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      Bronchom assuages airway hyperresponsiveness in house dust mite-induced mouse model of allergic asthma and moderates goblet cell metaplasia, sub-epithelial fibrosis along with changes in Th2 cytokines and chemokines

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          Abstract

          Background

          Asthma is a common obstructive airway disease with an inflammatory etiology. The main unmet need in the management of asthma is inadequate adherence to pharmacotherapy, leading to a poorly-controlled disease state, necessitating the development of novel therapies. Bronchom is a calcio-herbal formulation, which is purported to treat chronic asthma. The objective of the current study was to examine the in-vivo efficacy of Bronchom in mouse model of allergic asthma.

          Methods

          Ultra high performance liquid chromatography was utilized to analyze the phytocompounds in Bronchom. Further, the in-vivo efficacy of Bronchom was evaluated in House dust mite (HDM)-induced allergic asthma in mice. Mice were challenged with aerosolized methacholine to assess airway hyperresponsiveness. Subsequently, inflammatory cell influx was evaluated in bronchoalveolar lavage fluid (BALF) followed by lung histology, wherein airway remodeling features were studied. Simultaneously, the levels of Th2 cytokines and chemokines in the BALF was also evaluated. Additionally, the mRNA expression of pro-inflammatory and Th2 cytokines was also assessed in the lung along with the oxidative stress markers.

          Results

          Phytocompounds present in Bronchom included, gallic acid, protocatechuic acid, methyl gallate, rosmarinic acid, glycyrrhizin, eugenol, 6-gingerol and piperine. Bronchom effectively suppressed HDM-induced airway hyperresponsiveness along with the influx of leukocytes in the BALF. Additionally, Bronchom reduced the infiltration of inflammatory cells in the lung and it also ameliorated goblet cell metaplasia, sub-epithelial fibrosis and increase in α-smooth muscle actin. Bronchom decreased Th2 cytokines (IL-4 and IL-5) and chemokines (Eotaxin and IP-10) in the BALF. Likewise, it could also suppress the mRNA expression of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-6 and IL-33), and IL-13. Moreover, Bronchom restored the HDM-induced diminution of endogenous anti-oxidants (GSH and SOD) and the increase in pro-oxidants (GSSG and MDA). Furthermore, Bronchom could also decrease the nitrosative stress by lowering the observed increase in nitrite levels.

          Conclusion

          Taken together, the results of the present study data convincingly demonstrate that Bronchom exhibits pharmacological effects in an animal model of allergic asthma. Bronchom mitigated airway hyperresponsiveness, inflammation and airway remodeling evoked by a clinically relevant allergen and accordingly it possesses therapeutic potential for the treatment of asthma.

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          A simple practice guide for dose conversion between animals and human

          Understanding the concept of extrapolation of dose between species is important for pharmaceutical researchers when initiating new animal or human experiments. Interspecies allometric scaling for dose conversion from animal to human studies is one of the most controversial areas in clinical pharmacology. Allometric approach considers the differences in body surface area, which is associated with animal weight while extrapolating the doses of therapeutic agents among the species. This review provides basic information about translation of doses between species and estimation of starting dose for clinical trials using allometric scaling. The method of calculation of injection volume for parenteral formulation based on human equivalent dose is also briefed.
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            Superoxide dismutase: improved assays and an assay applicable to acrylamide gels.

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              Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0

              Improving the reproducibility of biomedical research is a major challenge. Transparent and accurate reporting is vital to this process; it allows readers to assess the reliability of the findings and repeat or build upon the work of other researchers. The ARRIVE guidelines (Animal Research: Reporting In Vivo Experiments) were developed in 2010 to help authors and journals identify the minimum information necessary to report in publications describing in vivo experiments. Despite widespread endorsement by the scientific community, the impact of ARRIVE on the transparency of reporting in animal research publications has been limited. We have revised the ARRIVE guidelines to update them and facilitate their use in practice. The revised guidelines are published alongside this paper. This explanation and elaboration document was developed as part of the revision. It provides further information about each of the 21 items in ARRIVE 2.0, including the rationale and supporting evidence for their inclusion in the guidelines, elaboration of details to report, and examples of good reporting from the published literature. This document also covers advice and best practice in the design and conduct of animal studies to support researchers in improving standards from the start of the experimental design process through to publication.
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                Author and article information

                Contributors
                Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/2652568Role: Role: Role: Role: Role: Role: Role: Role:
                Role: Role: Role: Role:
                Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/1970422Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/601884Role: Role: Role: Role: Role:
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                14 May 2024
                2024
                : 15
                : 1384697
                Affiliations
                [1] 1Drug Discovery and Development Division, Patanjali Research Foundation , Haridwar, India
                [2] 2Department of Allied and Applied Sciences, University of Patanjali , Haridwar, India
                [3] 3Patanjali UK Trust , Glasgow, United Kingdom
                [4] 4Vedic Acharya Samaj Foundation, Inc. , Groveland, FL, United States
                [5] 5Special Centre for Systems Medicine, Jawaharlal Nehru University , New Delhi, India
                Author notes

                Edited by: Sathish Venkatachalem, North Dakota State University, United States

                Reviewed by: Julie Gunnells Ledford, University of Arizona, United States

                Bijayani Sahu, University of North Dakota, United States

                *Correspondence: Anurag Varshney, anurag@ 123456patanjali.res.in
                Article
                10.3389/fimmu.2024.1384697
                11130375
                38807596
                cc04e6c3-2737-45ea-9072-5c4ad4dd86ae
                Copyright © 2024 Balkrishna, Sinha, Karumuri, Maity, Dev and Varshney

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 10 February 2024
                : 19 April 2024
                Page count
                Figures: 11, Tables: 2, Equations: 2, References: 46, Pages: 21, Words: 10200
                Funding
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research work was supported by internal funds from Patanjali Research Foundation Trust, Haridwar, India.
                Categories
                Immunology
                Original Research
                Custom metadata
                Inflammation

                Immunology
                asthma,bronchom,house dust mite,inflammation,oxidative stress,ayurveda
                Immunology
                asthma, bronchom, house dust mite, inflammation, oxidative stress, ayurveda

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