Oncotarget

Research Papers: Pathology:

Inhibitory effect of thiacremonone on MPTP-induced dopaminergic neurodegeneration through inhibition of p38 activation

Chul Ju Hwang, Hee Pom Lee, Dong-Young Choi, Heon Sang Jeong, Tae Hoon Kim, Tae Hyung Lee, Young Min Kim, Dae Bong Moon, Sung Sik Park, Sun Young Kim, Ki-Wan Oh, Dae Yeon Hwang, Sang-Bae Han, Hwa-Jeong Lee and Jin Tae Hong _

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Oncotarget. 2016; 7:46943-46958. https://doi.org/10.18632/oncotarget.10504

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Abstract

Chul Ju Hwang1, Hee Pom Lee1, Dong-Young Choi2, Heon Sang Jeong3, Tae Hoon Kim1, Tae Hyung Lee1, Young Min Kim1, Dae Bong Moon1, Sung Sik Park1, Sun Young Kim1, Ki-Wan Oh1, Dae Yeon Hwang4, Sang-Bae Han1, Hwa-Jeong Lee1 and Jin Tae Hong1

1 College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong, Osong-eup, Heungduk-gu, Cheongju, Chungbuk, Republic of Korea

2 College of Pharmacy, Yeungnam University, Daehak-Ro, Gyeongsan, Gyeongbuk, Republic of Korea

3 College of Agriculture, Life and Environments Sciences, Chungbuk National University, Osongsaengmyeong, Osong-eup, Heungduk-gu, Cheongju, Chungbuk, Republic of Korea

4 College of Natural Resources & Life Science, Pusan National University, Pusan, Republic of Korea

Correspondence to:

Hwa-Jeong Lee, email:

Jin Tae Hong, email:

Keywords: garlic; neurodegeneration; P38 MAPK; Parkinson’s disease; thiacremonone; Pathology Section

Received: February 25, 2016 Accepted: June 30, 2016 Published: July 09, 2016

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.


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