Humulus japonicus Prevents Dopaminergic Neuron Death in 6-Hydroxydopamine-Induced Models of Parkinson's Disease.
Humulus japonicus (HJ), popularly known as Japanese hops, is a traditional herbal medicine widely used for the treatment of pulmonary disease, skin disease, and hypertension in Korea. HJ exerts scavenging effects against reactive oxygen species (ROS), such as superoxide radical, hydroxyl radical, and hydrogen peroxide. Moreover, dysfunction and damage of mitochondria elicited by ROS are of critical importance in the pathogenesis of Parkinson's disease (PD). The present study aimed to examine neuroprotective potential of extracts of HJ using in vitro and in vivo 6-hydroxydopamine (6-OHDA) models. SH-SY5Y cells were cultured to explore the mechanisms for the neuroprotective effect of HJ in vitro. Unilateral 6-OHDA-induced mouse model of PD was established to investigate the neuroprotective effect of HJ on dopaminergic neurons in substantia nigra pars compacta (SNc) and striatum in vivo. Methanol extract of HJ (HJM) significantly attenuated cytotoxicity and the mitochondrial apoptosis pathway caused by 6-OHDA in SH-SY5Y cells. In addition, HJM significantly increased glutathione levels and decreased phosphorylation of ERK1/2 in SH-SY5Y cells exposed to 6-OHDA. In the in vivo study, the administration of methanol or ethanol extract of HJ improved the motor dysfunction and notably reduced dopaminergic cell death and fiber loss in the SNc and striatum caused by 6-OHDA. Our findings demonstrate that HJ may have therapeutic potential to protect dopaminergic neuron degeneration in Parkinson's disease.
1 Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB) , Daejeon, Korea.|2 Department of Toxicology Evaluation, Konyang University , Daejeon, Korea.
Young-Kyoung
YK
Ryu
1 Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB) , Daejeon, Korea.
Young
Y
Kang
1 Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB) , Daejeon, Korea.
Jun
J
Go
1 Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB) , Daejeon, Korea.
Hye-Yeon
HY
Park
1 Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB) , Daejeon, Korea.
Jung-Ran
JR
Noh
1 Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB) , Daejeon, Korea.|3 Department of Functional Genomics, University of Science and Technology (UST) , Daejeon, Korea.
Yong-Hoon
YH
Kim
1 Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB) , Daejeon, Korea.
Jung Hwan
JH
Hwang
1 Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB) , Daejeon, Korea.
Dong-Hee
DH
Choi
2 Department of Toxicology Evaluation, Konyang University , Daejeon, Korea.
Sang-Seop
SS
Han
4 Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul, Korea.
Won-Keun
WK
Oh
1 Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB) , Daejeon, Korea.|3 Department of Functional Genomics, University of Science and Technology (UST) , Daejeon, Korea.
Chul-Ho
CH
Lee
1 Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB) , Daejeon, Korea.|3 Department of Functional Genomics, University of Science and Technology (UST) , Daejeon, Korea.
Kyoung-Shim
KS
Kim
D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D027582:Humulus / Q000737:chemistry*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D016627:Oxidopamine / Q000009:adverse effects; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010936:Plant Extracts / Q000008:administration & dosage*; D017382:Reactive Oxygen Species / Q000378:metabolism
D018696:Neuroprotective Agents; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D016627:Oxidopamine; D004298:Dopamine
6-OHDA; Humulus japonicus; Parkinson's disease; dopaminergic cell death; oxidative stress