Improved Endothelium-Dependent Relaxation of Thoracic Aorta in Niclosamide-Treated Diabetic Rats

Engin, Seçkin; Yaşar, Yeşim Kaya; Barut, Elif Nur; Sezen, Sena F.

doi:10.1007/s12012-021-09647-0

Cited by 6 publications

(4 citation statements)

References 39 publications

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“…It has been shown that endothelial dysfunction is associated with severe Covid-19, leading to pulmonary endothelial dysfunction and thrombotic disorders [ 73 ]. Experimental study demonstrated that NCL attenuate endothelial dysfunction through activation release of nitric oxide (NO) from vascular endothelium with stimulation of cyclic guanosine monophosphate (cAMP) [ 74 ]. Likewise, NCL reduces SARS-CoV-2-induced platelet hyper-reactivity and thrombotic disorders [ 75 ].…”

Section: Methods and Search Strategymentioning

confidence: 99%

Niclosamide for Covid-19: bridging the gap

et al. 2021

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Aim/purpose Niclosamide (NCL) is an anthelminthic drug, which is widely used to treat various diseases due to its pleiotropic anti-inflammatory and antiviral activities. NCL modulates of uncoupling oxidative phosphorylation and different signaling pathways in human biological processes . The wide-spectrum antiviral effect of NCL makes it a possible candidate for recent pandemic SARS-CoV-2 infection and may reduce Covid-19 severity. Therefore, the aim of the present study was to review and clarify the potential role of NCL in Covid-19. Methods This study reviewed and highlighted the protective role of NCL therapy in Covid-19. A related literature search in PubMed, Scopus, Web of Science, Google Scholar, and Science Direct was done. Results NCL has noteworthy anti-inflammatory and antiviral effects. The primary antiviral mechanism of NCL is through neutralization of endosomal PH and inhibition of viral protein maturation. NCL acts as a proton carrier, inhibits homeostasis of endosomal PH, which limiting of viral proliferation and release. The anti-inflammatory effects of NCL are mediated by suppression of inflammatory signaling pathways and release of pro-inflammatory cytokines. However, the major limitation in using NCL is low aqueous solubility, which reduces oral bioavailability and therapeutic serum concentration that reducing the in vivo effect of NCL against SARS-CoV-2. Conclusions NCL has anti-inflammatory and immune regulatory effects by modulating the release of pro-inflammatory cytokines, inhibition of NF-κB /NLRP3 inflammasome and mTOR signaling pathway. NCL has an anti-SARS-CoV-2 effect via interruption of viral life-cycle and/or induction of cytopathic effect. Prospective clinical studies and clinical trials are mandatory to confirm the potential role of NCL in patients with Covid-19 concerning the severity and clinical outcomes.

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Section: Methods and Search Strategymentioning

confidence: 99%

Niclosamide for Covid-19: bridging the gap

et al. 2021

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“…In general, the impaired vascular relaxation could be attributed to one or multiple mechanisms of action, including the decrease of NO sensitivity/exogenous NO evoked relaxation and/or the alteration of the NO/cyclic guanosine monophosphate (cGMP) pathway [ 50 ]. Recently, Enging and coworkers pointed out that phosphorylated vasodilator-stimulated phosphoprotein p-VASP Ser239 /total VASP and p-eNOS Ser1177 /total eNOS ratios were significantly lower in the diabetic rats' aortas compared to normal rats' aorta, indicating that diabetes prompts vascular smooth muscle impairment and endothelial dysfunction throughout the reduction of eNOS activity and the downregulation of the NO/cGMP signaling pathway [ 51 ]. In contrast, other reports showed that chronic hyperglycemia stimulates eNOS and iNOS gene expression and enhances NO production [ 52 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

Hypoglycemic and Hypotensive Effects of Calycotome villosa Subsp. intermedia Seeds in Meriones shawi Rats: In Vivo, Ex Vivo, and In Vitro Investigations

Lyoussi

Laaroussi

Cherkaoui-Tangi

et al. 2023

Evidence-Based Complementary and Alternative Medicine

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Calycotome villosa subsp. intermedia is used in traditional medicine for the prevention and self-treatment of a variety of illnesses, including diabetes mellitus, obesity, and hypertension. The present study aims to investigate the in vivo, ex vivo, and in vitro hypoglycemic and hypotensive effects of the lyophilized aqueous extract of Calycotome villosa subsp. intermedia seeds (CV) on Meriones shawi submitted to hypercaloric diet and physical inactivity (HCD/PI) for 12 weeks. This diet induces a type 2 diabetes/metabolic syndrome phenotype with hypertension. Furthermore, HCD/PI decreased aorta contraction due to noradrenaline, enhanced L-arginine, and depressed insulin-evoked relaxation, while the relaxing effects of the NO donor SNAP and of diazoxide were unchanged. In vivo experiments showed that the oral administration of the CV extract (50 mg/kg b.wt) for 3 consecutive weeks significantly attenuated the development of type 2 diabetes, obesity, dyslipidemia, and hypertension. These effects may involve the improvement of lipid metabolism, insulin sensitivity, systolic arterial pressure, and urine output. Additionally, ex vivo and in vitro investigations revealed that CV treatment improved vascular contraction to noradrenaline, induced a slight aorta relaxation in response to carbachol, increased the vasorelaxation effect evoked by insulin, and depressed the L-arginine evoked relaxation. However, CV did not change the endothelium-independent vasorelaxation response evoked by SNAP or diazoxide. Hence, the present study provides useful information and supports the traditional use of CV in the prevention and self-treatment of numerous ailments. Overall, it can be concluded that Calycotome villosa subsp. intermedia seed extracts might be useful in the management of type 2 diabetes and hypertension.

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“…Subsequently, the membranes were incubated with primary antibodies β‐catenin (Cell signaling #8814; 1:1000), p‐GSK‐3β (Cell signaling #5558; 1:1000) and WNT‐5A/B (Cell signaling #2530; 1:1000), p‐AKT (Cell signaling #9271; 1:1000), AKT (Cell signaling #9272; 1:1000), Smad‐2 (Cell signaling #3108; 1:1000), Smad‐3 (Cell signaling #9520; 1:1000), Smad‐2/3 (BD Biosciences, BD 610842; 1:1000), and fibronectin (ab2413; 1:1000) in TBST solution containing 3% BSA and 0.1% tween 20 at 4°C for 12 h. Later, the specific antigen‐antibody interactions were marked by goat anti‐rabbit IgG HRP‐linked secondary antibody (Abcam ab97080, 1:5000) incubation at room temperature for 1 h. β‐actin was used as the loading control. The band density was recorded with a CCD camera (ChemiDoc TM XRS + , Bio‐Rad) and analyzed using ImageJ software (Engin et al, 2021).…”

Section: Methodsmentioning

confidence: 99%

“…The band density was recorded with a CCD camera (ChemiDoc TM XRS + , Bio-Rad) and analyzed using ImageJ software (Engin et al, 2021).…”

Section: Western Blot Analysismentioning

confidence: 99%

The contribution of the WNT pathway to the therapeutic effects of montelukast in experimental murine airway inflammation induced by ovalbumin and lipopolysaccharide

Kaya‐Yasar,

Engin,

Barut

et al. 2024

Drug Development Research

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The wingless/integrase‐1 (WNT) pathway involved in the pathogenesis of inflammatory airway diseases has recently generated considerable research interest. Montelukast, a leukotriene receptor antagonist, provides therapeutic benefits in allergic asthma involving eosinophils. We aimed to investigate the role of the WNT pathway in the therapeutic actions of montelukast (MT) in a mixed type of allergic‐acute airway inflammation model induced by ovalbumin (OVA) and lipopolysaccharide (LPS) in mice. Female mice were sensitized with intraperitoneal OVA‐Al(OH)3 administration in the initiation phase and intranasal OVA followed by LPS administration in the challenge phase. The mice were divided into eight groups: control, asthmatic, and control/asthmatic treated with XAV939 (inhibitor of the canonical WNT pathway), LGK‐974 (inhibitor of the secretion of WNT ligands), or MT at different doses. The inhibition of the WNT pathway prevented tracheal 5‐HT and bradykinin hyperreactivity, while only the inhibition of the canonical WNT pathway partially reduced 5‐HT and bradykinin contractions compared to the inflammation group. Therefore, MT treatment hindered 5‐HT and bradykinin hyperreactivity associated with airway inflammation. Furthermore, MT prevented the increases in the phosphorylated GSK‐3β and WNT5A levels, which had been induced by airway inflammation, in a dose‐dependent manner. Conversely, the MT application caused a further increase in the fibronectin levels, while there was no significant alteration in the phosphorylation of the Smad‐2 levels in the isolated lungs of the mice. The MT treatment reversed the increase in the mRNA expression levels of interleukin‐17A. An increase in eosinophil and neutrophil counts was observed in bronchoalveolar lavage fluid samples obtained from the mice in the inflammation group, which was hampered by the MT treatment. The inhibition of the WNT pathway did not alter inflammatory cytokine expression or cell infiltration. The WNT pathway mediated the therapeutic effects of MT due to the inhibition of GSK‐3β phosphorylation as well as the reduction of WNT5A levels in a murine airway inflammation model.

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Improved Endothelium-Dependent Relaxation of Thoracic Aorta in Niclosamide-Treated Diabetic Rats

Cited by 6 publications

References 39 publications

Niclosamide for Covid-19: bridging the gap

Niclosamide for Covid-19: bridging the gap

Hypoglycemic and Hypotensive Effects of Calycotome villosa Subsp. intermedia Seeds in Meriones shawi Rats: In Vivo, Ex Vivo, and In Vitro Investigations

The contribution of the WNT pathway to the therapeutic effects of montelukast in experimental murine airway inflammation induced by ovalbumin and lipopolysaccharide

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