Effects of (-)-sesamin on 6-hydroxydopamine-induced neurotoxicity in PC12 cells and dopaminergic neuronal cells of Parkinson's disease rat models.
The present study investigated the effects of (-)-sesamin on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity using PC12 cells and dopaminergic neuronal cells of 6-OHDA-lesioned rat model of Parkinson's disease (PD). In PC12 cells, treatment with (-)-sesamin (25 µM) reduced 6-OHDA (100 µM)-induced cell death and induced transient extracellular signal-regulated kinase (ERK1/2) phosphorylation and Bad phosphorylation at Ser112 (BadSer112). In contrast, sustained ERK1/2 phosphorylation, p38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK1/2) phosphorylation, and cleaved-caspase-3 activity, all of which were induced by 6-OHDA (100 µM), were inhibited by treatment with (-)-sesamin (25 µM). Furthermore, co-treatment with (-)-sesamin (30 mg/kg, p.o.) once a day for 28 days significantly increased the number of tyrosine hydroxylase-immunopositive neuronal cells and the levels of dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid in the substantia nigra-striatum of 6-OHDA-lesioned rat model of PD with or without L-DOPA treatment. These results suggest that (-)-sesamin protects 6-OHDA-induced cytotoxicity via the activation of transient ERK1/2-BadSer112 system and the inhibition of sustained ERK-p38MAPK-JNK1/2-caspase-3 system in PC12 cells. (-)-Sesamin also shows protective effects on long-term L-DOPA therapy in dopaminergic neuronal cells of PD rat models. (-)-Sesamin may serve as adjuvant therapeutics in PD.
College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, 52, Naesudong-ro, Heungduk-gu, Cheongju 361-763, Republic of Korea.
Hyun Jin
HJ
Park
College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, 52, Naesudong-ro, Heungduk-gu, Cheongju 361-763, Republic of Korea.
Ting Ting
TT
Zhao
College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, 52, Naesudong-ro, Heungduk-gu, Cheongju 361-763, Republic of Korea.
Kyung Sook
KS
Lee
College of Pharmacy, Young Nam University, 214-1, Dae-dong, Kyeongsan 712-749, Republic of Korea.
Seung Ho
SH
Lee
College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, 52, Naesudong-ro, Heungduk-gu, Cheongju 361-763, Republic of Korea.
Keon Sung
KS
Shin
College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, 52, Naesudong-ro, Heungduk-gu, Cheongju 361-763, Republic of Korea.
Keun Hong
KH
Park
Department of Food and Nutrition, Chungcheong University, 38, Wuelgok-gil, Cheongwon-gun, Chungbuk 363-890, Republic of Korea.
Hyun Sook
HS
Choi
College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, 52, Naesudong-ro, Heungduk-gu, Cheongju 361-763, Republic of Korea. Electronic address: myklee@chungbuk.ac.kr.
Myung Koo
MK
Lee
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004149:Dioxoles / Q000494:pharmacology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology*; D016627:Oxidopamine / Q000494:pharmacology*; D016716:PC12 Cells / Q000187:drug effects; D010300:Parkinson Disease / Q000378:metabolism*; D051381:Rats; D013378:Substantia Nigra / Q000187:drug effects
D004149:Dioxoles; D017705:Lignans; D016627:Oxidopamine; D048049:Extracellular Signal-Regulated MAP Kinases; C054125:sesamin; D004298:Dopamine
(-)-Sesamin; 6-Hydroxydopamine-induced neurotoxicity; 6-Hydroxydopamine-lesioned rat model of Parkinson's disease; Adjuvant therapeutics; PC12 cells