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Protective effects of Phyllanthus amarus against lipopolysaccharide-induced neuroinflammation and cognitive impairment in rats

Background:Phyllanthus amarus (PA) is widely studied for its hepatoprotective properties but has recently received increasing attention due to its diverse anti-inflammatory effects. However, the effects of PA in modulating immune responses in the central nervous system leading to protection against...

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Main Authors: Alagan, Akilandeshwari, Jantan, Ibrahim, Kumolosasi, Endang, Ogawa, Satoshi, Abdullah, Maizaton Atmadini, Azmi, Norazrina
Format: Article
Language:English
Published: Frontiers Media 2019
Online Access:http://psasir.upm.edu.my/id/eprint/81875/1/Protective%20effects%20of%20Phyllanthus%20amarus%20.pdf
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spelling oai:psasir.upm.edu.my:81875 http://psasir.upm.edu.my/id/eprint/81875/ Protective effects of Phyllanthus amarus against lipopolysaccharide-induced neuroinflammation and cognitive impairment in rats Alagan, Akilandeshwari Jantan, Ibrahim Kumolosasi, Endang Ogawa, Satoshi Abdullah, Maizaton Atmadini Azmi, Norazrina Background:Phyllanthus amarus (PA) is widely studied for its hepatoprotective properties but has recently received increasing attention due to its diverse anti-inflammatory effects. However, the effects of PA in modulating immune responses in the central nervous system leading to protection against functional changes remain unexplored. Therefore, we sought to examine the protective effects of 80% v/v ethanol extract of PA on lipopolysaccharide (LPS)-induced non-spatial memory impairment and neuroinflammation. Methods: Selected major phytoconstituents of PA extract were identified and quantified using high-performance liquid chromatography. Subchronic neurotoxicity was performed in male Wistar rats given daily oral administration of 100, 200, and 400 mg/kg of the PA extract. Their neurobehavioral activities (functional observation battery and locomotor activity) were scored, and the extracted brains were examined for neuropathological changes. Rats were treated orally with vehicle (5% Tween 20), PA extract (100, 200, and 400 mg/kg), or ibuprofen (IBF; 40 mg/kg) for 14 and 28 days before being subjected to novel object discrimination test. All groups were challenged with LPS (1 mg/kg) given intraperitoneally a day prior to the behavioral tests except for the negative control group. At the end of the behavioral tests, the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, nitric oxide (NO), inducible nitric oxide synthase (iNOS), CD11b/c integrin expression, and synaptophysin immunoreactivity were determined in the brain tissues. Results: Gallic acid, ellagic acid, corilagin, geraniin, niranthin, phyllanthin, hypophyllanthin, phyltetralin, and isonirtetralin were identified in the PA extract. Subchronic administration of PA extract (100, 200, and 400 mg/kg) showed no abnormalities in neurobehavior and brain histology. PA extract administered at 200 and 400 mg/kg for 14 and 28 days effectively protected the rodents from LPS-induced memory impairment. Similar doses significantly (p < 0.05) decreased the release of proteins like TNF-α, IL-1β, and iNOS in the brain tissue. NO levels, CD11b/c integrin expression, and synaptophysin immunoreactivity were also reduced as compared with those in the LPS-challenged group. Conclusion: Pre-treatment with PA extract for 14 and 28 days was comparable with pre-treatment with IBF in prevention of memory impairment and alleviation of neuroinflammatory responses induced by LPS. Further studies are essential to identify the bioactive phytochemicals and the precise underlying mechanisms. Frontiers Media 2019-06 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/81875/1/Protective%20effects%20of%20Phyllanthus%20amarus%20.pdf Alagan, Akilandeshwari and Jantan, Ibrahim and Kumolosasi, Endang and Ogawa, Satoshi and Abdullah, Maizaton Atmadini and Azmi, Norazrina (2019) Protective effects of Phyllanthus amarus against lipopolysaccharide-induced neuroinflammation and cognitive impairment in rats. Frontiers in Pharmacology, 10. pp. 1-12. ISSN 1663-9812 https://www.frontiersin.org/articles/10.3389/fphar.2019.00632/full 10.3389/fphar.2019.00632
institution UPM IR
collection UPM IR
language English
description Background:Phyllanthus amarus (PA) is widely studied for its hepatoprotective properties but has recently received increasing attention due to its diverse anti-inflammatory effects. However, the effects of PA in modulating immune responses in the central nervous system leading to protection against functional changes remain unexplored. Therefore, we sought to examine the protective effects of 80% v/v ethanol extract of PA on lipopolysaccharide (LPS)-induced non-spatial memory impairment and neuroinflammation. Methods: Selected major phytoconstituents of PA extract were identified and quantified using high-performance liquid chromatography. Subchronic neurotoxicity was performed in male Wistar rats given daily oral administration of 100, 200, and 400 mg/kg of the PA extract. Their neurobehavioral activities (functional observation battery and locomotor activity) were scored, and the extracted brains were examined for neuropathological changes. Rats were treated orally with vehicle (5% Tween 20), PA extract (100, 200, and 400 mg/kg), or ibuprofen (IBF; 40 mg/kg) for 14 and 28 days before being subjected to novel object discrimination test. All groups were challenged with LPS (1 mg/kg) given intraperitoneally a day prior to the behavioral tests except for the negative control group. At the end of the behavioral tests, the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, nitric oxide (NO), inducible nitric oxide synthase (iNOS), CD11b/c integrin expression, and synaptophysin immunoreactivity were determined in the brain tissues. Results: Gallic acid, ellagic acid, corilagin, geraniin, niranthin, phyllanthin, hypophyllanthin, phyltetralin, and isonirtetralin were identified in the PA extract. Subchronic administration of PA extract (100, 200, and 400 mg/kg) showed no abnormalities in neurobehavior and brain histology. PA extract administered at 200 and 400 mg/kg for 14 and 28 days effectively protected the rodents from LPS-induced memory impairment. Similar doses significantly (p < 0.05) decreased the release of proteins like TNF-α, IL-1β, and iNOS in the brain tissue. NO levels, CD11b/c integrin expression, and synaptophysin immunoreactivity were also reduced as compared with those in the LPS-challenged group. Conclusion: Pre-treatment with PA extract for 14 and 28 days was comparable with pre-treatment with IBF in prevention of memory impairment and alleviation of neuroinflammatory responses induced by LPS. Further studies are essential to identify the bioactive phytochemicals and the precise underlying mechanisms.
format Article
author Alagan, Akilandeshwari
Jantan, Ibrahim
Kumolosasi, Endang
Ogawa, Satoshi
Abdullah, Maizaton Atmadini
Azmi, Norazrina
spellingShingle Alagan, Akilandeshwari
Jantan, Ibrahim
Kumolosasi, Endang
Ogawa, Satoshi
Abdullah, Maizaton Atmadini
Azmi, Norazrina
Protective effects of Phyllanthus amarus against lipopolysaccharide-induced neuroinflammation and cognitive impairment in rats
author_facet Alagan, Akilandeshwari
Jantan, Ibrahim
Kumolosasi, Endang
Ogawa, Satoshi
Abdullah, Maizaton Atmadini
Azmi, Norazrina
author_sort Alagan, Akilandeshwari
title Protective effects of Phyllanthus amarus against lipopolysaccharide-induced neuroinflammation and cognitive impairment in rats
title_short Protective effects of Phyllanthus amarus against lipopolysaccharide-induced neuroinflammation and cognitive impairment in rats
title_full Protective effects of Phyllanthus amarus against lipopolysaccharide-induced neuroinflammation and cognitive impairment in rats
title_fullStr Protective effects of Phyllanthus amarus against lipopolysaccharide-induced neuroinflammation and cognitive impairment in rats
title_full_unstemmed Protective effects of Phyllanthus amarus against lipopolysaccharide-induced neuroinflammation and cognitive impairment in rats
title_sort protective effects of phyllanthus amarus against lipopolysaccharide-induced neuroinflammation and cognitive impairment in rats
publisher Frontiers Media
publishDate 2019
url http://psasir.upm.edu.my/id/eprint/81875/1/Protective%20effects%20of%20Phyllanthus%20amarus%20.pdf
_version_ 1782759515781857280
score 12.935284

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