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European Journal of Medical Research
Published in: European Journal of Medical Research 1/2024

Open Access 01-12-2024 | Fenofibrate | Review

Role of fenofibrate in multiple sclerosis

Authors: Ahmad A. Abulaban, Hayder M. Al-kuraishy, Ali I. Al-Gareeb, Engy Elekhnawy, Asma Alanazi, Athanasios Alexiou, Marios Papadakis, Gaber El-Saber Batiha

Published in: European Journal of Medical Research | Issue 1/2024

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Abstract

Multiple sclerosis (MS) is the most frequent inflammatory and demyelinating disease of the central nervous system (CNS). The underlying pathophysiology of MS is the destruction of myelin sheath by immune cells. The formation of myelin plaques, inflammation, and injury of neuronal myelin sheath characterizes its neuropathology. MS plaques are multiple focal regions of demyelination disseminated in the brain's white matter, spinal cords, deep grey matter, and cerebral cortex. Fenofibrate is a peroxisome proliferative activated receptor alpha (PPAR-α) that attenuates the inflammatory reactions in MS. Fenofibrate inhibits differentiation of Th17 by inhibiting the expression of pro-inflammatory signaling. According to these findings, this review intended to illuminate the mechanistic immunoinflammatory role of fenofibrate in mitigating MS neuropathology. In conclusion, fenofibrate can attenuate MS neuropathology by modulating different pathways, including oxidative stress, autophagy, mitochondrial dysfunction, inflammatory-signaling pathways, and neuroinflammation.
Literature
1.
2.
Vecchio F, Miraglia F, Porcaro C, Cottone C, Cancelli A, Rossini PM, Tecchio F. Electroencephalography-derived sensory and motor network topology in multiple sclerosis fatigue. Neurorehabil Neural Repair. 2017;31(1):56–64.PubMedCrossRef
3.
4.
Buscarinu MC, Fornasiero A, Romano S, Ferraldeschi M, Mechelli R, Reniè R, Morena E, Romano C, Pellicciari G, Landi AC, Salvetti M. The contribution of gut barrier changes to multiple sclerosis pathophysiology. Front Immunol. 2019;10:1916.PubMedPubMedCentralCrossRef
5.
McGinley MP, Goldschmidt CH, Rae-Grant AD. Diagnosis and treatment of multiple sclerosis: a review. JAMA. 2021;325(8):765–79.PubMedCrossRef
6.
Lane J, Ng HS, Poyser C, Lucas RM, Tremlett H. Multiple sclerosis incidence: A systematic review of change over time by geographical region. Multiple Sclerosis Related Disorders. 2022;63: 103932.PubMedCrossRef
7.
Zeydan B, Kantarci OH. Impact of age on multiple sclerosis disease activity and progression. Curr Neurol Neurosci Rep. 2020;20:1–7.CrossRef
8.
Clanet M. Jean-Martin Charcot: 1825–1893. The International MS Journal. 2008;15(2):59–62.PubMed
9.
Derada Troletti C, Fontijn RD, Gowing E, Charabati M, van Het Hof B, Didouh I, van der Pol SM, Geerts D, Prat A, van Horssen J, Kooij G. Inflammation-induced endothelial to mesenchymal transition promotes brain endothelial cell dysfunction and occurs during multiple sclerosis pathophysiology. Cell Death Dis. 2019;10(2):45.PubMedPubMedCentralCrossRef
10.
Hedström AK, Hössjer O, Hillert J, Stridh P, Kockum I, Olsson T, Alfredsson L. The influence of human leukocyte antigen-DRB1* 15: 01 and its interaction with smoking in MS development is dependent on DQA1* 01: 01 status. Mult Scler J. 2020;26(13):1638–46.CrossRef
11.
Dyment DA, Ebers GC, Sadovnick AD. Genetics of multiple sclerosis. Lancet Neurol. 2004;3(2):104–10.PubMedCrossRef
12.
Gerdes LA, Janoschka C, Eveslage M, Mannig B, Wirth T, Schulte-Mecklenbeck A, Lauks S, Glau L, Gross CC, Tolosa E, Flierl-Hecht A. Immune signatures of prodromal multiple sclerosis in monozygotic twins. Proc Natl Acad Sci. 2020;117(35):21546–56.ADSPubMedPubMedCentralCrossRef
13.
International Multiple Sclerosis Genetics Consortium*†, ANZgene, IIBDGC, WTCCC2. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science. 2019;365(6460):eaav7188.
14.
Aloisi F, Cross AH. MINI-review of Epstein-Barr virus involvement in multiple sclerosis etiology and pathogenesis. J Neuroimmunol. 2022:577935.
15.
Coles A. Alastair Compston, Alasdair Coles. Lancet. 2008;372:1502–7.PubMed
16.
Marrie RA. Environmental risk factors in multiple sclerosis aetiology. Lancet Neurol. 2004;3(12):709–18.PubMedCrossRef
17.
Bolayir A, Cigdem B, Gokce SF, Yilmaz D. The relationship between neutrophil/lymphocyte ratio and uric acid levels in multiple sclerosis patients. Bratisl Lek Listy. 2021;122(5):357–61.PubMed
18.
Nourbakhsh B, Mowry EM. Multiple sclerosis risk factors and pathogenesis. CONTINUUM: Lifelong Learning in Neurology. 2019;25(3):596–610.
19.
Zéphir H. Progress in understanding the pathophysiology of multiple sclerosis. Revue neurologique. 2018;174(6):358–63.PubMedCrossRef
20.
Pinheiro MA, Kooij G, Mizee MR, Kamermans A, Enzmann G, Lyck R, Schwaninger M, Engelhardt B, de Vries HE. Immune cell trafficking across the barriers of the central nervous system in multiple sclerosis and stroke. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2016;1862(3):461–71.
21.
Grzegorski T, Losy J. Multiple sclerosis–the remarkable story of a baffling disease. Rev Neurosci. 2019;30(5):511–26.PubMedCrossRef
22.
Khatir AA, Hojjati SM, Ahangar AA, Naghshineh H, Saadat P. Multiple sclerosis and its pathophysiology: a narrative review. Tabari Biomedical Student Research Journal. 2020;20:89.
23.
Lassmann H, Brück W, Lucchinetti C. Heterogeneity of multiple sclerosis pathogenesis: implications for diagnosis and therapy. Trends Mol Med. 2001;7(3):115–21.PubMedCrossRef
24.
Lan M, Tang X, Zhang J, Yao Z. Insights in pathogenesis of multiple sclerosis: nitric oxide may induce mitochondrial dysfunction of oligodendrocytes. Reviews in th Lassmann H, Van Horssen J, Mahad D. Progressive multiple sclerosis: pathology and pathogenesis. Nature Reviews Neurology. 2012 Nov;8(11):647–56. e Neurosciences. 2018;29(1):39–53.
25.
Sedel F, Bernard D, Mock DM, Tourbah A. Targeting demyelination and virtual hypoxia with high-dose biotin as a treatment for progressive multiple sclerosis. Neuropharmacology. 2016;110:644–53.PubMedCrossRef
26.
27.
Martino G, Adorini L, Rieckmann P, Hillert J, Kallmann B, Comi G, Filippi M. Inflammation in multiple sclerosis: the good, the bad, and the complex. The Lancet Neurology. 2002;1(8):499–509.PubMedCrossRef
28.
Liu GZ, Fang LB, Hjelmström P, Gao XG. Increased CD8+ central memory T cells in patients with multiple sclerosis. Mult Scler J. 2007;13(2):149–55.CrossRef
29.
Elsayed NS, Aston P, Bayanagari VR, Shukla SK. The gut microbiome molecular mimicry piece in the multiple sclerosis puzzle. Front Immunol. 2022;13: 972160.PubMedPubMedCentralCrossRef
30.
31.
Rice GP, Hartung HP, Calabresi PA. Anti-α4 integrin therapy for multiple sclerosis: mechanisms and rationale. Neurology. 2005;64(8):1336–42.PubMedCrossRef
32.
Haarmann A, Nowak E, Deiß A, van der Pol S, Monoranu CM, Kooij G, Müller N, van der Valk P, Stoll G, de Vries HE, Berberich-Siebelt F. Soluble VCAM-1 impairs human brain endothelial barrier integrity via integrin α-4-transduced outside-in signalling. Acta Neuropathol. 2015;129:639–52.PubMedPubMedCentralCrossRef
33.
Mohammadhosayni M, Khosrojerdi A, Lorian K, Aslani S, Imani D, Razi B, Babaie F, Torkamandi S. Matrix metalloproteinases (MMPs) family gene polymorphisms and the risk of multiple sclerosis: systematic review and meta-analysis. BMC Neurol. 2020;20:1.CrossRef
34.
Martin R, Sospedra M, Eiermann T, Olsson T. Multiple sclerosis: doubling down on MHC. Trends Genet. 2021;37(9):784–97.PubMedCrossRef
35.
Balasa R, Barcutean L, Balasa A, Motataianu A, Roman-Filip C, Manu D. The action of TH17 cells on blood brain barrier in multiple sclerosis and experimental autoimmune encephalomyelitis. Hum Immunol. 2020;81(5):237–43.PubMedCrossRef
36.
James RE, Schalks R, Browne E, Eleftheriadou I, Munoz CP, Mazarakis ND, Reynolds R. Persistent elevation of intrathecal pro-inflammatory cytokines leads to multiple sclerosis-like cortical demyelination and neurodegeneration. Acta Neuropathol Commun. 2020;8(1):1–8.CrossRef
37.
Batiha GE, Al-Kuraishy HM, Al-Gareeb AI, Elekhnawy E. SIRT1 pathway in Parkinson’s disease: a faraway snapshot but so close. Inflammopharmacology. 2023;31(1):37–56.PubMedCrossRef
38.
Nadwa EH, Al-Kuraishy HM, Al-Gareeb AI, Elekhnawy E, Albogami SM, Alorabi M, Batiha GE, De Waard M. Cholinergic dysfunction in COVID-19: frantic search and hoping for the best. Naunyn Schmiedebergs Arch Pharmacol. 2023;396(3):453–68.PubMedCrossRef
39.
Al-Kuraishy HM, Al-Gareeb AI, Albogami SM, Jean-Marc S, Nadwa EH, Hafiz AA, A. Negm W, Kamal M, Al-Jouboury M, Elekhnawy E, Batiha GE. Potential therapeutic benefits of metformin alone and in combination with sitagliptin in the management of type 2 diabetes patients with COVID-19. Pharmaceuticals. 2022;15(11):1361.
40.
Mayo CD, Miksche K, Attwell-Pope K, Gawryluk JR. The relationship between physical activity and symptoms of fatigue, mood, and perceived cognitive impairment in adults with multiple sclerosis. J Clin Exp Neuropsychol. 2019;41(7):715–22.PubMedCrossRef
41.
Alhossan A, Alaifan NF, Althwaini BT, Ahmad A. Evaluation of antipyretics use and heat sensitivity in patients with multiple sclerosis. Farmacia. 2022;70(4):704–11.CrossRef
42.
Teoli D, Cabrero FR, Ghassemzadeh S. Lhermitte sign. InStatPearls. 2021. StatPearls Publishing.
43.
44.
Pitt D, Lo CH, Gauthier SA, Hickman RA, Longbrake E, Airas LM, Mao-Draayer Y, Riley C, De Jager PL, Wesley S, Boster A. Toward Precision Phenotyping of Multiple Sclerosis. Neurology-Neuroimmunology Neuroinflammation. 2022;9(6):89.CrossRef
45.
Tintore M, Vidal-Jordana A, Sastre-Garriga J. Treatment of multiple sclerosis—success from bench to bedside. Nat Rev Neurol. 2019;15(1):53–8.PubMedCrossRef
46.
VESPIGNANI M. Integrative Approaches to Multiple Sclerosis. Integrative Neurology. 2020;219.
47.
Xu J, Racke MK, Drew PD. Peroxisome proliferator-activated receptor-α agonist fenofibrate regulates IL-12 family cytokine expression in the CNS: relevance to multiple sclerosis. J Neurochem. 2007;103(5):1801–10.PubMedPubMedCentralCrossRef
48.
Zhou Z, Sun W, Liang Y, Gao Y, Kong W, Guan Y, Feng J, Wang X. Fenofibrate inhibited the differentiation of T helper 17 cells in vitro. PPAR research. 2012;2012.
49.
50.
Alkhayyat SS, Al-Kuraishy HM, Al-Gareeb AI, El-Bouseary MM, AboKamer AM, Batiha GE, Simal-Gandara J. Fenofibrate for COVID-19 and related complications as an approach to improve treatment outcomes: the missed key for Holy Grail. Inflamm Res. 2022;89:1–9.
51.
Rasheed HA, Hussien NR, Al-Naimi MS, Al-Kuraishy HM, Al-Gareeb AI. Fenofibrate and Crataegus oxyacantha is an effectual combo for mixed dyslipidemia. Biomedical and Biotechnology Research Journal (BBRJ). 2020;4(3):259.2
52.
Qiu F, Meng T, Chen Q, Zhou K, Shao Y, Matlock G, Ma X, Wu W, Du Y, Wang X, Deng G. Fenofibrate-loaded biodegradable nanoparticles for the treatment of experimental diabetic retinopathy and neovascular age-related macular degeneration. Mol Pharm. 2019;16(5):1958–70.PubMedPubMedCentralCrossRef
53.
Ferreira JP, Vasques-Nóvoa F, Ferrão D, Saraiva F, Falcão-Pires I, Neves JS, Sharma A, Rossignol P, Zannad F, Leite-Moreira A. Fenofibrate and heart failure outcomes in patients with type 2 diabetes: analysis from ACCORD. Diabetes Care. 2022;45(7):1584–91.PubMedPubMedCentralCrossRef
54.
Aslibekyan S, Kabagambe EK, Irvin MR, Straka RJ, Borecki IB, Tiwari HK, Tsai MY, Hopkins PN, Shen J, Lai CQ, Ordovas JM. A genome-wide association study of inflammatory biomarker changes in response to fenofibrate treatment in the Genetics of Lipid Lowering Drug and Diet Network. Pharmacogenet Genomics. 2012;22(3):191–7.PubMedPubMedCentralCrossRef
55.
Janssens K, Slaets H, Hellings N. Immunomodulatory properties of the IL-6 cytokine family in multiple sclerosis. Ann N Y Acad Sci. 2015;1351(1):52–60.ADSPubMedCrossRef
56.
Ashikawa Y, Nishimura Y, Okabe S, Sasagawa S, Murakami S, Yuge M, Kawaguchi K, Kawase R, Tanaka T. Activation of sterol regulatory element binding factors by fenofibrate and gemfibrozil stimulates myelination in zebrafish. Front Pharmacol. 2016;7:206.PubMedPubMedCentralCrossRef
57.
Riccio P. The molecular basis of nutritional intervention in multiple sclerosis: a narrative review. Complement Ther Med. 2011;19(4):228–37.PubMedCrossRef
58.
Xu J, Storer PD, Chavis JA, Racke MK, Drew PD. Agonists for the peroxisome proliferator-activated receptor-α and the retinoid X receptor inhibit inflammatory responses of microglia. J Neurosci Res. 2005;81(3):403–11.PubMedCrossRef
59.
Idowu OK, Ajayi SO, Oluyomi OO, Atobatele NM, Okesina AA. Effect of Fenofibrate on Hippocampal Insulin Resistance and Cognitive Function in a Rat Model of Type 2 Diabetes Mellitus. Journal of Krishna Institute of Medical Sciences (JKIMSU). 2021;10(1):23.
60.
Ali EM, Abouelella AM. Brain derived neurotrophic factor has a role in the antidepressant effect of atorvastatin and fenofibrate in Wistar rats. Records of Pharmaceutical and Biomedical Sciences. 2022;6(3):179–94.CrossRef
61.
Wens I, Keytsman C, Deckx N, Cools N, Dalgas U, Eijnde BO. Brain derived neurotrophic factor in multiple sclerosis: effect of 24 weeks endurance and resistance training. Eur J Neurol. 2016;23(6):1028–35.PubMedCrossRef
62.
Racke MK, Gocke AR, Muir M, Diab A, Drew PD, Lovett-Racke AE. Nuclear receptors and autoimmune disease: the potential of PPAR agonists to treat multiple sclerosis. J Nutr. 2006;136(3):700–3.PubMedCrossRef
63.
Guo X, Dang W, Li N, Wang Y, Sun D, Nian H, Wei R. PPAR-α Agonist Fenofibrate Ameliorates Sjögren Syndrome–Like Dacryoadenitis by Modulating Th1/Th17 and Treg Cell Responses in NOD Mice. Investigative ophthalmology & visual science. 2022;63(6):12-.
64.
Yang Y, Gocke AR, Lovett-Racke A, Drew PD, Racke MK. PPAR alpha regulation of the immune response and autoimmune encephalomyelitis. PPAR research. 2008;2008.
65.
Yu J, Ip E, dela Pena A, Hou JY, Sesha J, Pera N, Hall P, Kirsch R, Leclercq I, Farrell GC. COX-2 induction in mice with experimental nutritional steatohepatitis: role as pro-inflammatory mediator. Hepatology. 2006;43(4):826–36.PubMedCrossRef
66.
Huang D, Zhao Q, Liu H, Guo Y, Xu H. PPAR-α agonist WY-14643 inhibits LPS-induced inflammation in synovial fibroblasts via NF-kB pathway. J Mol Neurosci. 2016;59:544–53.PubMedCrossRef
67.
Gallucci GM, Alsuwayt B, Auclair AM, Boyer JL, Assis DN, Ghonem NS. Fenofibrate Downregulates NF-κB Signaling to Inhibit Pro-inflammatory Cytokine Secretion in Human THP-1 Macrophages and During Primary Biliary Cholangitis. Inflammation. 2022;45(6):2570–81.PubMedCrossRef
68.
Bahrambeigi S, Molaparast M, Sohrabi F, Seifi L, Faraji A, Fani S, Shafiei-Irannejad V. Targeting PPAR ligands as possible approaches for metabolic reprogramming of T cells in cancer immunotherapy. Immunol Lett. 2020;220:32–7.PubMedCrossRef
69.
Naegelin Y, Saeuberli K, Schaedelin S, Dingsdale H, Magon S, Baranzini S, Amann M, Parmar K, Tsagkas C, Calabrese P, Penner IK. Levels of brain-derived neurotrophic factor in patients with multiple sclerosis. Annals of clinical and translational neurology. 2020;7(11):2251–61.PubMedPubMedCentralCrossRef
70.
Karimi N, Ashourizadeh H, Pasha BA, Haghshomar M, Jouzdani T, Shobeiri P, Teixeira AL, Rezaei N. Blood levels of brain-derived neurotrophic factor (BDNF) in people with multiple sclerosis (MS): A systematic review and meta-analysis. Multiple Sclerosis and Related Disorders. 2022;65: 103984.PubMedCrossRef
71.
Prowse N, Hayley S. Microglia and BDNF at the crossroads of stressor related disorders: Towards a unique trophic phenotype. Neurosci Biobehav Rev. 2021;131:135–63.PubMedCrossRef
72.
73.
Ohl K, Tenbrock K, Kipp M. Oxidative stress in multiple sclerosis: Central and peripheral mode of action. Exp Neurol. 2016;277:58–67.PubMedCrossRef
74.
Ortiz GG, Pacheco-Moisés FP, Bitzer-Quintero OK, Ramírez-Anguiano AC, Flores-Alvarado LJ, Ramírez-Ramírez V, Macias-Islas MA, Torres-Sánchez ED. Immunology and oxidative stress in multiple sclerosis: clinical and basic approach. Clinical and developmental immunology. 2013;2013.
75.
Padureanu R, Albu CV, Mititelu RR, Bacanoiu MV, Docea AO, Calina D, Padureanu V, Olaru G, Sandu RE, Malin RD, Buga AM. Oxidative stress and inflammation interdependence in multiple sclerosis. J Clin Med. 2019;8(11):1815.PubMedPubMedCentralCrossRef
76.
Carlson NG, Rose JW. Antioxidants in multiple sclerosis: do they have a role in therapy? CNS Drugs. 2006;20:433–41.PubMedCrossRef
77.
Waslo C, Bourdette D, Gray N, Wright K, Spain R. Lipoic acid and other antioxidants as therapies for multiple sclerosis. Curr Treat Options Neurol. 2019;21:1–21.CrossRef
78.
Qu XX, He JH, Cui ZQ, Yang T, Sun XH. PPAR-α agonist GW7647 protects against oxidative stress and iron deposit via GPx4 in a transgenic mouse model of Alzheimer’s diseases. ACS Chem Neurosci. 2021;13(2):207–16.PubMedCrossRef
79.
Oyagbemi AA, Adebiyi OE, Adigun KO, Ogunpolu BS, Falayi OO, Hassan FO, Folarin OR, Adebayo AK, Adejumobi OA, Asenuga ER, Ola-Davies OE. Clofibrate, a PPAR-α agonist, abrogates sodium fluoride-induced neuroinflammation, oxidative stress, and motor incoordination via modulation of GFAP/Iba-1/anti-calbindin signaling pathways. Environ Toxicol. 2020;35(2):242–53.ADSPubMedCrossRef
80.
Witte ME, Mahad DJ, Lassmann H, van Horssen J. Mitochondrial dysfunction contributes to neurodegeneration in multiple sclerosis. Trends Mol Med. 2014;20(3):179–87.PubMedCrossRef
81.
82.
Merlini E, Coleman MP, Loreto A. Mitochondrial dysfunction as a trigger of programmed axon death. Trends Neurosci. 2022;45(1):53–63.PubMedCrossRef
83.
Hewedi K, Abd El Aziz AF, Essmat A, Faheem M. Laboratory Evaluation for Mitochondrial Dysfunction in Multiple Sclerosis Patients. Al-Azhar International Medical Journal. 2020;1(11):190–2.
84.
Signorile A, Ferretta A, Ruggieri M, Paolicelli D, Lattanzio P, Trojano M, De Rasmo D. Mitochondria, oxidative stress, cAMP signalling and apoptosis: a crossroads in lymphocytes of multiple sclerosis, a possible role of nutraceutics. Antioxidants. 2020;10(1):21.PubMedPubMedCentralCrossRef
85.
Lee TW, Bai KJ, Lee TI, Chao TF, Kao YH, Chen YJ. PPARs modulate cardiac metabolism and mitochondrial function in diabetes. J Biomed Sci. 2017;24(1):1–9.CrossRef
86.
Cree MG, Zwetsloot JJ, Herndon DN, Qian T, Morio B, Fram R. Insulin sensitivity and mitochondrial function are improved in children with burn injury during a randomized controlled trial of fenofibrate. Ann Surg. 2007;245:214–21.PubMedPubMedCentralCrossRef
87.
Mohagheghi F, Ahmadiani A, Rahmani B, Moradi F, Romond N, Khalaj L. Gemfibrozil pretreatment resulted in a sexually dimorphic outcome in the Rat models of global cerebral ischemia–reperfusion via modulation of mitochondrial Pro-survival and apoptotic cell death factors as well as MAPKs. J Mol Neurosci. 2013;50:379–93.PubMedCrossRef
88.
Patterson AD, Shah YM, Matsubara T, Krausz KW, Gonzalez FJ. PPARα-dependent induction of uncoupling protein 2 protects against acetaminophen-induced liver toxicity. Hepatology. 2012;56:281–90.PubMedCrossRef
89.
Brunmair B, Lest A, Staniek K, Gras F, Scharf N, Roden M. Fenofibrate impairs Rat mitochondrial function by inhibition of respiratory complex I. J Pharmacol Exp Ther. 2004;311:109–14.PubMedCrossRef
90.
91.
Shen D, Liu K, Wang H, Wang H. Autophagy modulation in multiple sclerosis and experimental autoimmune encephalomyelitis. Clin Exp Immunol. 2022;209(2):140–50.PubMedPubMedCentralCrossRef
92.
93.
Zhang J, Cheng Y, Gu J, Wang S, Zhou S, Wang Y, Tan Y, Feng W, Fu Y, Mellen N, Cheng R. Fenofibrate increases cardiac autophagy via FGF21/SIRT1 and prevents fibrosis and inflammation in the hearts of Type 1 diabetic mice. Clin Sci. 2016;130(8):625–41.CrossRef
94.
Sohn M, Kim K, Uddin MJ, Lee G, Hwang I, Kang H, Kim H, Lee JH, Ha H. Delayed treatment with fenofibrate protects against high-fat diet-induced kidney injury in mice: the possible role of AMPK autophagy. American Journal of Physiology-Renal Physiology. 2017;312(2):F323–34.PubMedCrossRef
95.
Liu Y, Xu Y, Zhu J, Li H, Zhang J, Yang G, Sun Z. Metformin prevents progression of experimental pulmonary hypertension via inhibition of autophagy and activation of adenosine monophosphate-activated protein kinase. J Vasc Res. 2019;56(3):117–28.PubMedCrossRef
96.
Wu Y, Li X, Zhu JX, Xie W, Le W, Fan Z, Jankovic J, Pan T. Resveratrol-activated AMPK/SIRT1/autophagy in cellular models of Parkinson’s disease. Neurosignals. 2011;19(3):163–74.PubMedPubMedCentralCrossRef
97.
Al-Kuraishy HM, Al-Fakhrany OM, Elekhnawy E, Al-Gareeb AI, Alorabi M, De Waard M, Albogami SM, Batiha GE. Traditional herbs against COVID-19: back to old weapons to combat the new pandemic. Eur J Med Res. 2022;27(1):186.PubMedPubMedCentralCrossRef
98.
Al-Kuraishy HM, Al-Gareeb AI, Fageyinbo MS, Batiha GE. Vinpocetine is the forthcoming adjuvant agent in the management of COVID-19. Future Science OA. 2022;8(5):FSO797.
99.
Batiha GE, Al-Gareeb AI, Rotimi D, Adeyemi OS, Al-Kuraishy HM. Common NLRP3 inflammasome inhibitors and Covid-19: divide and conquer. Scientific African. 2022;18: e01407.PubMedPubMedCentralCrossRef
100.
Batiha GE, Al-Gareeb AI, Rotimi D, Adeyemi OS, Al-Kuraishy HM. Common NLRP3 inflammasome inhibitors and Covid-19: Divide and Conquer. Scientific African. 2022;22: e01407.CrossRef
101.
Holbrook JA, Jarosz-Griffiths HH, Caseley E, Lara-Reyna S, Poulter JA, Williams-Gray CH, Peckham D, McDermott MF. Neurodegenerative disease and the NLRP3 inflammasome. Front Pharmacol. 2021;12: 643254.PubMedPubMedCentralCrossRef
102.
Leibowitz SM, Yan J. NF-κB Pathways in the Pathogenesis of Multiple Sclerosis and the Therapeutic Implications. Front Mol Neurosci. 2016;9:8.CrossRef
103.
Chen D, Ireland SJ, Remington G, Alvarez E, Racke MK, Greenberg B, Frohman EM, Monson NL. CD40-mediated NF-κB activation in B cells is increased in multiple sclerosis and modulated by therapeutics. J Immunol. 2016;197(11):4257–65.PubMedCrossRef
104.
Olcum M, Tastan B, Kiser C, Genc S, Genc K. Microglial NLRP3 inflammasome activation in multiple sclerosis. Adv Protein Chem Struct Biol. 2020;119:247–308.PubMedCrossRef
105.
Shao S, Chen C, Shi G, Zhou Y, Wei Y, Fan N, Yang Y, Wu L, Zhang T. Therapeutic potential of the target on NLRP3 inflammasome in multiple sclerosis. Pharmacol Ther. 2021;227: 107880.PubMedCrossRef
106.
Tien CP, Chang YC, Hung SC, Hsiao M. Abstract B20: Repurposing of fenofibrate to prevent and treat PM-induced pulmonary fibroblast-mediated inflammation: Mechanism involved in SIRT1-SREBP1-PIR/NLRP3 inflammasome axis. Cancer Immunology Research. 2020;8(3_Supplement):B20-.
107.
Garcia-Ramírez M, Hernández C, Palomer X, Vázquez-Carrera M, Simó R. Fenofibrate prevents the disruption of the outer blood retinal barrier through downregulation of NF-κB activity. Acta Diabetol. 2016;53:109–18.PubMedCrossRef
108.
Liu Q, Zhang F, Zhang X, Cheng R, Ma JX, Yi J, Li J. Fenofibrate ameliorates diabetic retinopathy by modulating Nrf2 signaling and NLRP3 inflammasome activation. Mol Cell Biochem. 2018;445:105–15.PubMedCrossRef
109.
Batiha GE, Al-Kuraishy HM, Al-Gareeb AI, Elekhnawy E. SIRT1 pathway in Parkinson’s disease: a faraway snapshot but so close. Inflammopharmacology. 2022;29:1–20.
110.
Alherz FA, Negm WA, Elekhnawy E, El-Masry TA, Haggag EM, Alqahtani MJ, Hussein IA. Silver nanoparticles prepared using encephalartos laurentianus de wild leaf extract have inhibitory activity against candida albicans clinical isolates. Journal of Fungi. 2022;8(10):1005.PubMedPubMedCentralCrossRef
111.
Naegele M, Martin R. The good and the bad of neuroinflammation in multiple sclerosis. Handb Clin Neurol. 2014;122:59–87.PubMedCrossRef
112.
Al-kuraishy HM, Al-Gareeb AI, Elekhnawy E, Batiha GE. Dipyridamole and adenosinergic pathway in Covid-19: a juice or holy grail. Egyptian Journal of Medical Human Genetics. 2022;23(1):140.PubMedCrossRef
113.
Gatta V, Mengod G, Reale M, Tata AM. Possible correlation between cholinergic system alterations and neuro/inflammation in multiple sclerosis. Biomedicines. 2020;8(6):153.PubMedPubMedCentralCrossRef
114.
Chen XR, Besson VC, Palmier B, Garcia Y, Plotkine M, Marchand-Leroux C. Neurological recovery-promoting, anti-inflammatory, and anti-oxidative effects afforded by fenofibrate, a PPAR alpha agonist, in traumatic brain injury. J Neurotrauma. 2007;24(7):1119–31.PubMedCrossRef
115.
Esmaeili MA, Yadav S, Gupta RK, Waggoner GR, Deloach A, Calingasan NY, Beal MF, Kiaei M. Preferential PPAR-α activation reduces neuroinflammation, and blocks neurodegeneration in vivo. Hum Mol Genet. 2016;25(2):317–27.PubMedCrossRef
116.
Melis M, Scheggi S, Carta G, Madeddu C, Lecca S, Luchicchi A, Cadeddu F, Frau R, Fattore L, Fadda P, Ennas MG. PPARα regulates cholinergic-driven activity of midbrain dopamine neurons via a novel mechanism involving α7 nicotinic acetylcholine receptors. J Neurosci. 2013;33(14):6203–11.PubMedPubMedCentralCrossRef
117.
Gran B, Nyirenda MH, Crooks J. The role of Toll-like receptors in multiple sclerosis and experimental autoimmune encephalomyelitis. Multiple Sclerosis Immunology: A Foundation for Current and Future Treatments. 2013:149–76.
118.
Marta M, Meier UC, Lobell A. Regulation of autoimmune encephalomyelitis by toll-like receptors. Autoimmun Rev. 2009;8(6):506–9.PubMedCrossRef
119.
Dana N, Vaseghi G, Javanmard SH. Crosstalk between peroxisome proliferator-activated receptors and toll-like receptors: A systematic review. Advanced pharmaceutical bulletin. 2019;9(1):12.PubMedPubMedCentralCrossRef
120.
121.
Shen Q, Otoki Y, Sobel RA, Nagra RM, Taha AY. Evidence of increased sequestration of pro-resolving lipid mediators within brain esterified lipid pools of multiple sclerosis patients. Multiple Sclerosis and Related Disorders. 2022;68: 104236.PubMedCrossRef
122.
Dasgupta S, Roy A, Jana M, Hartley DM, Pahan K. Gemfibrozil ameliorates relapsing-remitting experimental autoimmune encephalomyelitis independent of peroxisome proliferator-activated receptor-α. Mol Pharmacol. 2007;72(4):934–46.PubMedCrossRef
123.
Lovett-Racke AE, Hussain RZ, Northrop S, Choy J, Rocchini A, Matthes L, Chavis JA, Diab A, Drew PD, Racke MK. Peroxisome proliferator-activated receptor α agonists as therapy for autoimmune disease. J Immunol. 2004;172(9):5790–8.PubMedCrossRef
124.
Khan MS, Ghumman GM, Baqi A, Shah J, Aziz M, Mir T, Tahir A, Katragadda S, Singh H, Taleb M, Ali SS. Efficacy of pemafibrate versus fenofibrate administration on serum lipid levels in patients with dyslipidemia: Network meta-analysis and systematic review. Am J Cardiovasc Drugs. 2023;23(5):547–58.PubMedCrossRef
125.
Milo R, Korczyn AD, Manouchehri N, Stüve O. The temporal and causal relationship between inflammation and neurodegeneration in multiple sclerosis. Mult Scler J. 2020;26(8):876–86.CrossRef
126.
Bross M, Hackett M, Bernitsas E. Approved and emerging disease modifying therapies on neurodegeneration in multiple sclerosis. Int J Mol Sci. 2020;21(12):4312.PubMedPubMedCentralCrossRef
127.
Celarain N, Tomas-Roig J. Aberrant DNA methylation profile exacerbates inflammation and neurodegeneration in multiple sclerosis patients. J Neuroinflammation. 2020;17(1):1–7.CrossRef
128.
Bogdanov P, Hernández C, Corraliza L, Carvalho AR, Simó R. Effect of fenofibrate on retinal neurodegeneration in an experimental model of type 2 diabetes. Acta Diabetol. 2015;52:113–22.PubMedCrossRef
129.
Barbiero JK, Ramos DC, Boschen S, Bassani T, Da Cunha C, Vital MA. Fenofibrate promotes neuroprotection in a model of rotenone-induced Parkinson’s disease. Behav Pharmacol. 2022;33(8):513–26.PubMedCrossRef
130.
Jin L, Hua H, Ji Y, Jia Z, Peng M, Huang S. Anti-inflammatory role of fenofibrate in treating diseases. Biomolecules and Biomedicine. 2023;23(3):376.PubMedPubMedCentral
131.
Reale M, Sanchez-Ramon S. Lipids at the cross-road of autoimmunity in multiple sclerosis. Curr Med Chem. 2017;24(2):176–92.PubMedCrossRef
132.
Rádiková Ž, Penesová A, Vlček M, Havranová A, Siváková M, Šiarnik P, Žitňanová I, Imrich R, Turčáni P, Kollár B. Lipoprotein profiling in early multiple sclerosis patients: effect of chronic inflammation? Lipids Health Dis. 2020;19(1):1.CrossRef
133.
Flores-Castillo C, Luna-Luna M, Carreón-Torres E, López-Olmos V, Frías S, Juárez-Oropeza MA, Franco M, Fragoso JM, Vargas-Alarcón G, Pérez-Méndez Ó. Atorvastatin and fenofibrate increase the content of unsaturated acyl chains in HDL and modify in vivo kinetics of HDL-cholesteryl esters in New Zealand White Rabbits. Int J Mol Sci. 2019;20(10):2521.PubMedPubMedCentralCrossRef
134.
Cho EB, Cho HJ, Choi M, Seok JM, Shin HY, Kim BJ, Min JH. Low high-density lipoprotein cholesterol and high triglycerides lipid profile in neuromyelitis optica spectrum disorder: Associations with disease activity and disability. Multiple Sclerosis and Related Disorders. 2020;40: 101981.PubMedCrossRef
135.
Weinstock-Guttman B, Zivadinov R, Mahfooz N, Carl E, Drake A, Schneider J, Teter B, Hussein S, Mehta B, Weiskopf M, Durfee J. Serum lipid profiles are associated with disability and MRI outcomes in multiple sclerosis. J Neuroinflammation. 2011;8:1–7.CrossRef
136.
Alkhayyat SS, Al-Kuraishy HM, Al-Gareeb AI, El-Bouseary MM, AboKamer AM, Batiha GE, Simal-Gandara J. Fenofibrate for COVID-19 and related complications as an approach to improve treatment outcomes: the missed key for Holy Grail. Inflamm Res. 2022;71(10–11):1159–67.PubMedPubMedCentralCrossRef
137.
Rasheed HA, Hussien NR, Al-Naimi MS, Al-Kuraishy HM, Al-Gareeb AI. Fenofibrate and Crataegus oxyacantha is an effectual combo for mixed dyslipidemia. Biomed Biotechnol Res J. 2020;4(3):259.CrossRef
138.
Wójtowicz S, Strosznajder AK, Jeżyna M, Strosznajder JB. The novel role of PPAR alpha in the brain: promising target in therapy of Alzheimer’s disease and other neurodegenerative disorders. Neurochem Res. 2020;45:972–88.PubMedPubMedCentralCrossRef
139.
Batiha GE, Al-Gareeb AI, Elekhnawy E, Al-Kuraishy HM. Potential role of lipoxin in the management of COVID-19: a narrative review. Inflammopharmacology. 2022;30(6):1993–2001.PubMedPubMedCentralCrossRef
140.
Al-Kuraishy HM, Jabir MS, Al-Gareeb AI, Albuhadily AK, Albukhaty S, Sulaiman GM, Batiha GE. Evaluation and targeting of amyloid precursor protein (APP)/amyloid beta (Aβ) axis in amyloidogenic and non-amyloidogenic pathways: A time outside the tunnel. Ageing Res Rev. 2023;4: 102119.CrossRef
141.
142.
Al-Kuraishy HM, Hamada MT, Al-Samerraie AY. Effects of metformin on omentin levels in a newly diagnosed type II diabetes mellitus: Randomized, placebo controlled study. Mustansiriya Med J. 2016;15:49–55.CrossRef
143.
Al-Buhadily AK, Al-Uqabi RU, Al-Gareeb AI. Evaluation of Protective Effect of Metformin in Rats with Experimental Osteoarthritis. Mustansiriya Medical Journal. 2023;22(1):50–3.CrossRef
144.
Al-Kuraishy HM, Jabir MS, Al-Gareeb AI, Albuhadily AK. The conceivable role of prolactin hormone in Parkinson disease: The same goal but with different ways. Ageing Res Rev. 2023;89: 102075.CrossRef
145.
Almukainzi M, El-Masry TA, Negm WA, Elekhnawy E, Saleh A, Sayed AE, Ahmed HM, Abdelkader DH. Co-delivery of gentiopicroside and thymoquinone using electrospun m-PEG/PVP nanofibers: In-vitro and In vivo studies for antibacterial wound dressing in diabetic rats. Int J Pharm. 2022;625: 122106.PubMedCrossRef
146.
Al-Kuraishy HM, Jabir MS, Albuhadily AK, Al-Gareeb AI, Rafeeq MF. The link between Alzheimer disease and metabolic syndrome: A mutual relationship and long rigorous investigation. Ageing Res Rev. 2023;5: 102084.CrossRef
147.
Attallah NG, Al-Fakhrany OM, Elekhnawy E, Hussein IA, Shaldam MA, Altwaijry N, Alqahtani MJ, Negm WA. Anti-biofilm and antibacterial activities of Cycas media R. Br secondary metabolites: In silico, in vitro, and in vivo approaches. Antibiotics. 2022;11(8):993.
148.
Elekhnawy E, Negm WA. The potential application of probiotics for the prevention and treatment of COVID-19. Egyptian Journal of Medical Human Genetics. 2022;23(1):1–9.CrossRef
149.
Alrouji M, Al-Kuraishy HM, Al-Gareeb AI, Zaafar D, Batiha GE. Orexin pathway in Parkinson’s disease: a review. Mol Biol Rep. 2023;8:1–4.
150.
Al-Kuraishy HM, Al-Gareeb AI, Alsayegh AA, Abusudah WF, Almohmadi NH, Eldahshan OA, Ahmed EA, Batiha GE. Insights on benzodiazepines’ potential in Alzheimer’s disease. Life Sci. 2023;8: 121532.CrossRef
151.
Elekhnawy EA, Sonbol FI, Elbanna TE, Abdelaziz AA. Evaluation of the impact of adaptation of Klebsiella pneumoniae clinical isolates to benzalkonium chloride on biofilm formation. Egyptian Journal of Medical Human Genetics. 2021;22(1):1–6.CrossRef
152.
Ali NH, Alhamdan NA, Al-Kuraishy HM, Al-Gareeb AI, Elekhnawy E, Batiha GE. Irisin/PGC-1α/FNDC5 pathway in Parkinson’s disease: truth under the throes. Naunyn Schmiedebergs Arch Pharmacol. 2023;11:1–1.
153.
Elekhnawy E, Sonbol F, Abdelaziz A, Elbanna T. An investigation of the impact of triclosan adaptation on Proteus mirabilis clinical isolates from an Egyptian university hospital. Braz J Microbiol. 2021;52:927–37.PubMedPubMedCentralCrossRef
154.
Alrouji M, Al-Kuraishy HM, Al-Buhadily AK, Al-Gareeb AI, Elekhnawy E, Batiha GE. DPP-4 inhibitors and type 2 diabetes mellitus in Parkinson’s disease: a mutual relationship. Pharmacol Rep. 2023;3:1–4.
155.
El-Banna T, Abd El-Aziz A, Sonbol F, El-Ekhnawy E. Adaptation of Pseudomonas aeruginosa clinical isolates to benzalkonium chloride retards its growth and enhances biofilm production. Mol Biol Rep. 2019;46:3437–43.PubMedCrossRef
156.
Abdelaziz A, Sonbol F, Elbanna T, El-Ekhnawy E. Exposure to sublethal concentrations of benzalkonium chloride induces antimicrobial resistance and cellular changes in Klebsiellae pneumoniae clinical isolates. Microb Drug Resist. 2019;25(5):631–8.PubMedCrossRef
157.
Sonbol FI, El-Banna TE, Abd El-Aziz AA, El-Ekhnawy E. Impact of triclosan adaptation on membrane properties, efflux and antimicrobial resistance of Escherichia coli clinical isolates. J Appl Microbiol. 2019;126(3):730–9.PubMedCrossRef
158.
Hussien NR, Al-Naimi MS, Rasheed HA, Al-Kuraishy HM, Al-Gareeb AI. Sulfonylurea and neuroprotection: the bright side of the moon. Journal of Advanced Pharmaceutical Technology & Research. 2018;9(4):120–3.CrossRef
159.
Alkuraishy HM, Al-Gareeb AI, Waheed HJ. Lipoprotein-associated phospholipase A2 is linked with poor cardio-metabolic profile in patients with ischemic stroke: A study of effects of statins. Journal of neurosciences in rural practice. 2018;9(04):496–503.PubMedPubMedCentralCrossRef
160.
Al-Kuraishy HM, Al-Gareeb AI. Effect of orlistat alone or in combination with Garcinia cambogia on visceral adiposity index in obese patients. Journal of intercultural ethnopharmacology. 2016;5(4):408.PubMedPubMedCentralCrossRef
161.
162.
Negm WA, El-Aasr M, Kamer AA, Elekhnawy E. Investigation of the antibacterial activity and efflux pump inhibitory effect of Cycas thouarsii R. Br. extract against Klebsiella pneumoniae clinical isolates. Pharmaceuticals. 2021;14(8):756.
163.
Alotaibi B, El-Masry TA, Elekhnawy E, El-Kadem AH, Saleh A, Negm WA, Abdelkader DH. Aqueous core epigallocatechin gallate PLGA nanocapsules: Characterization, antibacterial activity against uropathogens, and in vivo reno-protective effect in cisplatin induced nephrotoxicity. Drug Delivery. 2022;29(1):1848–62.PubMedPubMedCentralCrossRef
164.
Al-Kuraishy HM, Al-Gareeb AI, Qusti S, Alshammari EM, Atanu FO, Batiha GE. Arginine vasopressin and pathophysiology of COVID-19: An innovative perspective. Biomed Pharmacother. 2021;143: 112193.PubMedPubMedCentralCrossRef
165.
Rasheed HA, Al-Kuraishy HM, Al-Gareeb AI, Hussien NR, Al-Nami MS. Effects of diabetic pharmacotherapy on prolactin hormone in patients with type 2 diabetes mellitus: Bane or Boon. Journal of advanced pharmaceutical technology & research. 2019;10(4):163.CrossRef
Metadata
Title
Role of fenofibrate in multiple sclerosis
Authors
Ahmad A. Abulaban
Hayder M. Al-kuraishy
Ali I. Al-Gareeb
Engy Elekhnawy
Asma Alanazi
Athanasios Alexiou
Marios Papadakis
Gaber El-Saber Batiha
Publication date
01-12-2024
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 1/2024
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-024-01700-2

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