title: Protective effects of a herbal extract combination of Bupleurum falcatum, Paeonia suffruticosa, and Angelica dahurica against MPTP-induced neurotoxicity via regulation of nuclear receptor-related 1 protein.
abstract: Parkinson's disease (PD) is one of the progressive neurodegenerative diseases of whose condition is characterized by dopaminergic neuronal cell loss and dysfunction in the substantia nigra pars compacta (SNpc) and the striatum. Recent studies have demonstrated that the nuclear receptor-related 1 protein (Nurr1) is critical of dopaminergic phenotype induction in mesencephalic dopaminergic neurons. Further, Nurr1 engages in synthesizing and storing dopamine through regulating levels of tyrosine hydroxylase (TH), dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2). The aim of this study was to investigate the protective effects of a herbal extract combination, consisting of Bupleurum falcatum, Paeonia suffruticosa, and Angelica dahurica (MABH), on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD-like symptoms and to elucidate possible mechanisms of action focusing on Nurr1. In a subacute mouse model of MPTP-induced PD, MABH treatment resulted in recovery from movement impairments. MABH prevented dopamine depletion and protected against dopaminergic neuronal degradation induced by MPTP. Additionally, MABH increased Nurr1 expression in the SNpc of mice. To evaluate the effects of MABH on Nurr1 expression, we measured the protein levels of Nurr1 and its regulating factors using Western blot analysis in PC12 cells. MABH treatment induced the phosphorylation of extracellular signal-regulated kinase protein via increasing the protein expression levels of Nurr1 and ultimately the levels of TH, VMAT2, and DAT. These results indicate that MABH has protective effects on dopaminergic neurons in a mouse model of PD by regulating Nurr1.
authors: Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
authors: Yeomoon
authors: Y
authors: Sim
authors: Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
authors: Gunhyuk
authors: G
authors: Park
authors: Department of Oriental Pharmaceutical Science, College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
authors: Hyeyoon
authors: H
authors: Eo
authors: Department of Oriental Pharmaceutical Science, College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea; Department of Herbal Pharmacology, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
authors: Eugene
authors: E
authors: Huh
authors: Department of Oriental Pharmaceutical Science, College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
authors: Pil Sung
authors: PS
authors: Gu
authors: Department of Oriental Pharmaceutical Science, College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
authors: Seon-Pyo
authors: SP
authors: Hong
authors: Neurodegeneration Control Research Center, Department of Physiology, College of Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
authors: Youngmi Kim
authors: YK
authors: Pak
authors: Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea; Department of Oriental Pharmaceutical Science, College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea. Electronic address: msohok@khu.ac.kr.
authors: Myung Sook
authors: MS
authors: Oh
mesh_terms: D029969:Angelica; D000818:Animals; D029972:Bupleurum; D004298:Dopamine / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D020267:MPTP Poisoning / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000378:metabolism; D016716:PC12 Cells; D029596:Paeonia; D065842:Pars Compacta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats
chemical_list: D018696:Neuroprotective Agents; C539883:Nr4a2 protein, mouse; C539884:Nr4a2 protein, rat; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D010936:Plant Extracts; D004298:Dopamine
keywords: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Angelica dahurica; Bupleurum falcatum; Paeonia suffruticosa; Parkinson’s disease; nuclear receptor-related 1 protein