Mitigation Effects of a Novel Herbal Medicine, Hepad, on Neuroinflammation, Neuroapoptosis, and Neuro-Oxidation

Parkinson’s disease (PD), a common adult-onset neurodegenerative disorder with complex pathological mechanisms, is characterized by the degeneration of dopaminergic nigrostriatal neurons. The present study demonstrated that the herbal medicines Hepad 1 and 2 protected against 1-methyl-4-ph...

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Main Authors: Da Hye Song, Gyeong-Ji Kim, Kwon Jai Lee, Jae Soo Shin, Dong-Hee Kim, Byung-Jun Park, Jeung Hee An
Format: Article
Language:English
Published: MDPI AG 2018-11-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/23/11/2920
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author Da Hye Song
Gyeong-Ji Kim
Kwon Jai Lee
Jae Soo Shin
Dong-Hee Kim
Byung-Jun Park
Jeung Hee An
author_facet Da Hye Song
Gyeong-Ji Kim
Kwon Jai Lee
Jae Soo Shin
Dong-Hee Kim
Byung-Jun Park
Jeung Hee An
author_sort Da Hye Song
collection DOAJ
description Parkinson’s disease (PD), a common adult-onset neurodegenerative disorder with complex pathological mechanisms, is characterized by the degeneration of dopaminergic nigrostriatal neurons. The present study demonstrated that the herbal medicines Hepad 1 and 2 protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity in C57BL/6 mice and SH-SY5Y cells. Hepad 1 and 2 remarkably alleviated the enhanced expression of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, cyclooxygenase-2, macrophage-1, and phosphorylated iκB-α) and apoptotic signals (Bcl-2-associated X protein, caspase-3, and poly [ADP-ribose] polymerase-1). Additionally, Hepad reduced MPTP-induced oxidative damage by increasing the expression of anti-oxidant defense enzymes (superoxide dismutase and glutathione S-transferase) and downregulating the levels of nicotinamide adenine dinucleotide phosphate oxidase 4. This study also showed that the neuroprotective effects of Hepad include anti-inflammatory, anti-apoptotic, and anti-oxidative properties, in addition to activation of the protein kinase B, extracellular-signal-regulated kinase, and c-Jun N-terminal kinase signaling pathways. Furthermore, oral administration of Hepad 1 and 2 attenuated the death of tyrosine hydroxylase-positive substantia nigra neurons that was induced by 20 mg/kg MPTP. Therefore, our results suggest that Hepad 1 and 2 are useful for treating PD and other disorders associated with neuro-inflammatory, neuro-apoptotic, and neuro-oxidative damage.
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spelling doaj.art-bc3fb06bf8e84be285459c0b57b8608c2022-12-22T00:55:36ZengMDPI AGMolecules1420-30492018-11-012311292010.3390/molecules23112920molecules23112920Mitigation Effects of a Novel Herbal Medicine, Hepad, on Neuroinflammation, Neuroapoptosis, and Neuro-OxidationDa Hye Song0Gyeong-Ji Kim1Kwon Jai Lee2Jae Soo Shin3Dong-Hee Kim4Byung-Jun Park5Jeung Hee An6Department of Food Science and Technology, Seoul National University of Science & Technology, Seoul 01811, KoreaDivision of Food Bioscience, Konkuk University, Chungju 27478, KoreaDepartment of Advanced Materials Engineering, Daejeon University, Daejeon 34520, KoreaDepartment of Advanced Materials Engineering, Daejeon University, Daejeon 34520, KoreaDepartment of Pathology, College of Oriental Medicine, Daejeon University, Daejeon 34520, KoreaDepartment of Pathology, College of Oriental Medicine, Daejeon University, Daejeon 34520, KoreaDivision of Food Bioscience, Konkuk University, Chungju 27478, KoreaParkinson’s disease (PD), a common adult-onset neurodegenerative disorder with complex pathological mechanisms, is characterized by the degeneration of dopaminergic nigrostriatal neurons. The present study demonstrated that the herbal medicines Hepad 1 and 2 protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity in C57BL/6 mice and SH-SY5Y cells. Hepad 1 and 2 remarkably alleviated the enhanced expression of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, cyclooxygenase-2, macrophage-1, and phosphorylated iκB-α) and apoptotic signals (Bcl-2-associated X protein, caspase-3, and poly [ADP-ribose] polymerase-1). Additionally, Hepad reduced MPTP-induced oxidative damage by increasing the expression of anti-oxidant defense enzymes (superoxide dismutase and glutathione S-transferase) and downregulating the levels of nicotinamide adenine dinucleotide phosphate oxidase 4. This study also showed that the neuroprotective effects of Hepad include anti-inflammatory, anti-apoptotic, and anti-oxidative properties, in addition to activation of the protein kinase B, extracellular-signal-regulated kinase, and c-Jun N-terminal kinase signaling pathways. Furthermore, oral administration of Hepad 1 and 2 attenuated the death of tyrosine hydroxylase-positive substantia nigra neurons that was induced by 20 mg/kg MPTP. Therefore, our results suggest that Hepad 1 and 2 are useful for treating PD and other disorders associated with neuro-inflammatory, neuro-apoptotic, and neuro-oxidative damage.https://www.mdpi.com/1420-3049/23/11/2920Parkinson’s disease1-methyl-4-phenyl-1,2,3,6-tetrahydropyridineHepadMitigation effectSH-SY5Y cellsSubstantia nigra
spellingShingle Da Hye Song
Gyeong-Ji Kim
Kwon Jai Lee
Jae Soo Shin
Dong-Hee Kim
Byung-Jun Park
Jeung Hee An
Mitigation Effects of a Novel Herbal Medicine, Hepad, on Neuroinflammation, Neuroapoptosis, and Neuro-Oxidation
Molecules
Parkinson’s disease
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Hepad
Mitigation effect
SH-SY5Y cells
Substantia nigra
title Mitigation Effects of a Novel Herbal Medicine, Hepad, on Neuroinflammation, Neuroapoptosis, and Neuro-Oxidation
title_full Mitigation Effects of a Novel Herbal Medicine, Hepad, on Neuroinflammation, Neuroapoptosis, and Neuro-Oxidation
title_fullStr Mitigation Effects of a Novel Herbal Medicine, Hepad, on Neuroinflammation, Neuroapoptosis, and Neuro-Oxidation
title_full_unstemmed Mitigation Effects of a Novel Herbal Medicine, Hepad, on Neuroinflammation, Neuroapoptosis, and Neuro-Oxidation
title_short Mitigation Effects of a Novel Herbal Medicine, Hepad, on Neuroinflammation, Neuroapoptosis, and Neuro-Oxidation
title_sort mitigation effects of a novel herbal medicine hepad on neuroinflammation neuroapoptosis and neuro oxidation
topic Parkinson’s disease
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Hepad
Mitigation effect
SH-SY5Y cells
Substantia nigra
url https://www.mdpi.com/1420-3049/23/11/2920
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