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Antiaggregation Potential of Padina gymnospora against the Toxic Alzheimer's Beta-Amyloid Peptide 25-35 and Cholinesterase Inhibitory Property of Its Bioactive Compounds.

Shanmuganathan B, Sheeja Malar D, Sathya S, Pandima Devi K - PLoS ONE (2015)

Bottom Line: The results were further confirmed by confocal laser scanning microscopy (CLSM) analysis and Fourier transform infrared (FTIR) spectroscopic analysis.Finally, the active fraction was subjected to LC-MS/MS analysis for the identification of bioactive compounds.Overall, the results suggest that the bioactive compound alpha bisabolol present in the alga might be responsible for the observed cholinesterase inhibition with the IC50 value < 10 μg/ml for both AChE and BuChE when compared to standard drug donepezil (IC50 value < 6 μg/ml) and support its use for the treatment of neurological disorders.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology, Alagappa University (Science campus), Karaikudi- 630 004, Tamil Nadu, India.

ABSTRACT
Inhibition of β-amyloid (Aβ) aggregation in the cerebral cortex of the brain is a promising therapeutic and defensive strategy in identification of disease modifying agents for Alzheimer's disease (AD). Since natural products are considered as the current alternative trend for the discovery of AD drugs, the present study aims at the evaluation of anti-amyloidogenic potential of the marine seaweed Padina gymnospora. Prevention of aggregation and disaggregation of the mature fibril formation of Aβ 25-35 by acetone extracts of P. gymnospora (ACTPG) was evaluated in two phases by Thioflavin T assay. The results were further confirmed by confocal laser scanning microscopy (CLSM) analysis and Fourier transform infrared (FTIR) spectroscopic analysis. The results of antiaggregation and disaggregation assay showed that the increase in fluorescence intensity of aggregated Aβ and the co-treatment of ACTPG (250 μg/ml) with Aβ 25-35, an extensive decrease in the fluorescence intensity was observed in both phases, which suggests that ACTPG prevents the oligomers formation and disaggregation of mature fibrils. In addition, ACTPG was subjected to column chromatography and the bioactivity was screened based on the cholinesterase inhibitory activity. Finally, the active fraction was subjected to LC-MS/MS analysis for the identification of bioactive compounds. Overall, the results suggest that the bioactive compound alpha bisabolol present in the alga might be responsible for the observed cholinesterase inhibition with the IC50 value < 10 μg/ml for both AChE and BuChE when compared to standard drug donepezil (IC50 value < 6 μg/ml) and support its use for the treatment of neurological disorders.

No MeSH data available.


Related in: MedlinePlus

Butyrylcholinesterase inhibitory activity of the active compounds (10–50 μg/ml).The result of BuChE inhibitory activity clearly shows that among the different treatment groups, alpha-bisabolol alone treatment possessed a maximum BuChE inhibitory activity(66%), with the IC50 value <10 μg/ml and showed significant inhibition (*p<0.1) at 50 μg/ml. Further, standard drug donepezil (IC50 value <6 μg/ml) and the compound of our interest, alpha-bisabolol displayed a significant inhibition on BuChE. Values are expressed as Mean ± SD (n = 3).
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pone.0141708.g009: Butyrylcholinesterase inhibitory activity of the active compounds (10–50 μg/ml).The result of BuChE inhibitory activity clearly shows that among the different treatment groups, alpha-bisabolol alone treatment possessed a maximum BuChE inhibitory activity(66%), with the IC50 value <10 μg/ml and showed significant inhibition (*p<0.1) at 50 μg/ml. Further, standard drug donepezil (IC50 value <6 μg/ml) and the compound of our interest, alpha-bisabolol displayed a significant inhibition on BuChE. Values are expressed as Mean ± SD (n = 3).

Mentions: AChE is also involved in secondary cholinergic functions by promoting Aβ (amyloid-beta) deposition in the form of senile plaque or neurofibrillary tangles, which is considered to be an important hallmark for the progression of AD [32]. Inhibition of AChE not only plays a key role in enhancing the cholinergic neurotransmission in the brain, but also aids in reducing the aggregation of β-amyloid, the key factor in AD. On the other hand, the enzyme butyrylcholinesterase (BuChE) acts as a co-regulator of cholinergic neurotransmitter by hydrolyzing ACh in synaptic cleft [33]. Level of BuChE in AD brain was found to be elevated by two fold, which in turn enhanced the neurotoxicity of neuritic plaques [34]. Hence inhibition of AChE and BuChE is considered as a promising approach for the treatment of AD. The results (Figs 8 and 9) indicate that, among the different treatment groups [treated with the compounds L-carnosine, caffeine, alpha-bisabolol alone or in combinations of alpha bisabolol & L-carnosine (1:1) and alpha bisabolol & caffeine (1:1)], alpha-bisabolol alone treatment possessed a maximum cholinergic inhibitory activity, with the IC50 value < 10 μg/ml for both AChE(87%) and BuChE(66%) and showed significant inhibition for both AChE and BuChE (p<0.1) at 50 μg/ml respectively. Further, standard drug donepezil (IC50 value < 6 μg/ml) and the compound of our interest, alpha-bisabolol displayed a significant inhibition on ChE when compared to the previously reported compounds L-Carnosine and Caffeine [35, 36]. Inhibition of AChE and BuChE plays a major role in reducing the aggregation pattern of β-amyloid, which is an important key factor in AD pathology. The present study clearly indicates that alpha-bisabolol possibly plays a substantial role by modulating the amyloidogenic properties of Aβ. Finally we conclude that, alpha-bisabolol could be used as a potent anti-amyloidogenic drug for AD treatment.


Antiaggregation Potential of Padina gymnospora against the Toxic Alzheimer's Beta-Amyloid Peptide 25-35 and Cholinesterase Inhibitory Property of Its Bioactive Compounds.

Shanmuganathan B, Sheeja Malar D, Sathya S, Pandima Devi K - PLoS ONE (2015)

Butyrylcholinesterase inhibitory activity of the active compounds (10–50 μg/ml).The result of BuChE inhibitory activity clearly shows that among the different treatment groups, alpha-bisabolol alone treatment possessed a maximum BuChE inhibitory activity(66%), with the IC50 value <10 μg/ml and showed significant inhibition (*p<0.1) at 50 μg/ml. Further, standard drug donepezil (IC50 value <6 μg/ml) and the compound of our interest, alpha-bisabolol displayed a significant inhibition on BuChE. Values are expressed as Mean ± SD (n = 3).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4633220&req=5

pone.0141708.g009: Butyrylcholinesterase inhibitory activity of the active compounds (10–50 μg/ml).The result of BuChE inhibitory activity clearly shows that among the different treatment groups, alpha-bisabolol alone treatment possessed a maximum BuChE inhibitory activity(66%), with the IC50 value <10 μg/ml and showed significant inhibition (*p<0.1) at 50 μg/ml. Further, standard drug donepezil (IC50 value <6 μg/ml) and the compound of our interest, alpha-bisabolol displayed a significant inhibition on BuChE. Values are expressed as Mean ± SD (n = 3).
Mentions: AChE is also involved in secondary cholinergic functions by promoting Aβ (amyloid-beta) deposition in the form of senile plaque or neurofibrillary tangles, which is considered to be an important hallmark for the progression of AD [32]. Inhibition of AChE not only plays a key role in enhancing the cholinergic neurotransmission in the brain, but also aids in reducing the aggregation of β-amyloid, the key factor in AD. On the other hand, the enzyme butyrylcholinesterase (BuChE) acts as a co-regulator of cholinergic neurotransmitter by hydrolyzing ACh in synaptic cleft [33]. Level of BuChE in AD brain was found to be elevated by two fold, which in turn enhanced the neurotoxicity of neuritic plaques [34]. Hence inhibition of AChE and BuChE is considered as a promising approach for the treatment of AD. The results (Figs 8 and 9) indicate that, among the different treatment groups [treated with the compounds L-carnosine, caffeine, alpha-bisabolol alone or in combinations of alpha bisabolol & L-carnosine (1:1) and alpha bisabolol & caffeine (1:1)], alpha-bisabolol alone treatment possessed a maximum cholinergic inhibitory activity, with the IC50 value < 10 μg/ml for both AChE(87%) and BuChE(66%) and showed significant inhibition for both AChE and BuChE (p<0.1) at 50 μg/ml respectively. Further, standard drug donepezil (IC50 value < 6 μg/ml) and the compound of our interest, alpha-bisabolol displayed a significant inhibition on ChE when compared to the previously reported compounds L-Carnosine and Caffeine [35, 36]. Inhibition of AChE and BuChE plays a major role in reducing the aggregation pattern of β-amyloid, which is an important key factor in AD pathology. The present study clearly indicates that alpha-bisabolol possibly plays a substantial role by modulating the amyloidogenic properties of Aβ. Finally we conclude that, alpha-bisabolol could be used as a potent anti-amyloidogenic drug for AD treatment.

Bottom Line: The results were further confirmed by confocal laser scanning microscopy (CLSM) analysis and Fourier transform infrared (FTIR) spectroscopic analysis.Finally, the active fraction was subjected to LC-MS/MS analysis for the identification of bioactive compounds.Overall, the results suggest that the bioactive compound alpha bisabolol present in the alga might be responsible for the observed cholinesterase inhibition with the IC50 value < 10 μg/ml for both AChE and BuChE when compared to standard drug donepezil (IC50 value < 6 μg/ml) and support its use for the treatment of neurological disorders.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology, Alagappa University (Science campus), Karaikudi- 630 004, Tamil Nadu, India.

ABSTRACT
Inhibition of β-amyloid (Aβ) aggregation in the cerebral cortex of the brain is a promising therapeutic and defensive strategy in identification of disease modifying agents for Alzheimer's disease (AD). Since natural products are considered as the current alternative trend for the discovery of AD drugs, the present study aims at the evaluation of anti-amyloidogenic potential of the marine seaweed Padina gymnospora. Prevention of aggregation and disaggregation of the mature fibril formation of Aβ 25-35 by acetone extracts of P. gymnospora (ACTPG) was evaluated in two phases by Thioflavin T assay. The results were further confirmed by confocal laser scanning microscopy (CLSM) analysis and Fourier transform infrared (FTIR) spectroscopic analysis. The results of antiaggregation and disaggregation assay showed that the increase in fluorescence intensity of aggregated Aβ and the co-treatment of ACTPG (250 μg/ml) with Aβ 25-35, an extensive decrease in the fluorescence intensity was observed in both phases, which suggests that ACTPG prevents the oligomers formation and disaggregation of mature fibrils. In addition, ACTPG was subjected to column chromatography and the bioactivity was screened based on the cholinesterase inhibitory activity. Finally, the active fraction was subjected to LC-MS/MS analysis for the identification of bioactive compounds. Overall, the results suggest that the bioactive compound alpha bisabolol present in the alga might be responsible for the observed cholinesterase inhibition with the IC50 value < 10 μg/ml for both AChE and BuChE when compared to standard drug donepezil (IC50 value < 6 μg/ml) and support its use for the treatment of neurological disorders.

No MeSH data available.


Related in: MedlinePlus