Anti-Amyloidogenic Effect of Thiacremonone through Anti-Inflamation In Vitro and In Vivo Models

Article type: Research Article

Authors: Lin, Gui Hua^{a; b; 1} | Lee, Young-Jung^{a; b; 1} | Choi, Dong-Young^{a; b} | Han, Sang Bae^{a; b} | Jung, Jae Kyung^{a; b} | Hwang, Bang Yeon^{a; b} | Moon, Dong Cheul^a | Kim, Youngsoo^{a; b} | Lee, Myung Koo^a | Oh, Ki-Wan^{a; b} | Jeong, Heon Sang^c | Leem, Jae Yoon^d | Shin, Hwa Kyoung^e | Lee, Jung Hwa^f | Hong, Jin Tae^{a; b; *}

Affiliations: [a] College of Pharmacy, Chungbuk National University, Heungduk-gu, Cheongju, Chungbuk, Republic of Korea | [b] Medical Research Center, Chungbuk National University, Heungduk-gu, Cheongju, Chungbuk, Republic of Korea | [c] College of Agriculture, Life and Environments Sciences, Chungbuk National University, Heungduk-gu, Cheongju, Chungbuk, Republic of Korea | [d] College of Pharmacy, Woosuk University, Jeonbuk, Republic of Korea | [e] Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam, Republic of Korea | [f] Department of Pediatrics, School of Medicine, Konkuk University, Chungju, Chunbuk, Republic of Korea

Correspondence: [*] Correspondence to: Jin Tae Hong, Ph.D., College of Pharmacy, Chungbuk National University, 12, Gaeshin-dong, Heungduk-gu, Cheongju, 361–763 Chungbuk, Korea. Tel.: +82 43 261 2813; Fax: +82 43 268 2732; E-mail: jinthong@chungbuk.ac.kr.

Note: [1] Both authors contributed equally to this work.

Abstract: Neuroinflammation is implicated for amyloidogenesis. 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. To investigate thiacremonone's potential effect on anti-neuroinflammation and anti-amyloidogenesis, 4 week old ICR mice were given different doses of thiacremonone (1, 3, and 10 mg/kg) in drinking water for 1 month and received intraperitoneal injection of lipopolysaccharide (LPS) (250 μg/kg/day) at last 7 days of treatment. Our data show thiacremonone decreased LPS-induced memory impairment, glial activation, pro-inflammatory mediators' expression, and amyloidogenesis. In an in vitro study, we obtained similar results, with thiacremonone (1, 2, and 5 μg/ml) effectively decreased LPS (1 μg/ml)-induced glial activation and inflammatory mediators generation which are implicated in amyloidogenesis. Our data also demonstrated that thiacremonone inhibited LPS-induced amyloidogenesis in cultured astrocytes and microglial BV-2 cells. NF-κB, a critical transcriptional factor regulating not only inflammation but also amyloid-β generation, was inhibited by thiacremonone via blocking of phosphorylation of IκBα in mice brain as well as cultured astrocytes and microglial BV-2 cells. These results indicated that the anti-inflammatory compound, thiacremonone, inhibited neuroinflammation and amyloidogenesis through inhibition of NF-κB activity, and thus could be applied for intervention of inflammation-related neurodegenerative disease including Alzheimer's disease.

Keywords: Amyloidogenesis, neuroinflammation, NF-κb, thiacremonone

DOI: 10.3233/JAD-2012-111709

Journal: Journal of Alzheimer's Disease, vol. 29, no. 3, pp. 659-676, 2012