DA-9805 protects dopaminergic neurons from endoplasmic reticulum stress and inflammation

Parkinson’s disease (PD) is a multifactorial neurodegenerative disease with damages to mitochondria and endoplasmic reticulum (ER), followed by neuroinflammation. We previously reported that a triple herbal extract DA-9805 in experimental PD toxin-models had neuroprotective effects by alleviating mi...

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Autores principales:	Sora Kang, Ying Piao, Young Cheol Kang, Suyeol Lim, Youngmi Kim Pak
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Mitochondria Herbal medicine ER stress Neuroinflammation Parkinson’s disease Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/65aa199b55c04aa0afd788a47da8dd59
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spelling	oai:doaj.org-article:65aa199b55c04aa0afd788a47da8dd592021-11-14T04:30:27ZDA-9805 protects dopaminergic neurons from endoplasmic reticulum stress and inflammation0753-332210.1016/j.biopha.2021.112389https://doaj.org/article/65aa199b55c04aa0afd788a47da8dd592022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221011756https://doaj.org/toc/0753-3322Parkinson’s disease (PD) is a multifactorial neurodegenerative disease with damages to mitochondria and endoplasmic reticulum (ER), followed by neuroinflammation. We previously reported that a triple herbal extract DA-9805 in experimental PD toxin-models had neuroprotective effects by alleviating mitochondrial damage and oxidative stress. In the present study, we investigated whether DA-9805 could suppress ER stress and neuroinflammation in vitro and/or in vivo. Pre-treatment with DA-9805 (1 μg/ml) attenuated upregulation of glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP) and cleaved caspase-3 in SH-SY5Y neuroblastoma cells treated with thapsigargin (1 µg/ml) or tunicamycin (2 µg/ml). In addition, DA-9805 prevented the production of IL-1β, IL-6, TNF-α and nitric oxide through inhibition of NF-κB activation in BV2 microglial cells stimulated with lipopolysaccharides (LPS). Intraperitoneal injection of LPS (10 mg/kg) into mice can induce acute neuroinflammation and dopaminergic neuronal cell death. Oral administration of DA-9805 (10 or 30 mg/kg/day for 3 days before LPS injection) prevented loss of dopaminergic neurons and activation of microglia and astrocytes in the substantia nigra in LPS-injected mouse models. Taken together, these results indicate that DA-9805 can effectively prevent ER stress and neuroinflammation, suggesting that DA-9805 is a multitargeting and disease-modifying therapeutic candidate for PD.Sora KangYing PiaoYoung Cheol KangSuyeol LimYoungmi Kim PakElsevierarticleMitochondriaHerbal medicineER stressNeuroinflammationParkinson’s diseaseTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 145, Iss , Pp 112389- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mitochondria Herbal medicine ER stress Neuroinflammation Parkinson’s disease Therapeutics. Pharmacology RM1-950
spellingShingle	Mitochondria Herbal medicine ER stress Neuroinflammation Parkinson’s disease Therapeutics. Pharmacology RM1-950 Sora Kang Ying Piao Young Cheol Kang Suyeol Lim Youngmi Kim Pak DA-9805 protects dopaminergic neurons from endoplasmic reticulum stress and inflammation
description	Parkinson’s disease (PD) is a multifactorial neurodegenerative disease with damages to mitochondria and endoplasmic reticulum (ER), followed by neuroinflammation. We previously reported that a triple herbal extract DA-9805 in experimental PD toxin-models had neuroprotective effects by alleviating mitochondrial damage and oxidative stress. In the present study, we investigated whether DA-9805 could suppress ER stress and neuroinflammation in vitro and/or in vivo. Pre-treatment with DA-9805 (1 μg/ml) attenuated upregulation of glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP) and cleaved caspase-3 in SH-SY5Y neuroblastoma cells treated with thapsigargin (1 µg/ml) or tunicamycin (2 µg/ml). In addition, DA-9805 prevented the production of IL-1β, IL-6, TNF-α and nitric oxide through inhibition of NF-κB activation in BV2 microglial cells stimulated with lipopolysaccharides (LPS). Intraperitoneal injection of LPS (10 mg/kg) into mice can induce acute neuroinflammation and dopaminergic neuronal cell death. Oral administration of DA-9805 (10 or 30 mg/kg/day for 3 days before LPS injection) prevented loss of dopaminergic neurons and activation of microglia and astrocytes in the substantia nigra in LPS-injected mouse models. Taken together, these results indicate that DA-9805 can effectively prevent ER stress and neuroinflammation, suggesting that DA-9805 is a multitargeting and disease-modifying therapeutic candidate for PD.
format	article
author	Sora Kang Ying Piao Young Cheol Kang Suyeol Lim Youngmi Kim Pak
author_facet	Sora Kang Ying Piao Young Cheol Kang Suyeol Lim Youngmi Kim Pak
author_sort	Sora Kang
title	DA-9805 protects dopaminergic neurons from endoplasmic reticulum stress and inflammation
title_short	DA-9805 protects dopaminergic neurons from endoplasmic reticulum stress and inflammation
title_full	DA-9805 protects dopaminergic neurons from endoplasmic reticulum stress and inflammation
title_fullStr	DA-9805 protects dopaminergic neurons from endoplasmic reticulum stress and inflammation
title_full_unstemmed	DA-9805 protects dopaminergic neurons from endoplasmic reticulum stress and inflammation
title_sort	da-9805 protects dopaminergic neurons from endoplasmic reticulum stress and inflammation
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/65aa199b55c04aa0afd788a47da8dd59
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DA-9805 protects dopaminergic neurons from endoplasmic reticulum stress and inflammation

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