Niclosamide: Beyond an antihelminthic drug

Chen, Wei; Mook, Robert A.; Premont, Richard T.; Wang, Jiangbo

doi:10.1016/j.cellsig.2017.04.001

Cited by 342 publications

(282 citation statements)

References 109 publications

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“…The mechanism of action of niclosamide and AM85 appears to be indirect and mediated by their mitochondrial uncoupling properties, although this is not sufficient to explain the greater potency of AM85 in neurons. Niclosamide has been used safely in humans for over half a century to treat helminth infections and is currently being tested in multiple clinical trials in a variety of human cancers, as well as rheumatoid arthritis . Our data suggests that niclosamide and/or its analogues could have therapeutic benefit in slowing down PD progression through the activation of PINK1.…”

Section: Figurementioning

confidence: 80%

The Anthelmintic Drug Niclosamide and Its Analogues Activate the Parkinson's Disease Associated Protein Kinase PINK1

et al. 2018

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Mutations in PINK1, which impair its catalytic kinase activity, are causal for autosomal recessive early‐onset Parkinson's disease (PD). Various studies have indicated that the activation of PINK1 could be a useful strategy in treating neurodegenerative diseases, such as PD. Herein, it is shown that the anthelmintic drug niclosamide and its analogues are capable of activating PINK1 in cells through the reversible impairment of the mitochondrial membrane potential. With these compounds, for the first time, it is demonstrated that the PINK1 pathway is active and detectable in primary neurons. These findings suggest that niclosamide and its analogues are robust compounds for the study of the PINK1 pathway and may hold promise as a therapeutic strategy in PD and related disorders.

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Section: Figurementioning

confidence: 80%

The Anthelmintic Drug Niclosamide and Its Analogues Activate the Parkinson's Disease Associated Protein Kinase PINK1

et al. 2018

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“…[12][13][14] NCL is an FDA approved anthelmintic that has a wide safety profile with little side effects, which allow using the drug safely and for long periods in the treatment of chronic diseases. 4 In 2015, Liang et al 6 evaluated the antiinflammatory effect of NCL. They demonstrated the ability of this drug in reducing cytokine expression and release from TNF-a-induced human RA FLS in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

“…Arch Rheumatol 2019;34(4):426-433. inflammatory diseases. 4 The drug has fewer side effects with a wide margin of safety even when used for long periods of time. 5 The anti-inflammatory effect of NCL is mainly due to its ability in reducing cytokine expression and release from tumor necrosis factor alpha (TNF-a)-induced human RA fibroblast-like synoviocytes (FLS) in a dose-dependent manner.…”

mentioning

confidence: 99%

The Anti-Rheumatoid Activity of Niclosamide in Collagen-Induced Arthritis in Rats

Al-Gareeb

Gorial

Mahmood³

2019

Arch Rheumatol

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Objectives:This study aims to evaluate the anti-arthritic effect of orally administered niclosamide (NCL) on collagen-induced arthritis (CIA) in rats. Materials and methods:The study included 35 Sprague Dawley rats (age range, 3 to 4 months; average weight, 100±10 g) of which seven were used as a negative control group (group A) whereas 28, in which arthritis was induced by injection of collagen type II emulsified by incomplete Freund's adjuvant and which were considered as CIA rats, were randomly divided equally into four groups and treated for 28 days with: normal saline (group B), low-dose NCL (group C), high-dose NCL (group D), and diclofenac sodium (group E). Body weight, arthritis index, ankle swelling, and footpad thickness were monitored before and after treatment in all groups. At the end of the treatment period, serum levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and IL-6 were measured together with a collection of articular synovial tissue to evaluate the pathological changes. Results: After four weeks of treatment period, a high dose of orally administered NCL significantly reduced the arthritis index, footpad thickness, and ankle swelling. Significantly decreased serum levels of inflammatory biomarkers including TNF-α, IL-1β, and IL-6 were observed in rats treated with high-dose oral NCL or intramuscular injection of diclofenac sodium, compared with groups B and C. Histopathological examination revealed that a high dose of NCL significantly reduced the infiltration of inflammatory cells, synovial hyperplasia, and bone and cartilage destruction. Conclusion: Niclosamide can effectively decrease the clinical scores, joint swelling, inflammatory markers, and pathological changes in arthritic rats.

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“…Niclosamide, on the other hand, is known for its poor water solubility and bioavailability (34). Plasma concentration of niclosamide is restricted by its poor absorption in the intestinal tract (if administered via the oral route).…”

Section: Combination Of Niclosamide and Colistin Enhanced Bacterial Kmentioning

confidence: 99%

The Anthelmintic Drug Niclosamide Synergizes with Colistin and Reverses Colistin Resistance in Gram-Negative Bacilli

Domalaon

Silva

Kumar

et al. 2019

Antimicrob Agents Chemother

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There is an urgent need for new therapies to overcome antimicrobial resistance especially in Gram-negative bacilli (GNB). Repurposing old U.S. Food and Drug Administration-approved drugs as complementary agents to existing antibiotics in a synergistic combination presents an attractive strategy. Here, we demonstrate that the anthelmintic drug niclosamide selectively synergized with the lipopeptide antibiotic colistin against colistin-susceptible but more importantly against colistin-resistant GNB, including clinical isolates that harbor the mcr-1 gene. Breakpoints for colistin susceptibility in resistant Gram-negative bacilli were reached in the presence of 1 g/ml (3 M) niclosamide. Reversal of colistin resistance was also observed in combinations of niclosamide and polymyxin B. Enhanced bacterial killing was evident for the combination, in comparison to colistin monotherapy, against resistant Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae. Accumulating evidence in the literature, along with our results, strongly suggests the potential for the combination of niclosamide and colistin to treat colistin-resistant Gram-negative bacillary infections. Our finding is significant since colistin is an antibiotic of last resort for multidrugresistant Gram-negative bacterial infections that are nonresponsive to conventional treatments. With the recent global dissemination of plasmid-encoded colistin resistance, the addition of niclosamide to colistin therapy may hold the key to overcome colistin resistance.

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Niclosamide: Beyond an antihelminthic drug

Cited by 342 publications

References 109 publications

The Anthelmintic Drug Niclosamide and Its Analogues Activate the Parkinson's Disease Associated Protein Kinase PINK1

The Anthelmintic Drug Niclosamide and Its Analogues Activate the Parkinson's Disease Associated Protein Kinase PINK1

The Anti-Rheumatoid Activity of Niclosamide in Collagen-Induced Arthritis in Rats

The Anthelmintic Drug Niclosamide Synergizes with Colistin and Reverses Colistin Resistance in Gram-Negative Bacilli

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