ALPHA-PINENE ATTENUATES MICROGLIAL NF-ΚB ACTIVATION AND INOS EXPRESSION IN GP120-INDUCED NEUROINFLAMMATION
Background: Neuro-inflammation plays a role in the pathogenesis of HIV-associated dementia (HIV). Activation of microglia is essential for triggering inflammatory-mediated neurotoxicity. HIV-1 120 kDa envelope glycoprotein (gp120) induces microglial NF-κB signaling which in turn induce pro-inflammat...
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University of Brawijaya
2021
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oai:doaj.org-article:8d7e1bf25193415f8645f238870013932021-11-23T03:33:46ZALPHA-PINENE ATTENUATES MICROGLIAL NF-ΚB ACTIVATION AND INOS EXPRESSION IN GP120-INDUCED NEUROINFLAMMATION10.21776/ub.mnj.2020.007.01.162407-67242442-5001https://doaj.org/article/8d7e1bf25193415f8645f238870013932021-01-01T00:00:00Zhttps://mnj.ub.ac.id/index.php/mnj/article/view/511https://doaj.org/toc/2407-6724https://doaj.org/toc/2442-5001Background: Neuro-inflammation plays a role in the pathogenesis of HIV-associated dementia (HIV). Activation of microglia is essential for triggering inflammatory-mediated neurotoxicity. HIV-1 120 kDa envelope glycoprotein (gp120) induces microglial NF-κB signaling which in turn induce pro-inflammatory and iNOS gene transcription. Continuous or excessive activation of NF-κB signaling lead to persistent production of TNF-α and nitric oxide by microglia and induce neuronal apoptosis. Alpha-pinene is a natural substance found in pine tree and has efficacy on inhibiting NF-κB signaling. Objective: This study was designed as a true experimental study and aimed to investigate the effect of alpha-pinene administration toward inflammatory response represented by the percentage of microglia containing activated NF-κB and iNOS expression. Methods: Neuron-glia primary culture from brain tissue of rat fetus was divided into 5 groups as follows: negative control; positive control (gp120 1nM); treatment I, II, and III (gp120 1 nM + alpha-pinene 0.4 µg/mL, 2 µg/mL, and 10 µg/mL, respectively). Microglial NF-κB and iNOS expression were analyzed using immunohistochemistry method. Neuronal apoptosis was measured by TUNNEL method. Results: Result showed that alpha-pinene administration on gp120-treated neuron-glia at all dosages decrease NF-kB activation, iNOS expression, and apoptotic neuron significantly as compared to the gp120-only treated group (p<0.05). Furthermore, alpha-pinene did not affect NF-kB activation and neuronal apoptosis (p>0.05), but significantly elevate iNOS expression (p<0.05) mainly in dosage I and II. Conclusion: We concluded that alpha-pinene has neuroprotective effect on gp120-treated neuron-glia cells through modulation of NF-kB and iNOS expression thus inhibit neuronal apoptosis.Masruroh RahayuM Aris WidodoDiana LyrawatiEdi WidjadjantoUniversity of Brawijayaarticleapoptosisgp120inosneuroinflammationnf-kbMedicineRNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENIDMalang Neurology Journal, Vol 7, Iss 1, Pp 80-84 (2021) |
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apoptosis gp120 inos neuroinflammation nf-kb Medicine R Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 |
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apoptosis gp120 inos neuroinflammation nf-kb Medicine R Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Masruroh Rahayu M Aris Widodo Diana Lyrawati Edi Widjadjanto ALPHA-PINENE ATTENUATES MICROGLIAL NF-ΚB ACTIVATION AND INOS EXPRESSION IN GP120-INDUCED NEUROINFLAMMATION |
description |
Background: Neuro-inflammation plays a role in the pathogenesis of HIV-associated dementia (HIV). Activation of microglia is essential for triggering inflammatory-mediated neurotoxicity. HIV-1 120 kDa envelope glycoprotein (gp120) induces microglial NF-κB signaling which in turn induce pro-inflammatory and iNOS gene transcription. Continuous or excessive activation of NF-κB signaling lead to persistent production of TNF-α and nitric oxide by microglia and induce neuronal apoptosis. Alpha-pinene is a natural substance found in pine tree and has efficacy on inhibiting NF-κB signaling.
Objective: This study was designed as a true experimental study and aimed to investigate the effect of alpha-pinene administration toward inflammatory response represented by the percentage of microglia containing activated NF-κB and iNOS expression.
Methods: Neuron-glia primary culture from brain tissue of rat fetus was divided into 5 groups as follows: negative control; positive control (gp120 1nM); treatment I, II, and III (gp120 1 nM + alpha-pinene 0.4 µg/mL, 2 µg/mL, and 10 µg/mL, respectively). Microglial NF-κB and iNOS expression were analyzed using immunohistochemistry method. Neuronal apoptosis was measured by TUNNEL method.
Results: Result showed that alpha-pinene administration on gp120-treated neuron-glia at all dosages decrease NF-kB activation, iNOS expression, and apoptotic neuron significantly as compared to the gp120-only treated group (p<0.05). Furthermore, alpha-pinene did not affect NF-kB activation and neuronal apoptosis (p>0.05), but significantly elevate iNOS expression (p<0.05) mainly in dosage I and II.
Conclusion: We concluded that alpha-pinene has neuroprotective effect on gp120-treated neuron-glia cells through modulation of NF-kB and iNOS expression thus inhibit neuronal apoptosis. |
format |
article |
author |
Masruroh Rahayu M Aris Widodo Diana Lyrawati Edi Widjadjanto |
author_facet |
Masruroh Rahayu M Aris Widodo Diana Lyrawati Edi Widjadjanto |
author_sort |
Masruroh Rahayu |
title |
ALPHA-PINENE ATTENUATES MICROGLIAL NF-ΚB ACTIVATION AND INOS EXPRESSION IN GP120-INDUCED NEUROINFLAMMATION |
title_short |
ALPHA-PINENE ATTENUATES MICROGLIAL NF-ΚB ACTIVATION AND INOS EXPRESSION IN GP120-INDUCED NEUROINFLAMMATION |
title_full |
ALPHA-PINENE ATTENUATES MICROGLIAL NF-ΚB ACTIVATION AND INOS EXPRESSION IN GP120-INDUCED NEUROINFLAMMATION |
title_fullStr |
ALPHA-PINENE ATTENUATES MICROGLIAL NF-ΚB ACTIVATION AND INOS EXPRESSION IN GP120-INDUCED NEUROINFLAMMATION |
title_full_unstemmed |
ALPHA-PINENE ATTENUATES MICROGLIAL NF-ΚB ACTIVATION AND INOS EXPRESSION IN GP120-INDUCED NEUROINFLAMMATION |
title_sort |
alpha-pinene attenuates microglial nf-κb activation and inos expression in gp120-induced neuroinflammation |
publisher |
University of Brawijaya |
publishDate |
2021 |
url |
https://doaj.org/article/8d7e1bf25193415f8645f23887001393 |
work_keys_str_mv |
AT masrurohrahayu alphapineneattenuatesmicroglialnfkbactivationandinosexpressioningp120inducedneuroinflammation AT mariswidodo alphapineneattenuatesmicroglialnfkbactivationandinosexpressioningp120inducedneuroinflammation AT dianalyrawati alphapineneattenuatesmicroglialnfkbactivationandinosexpressioningp120inducedneuroinflammation AT ediwidjadjanto alphapineneattenuatesmicroglialnfkbactivationandinosexpressioningp120inducedneuroinflammation |
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