Skip to main content
Key Specialties
Anesthesiology Cardiology Dermatology Diabetology Endocrinology Gastroenterology General Medicine Geriatrics Hematology Infectious Diseases Internal Medicine Nephrology Neurology Obstetrics and Gynecology Oncology Ophthalmology Pediatrics Psychiatry Radiology Respiratory Medicine Rheumatology Surgery Urology
Congress Coverage
ASH 2024 Annual Meeting 2024 ESMO Congress 2024 ERS Congress 2024 EASD Congress 2024 ESC Congress 2024 EAN Congress 2024 ASCO Annual Meeting 2024 ACC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on adolescent vaping

LIVE: Wednesday 29th January, 18:00-19:30 CET

Growing numbers of young people are using e-cigarettes, despite warnings of respiratory effects and addiction. How can doctors tackle the epidemic, and what health effects should you prepare to manage in your clinics?
ADVANCED SEARCH
Log in
Top
Inflammopharmacology
Published in:

28-09-2024 | Celecoxib | Original Article

Repurposing celecoxib as adjuvant therapy in patients with Parkinsonian disease: a new therapeutic dawn: randomized controlled pilot study

Authors: Mohannad O. Khrieba, Sahar K. Hegazy, Wessam Mustafa, Sahar M. El‑Haggar

Published in: Inflammopharmacology | Issue 6/2024

Login to get access

Abstract

Background

The clinical presentations of Parkinson’s disease (PD), a chronic neurodegenerative condition, include bradykinesia, hypokinesia, stiffness, resting tremor, and postural instability. Recently, neuroinflammation is involved in pathogenesis of PD. Application of nonsteroidal anti-inflammatory drugs captured attention to treat these neuroinflammation.

Aim

To investigate the possible effectiveness of celecoxib in patients with PD treated with conventional treatment.

Methods

Sixty outpatients who fulfilled the inclusion requirements for PD were enrolled in this randomized, prospective, and controlled study. The patients were allocated into two groups at random (n = 30); the control group received standard PD treatment, consisting of levodopa/carbidopa, and the celecoxib group received standard PD treatment plus celecoxib. A neurologist evaluated each patient at the beginning of the treatment and after 6 months. Assessment of Unified Parkinson’s disease rating scale (UPDRS) for each patient. Before and after treatment, α -synuclein (α-Syn), tumor necrosis factor alpha (TNF-α), Toll like receptors-4 (TLR-4), nuclear factor erythroid 2–related factor 2 (Nrf-2) and brain-derived neurotropic factor (BDNF) were assessed. Paired and unpaired t tests were used to assess statistical significance within and between groups respectively.

Results

The celecoxib group exhibited a significant and statistical reduction in the level of measured parameters by unpaired t test as followed: TLR-4 (p = 0.004), TNF-α (p = 0.042), and α-Syn (p = 0.004) apart from a significant increase in BDNF (p = 0.0005) and Nrf-2 (p = 0.004), in comparison with the control group. Also, UPDRS was significantly decreased in celecoxib group (p < 0.05).

Conclusion

Celecoxib could be a promising adjuvant therapy in managing patients with PD.

Trial registration number

NCT05962957.
Literature
Abeliovich A, Schmitz Y, Fariñas I et al (2000) Mice lacking α-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron 25(1):239–252PubMedCrossRef
Al Kury LT, Zeb A, Abidin ZU et al (2019) Neuroprotective effects of melatonin and celecoxib against ethanol-induced neurodegeneration: a computational and pharmacological approach. Drug Des Dev Ther 13:2715–2727CrossRef
Al-Kuraishy HM, Al-Gareeb AI, Alexiou A et al (2023) Calprotectin in Parkinsonian disease: anticipation and dedication. Ageing Res Rev 93:102143PubMedCrossRef
Al-Rashed F, Calay D, Lang M et al (2018) Celecoxib exerts protective effects in the vascular endothelium via COX-2-independent activation of AMPK-CREB-Nrf2 signalling. Sci Rep 8(1):6271PubMedPubMedCentralCrossRef
Alrouji M, Al-Kuraishy HM, Al-Gareeb AI et al (2023) A story of the potential effect of non-steroidal anti-inflammatory drugs (NSAIDs) in Parkinson’s disease: beneficial or detrimental effects. Inflammopharmacology 31(2):673–688PubMedCrossRef
Asanuma M, Nishibayashi-Asanuma S, Miyazaki I et al (2001) Neuroprotective effects of non-steroidal anti-inflammatory drugs by direct scavenging of nitric oxide radicals. J Neurochem 76(6):1895–1904PubMedCrossRef
Badawoud AM, Ali LS, Abdallah MS, Elsabaa RM, Bahaa MM, Elmasry TA, Wahsh E, Yasser M, Eltantawy N, Eldesoqui M, Hamouda MA (2024) The relation between Parkinson’s disease and non-steroidal anti-inflammatories; a systematic review and meta-analysis. Front Pharmacol 15:1434512PubMedPubMedCentralCrossRef
Basar N, Nahar L, Oridupa OA et al (2016) Utilization of the ability to induce activation of the nuclear factor (erythroid-derived 2)-like factor 2 (Nrf2) to assess potential cancer chemopreventive activity of liquorice samples. Phytochem Anal 27(5):233–238PubMedCrossRef
Calabresi P, Mechelli A, Natale G et al (2023) Alpha-synuclein in Parkinson’s disease and other synucleinopathies: from overt neurodegeneration back to early synaptic dysfunction. Cell Death Dis 14(3):176PubMedPubMedCentralCrossRef
Chang E, Wang J (2021) Brain-derived neurotrophic factor attenuates cognitive impairment and motor deficits in a mouse model of Parkinson’s disease. Brain Behav 11(8):e2251PubMedPubMedCentralCrossRef
Contin M, Martinelli P (2010) Pharmacokinetics of levodopa. J Neurol 257:253–261CrossRef
Dassati S, Schweigreiter R, Buechner S et al (2021) Celecoxib promotes survival and upregulates the expression of neuroprotective marker genes in two different in vitro models of Parkinson’s disease. Neuropharmacology 194:108378PubMedCrossRef
Derry S, Barden J, McQuay HJ et al. (2008) Single dose oral celecoxib for acute postoperative pain in adults. In: Cochrane database of systematic reviews(4)
Di Matteo V, Pierucci M, Di Giovanni G et al (2006) Aspirin protects striatal dopaminergic neurons from neurotoxin-induced degeneration: an in vivo microdialysis study. Brain Res 1095(1):167–177PubMedCrossRef
Dixit A, Pandey P, Dhasmana D (2020) In vivo effects of nonselective, partially selective, and selective non steroidal anti-inflammatory drugs on lipid peroxidation and antioxidant enzymes in patients with rheumatoid arthritis: a clinical study. Int J Appl Basic Med Res 10(3):167–172PubMedPubMedCentralCrossRef
Dokmeci D (2004) Ibuprofen and Alzheimer’s disease. Folia Med 46(2):5–10
Fyfe I (2020) Aspirin and ibuprofen could lower risk of LRRK2 Parkinson disease. Nat Rev Neurol 16(9):460–460PubMedCrossRef
Gelders G, Baekelandt V, Van der Perren A (2018) Linking neuroinflammation and neurodegeneration in Parkinson’s disease. J Immunol Res 2018(1):4784268PubMedPubMedCentral
Gong L, Thorn CF, Bertagnolli MM et al (2012) Celecoxib pathways: pharmacokinetics and pharmacodynamics. Pharmacogenet Genom 22(4):310–318CrossRef
Grilli M, Pizzi M, Memo M et al (1996) Neuroprotection by aspirin and sodium salicylate through blockade of NF-κB activation. Science 274(5291):1383–1385PubMedCrossRef
Hirohata M, Ono K, Morinaga A et al (2008) Non-steroidal anti-inflammatory drugs have potent anti-fibrillogenic and fibril-destabilizing effects for α-synuclein fibrils in vitro. Neuropharmacology 54(3):620–627PubMedCrossRef
Huang X-J, Choi Y-K, Im H-S et al (2006) Aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) detection techniques. Sensors 6(7):756–782PubMedCentralCrossRef
Husdan H, Rapoport A (1968) Estimation of creatinine by the Jaffe reaction: a comparison of three methods. Clin Chem 14(3):222–238PubMedCrossRef
Ingman K, Naukkarinen T, Vahteristo M et al (2012) The effect of different dosing regimens of levodopa/carbidopa/entacapone on plasma levodopa concentrations. Eur J Clin Pharmacol 68:281–289PubMedCrossRef
Jiang L, Zhang H, Wang C et al (2019) Serum level of brain-derived neurotrophic factor in Parkinson’s disease: a meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry 88:168–174PubMedCrossRef
Kaizaki A, Tien L-T, Pang Y et al (2013) Celecoxib reduces brain dopaminergic neuronaldysfunction, and improves sensorimotor behavioral performance in neonatal rats exposed to systemic lipopolysaccharide. J Neuroinflamm 10:1–14CrossRef
Maharaj H, Maharaj D, Daya S (2006) Acetylsalicylic acid and acetaminophen protect against MPP+-induced mitochondrial damage and superoxide anion generation. Life Sci 78(21):2438–2443PubMedCrossRef
Martínez-Martín P, Rodríguez-Blázquez C, Alvarez M et al (2015) Parkinson’s disease severity levels and MDS-Unified Parkinson’s Disease Rating Scale. Parkinsonism Relat Disord 21(1):50–54PubMedCrossRef
Mhillaj E, Morgese MG, Tucci P et al (2018) Celecoxib prevents cognitive impairment and neuroinflammation in soluble amyloid β-treated rats. Neuroscience 372:58–73PubMedCrossRef
Miyoshi Y, Zhang Z, Ovadia A et al (1997) Glial cell line-derived neurotrophic factor-levodopa interactions and reduction of side effects in parkinsonian monkeys. Ann Neurol 42(2):208–214PubMedCrossRef
Morales-Sosa M, Orozco-Suárez S, Vega-García A et al (2018) Immunomodulatory effect of Celecoxib on HMGB1/TLR4 pathway in a recurrent seizures model in immature rats. Pharmacol Biochem Behav 170:79–86PubMedCrossRef
Novakova I, Subileau E-A, Toegel S et al (2014) Transport rankings of non-steroidal antiinflammatory drugs across blood-brain barrier in vitro models. PLoS ONE 9(1):e86806PubMedPubMedCentralCrossRef
Ramazani E, Tayarani-Najaran Z, Fereidoni M (2019) Celecoxib, indomethacin, and ibuprofen prevent 6-hydroxydopamine-induced PC12 cell death through the inhibition of NFκB and SAPK/JNK pathways. Iran J Basic Med Sci 22(5):477PubMedPubMedCentral
Rinne U, Molsa P (1979) Levodopa with benserazide or carbidopa in Parkinson disease. Neurology 29(12):1584–1589PubMedCrossRef
Sánchez-Pernaute R, Ferree A, Cooper O et al (2004) Selective COX-2 inhibition prevents progressive dopamine neuron degeneration in a rat model of Parkinson’s disease. J Neuroinflamm 1:1–11CrossRef
Shimada T, Takemiya T, Sugiura H, Yamagata K (2014) Role of inflammatory mediators in the pathogenesis of epilepsy. Mediat Inflamm 2014(1):901902
Tambasco N, Romoli M, Calabresi P (2018) Levodopa in Parkinson’s disease: current status and future developments. Curr Neuropharmacol 16(8):1239–1252PubMedPubMedCentralCrossRef
Wang Q, Chen Q, Sui J et al (2021) Celecoxib prevents tumor necrosis factor-α (TNF-α)-induced cellular senescence in human chondrocytes. Bioengineered 12(2):12812–12820PubMedPubMedCentralCrossRef
Wei P-C, Lee-Chen G-J, Chen C-M et al (2019) Neuroprotection of indole-derivative compound NC001-8 by the regulation of the NRF2 pathway in Parkinson’s disease cell models. Oxid Med Cell Longev 2019:1–15
Xu L, Pu J (2016) Alpha-synuclein in Parkinson’s disease: from pathogenetic dysfunction to potential clinical application. Parkinson’s Dis 2016:1–10
Yagami T, Koma H, Yamamoto Y (2016) Pathophysiological roles of cyclooxygenases and prostaglandins in the central nervous system. Mol Neurobiol 53:4754–4771PubMedCrossRef
Yang Y, Gao L (2017) Celecoxib alleviates memory deficits by downregulation of COX-2 expression and upregulation of the BDNF-TrkB signaling pathway in a diabetic rat model. J Mol Neurosci 62:188–198PubMedPubMedCentralCrossRef
Yoshioka Y, Sugino Y, Yamamuro A et al (2022) Dopamine inhibits the expression of proinflammatory cytokines of microglial cells through the formation of dopamine quinone in the mouse striatum. J Pharmacol Sci 148(1):41–50PubMedCrossRef
Metadata
Title
Repurposing celecoxib as adjuvant therapy in patients with Parkinsonian disease: a new therapeutic dawn: randomized controlled pilot study
Authors
Mohannad O. Khrieba
Sahar K. Hegazy
Wessam Mustafa
Sahar M. El‑Haggar
Publication date
28-09-2024
Publisher
Springer International Publishing
Published in
Inflammopharmacology / Issue 6/2024
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI
https://doi.org/10.1007/s10787-024-01567-z

Other articles of this Issue 6/2024

Neuroprotective efficiency of celecoxib vesicular bilosomes for the management of lipopolysaccharide-induced Alzheimer in mice employing 23 full factorial design

β-Citronellol: a potential anti-inflammatory and gastro-protective agent-mechanistic insights into its modulatory effects on COX-II, 5-LOX, eNOS, and ICAM-1 pathways through in vitro, in vivo, in silico, and network pharmacology studies

Essential oils: a potential alternative with promising active ingredients for pharmaceutical formulations in chronic wound management

Opuntia ficus-indica cladodes extract inhibits human neutrophil pro-inflammatory functions and protects rats from acetic acid-induced ulcerative colitis

Unlocking the therapeutic potential of Geraniol: an alternative perspective for metabolic disease management

The role of traditional NSAIDs and selective COX-2 inhibitors on COVID-19 outcomes: a real-world data study