Madecassoside encapsulated in alginate chitosan nanoparticles exerts anti-excitotoxicity effects in pilocarpine-induced seizure

Madecassoside (MAD), a pentacyclic triterpenoid saponin, and its source herb Centella asiatica are best known for their memory enhancing and neuroprotective properties. The effects of MAD- and similar secondary metabolite-encapsulated nanoparticles on brain are least explored. Henceforth, we have de...

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Main Authors: Renju Kunjumon, Gayathri Viswanathan, Devi Velayudhan Jayasree, Prabath Gopalakrishnan Biju, Prabha Prakash, Baby Chakrapani Pulikkaparambil Sasidharan, Sabulal Baby
Format: Article
Language:English
Published: Elsevier 2021-02-01
Series:Phytomedicine Plus
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S266703132030004X
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author Renju Kunjumon
Gayathri Viswanathan
Devi Velayudhan Jayasree
Prabath Gopalakrishnan Biju
Prabha Prakash
Baby Chakrapani Pulikkaparambil Sasidharan
Sabulal Baby
author_facet Renju Kunjumon
Gayathri Viswanathan
Devi Velayudhan Jayasree
Prabath Gopalakrishnan Biju
Prabha Prakash
Baby Chakrapani Pulikkaparambil Sasidharan
Sabulal Baby
author_sort Renju Kunjumon
collection DOAJ
description Madecassoside (MAD), a pentacyclic triterpenoid saponin, and its source herb Centella asiatica are best known for their memory enhancing and neuroprotective properties. The effects of MAD- and similar secondary metabolite-encapsulated nanoparticles on brain are least explored. Henceforth, we have developed MAD encapsulated alginate chitosan nanoparticles (MACNPs), and their therapeutic potential is studied against pilocarpine (PC) rodent seizure model. MACNPs were synthesized by ionic-gelation polyelectrolyte technique and characterized by DLS, SEM, TEM and XRD. MAD encapsulation and release profile of MACNPs were studied in vitro. MACNPs distribution in mice brain tissues was also evaluated by SEM and TEM. MACNPs offered a negative zeta potential, considerable hydrodynamic size and spherical morphology. They significantly reduced the number of animals experiencing the most severe seizures, showed enhanced bioavailability and membrane integrity. Protection of tissues by MACNPs on PC toxicity in mice was assessed by histopathology on challenged mice brain. mRNA overexpression of MAPK1, MAPK14 genes together with bcl2, caspase 3 and hspa1b for oxidative stress and inflammation was observed. However, regulated expression of mRNA in p53 gene was noted. Our results describing the anti-seizure profile, combined with its observed mRNA expression and biodistribution, strongly support MACNP as a therapeutic candidate for a diverse range of epilepsies and related stress-inflammation.
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spelling doaj.art-43fd25e56d8247778b0613cfbbc884a02022-12-21T22:53:05ZengElsevierPhytomedicine Plus2667-03132021-02-0111100004Madecassoside encapsulated in alginate chitosan nanoparticles exerts anti-excitotoxicity effects in pilocarpine-induced seizureRenju Kunjumon0Gayathri Viswanathan1Devi Velayudhan Jayasree2Prabath Gopalakrishnan Biju3Prabha Prakash4Baby Chakrapani Pulikkaparambil Sasidharan5Sabulal Baby6Phytochemistry and Phytopharmacology Division, KSCSTE-Jawaharlal Nehru Tropical Botanic Garden and Research Institute (KSCSTE-JNTBGRI), Palode, Thiruvananthapuram 695562, Kerala, India; University of Kerala, Thiruvananthapuram 695034, Kerala, India; Theses authors contributed equally and are co-first authors.Phytochemistry and Phytopharmacology Division, KSCSTE-Jawaharlal Nehru Tropical Botanic Garden and Research Institute (KSCSTE-JNTBGRI), Palode, Thiruvananthapuram 695562, Kerala, India; Theses authors contributed equally and are co-first authors.Department of Biochemistry, University of Kerala, Kariavattom Campus, Thiruvananthapuram 695581, Kerala, IndiaDepartment of Biochemistry, University of Kerala, Kariavattom Campus, Thiruvananthapuram 695581, Kerala, IndiaCentre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology (CUSAT), Kochi 682022, Kerala, IndiaCentre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology (CUSAT), Kochi 682022, Kerala, India; Inter-University Centre for Nanomaterials and Devices (IUCND), Cochin University of Science and Technology (CUSAT), Kochi 682022, Kerala, IndiaPhytochemistry and Phytopharmacology Division, KSCSTE-Jawaharlal Nehru Tropical Botanic Garden and Research Institute (KSCSTE-JNTBGRI), Palode, Thiruvananthapuram 695562, Kerala, India; Corresponding author.Madecassoside (MAD), a pentacyclic triterpenoid saponin, and its source herb Centella asiatica are best known for their memory enhancing and neuroprotective properties. The effects of MAD- and similar secondary metabolite-encapsulated nanoparticles on brain are least explored. Henceforth, we have developed MAD encapsulated alginate chitosan nanoparticles (MACNPs), and their therapeutic potential is studied against pilocarpine (PC) rodent seizure model. MACNPs were synthesized by ionic-gelation polyelectrolyte technique and characterized by DLS, SEM, TEM and XRD. MAD encapsulation and release profile of MACNPs were studied in vitro. MACNPs distribution in mice brain tissues was also evaluated by SEM and TEM. MACNPs offered a negative zeta potential, considerable hydrodynamic size and spherical morphology. They significantly reduced the number of animals experiencing the most severe seizures, showed enhanced bioavailability and membrane integrity. Protection of tissues by MACNPs on PC toxicity in mice was assessed by histopathology on challenged mice brain. mRNA overexpression of MAPK1, MAPK14 genes together with bcl2, caspase 3 and hspa1b for oxidative stress and inflammation was observed. However, regulated expression of mRNA in p53 gene was noted. Our results describing the anti-seizure profile, combined with its observed mRNA expression and biodistribution, strongly support MACNP as a therapeutic candidate for a diverse range of epilepsies and related stress-inflammation.http://www.sciencedirect.com/science/article/pii/S266703132030004XMadecassosideNanoparticlesPilocarpineGene expressionExcitotoxicitySeizures
spellingShingle Renju Kunjumon
Gayathri Viswanathan
Devi Velayudhan Jayasree
Prabath Gopalakrishnan Biju
Prabha Prakash
Baby Chakrapani Pulikkaparambil Sasidharan
Sabulal Baby
Madecassoside encapsulated in alginate chitosan nanoparticles exerts anti-excitotoxicity effects in pilocarpine-induced seizure
Phytomedicine Plus
Madecassoside
Nanoparticles
Pilocarpine
Gene expression
Excitotoxicity
Seizures
title Madecassoside encapsulated in alginate chitosan nanoparticles exerts anti-excitotoxicity effects in pilocarpine-induced seizure
title_full Madecassoside encapsulated in alginate chitosan nanoparticles exerts anti-excitotoxicity effects in pilocarpine-induced seizure
title_fullStr Madecassoside encapsulated in alginate chitosan nanoparticles exerts anti-excitotoxicity effects in pilocarpine-induced seizure
title_full_unstemmed Madecassoside encapsulated in alginate chitosan nanoparticles exerts anti-excitotoxicity effects in pilocarpine-induced seizure
title_short Madecassoside encapsulated in alginate chitosan nanoparticles exerts anti-excitotoxicity effects in pilocarpine-induced seizure
title_sort madecassoside encapsulated in alginate chitosan nanoparticles exerts anti excitotoxicity effects in pilocarpine induced seizure
topic Madecassoside
Nanoparticles
Pilocarpine
Gene expression
Excitotoxicity
Seizures
url http://www.sciencedirect.com/science/article/pii/S266703132030004X
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