Anti-TNF effect of combined pravastatin and cilostazol treatment in an <i>in vivo</i> mouse model

Lee, Haeri; Jo, Minkyung; Park, Kyung-Yeon; Jang, Youjin; Heo, Tae‐Hwe

doi:10.1080/08923973.2019.1569045

Cited by 6 publications

(11 citation statements)

References 34 publications

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“…11,36 Thus, higher response and remission rates in the CLS combination group could be related to its neurotrophic and antiinflammatory actions, which resulted in a significant increase in the CREB1, BDNF, and 5-HT serum levels along with a significant decrease in the TNFα, NF-κB, and FAM19A5 serum levels. 20,22,29,37,38 CLS could improve brain plasticity by modulating the levels of neurotrophic factor, like BDNF, via CREB activation as reported in preclinical and clinical studies. 22,29,39 Different clinical studies have showed that BDNF could mediate the antidepressants' therapeutic activities by enhancing the neuronal plasticity as MDD patients have a decreased level of BDNF, which was restored to the normal levels by the antidepressant therapy.…”

Section: Discussionmentioning

confidence: 88%

“…22,23 Besides CLS can overcome the inflammation-based hypothesis for the development of MDD by its ability to suppress TNF-mediated nuclear factor kappa B (NF-κB) and the release of cytokines. 20,24 These findings suggest it to be beneficial adjunctive therapy for patients with MDD.…”

Section: Introductionmentioning

confidence: 91%

“…18 Cilostazol (CLS), a selective phosphodiesterase-3 (PDE-3) inhibitor, acts as an antiplatelet agent with neurotrophic and antiinflammatory properties. 19,20 It has strong pleiotropic effects by restoring cAMP/CREB signaling and stimulating BDNF gene expression. 21,22 It showed antidepressant action in post-stroke depression and in animal models through inhibition of neurodegeneration and promotion of neurogenesis.…”

Section: Introductionmentioning

confidence: 99%

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RETRACTED: Double‐blind, randomized, placebo‐controlled pilot study of the phosphodiesterase‐3 inhibitor cilostazol as an adjunctive to antidepressants in patients with major depressive disorder

et al. 2021

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Aims: Cilostazol (CLS) has shown antidepressant effect in cardiovascular patients, post-stroke depression, and animal models through its neurotrophic and antiinflammatory activities. Consequently, we aimed to investigate its safety and efficacy in patients with MDD by conducting double-blind, randomized, placebo-controlled pilot study. Methods: 80 participants with MDD (DSM-IV criteria) and Hamilton DepressionRating Scale (HDRS) score >20 were treated with CLS 50 mg or placebo twice daily plus escitalopram (ESC) 20 mg once daily for six weeks. Patients were evaluated by HDRS scores (weeks 0, 2, 4, and 6). Serum levels of CREB1, BDNF, 5-HT, TNFα, NF-κB, and FAM19A5 were assessed pre-and post-treatment.Results: Co-administration of CLS had markedly decreased HDRS score at all-time points compared to the placebo group (p < 0.001). Early improvement, response, and remission rates after 6 weeks were significantly higher in the CLS group (90%, 90%, 80%, respectively) than in the placebo group (25%, 65%, 50% respectively) (p < 0.001). Moreover, the CLS group was superior to the placebo group in modulation of the measured neurotrophic and inflammatory biomarkers. Conclusion:CLS is safe and effective short-term adjunctive therapy in patients with MDD with no other comorbid conditions.Trial registration ID:NCT04069819.

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Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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RETRACTED: Double‐blind, randomized, placebo‐controlled pilot study of the phosphodiesterase‐3 inhibitor cilostazol as an adjunctive to antidepressants in patients with major depressive disorder

et al. 2021

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“…Accumulating reports support the notion that antiplatelet agents have beneficial pleiotropic effects such as anti‐inflammatory activity in various inflammatory‐related disorders. Our previous report also showed that cilostazol combined with pravastatin or rosuvastatin was superior to either drug or caused a reduction in acute inflammation via its anti‐TNF effects ; combination therapy comprising cilostazol and statins exerted better anti‐TNF effect than clopidogrel and statin therapy…”

Section: Discussionmentioning

confidence: 89%

“…Moreover, our previous study showed that adding an anti‐TNF agent (etanercept) via combination with pravastatin and sarpogrelate significantly suppressed the development of aging‐related atherosclerosis . Our previous report also showed that a combination of cilostazol and pravastatin has the beneficial effect to suppress inflammatory responses via anti‐TNF functions and combination therapy comprising cilostazol and statins exerted better anti‐TNF effect than clopidogrel and statin therapy . In addition, increased circulating levels of TNF‐induced platelet hyperfunction was documented; TNF could activate platelets by stimulating the arachidonic acid pathway .…”

Section: Introductionmentioning

confidence: 98%

Comparative effectiveness of different antiplatelet agents at reducing TNF‐driven inflammatory responses in a mouse model

Lee

Park

Jeong

et al. 2019

Clin Exp Pharma Physio

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Platelets play an important role in the regulation of vascular integrity and haemostasis. However, a massive activation and aggregation of platelets can lead to the formation of an arterial thrombus at the site of an atherosclerotic lesion, subsequently increasing the prevalence of ischaemic diseases. 1 Platelet-mediated inflammatory responses are due to highly potent platelet-derived cytokines and the pleiotropic effect on immune cells, which produce a side effect, namely systemic inflammation. 2 Thus, platelet stimulation and activation are known to contribute to inflammation and vascular injury, as well as the initiation of clot formation. This pathophysiological role of platelets reveals the importance of antiplatelet agents as crucial targets in the antiplatelet therapeutic strategy for patients with cardiovascular disorder.Clopidogrel is an oral antiplatelet agent that hinders blood clots by inhibiting the P2Y2 receptor-induced platelet aggregation.Clopidogrel has been proposed to possess pleiotropic biological AbstractAntiplatelet drugs are conventionally used as treatments because of their anti-coagulation functions. However, their pleiotropic effects are of great significance to the treatment of ischaemic cardiovascular diseases. Many studies have reported that an excessive amount of inflammation driven by tumour necrosis factor (TNF) is closely related to the prevalence of atherosclerosis. As the drug selection criteria and evaluation methods related to the anti-TNF activity of antiplatelet drugs remain limited, our investigation of these drugs should prove beneficial. In this study, we compared the anti-TNF activity of three antiplatelet agents, namely clopidogrel, sarpogrelate, and cilostazol, using the TNF-induced inflammatory mouse model. After the oral administration of these drugs, acute inflammation was induced via injection of lipopolysaccharide (LPS) or D-galactosamine (D-gal) and TNF. Serum TNF levels, and the mRNA and protein expression levels of TNF in mouse heart tissue, macrophage accumulation in aortic lesions, and mouse survival were analysed to compare the anti-TNF effects of the three antiplatelet agents. Of the three antiplatelet agents, cilostazol significantly reduced the different levels under the most effective observation. In addition, cilostazol was found to attenuate the TNF-stimulated phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chainenhancer of activated B cell (NF-κB) p65 in the aortic vascular smooth muscle cell line, MOVAS-1 and the D-gal plus TNF-challenged heart tissue of mouse. Therefore, cilostazol is the most ideal of the three antiplatelet drugs for the treatment of TNFmediated inflammatory disorders. K E Y W O R D S

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Advancing combination treatment with cilostazol and caffeine for Alzheimer's disease in high fat-high fructose-STZ induced model of amnesia

Gomaa

Farghaly

Ahmed

et al. 2022

European Journal of Pharmacology

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Anti-TNF effect of combined pravastatin and cilostazol treatment in an in vivo mouse model

Cited by 6 publications

References 34 publications

RETRACTED: Double‐blind, randomized, placebo‐controlled pilot study of the phosphodiesterase‐3 inhibitor cilostazol as an adjunctive to antidepressants in patients with major depressive disorder

RETRACTED: Double‐blind, randomized, placebo‐controlled pilot study of the phosphodiesterase‐3 inhibitor cilostazol as an adjunctive to antidepressants in patients with major depressive disorder

Comparative effectiveness of different antiplatelet agents at reducing TNF‐driven inflammatory responses in a mouse model

Advancing combination treatment with cilostazol and caffeine for Alzheimer's disease in high fat-high fructose-STZ induced model of amnesia

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