Chrysin-loaded PLGA attenuates OVA-induced allergic asthma by modulating TLR/NF-κB/NLRP3 axis

Nanomedicine. 2020 Nov:30:102292. doi: 10.1016/j.nano.2020.102292. Epub 2020 Aug 25.

Abstract

Asthma, one of the significant public health problems, is triggered by certain inflammatory processes in the airways that are not addressed propitiously by current therapies. Though pieces of evidence on allergic asthma mitigation by the anti-inflammatory bioflavonoid chrysin (CHR) are accumulating, poor bioavailability, and low solubility curtail drug development. To overcome these shortcomings, CHR loaded nanoparticle (CHR-NP) was formulated, and its salutary effect in preclinical murine allergic asthma model via the peroral route was evaluated. The spherical nanosized particles showed slow, sustained release in vitro. Moreover, CHR-NP dramatically reduced the serum IgE, ovalbumin (OVA)-induced lung histological alteration, as well as Th2 (T-helper 2) cytokines in the bronchoalveolar lavage fluid (BALF). It also suppressed the elevated serum pro-inflammatory cytokines and their upstream TLR/NF-κB/NLRP3 pathway activation in lung superior to CHR and almost identical to dexamethasone (DEX). Thus this study suggests the potentiality of CHR-NP in ameliorating allergic asthma progression.

Keywords: Chrysin; Murine allergic asthma model; TLR/NF-κB/NLRP3 pathway; Th2 cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Asthma / chemically induced*
  • Bronchoalveolar Lavage Fluid
  • Cytokines / metabolism
  • Flavonoids / administration & dosage*
  • Humans
  • Hypersensitivity / etiology*
  • Immunoglobulin E / blood
  • Inflammation Mediators / metabolism
  • Lung / immunology
  • Lung / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Atomic Force
  • Microscopy, Electron, Transmission
  • NF-kappa B / metabolism*
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Ovalbumin / administration & dosage*
  • Polylactic Acid-Polyglycolic Acid Copolymer / administration & dosage*
  • Toll-Like Receptors / metabolism*

Substances

  • Cytokines
  • Flavonoids
  • Inflammation Mediators
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Toll-Like Receptors
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Immunoglobulin E
  • chrysin
  • Ovalbumin