ovalbumin and agnuside

Attributes of agnuside, a nontoxic, iridoid glycoside have been advocated for inflammatory disorders. However, information on its efficacy in alleviating allergic asthma largely remain ambiguous and yet to be deciphered. Present study aimed to assess efficacy of agnuside in targeting vicious circle of oxi-inflammation, autophagy and fibrosis, together with investigating its underlying molecular mechanism during OVA-LPS induced allergic asthma. Results revealed that agnuside showed prophylactic effect in assuaging asthmatic lung architecture impairment (p ≤ 0.01) as indicated by suppression of inflammatory cell infiltration, congestion, fibrosis, airway remodeling and alveolar collapse in OVA-LPS sensitized group. Decreased expression level (p ≤ 0.05) of allergic inflammatory mediators such as IgE, Th1/Th2, IL-4/IFN-γ, IL-4/IL-10, chemokines, endopeptidases and TGF-β, Smad2/4, Caspase9/3, connexin 43/50 observed in agnuside treatments. Analysis of redox molecular signaling cascade and autophagic proteins revealed concurrent upregulation in p-NF-κB, p-PI3K, p-Akt, p-p38, p-Stat3 activation, GATA3, LC3B expression and reduction in Bcl2/Bax, Beclin1 and p62 expression in sensitized mice (p ≤ 0.05) which were intensely counteracted by administration of agnuside. Suppression in myeloid cells activation and augmentation (p ≤ 0.001) of Tregs established modulatory attribute of agnuside for innate and adaptive immune response during allergic asthma. Collectively, these outcomes confer prophylactic attribute of agnuside and signify it as promising strategy to thwart allergic asthma.

Topics: Animals; Apoptosis; Asthma; Autophagy; Bronchoalveolar Lavage Fluid; Cell Lineage; Cytokines; Disease Models, Animal; Fibrosis; Glucosides; Homeostasis; Lung; Mice; Mice, Inbred BALB C; Ovalbumin

Novel lipidated analogs of iridoids viz., Agnuside and Negundoside with different chain length were synthesized and tested for immune adjuvant activity in the presence of weak antigen ovalbumin. Based on in vitro assay, 6-O-palmitoyl Agnuside (AG-3) was further taken up for detailed in vivo activity and found to significantly enhance the production of anti OVA IgG titer, neutralizing antibody (IgG1 and IgG2a) titer as well as soluble mediators of a Th1 (IL-2, IFN-γ)/Th2 response (IL-4) and proliferation of T lymphocyte subsets (CD4/CD8) and co stimulatory molecules CD80/CD86. Furthermore, the SAR studies revealed that presence of acyl group at aglycon moiety of these iridoid glycosides is crucial for immune adjuvant activity.

Topics: Adjuvants, Immunologic; Animals; Antigens; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Proliferation; Cytokines; Glucosides; Immunoglobulin G; Iridoid Glycosides; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Spleen; T-Lymphocyte Subsets