title: Inhibitory effect of thiacremonone on MPTP-induced dopaminergic neurodegeneration through inhibition of p38 activation.
abstract: Neuroinflammation is implicated for dopaminergic neurodegeneration. Sulfur compounds extracted from garlic have been shown to have anti-inflammatory properties. Previously, we have investigated that thiacremonone, a sulfur compound isolated from garlic has anti-inflammatory effects on several inflammatory disease models. To investigate the protective effect of thiacremonone against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced behavioral impairment and dopaminergic neurodegeneration, 8 week old ICR mice were given thiacremonone (10 mg/kg) in drinking water for 1 month and received intraperitoneal injection of MPTP (15 mg/kg, four times with 2 h interval) during the last 7 days of treatment. Our data showed that thiacremonone decreased MPTP-induced behavioral impairments (Rotarod test, Pole test, and Gait test), dopamine depletion and microglia and astrocytes activations as well as neuroinflammation. Higher activation of p38 was found in the substantia nigra and striatum after MPTP injection, but p38 activation was reduced in thiacremonone treated group. In an in vitro study, thiacremonone (1, 2, and 5 μg/ml) effectively decreased MPP+ (0.5 mM)-induced glial activation, inflammatory mediators generation and dopaminergic neurodegeneration in cultured astrocytes and microglial BV-2 cells. Moreover, treatment of p38 MAPK inhibitor SB203580 (10 μM) further inhibited thiacremonone induced reduction of neurodegeneration and neuroinflammation. These results indicated that the anti-inflammatory compound, thiacremonone, inhibited neuroinflammation and dopaminergic neurodegeneration through inhibition of p38 activation.
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong, Osong-eup, Heungduk-gu, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Chul Ju
authors.initials: CJ
authors.lastname: Hwang
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong, Osong-eup, Heungduk-gu, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Hee Pom
authors.initials: HP
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Yeungnam University, Daehak-Ro, Gyeongsan, Gyeongbuk, Republic of Korea.
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Choi
authors.affiliation: College of Agriculture, Life and Environments Sciences, Chungbuk National University, Osongsaengmyeong, Osong-eup, Heungduk-gu, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Heon Sang
authors.initials: HS
authors.lastname: Jeong
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong, Osong-eup, Heungduk-gu, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong, Osong-eup, Heungduk-gu, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Tae Hyung
authors.initials: TH
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong, Osong-eup, Heungduk-gu, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Young Min
authors.initials: YM
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong, Osong-eup, Heungduk-gu, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Dae Bong
authors.initials: DB
authors.lastname: Moon
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong, Osong-eup, Heungduk-gu, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Sung Sik
authors.initials: SS
authors.lastname: Park
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong, Osong-eup, Heungduk-gu, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong, Osong-eup, Heungduk-gu, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Ki-Wan
authors.initials: KW
authors.lastname: Oh
authors.affiliation: College of Natural Resources & Life Science, Pusan National University, Pusan, Republic of Korea.
authors.forename: Dae Yeon
authors.initials: DY
authors.lastname: Hwang
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong, Osong-eup, Heungduk-gu, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Han
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong, Osong-eup, Heungduk-gu, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Hwa-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong, Osong-eup, Heungduk-gu, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001253:Astrocytes / Q000187:drug effects; D001526:Behavioral Symptoms / Q000139:chemically induced / Q000188:drug therapy*; D002460:Cell Line; D003342:Corpus Striatum / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000473:pathology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017628:Microglia / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000378:metabolism; D013876:Thiophenes / Q000627:therapeutic use*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D007093:Imidazoles; D018696:Neuroprotective Agents; D011725:Pyridines; D013876:Thiophenes; C524083:thiacremonone; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; D004298:Dopamine
keywords: P38 MAPK; Pathology Section; garlic; thiacremonone; neurodegeneration; Parkinson’s disease