Honokiol: A polyphenol neolignan ameliorates pulmonary fibrosis by inhibiting TGF-β/Smad signaling, matrix proteins and IL-6/CD44/STAT3 axis both in vitro and in vivo

Toxicol Appl Pharmacol. 2020 Mar 15:391:114913. doi: 10.1016/j.taap.2020.114913. Epub 2020 Feb 4.


Pulmonary fibrosis (PF) is an epithelial/fibroblastic crosstalk disorder of the lungs with highly complex etiopathogenesis. Limited treatment possibilities are responsible for poor prognosis and mean survival rate of 3 to 5 years of PF patients after definite diagnosis. Once thought to be an irreversible disorder, recent evidences have brought into existence the concept of organ fibrosis reversibility due to plastic nature of fibrotic tissues. These findings have kindled interest among the scientific community and given a new direction for research in the arena of fibrosis for developing new anti-fibrotic therapies. The current study is designed to evaluate the anti-fibrotic effects of Honokiol (HNK), a neolignan active constituent from Magnolia officinalis. This study has been conducted in TGF-β1 induced in vitro model and 21 day in vivo murine model of Bleomycin induced PF. The findings of our study suggest that HNK was able to inhibit fundamental pathways of epithelial to mesenchymal transition (EMT) and TGF-β/Smad signaling both in vitro and in vivo. Additionally, HNK also attenuated collagen deposition and inflammation associated with fibrosis. We also hypothesized that HNK interfered with IL-6/CD44/STAT3 axis. As hypothesized, HNK significantly mitigated IL-6/CD44/STAT3 axis both in vitro and in vivo as evident from outcomes of various protein expression studies like western blotting, immunohistochemistry and ELISA. Taken together, it can be concluded that HNK reversed pulmonary fibrotic changes in both in vitro and in vivo experimental models of PF and exerted anti-fibrotic effects majorly by attenuating EMT, TGF-β/Smad signaling and partly by inhibiting IL-6/CD44/STAT3 signaling axis.

Keywords: Bleomycin; Honokiol; IL-6/CD44/STAT3 axis; Pulmonary fibrosis; TGF-beta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biphenyl Compounds / pharmacology
  • Biphenyl Compounds / therapeutic use*
  • Bleomycin
  • Bronchoalveolar Lavage Fluid
  • Cell Line
  • Cell Movement / drug effects
  • Collagen / metabolism
  • Cytokines / blood
  • Epithelial-Mesenchymal Transition / drug effects
  • Humans
  • Hyaluronan Receptors
  • Interleukin-6
  • Lignans / pharmacology
  • Lignans / therapeutic use*
  • Lung / metabolism
  • Lung / pathology
  • Mice
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / drug therapy*
  • Pulmonary Fibrosis / pathology
  • STAT3 Transcription Factor / drug effects
  • Signal Transduction / drug effects*
  • Smad Proteins / drug effects
  • Transforming Growth Factor beta / drug effects


  • Biphenyl Compounds
  • Cd44 protein, mouse
  • Cytokines
  • Hyaluronan Receptors
  • Interleukin-6
  • Lignans
  • STAT3 Transcription Factor
  • Smad Proteins
  • Stat3 protein, mouse
  • Transforming Growth Factor beta
  • Bleomycin
  • honokiol
  • Collagen