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).