Neuroprotective Effects of Curcumin-Loaded Emulsomes in a Laser Axotomy-Induced CNS Injury Model

Elif Nur Yilmaz,1,2 Sadik Bay,1 Gurkan Ozturk,1,3 Mehmet Hikmet Ucisik1,4 1Regenerative and Restorative Medicine Research Center (REMER), Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Beykoz, Istanbul, Turkey; 2Graduate School of Engineering and Natur...

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Autores principales:	Yilmaz EN, Bay S, Ozturk G, Ucisik MH
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	curcumin lipid-based nanodrug delivery neurodegeneration hippocampus axon injury. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/523bdc23350947a5bf6670004c5f79a2
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spelling	oai:doaj.org-article:523bdc23350947a5bf6670004c5f79a22021-12-02T14:59:19ZNeuroprotective Effects of Curcumin-Loaded Emulsomes in a Laser Axotomy-Induced CNS Injury Model1178-2013https://doaj.org/article/523bdc23350947a5bf6670004c5f79a22020-11-01T00:00:00Zhttps://www.dovepress.com/neuroprotective-effects-of-curcumin-loaded-emulsomes-in-a-laser-axotom-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Elif Nur Yilmaz,1,2 Sadik Bay,1 Gurkan Ozturk,1,3 Mehmet Hikmet Ucisik1,4 1Regenerative and Restorative Medicine Research Center (REMER), Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Beykoz, Istanbul, Turkey; 2Graduate School of Engineering and Natural Sciences, Istanbul Medipol University, Beykoz, Istanbul, Turkey; 3Department of Physiology, International School of Medicine, Istanbul Medipol University, Beykoz, Istanbul, Turkey; 4Department of Biomedical Engineering, School of Engineering and Natural Sciences, Istanbul Medipol University, Beykoz, Istanbul, TurkeyCorrespondence: Mehmet Hikmet UcisikDepartment of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, 34755 Istanbul TurkeyTel +90 216 578 0000 - 3259Fax +90 216 578 0829Email m.h.ucisik@gmail.comPurpose: Curcumin, a polyphenol isolated from the rhizomes of turmeric, holds great potential as a neuroprotective agent in addition to its anti-inflammatory and antioxidant characteristics. The poor bioavailability and low stability of curcumin are the greatest barriers to its clinical use. This study aims to investigate the neuroprotective effect of curcumin on axonal injury, by delivering the lipophilic polyphenol to a primary hippocampal neuron culture by means of a lipid-based drug delivery system, named emulsomes.Methods: To study neuroregeneration ex vivo, an injury model was established through single-cell laser axotomy on hippocampal neurites. Upon treatment with curcumin-loaded emulsomes (CurcuEmulsomes), curcumin and CurcuEmulsome uptake into neurons was verified by three-dimensional Z-stack images acquired with confocal microscopy. Neuron survival after axonal injury was tracked by propidium iodide (PI) and Hoechst staining. Alterations in expression levels of physiological markers, such as anti-apoptotic marker Bcl2, apoptotic marker cleaved caspase 3, neuroprotective marker Wnt3a and the neuronal survival marker mTOR, were investigated by immunocytochemistry analyses.Results: The results indicated significant improvement in the survival rate of injured neurons upon CurcuEmulsome treatment. Bcl2 expression was significantly higher for injured neurons treated with curcumin or CurcuEmulsome. Reduction in caspase 3 expression was seen in both curcumin and CurcuEmulsome treatment, whereas there were no significant changes in Wnt3a and mTOR expression.Conclusion: The established laser-axotomy model was proven as a reliable methodology to study neurodegenerative models ex vivo. CurcuEmulsomes delivered curcumin to primary hippocampal neurons successfully. Treated with CurcuEmulsomes, injured hippocampal neurons benefit from the neuroprotective effects of curcumin, exhibiting a higher survival rate and increased anti-apoptotic marker levels.Keywords: curcumin, lipid-based nanodrug delivery, neurodegeneration, hippocampus, axon injuryYilmaz ENBay SOzturk GUcisik MHDove Medical Pressarticlecurcuminlipid-based nanodrug deliveryneurodegenerationhippocampusaxon injury.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 9211-9229 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	curcumin lipid-based nanodrug delivery neurodegeneration hippocampus axon injury. Medicine (General) R5-920
spellingShingle	curcumin lipid-based nanodrug delivery neurodegeneration hippocampus axon injury. Medicine (General) R5-920 Yilmaz EN Bay S Ozturk G Ucisik MH Neuroprotective Effects of Curcumin-Loaded Emulsomes in a Laser Axotomy-Induced CNS Injury Model
description	Elif Nur Yilmaz,1,2 Sadik Bay,1 Gurkan Ozturk,1,3 Mehmet Hikmet Ucisik1,4 1Regenerative and Restorative Medicine Research Center (REMER), Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Beykoz, Istanbul, Turkey; 2Graduate School of Engineering and Natural Sciences, Istanbul Medipol University, Beykoz, Istanbul, Turkey; 3Department of Physiology, International School of Medicine, Istanbul Medipol University, Beykoz, Istanbul, Turkey; 4Department of Biomedical Engineering, School of Engineering and Natural Sciences, Istanbul Medipol University, Beykoz, Istanbul, TurkeyCorrespondence: Mehmet Hikmet UcisikDepartment of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, 34755 Istanbul TurkeyTel +90 216 578 0000 - 3259Fax +90 216 578 0829Email m.h.ucisik@gmail.comPurpose: Curcumin, a polyphenol isolated from the rhizomes of turmeric, holds great potential as a neuroprotective agent in addition to its anti-inflammatory and antioxidant characteristics. The poor bioavailability and low stability of curcumin are the greatest barriers to its clinical use. This study aims to investigate the neuroprotective effect of curcumin on axonal injury, by delivering the lipophilic polyphenol to a primary hippocampal neuron culture by means of a lipid-based drug delivery system, named emulsomes.Methods: To study neuroregeneration ex vivo, an injury model was established through single-cell laser axotomy on hippocampal neurites. Upon treatment with curcumin-loaded emulsomes (CurcuEmulsomes), curcumin and CurcuEmulsome uptake into neurons was verified by three-dimensional Z-stack images acquired with confocal microscopy. Neuron survival after axonal injury was tracked by propidium iodide (PI) and Hoechst staining. Alterations in expression levels of physiological markers, such as anti-apoptotic marker Bcl2, apoptotic marker cleaved caspase 3, neuroprotective marker Wnt3a and the neuronal survival marker mTOR, were investigated by immunocytochemistry analyses.Results: The results indicated significant improvement in the survival rate of injured neurons upon CurcuEmulsome treatment. Bcl2 expression was significantly higher for injured neurons treated with curcumin or CurcuEmulsome. Reduction in caspase 3 expression was seen in both curcumin and CurcuEmulsome treatment, whereas there were no significant changes in Wnt3a and mTOR expression.Conclusion: The established laser-axotomy model was proven as a reliable methodology to study neurodegenerative models ex vivo. CurcuEmulsomes delivered curcumin to primary hippocampal neurons successfully. Treated with CurcuEmulsomes, injured hippocampal neurons benefit from the neuroprotective effects of curcumin, exhibiting a higher survival rate and increased anti-apoptotic marker levels.Keywords: curcumin, lipid-based nanodrug delivery, neurodegeneration, hippocampus, axon injury
format	article
author	Yilmaz EN Bay S Ozturk G Ucisik MH
author_facet	Yilmaz EN Bay S Ozturk G Ucisik MH
author_sort	Yilmaz EN
title	Neuroprotective Effects of Curcumin-Loaded Emulsomes in a Laser Axotomy-Induced CNS Injury Model
title_short	Neuroprotective Effects of Curcumin-Loaded Emulsomes in a Laser Axotomy-Induced CNS Injury Model
title_full	Neuroprotective Effects of Curcumin-Loaded Emulsomes in a Laser Axotomy-Induced CNS Injury Model
title_fullStr	Neuroprotective Effects of Curcumin-Loaded Emulsomes in a Laser Axotomy-Induced CNS Injury Model
title_full_unstemmed	Neuroprotective Effects of Curcumin-Loaded Emulsomes in a Laser Axotomy-Induced CNS Injury Model
title_sort	neuroprotective effects of curcumin-loaded emulsomes in a laser axotomy-induced cns injury model
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/523bdc23350947a5bf6670004c5f79a2
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Neuroprotective Effects of Curcumin-Loaded Emulsomes in a Laser Axotomy-Induced CNS Injury Model

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