranging from invertebrate to primate models in the study of airway remodeling? Future studies are required addressing particularly pheno-/endotype-specific aspects of airway remodeling using both endotype-specific animal models and “endotyped” human asthmatics. Hopefully, novel in vivo imaging techniques will be further advanced to allow monitoring development, growth and inflammation of the airways already at a very early stage in life.
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                Author and article information

                Journal
                J Pharmacopuncture
                J Pharmacopuncture
                Journal of Pharmacopuncture
                The Korean Pharmacopuncture Institute (KPI)
                2093-6966
                2234-6856
                30 June 2023
                30 June 2023
                30 June 2023
                : 26
                : 2
                : 158-166
                Affiliations
                [1 ]Department of Pharmacology, Hamdard Institute of Medical Sciences and Research (HIMSR), Jamia Hamdard University, New Delhi, India
                [2 ]Department of Pharmacology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India
                Author notes
                [* ]Corresponding Author Arunabha Ray, Department of Pharmacology, Hamdard Institute of Medical Sciences and Research (HIMSR), Jamia Hamdard University, New Delhi 110062, India, Tel: +91-981-803-7595, E-mail: arunabha14@ 123456yahoo.co.in
                Author information
                https://orcid.org/0000-0003-0524-9107
                https://orcid.org/0000-0001-8183-1778
                https://orcid.org/0000-0002-2349-3771
                https://orcid.org/0000-0002-8815-1879
                https://orcid.org/0000-0003-0886-7875
                Article
                jop-26-2-158
                10.3831/KPI.2023.26.2.158
                10315884
                a9e31ddf-6a17-4e1a-bb69-dd55db6f23ca
                © 2023 Korean Pharmacopuncture Institute

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 9 November 2022
                : 14 November 2022
                : 27 February 2023
                Categories
                Original Article

                bronchial asthma,airway remodeling,withania somnifera,cytokines,oxidative stress

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