6-Shogaol has anti-amyloidogenic activity and ameliorates Alzheimer's disease via CysLT1R-mediated inhibition of cathepsin B.
Although 6-shogaol, a constituent of ginger, has been reported to have anti-inflammatory and anti-oxidant effects on neuronal cells, the effects of 6-shogaol on Alzheimer's disease (AD) have not yet been investigated. Here we aimed to determine whether 6-shogaol exerts neuroprotective effects against AD. Specifically, we investigated the effects of 6-shogaol on the cysteinyl leukotriene 1 receptor (CysLT1R), a major factor in AD pathogenesis. Moreover, we clarified the relationship between CysLT1R and cathepsin B, a cysteine protease. We used in vitro and in vivo models to determine whether 6-shogaol inhibits CysLT1R/cathepsin B in an amyloid-beta (Aβ; 1-42)-induced model of neurotoxicity. We first confirmed that CysLT1R and cathepsin B are upregulated by Aβ (1-42) and that CysLT1R activation induces cathepsin B. In contrast, we found that 6-shogaol-mediated inhibition of CysLT1R downregulates cathepsin B in both in vitro and in vivo models. Furthermore, we found that 6-shogaol-mediated inhibition of CysLT1R/cathepsin B reduces Aβ deposition in the brain and ameliorates behavioral deficits in APPSw/PS1-dE9 Tg mice. Our results indicate that 6-shogaol is a CysLT1R/cathepsin B inhibitor and is a novel potential therapeutic agent for the treatment of various neurodegenerative diseases, including AD.
Department of Laboratory Animal Medicine, College of Veterinary Medicine, Chonbuk National University, 79 Gobongro, Iksan, 54596, Republic of Korea.
Ji-Young
JY
Na
Department of Laboratory Animal Medicine, College of Veterinary Medicine, Chonbuk National University, 79 Gobongro, Iksan, 54596, Republic of Korea.
Kibbeum
K
Song
Central Research and Development, Between Co. LTD., Iksan, 54596, Republic of Korea.
Ju-Woon
JW
Lee
Department of Laboratory Animal Medicine, College of Veterinary Medicine, Chonbuk National University, 79 Gobongro, Iksan, 54596, Republic of Korea. Electronic address: raios@hanmail.net.
Sokho
S
Kim
Department of Laboratory Animal Medicine, College of Veterinary Medicine, Chonbuk National University, 79 Gobongro, Iksan, 54596, Republic of Korea; Central Research and Development, Between Co. LTD., Iksan, 54596, Republic of Korea. Electronic address: jkwon@jbnu.ac.kr.
Jungkee
J
Kwon
D000544:Alzheimer Disease / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002396:Catechols / Q000494:pharmacology*; D002401:Cathepsin B / Q000037:antagonists & inhibitors*; D002460:Cell Line; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000037:antagonists & inhibitors*; D018077:Receptors, Leukotriene / Q000502:physiology*
D016229:Amyloid beta-Peptides; D002396:Catechols; D010446:Peptide Fragments; D018077:Receptors, Leukotriene; C075222:amyloid beta-protein (1-42); C040115:shogaol; D002401:Cathepsin B; C083169:leukotriene D4 receptor
6-Shogaol; Alzheimer’s disease; Cathepsin B; Cysteinyl leukotriene 1 receptor; Ginger