Inhibition of matrix metalloproteinase-2 and 9 by Piroxicam confer neuroprotection in cerebral ischemia: An in silico evaluation of the hypothesis

Mazumder, Muhammed Khairujjaman; Bhattacharya, Pallab; Borah, Anupom

doi:10.1016/j.mehy.2014.09.021

Cited by 29 publications

(20 citation statements)

References 49 publications

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“…There are twenty-five MMPs, of which the gelatinases, MMP-2 and MMP-9, have been implicated in IA and ischemic stroke [30]. Both in vivoanimal and clinical studies suggest that NSAIDs, in particular aspirin, inhibit MMPs and prevent IA destabilization and subsequent rupture.…”

Section: Evidence That Nsaids Prevent Ia Rupturementioning

confidence: 99%

“…In silico experiments have been conducted to assess the potential effectiveness of the NSAID and nonselective COX inhibitor piroxicam at inhibiting MMPs [30]. The 3-D structures of MMP-2 and MMP-9 receptors and previous pharmacophore information for reference NSAIDs and MMP inhibitors were used to determine how piroxicam would interact with the given molecules in vivo.…”

Section: Evidence That Nsaids Prevent Ia Rupturementioning

confidence: 99%

“…The 3-D structures of MMP-2 and MMP-9 receptors and previous pharmacophore information for reference NSAIDs and MMP inhibitors were used to determine how piroxicam would interact with the given molecules in vivo. The active sites of MMP-2 and MMP-9 were investigated and key residues important for MMP enzymatic inhibition were identified, including alanine 84 and leucine 83 on MMP-2 and proline 421 on MMP-9 [30]. Modeling suggests that piroxicam forms stronger hydrogen bonds to the identified critical residues on MMP-2 and MMP-9 compared to other MMP-inhibitors, melatonin and doxycycline.…”

Section: Evidence That Nsaids Prevent Ia Rupturementioning

confidence: 99%

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Nonsteroidal Anti-Inflammatory Drugs: A Potential Pharmacological Treatment for Intracranial Aneurysm

Fisher

Demel

2019

Cerebrovasc Dis Extra

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Background: Saccular intracranial aneurysms (IAs) are outpouchings of the vessel wall of intracranial arteries. Rupture of IAs results in subarachnoid hemorrhage which is associated with high morbidity and mortality. Surgical interventions, such as clipping and coiling, have associated risks. Currently, there are no proven pharmacological treatments to prevent the growth or rupture of IAs. Infiltration of proinflammatory cytokines in response to increased wall sheer stress is a hallmark of IA. Nonsteroidal anti-inflammatory drugs (NSAIDs) are being investigated as potential therapeutic agents for reduction in growth and/or prevention of IA through inhibition of inflammatory pathways. Summary: This review will discuss the role of NSAIDs in attenuating the inflammation that drives IA progression and rupture. There are two main subtypes of NSAIDs, nonselective COX and selective COX-2 inhibitors, both of which have merit in treating IA. Evidence will be presented which shows that NSAIDs inhibit several key inflammatory mediators involved in IA progression including nuclear factor-κB, tumor necrosis factor-α, and matrix metalloproteinases. In addition, the role of NSAIDs in limiting inflammatory cell adhesion to endothelial cells and attenuating endothelial cell senescence will be discussed. Key Messages: There is an abundance of basic science and preclinical data that support NSAIDs as a promising treatment for IA. Additionally, a combination treatment strategy of low-dose aspirin given concomitantly with a selective COX-2 inhibitor may result in a reduced side effect profile compared to aspirin or selective COX-2 inhibitor use alone. Several large clinical trials are currently planned to further investigate the efficacy of NSAIDs as an effective nonsurgical treatment for IAs.

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Section: Evidence That Nsaids Prevent Ia Rupturementioning

confidence: 99%

Section: Evidence That Nsaids Prevent Ia Rupturementioning

confidence: 99%

Section: Evidence That Nsaids Prevent Ia Rupturementioning

confidence: 99%

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Nonsteroidal Anti-Inflammatory Drugs: A Potential Pharmacological Treatment for Intracranial Aneurysm

Fisher

Demel

2019

Cerebrovasc Dis Extra

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“…Diese Stoffwechselwege sind an der Karzinogenese der Haut beteiligt [20]. Anders als Diclofenac ist Piroxicam zudem in der Lage, eine Apoptose zu induzieren und es supprimiert die Aktivität der Metalloproteinasen 2 und 9 [21,22], der wichtigsten Proteinasefamilie im Zusammenhang mit der Tumorentstehung [23]. Kürzlich wurde die Anwendung eines P+SS-haltigen Medizinprodukts bei AK-Patienten beurteilt.…”

Section: Diskussionunclassified

Behandlung der multiplen aktinischen Keratose und Feldkanzerisierung mit topischem Piroxicam 0,8% und Sonnenschutz (LSF 50+) bei Organtransplantat-Empfängern: Eine Serie von 10 Fällen

et al. 2018

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Empfänger von Organtransplantaten (organ transplant recipients, OTR) haben ein hohes Risiko, Hautkrebs wie z.B. ein Plattenepithelkarzinom und ein Basalzellkarzinom zu entwickeln. Die aktinische Keratose (AK) wird als Vorstufe dieser nicht-melanozytären Hautkrebsarten angesehen. Sonnenschutz ist für Patienten mit AK unerlässlich und eine wichtige vorbeugende Maßnahme bei Organtransplantat-Empfängern. Die Behandlung der Feldkanzerisierung ist außerdem entscheidend, um das Risiko für ein Rezidiv der Hautläsionen bei AK und bei Patienten mit nicht-melanozytärem Hautkrebs zu reduzieren. Bei der Pathogenese von Hautkrebserkrankungen spielt die Aktivierung von Cyclooxygenase-1- und -2-Enzymen eine wichtige Rolle. Die topische Anwendung von Cyclooxygenase-Inhibitoren wie Diclofenac und, seit Kurzem, Piroxicam hat sich bei der Verringerung der AK-Läsionen bei immunkompetenten Patienten als wirksam erwiesen. Es wurde gezeigt, dass ein Medizinprodukt, das Piroxicam und Sonnenschutz (LSF 50+) (P+SS) enthält, die AK-Läsionen reduziert und die Feldkanzerisierung verbessert. Wir berichten über den Effekt der Anwendung von P+SS über 16 Wochen in einer Fallserie mit 10 Patienten mit multiplen AK-Läsionen. Die Behandlung mit P+SS führte bei 7 Patienten zu einem klinisch relevanten Rückgang der AK-Läsionen (>75%) (mit vollständiger Abheilung bei 3 Patienten) und zu einer Besserung der Feldkanzerisierung: Dieses Medizinprodukt kann als Erfolg versprechende kurative und präventive Langzeittherapie bei OTR-Patienten mit hohem Risiko für nicht-melanozytären Hautkrebs angesehen werden. Übersetzung aus Case Rep Dermatol 2017;9:211-216 (DOI: 10.1159/000481770)

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“…Following focal cerebral ischemia and refusion (I/R), the disruption of the blood-brain barrier (BBB) is aggravated via the increased expression of matrix metalloproteinases (MMPs), especially matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) while promoting brain edema and hemorrhage [4,5]. Mitogen-activated protein kinases (MAPKs) are activated and serve critical roles in neuronal survival [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Longshengzhi Capsules Improve Ischemic Stroke Outcomes and Reperfusion Injury via the Promotion of Anti‐Inflammatory and Neuroprotective Effects in MCAO/R Rats

Yang

Zhang

Chen

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Stroke is the leading cause of death in the elderly. Traditional Chinese medicine provides an exciting strategy for treating stroke. Previous reports indicated that Longshengzhi capsules (LSZ), a modified Chinese formula, reduced formed thrombi and oxidative stress and were promising in the clinical treatment of ischemic stroke. However, the specific therapeutic effect and mechanism of LSZ are still ambiguous. This study aimed to define the effects of LSZ on proinflammatory mediators and neuroprotective effects on middle cerebral artery occlusion and refusion (MCAO/R) rats. Rats were treated with different doses of LSZ (0.54, 1.62, and 4.32 g/(kg·d)) in a week after model building. LSZ could improve the survival rate, ischemic stroke outcome, and infarct volume. In addition, significant decrease was observed in reactive oxygen species (ROS) levels and inflammatory factor levels in LSZ-treated groups, concomitant with increase in activities of superoxide dismutase (SOD), neurosynaptic remodeling, and decrease in brain edema. It is proposed that LSZ has anti-inflammatory and neuroprotective effects resulting in downregulating matrix metalloproteinase 2/9 (MMP-2/9) and vascular endothelial growth factor (VEGF) and nuclear factor kappa-B (NF-κB) and upregulating microtubule-associated protein-2 (Map-2) and growth-associated protein-43 (GAP-43) via p38 MAPK and HIF-1α signaling pathways in MCAO/R rats. This study provides potential evidences that p38 MAPK and HIF-1α/VEGF signaling pathways play significant roles in the anti-inflammatory and neuroprotective effects of LSZ.

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Inhibition of matrix metalloproteinase-2 and 9 by Piroxicam confer neuroprotection in cerebral ischemia: An in silico evaluation of the hypothesis

Cited by 29 publications

References 49 publications

Nonsteroidal Anti-Inflammatory Drugs: A Potential Pharmacological Treatment for Intracranial Aneurysm

Nonsteroidal Anti-Inflammatory Drugs: A Potential Pharmacological Treatment for Intracranial Aneurysm

Behandlung der multiplen aktinischen Keratose und Feldkanzerisierung mit topischem Piroxicam 0,8% und Sonnenschutz (LSF 50+) bei Organtransplantat-Empfängern: Eine Serie von 10 Fällen

Longshengzhi Capsules Improve Ischemic Stroke Outcomes and Reperfusion Injury via the Promotion of Anti‐Inflammatory and Neuroprotective Effects in MCAO/R Rats

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