Characterization of nanoemulsion from ethanolic extract of centella asiatica (nanoseca) for memory and cognitive enhancement / Nor Atiqah Jusril

Characterization of nanoemulsion from ethanolic extract of centella asiatica (nanoseca) for memory and cognitive enhancement / Nor Atiqah Jusril

The evidence of the neuroprotective impact of Centella asiatica (C. asiatica) has been documented in recent years. It is a medicinal plant that possesses extensive antioxidant, anti-inflammatory and anti-acetylcholinesterase (AChE) activities. However, a major obstacle that remains to be overcome is...

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Main Author: Jusril, Nor Atiqah
Format: Thesis
Language:English
Published: 2022
Online Access:https://ir.uitm.edu.my/id/eprint/78533/1/78533.pdf
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spelling my-uitm-ir.785332023-05-29T04:31:02Z Characterization of nanoemulsion from ethanolic extract of centella asiatica (nanoseca) for memory and cognitive enhancement / Nor Atiqah Jusril 2022 Jusril, Nor Atiqah The evidence of the neuroprotective impact of Centella asiatica (C. asiatica) has been documented in recent years. It is a medicinal plant that possesses extensive antioxidant, anti-inflammatory and anti-acetylcholinesterase (AChE) activities. However, a major obstacle that remains to be overcome is the capacity of the active molecules in C. asiatica to cross the blood-brain barrier (BBB). Therefore, the present study developed a nanoemulsion from selected ethanolic extract of C. asiatica to improve brain bioavailability. C. asiatica accessions (CA-K017, CA-K018, CA-K019) were characterized and extracted, designated as SECA-K017, SECA-K018, SECA-K019. In addition, major triterpenes of SECA were identified and quantified using high performance liquid chromatography (HPLC). D-optimal mixture design was used to determine the optimal oil, water, and surfactant concentration. In this view, the biological activities of triterpenes, SECA accessions and NanoSECA were explored via in vitro (SH-SY5Y and RAW 264.7 cells) system. The antioxidant and anti inflammatory activities were also evaluated in vitro using lipopolysaccharide (LPS)- stimulated RAW 264.7 cells. Meanwhile, anti-acetylcholinesterase (AChE) was investigated using Ellman’s Spectrophotometric Method. Moreover, molecular docking was performed on active constituents of SECA. The prediction of substance permeability across biological membrane systems was evaluated using a parallel artificial membrane permeability assay (PAMPA). In vivo, experimental procedures were conducted on acute and sub-acute toxicity, neurobehavioral assessment, and preliminary pharmacokinetic and pharmacodynamic (PK/PD) study. The potential of NanoSECA in improving memory and cognitive functions was explored in the neurobehavioral task (Morris Water Maze), and biochemical assays AChE and ACh, antioxidant (glutathione; GSH and malondialdehyde; MDA) and anti-inflammatory (nitrite; NO, tumor necrosis factor-alpha; TNF-α and prostaglandin E2; PGE2). Results revealed that all accession contains a higher proportion of glycosides than the aglycones, with madecassoside in the highest proportion, followed by asiatic acid. It was found that the optimized NanoSECA has a particle size of 127.833 ± 8.280 nm, zeta potential (ZP) of -24.9 ± 0.011 m V, and polydispersity index (PDI) of -0.493 ± 4.681. All tested samples showed no toxicity effect at the concentration tested since its IC50 could not be determined in a concentration ranging from 7.8125 to 1000 µg/mL. Results revealed that treatment with NanoSECA significantly suppressed reactive oxygen species and moderately attenuated the nitrite and AChE production. This further reveals that madecassic acid and asiatic acid prevented acetylcholine (ACh) molecules from interacting with binding site residues, thus obstructing the hydrolysis reaction. This would cause an elevated ACh concentration, eventually increasing cholinergic transmission. NanoSECA tended to exhibit higher blood-brain barrier (BBB) permeation values (Pe: 15.19 ± 0.3 10-6 cm.s-1 ). Acute toxicity study revealed non-toxic of NanoSECA until a dose of 2000 mg/kg. However, a sub-acute toxicity study showed no mortality but mild congestion in several organs. Findings revealed that NanoSECA could be used as a memory enhancer through cholinergic activity, increased anti oxidant levels, and reduced oxidative stress. On the other hand, the analytical method for NanoSECA administration was well developed and validated. 2022 Thesis https://ir.uitm.edu.my/id/eprint/78533/ https://ir.uitm.edu.my/id/eprint/78533/1/78533.pdf text en public phd doctoral Universiti Teknologi MARA (UiTM) Faculty of Applied Sciences Adenan, Mohd Ilham
institution Universiti Teknologi MARA
collection UiTM Institutional Repository
language English
advisor Adenan, Mohd Ilham
description The evidence of the neuroprotective impact of Centella asiatica (C. asiatica) has been documented in recent years. It is a medicinal plant that possesses extensive antioxidant, anti-inflammatory and anti-acetylcholinesterase (AChE) activities. However, a major obstacle that remains to be overcome is the capacity of the active molecules in C. asiatica to cross the blood-brain barrier (BBB). Therefore, the present study developed a nanoemulsion from selected ethanolic extract of C. asiatica to improve brain bioavailability. C. asiatica accessions (CA-K017, CA-K018, CA-K019) were characterized and extracted, designated as SECA-K017, SECA-K018, SECA-K019. In addition, major triterpenes of SECA were identified and quantified using high performance liquid chromatography (HPLC). D-optimal mixture design was used to determine the optimal oil, water, and surfactant concentration. In this view, the biological activities of triterpenes, SECA accessions and NanoSECA were explored via in vitro (SH-SY5Y and RAW 264.7 cells) system. The antioxidant and anti inflammatory activities were also evaluated in vitro using lipopolysaccharide (LPS)- stimulated RAW 264.7 cells. Meanwhile, anti-acetylcholinesterase (AChE) was investigated using Ellman’s Spectrophotometric Method. Moreover, molecular docking was performed on active constituents of SECA. The prediction of substance permeability across biological membrane systems was evaluated using a parallel artificial membrane permeability assay (PAMPA). In vivo, experimental procedures were conducted on acute and sub-acute toxicity, neurobehavioral assessment, and preliminary pharmacokinetic and pharmacodynamic (PK/PD) study. The potential of NanoSECA in improving memory and cognitive functions was explored in the neurobehavioral task (Morris Water Maze), and biochemical assays AChE and ACh, antioxidant (glutathione; GSH and malondialdehyde; MDA) and anti-inflammatory (nitrite; NO, tumor necrosis factor-alpha; TNF-α and prostaglandin E2; PGE2). Results revealed that all accession contains a higher proportion of glycosides than the aglycones, with madecassoside in the highest proportion, followed by asiatic acid. It was found that the optimized NanoSECA has a particle size of 127.833 ± 8.280 nm, zeta potential (ZP) of -24.9 ± 0.011 m V, and polydispersity index (PDI) of -0.493 ± 4.681. All tested samples showed no toxicity effect at the concentration tested since its IC50 could not be determined in a concentration ranging from 7.8125 to 1000 µg/mL. Results revealed that treatment with NanoSECA significantly suppressed reactive oxygen species and moderately attenuated the nitrite and AChE production. This further reveals that madecassic acid and asiatic acid prevented acetylcholine (ACh) molecules from interacting with binding site residues, thus obstructing the hydrolysis reaction. This would cause an elevated ACh concentration, eventually increasing cholinergic transmission. NanoSECA tended to exhibit higher blood-brain barrier (BBB) permeation values (Pe: 15.19 ± 0.3 10-6 cm.s-1 ). Acute toxicity study revealed non-toxic of NanoSECA until a dose of 2000 mg/kg. However, a sub-acute toxicity study showed no mortality but mild congestion in several organs. Findings revealed that NanoSECA could be used as a memory enhancer through cholinergic activity, increased anti oxidant levels, and reduced oxidative stress. On the other hand, the analytical method for NanoSECA administration was well developed and validated.
format Thesis
qualification_name Doctor of Philosophy (PhD.)
qualification_level Doctorate
author Jusril, Nor Atiqah
spellingShingle Jusril, Nor Atiqah
Characterization of nanoemulsion from ethanolic extract of centella asiatica (nanoseca) for memory and cognitive enhancement / Nor Atiqah Jusril
author_facet Jusril, Nor Atiqah
author_sort Jusril, Nor Atiqah
title Characterization of nanoemulsion from ethanolic extract of centella asiatica (nanoseca) for memory and cognitive enhancement / Nor Atiqah Jusril
title_short Characterization of nanoemulsion from ethanolic extract of centella asiatica (nanoseca) for memory and cognitive enhancement / Nor Atiqah Jusril
title_full Characterization of nanoemulsion from ethanolic extract of centella asiatica (nanoseca) for memory and cognitive enhancement / Nor Atiqah Jusril
title_fullStr Characterization of nanoemulsion from ethanolic extract of centella asiatica (nanoseca) for memory and cognitive enhancement / Nor Atiqah Jusril
title_full_unstemmed Characterization of nanoemulsion from ethanolic extract of centella asiatica (nanoseca) for memory and cognitive enhancement / Nor Atiqah Jusril
title_sort characterization of nanoemulsion from ethanolic extract of centella asiatica (nanoseca) for memory and cognitive enhancement / nor atiqah jusril
granting_institution Universiti Teknologi MARA (UiTM)
granting_department Faculty of Applied Sciences
publishDate 2022
url https://ir.uitm.edu.my/id/eprint/78533/1/78533.pdf
_version_ 1783736255067979776

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