Niclosamide in chronic medical conditions
A seminal study from Tao et al., (2014) showed that niclosamide reduced
liver fat accumulation (steatosis) in mice fed a high fat diet. The
effects were also studied in human liver cells and demonstrated
increased lipid oxidation and up-regulation of the AMP-activated protein
kinase (AMPK) pathway, suggesting its potential use as an anti-obesity
agent. In an Iraqi study, patients with active rheumatoid arthritis on
etanercept showed a good response to adjuvant niclosamide therapy with
significant improvements in their joint and clinical severity indices
and a decrease in the serum levels of IL-1β, E-selectin, intercellular
adhesion molecule 1 (ICAM1) and vascular cell adhesion protein 1 (VCAM1)
(Al-Gareeb, Gorial, & Mahmood, 2018).
In a screen of ∼580,000 compounds, niclosamide was identified as a
TMEM16A antagonist, a calcium-activated chloride channel that
contributes to mucus hypersecretion and bronchoconstriction in reactive
airway disease (Miner et al., 2019). The study tested efficacy using
maximally contracted and cytokine-treated airways and confirmed that
niclosamide had a potent bronchodilator effect. Centeio et al., (2021)
further investigated these findings, demonstrating that niclosamide
inhibited mucus production and secretion in ovalbumin (OVA)-treated
mice, and also inhibited MUC5A and SAM pointed domain-containing
ETS-like factor (SPDEF) expression in CALU-3 cells. Niclosamide has been
found to exert anti-fibrotic effects via Wnt/β-catenin signaling in a
cellular model as well as in a bleomycin-induced murine pulmonary
fibrosis model (Boyapally, Pulivendala, Bale, & Godugu, 2019). In rats
with established pulmonary hypertension, it reduced vascular remodeling
and improved right heart function via STAT-3 inhibition (C. L. Braga et
al., 2020). There was reduced expression of TGF-β, hypoxia-inducible
factor 1α (HIF) and vimentin, a mesenchymal marker, along with reduced
epithelial to mesenchymal transition (EMT).