ReferenceID 6485

Vitexin restores lung homeostasis by targeting vicious loop between inflammatory aggravation and autophagy mediated via multiple redox cascade and myeloid cells alteration in experimental allergic asthma

Phytomedicine

Background: Allergic asthma is one of the leading respiratory diseases with complex pathology. Attributes of vitexin, a trihydroxyflavone, has been studied to alleviate Th2 cytokines response in allergic asthma. However,

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Reference Id
6485
Evidence Id
23075
Core Evidence Id
23075
Source Reference Id
6273
Herb2 Reference Id
HBREF007070
Subject Paper Key
HBIN048102_35026520
Pubmed Id
35026520
Doi
10.1016/j.phymed.2021.153902
Paper Title
Vitexin restores lung homeostasis by targeting vicious loop between inflammatory aggravation and autophagy mediated via multiple redox cascade and myeloid cells alteration in experimental allergic asthma
Paper Abstract
Background: Allergic asthma is one of the leading respiratory diseases with complex pathology. Attributes of vitexin, a trihydroxyflavone, has been studied to alleviate Th2 cytokines response in allergic asthma. However, its efficacy and underlying mechanism in mitigating allergic asthma particularly mediated by oxi-inflammatory stress, autophagy and apoptosis, yet to be delineated. Purpose: Present study aimed to decipher efficacy and governing molecular mechanism of vitexin in mitigating allergic asthma particularly mediated by vicious loop of oxi-inflammatory stress, autophagy and apoptosis. Methods: To ascertain this, OVA-LPS induced mice model was used and protective attributes of vitexin for different mediators, pathological facets and sensing pathways of allergic asthma were evaluated. Results: Vitexin treatment remarkably inhibited OVA-LPS induced inflammatory cell infiltration, mast cell activation, alveolar collapse, congestion, fibrosis in lung architecture. These results were accompanied by suppression of immune cells hyperactivation, mucus secretion, goblet cell proliferation, persistent inflammation which were affirmed by alleviation in levels of IgE, Th1/Th2/Th17, IL-4/IFN-γ, chemokines, endopeptidases (MMP-1, MMP-13), oxidative effectors with concomitant increase in IL-15, IL-10, MMP-9 and MMP-3. Additionally, noticeable decline in p-connexin 43, p-c-Fos, TGF-β, Smad2/3/4, Caspase9/3, LC3A/B expression and upregulation in beclin-1, p62 co-localization and Bcl2/Bax indicate reversal of lung vascular permeability, mast cell degranulation, fibrosis, apoptosis, autophagosome impairment. Subsequent allergic inflammatory cascades analysis revealed p-NF-κB, p-PI3K, p-Akt, p-p38, p-Stat3, GATA3 upregulation and p-PTEN downregulation in sensitized mice, which were decisively counteracted by vitexin. In silico studies signified target specificity of vitexin with these proteins. Suppression in myeloid cells activation and enhancements of Tregs demonstrated immunomodulatory potential of vitexin in allergic airways. Conclusion: Collectively, to our knowledge, this is the first report that confers vitexin meditated multi-faceted protective attribute in mitigation of allergic asthma that could be linked to its suppressive effects on vicious cycle of pathological process particularly regulated via oxi-inflammation, autophagy and apoptosis. Thus, signify vitexin as safe therapeutic strategy.
Journal
Phytomedicine
Publish Year
2022
Experiment Subject
mouse
Experiment Type
Animal Experiment
Phenotype Related
Allergic Asthma; Fibrosis; Allergic Airways; Autophagosome Impairment; Respiratory Diseases
Paper Title Cn
Paper Title En
Vitexin restores lung homeostasis by targeting vicious loop between inflammatory aggravation and autophagy mediated via multiple redox cascade and myeloid cells alteration in experimental allergic asthma
Bilingual Status
semi_complete