Tags

Type your tag names separated by a space and hit enter

Gallic Acid Attenuated LPS-Induced Neuroinflammation: Protein Aggregation and Necroptosis.
Mol Neurobiol. 2020 Jan; 57(1):96-104.MN

Abstract

Gallic acid (3,4,5-trihydroxybenzoic acid, GA), a phenolic acid, is ubiquitous in almost all parts of the plant. In the present study, a neuroinflammatory rat model using intranigral infusion of lipopolysaccharides (LPS, 4 μg/μL) was employed to study the neuroprotective effect of GA which was orally administered daily. Compared with the vehicle-treated rats, systemic administration of GA (100 mg/kg) significantly attenuated LPS-induced increases in glial fibrillary acidic protein (a biomarker of activated astrocytes) and ED-1 (a biomarker of activated microglia), as well as inducible nitric oxide synthase (iNOS, a proinflammatory enzyme) and interleukin-1β (a proinflammatory cytokine), in the LPS-infused substantia nigra (SN) of rat brain. At the same time, GA attenuated LPS-induced elevation in heme oxygenase-1 level (a redox-regulated protein) and α-synuclein aggregation (a hallmark of CNS neurodegeneration), suggesting that GA is capable of inhibiting LPS-induced oxidative stress and protein conjugation. Furthermore, GA prevented LPS-induced caspase 3 activation (a biomarker of programmed cell death) and LPS-induced increases in receptor-interacting protein kinase (RIPK)-1 and RIPK-3 levels (biomarkers of necroptosis), indicating that GA inhibited LPS-induced apoptosis and necroptosis in the nigrostriatal dopaminergic system of rat brain. Moreover, an in vitro study was employed to investigate the anti-inflammatory effect of GA on BV2 microglial cells which were subjected to LPS (1 μg/mL) treatment. Consistently, co-incubation of GA diminished LPS-induced increases in iNOS mRNA and iNOS protein expression in the treated BV-2 cells as well as NO production in the culture medium. The anti-oxidative activity of GA was evaluated using iron-induced lipid peroxidation of brain homogenates. After 3-h incubation at 37 °C, GA was more potent than glutathione and less potent than trolox in inhibiting iron-induced lipid peroxidation. Conclusively, the present study suggests that GA is anti-inflammatory via attenuating LPS-induced neuroinflammation, oxidative stress, and protein conjugation. Furthermore, GA prevented LPS-induced programmed cell deaths of nigrostriatal dopaminergic neurons of the rat brain, suggesting that GA may be neuroprotective by attenuating neuroinflammation in CNS neurodegenerative diseases.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Liu YL
Department of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
Hsu CC
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
Huang HJ
Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
Chang CJ
Faculty of Pharmacy, National Yang-Ming University, Taipei, Taiwan.
Sun SH
Department of Pharmacy, Far Eastern Memorial Hospital, Banciao, New Taipei City, 220, Taiwan. shuhui_sun@mail.femh.org.tw.
Lin AM
Department of Pharmacology, National Yang-Ming University, Taipei, Taiwan. myalin@gm.ym.edu.tw. Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan. myalin@gm.ym.edu.tw. Faculty of Pharmacy, National Yang-Ming University, Taipei, Taiwan. myalin@gm.ym.edu.tw.

MeSH

AnimalsAnti-Inflammatory AgentsCytokinesGallic AcidInflammationLipid PeroxidationLipopolysaccharidesMicrogliaNecroptosisNeuroprotective AgentsNitric Oxide Synthase Type IIOxidative StressProtein AggregatesRats, Sprague-DawleySubstantia Nigra

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31832973

Citation

Liu, Yu-Ling, et al. "Gallic Acid Attenuated LPS-Induced Neuroinflammation: Protein Aggregation and Necroptosis." Molecular Neurobiology, vol. 57, no. 1, 2020, pp. 96-104.
Liu YL, Hsu CC, Huang HJ, et al. Gallic Acid Attenuated LPS-Induced Neuroinflammation: Protein Aggregation and Necroptosis. Mol Neurobiol. 2020;57(1):96-104.
Liu, Y. L., Hsu, C. C., Huang, H. J., Chang, C. J., Sun, S. H., & Lin, A. M. (2020). Gallic Acid Attenuated LPS-Induced Neuroinflammation: Protein Aggregation and Necroptosis. Molecular Neurobiology, 57(1), 96-104. https://doi.org/10.1007/s12035-019-01759-7
Liu YL, et al. Gallic Acid Attenuated LPS-Induced Neuroinflammation: Protein Aggregation and Necroptosis. Mol Neurobiol. 2020;57(1):96-104. PubMed PMID: 31832973.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gallic Acid Attenuated LPS-Induced Neuroinflammation: Protein Aggregation and Necroptosis. AU - Liu,Yu-Ling, AU - Hsu,Chia-Chi, AU - Huang,Hui-Ju, AU - Chang,Chih-Jung, AU - Sun,Shu-Hui, AU - Lin,Anya Maan-Yuh, Y1 - 2019/12/12/ PY - 2019/08/29/received PY - 2019/08/29/accepted PY - 2019/12/14/pubmed PY - 2020/11/20/medline PY - 2019/12/14/entrez KW - Gallic acid KW - LPS KW - Necroptosis KW - Neuroinflammation KW - Protein aggregation SP - 96 EP - 104 JF - Molecular neurobiology JO - Mol Neurobiol VL - 57 IS - 1 N2 - Gallic acid (3,4,5-trihydroxybenzoic acid, GA), a phenolic acid, is ubiquitous in almost all parts of the plant. In the present study, a neuroinflammatory rat model using intranigral infusion of lipopolysaccharides (LPS, 4 μg/μL) was employed to study the neuroprotective effect of GA which was orally administered daily. Compared with the vehicle-treated rats, systemic administration of GA (100 mg/kg) significantly attenuated LPS-induced increases in glial fibrillary acidic protein (a biomarker of activated astrocytes) and ED-1 (a biomarker of activated microglia), as well as inducible nitric oxide synthase (iNOS, a proinflammatory enzyme) and interleukin-1β (a proinflammatory cytokine), in the LPS-infused substantia nigra (SN) of rat brain. At the same time, GA attenuated LPS-induced elevation in heme oxygenase-1 level (a redox-regulated protein) and α-synuclein aggregation (a hallmark of CNS neurodegeneration), suggesting that GA is capable of inhibiting LPS-induced oxidative stress and protein conjugation. Furthermore, GA prevented LPS-induced caspase 3 activation (a biomarker of programmed cell death) and LPS-induced increases in receptor-interacting protein kinase (RIPK)-1 and RIPK-3 levels (biomarkers of necroptosis), indicating that GA inhibited LPS-induced apoptosis and necroptosis in the nigrostriatal dopaminergic system of rat brain. Moreover, an in vitro study was employed to investigate the anti-inflammatory effect of GA on BV2 microglial cells which were subjected to LPS (1 μg/mL) treatment. Consistently, co-incubation of GA diminished LPS-induced increases in iNOS mRNA and iNOS protein expression in the treated BV-2 cells as well as NO production in the culture medium. The anti-oxidative activity of GA was evaluated using iron-induced lipid peroxidation of brain homogenates. After 3-h incubation at 37 °C, GA was more potent than glutathione and less potent than trolox in inhibiting iron-induced lipid peroxidation. Conclusively, the present study suggests that GA is anti-inflammatory via attenuating LPS-induced neuroinflammation, oxidative stress, and protein conjugation. Furthermore, GA prevented LPS-induced programmed cell deaths of nigrostriatal dopaminergic neurons of the rat brain, suggesting that GA may be neuroprotective by attenuating neuroinflammation in CNS neurodegenerative diseases. SN - 1559-1182 UR - https://www.unboundmedicine.com/medline/citation/31832973/Gallic_Acid_Attenuated_LPS_Induced_Neuroinflammation:_Protein_Aggregation_and_Necroptosis_ DB - PRIME DP - Unbound Medicine ER -