Hypericin inhibits oligomeric amyloid β42-induced inflammation response in microglia and ameliorates cognitive deficits in an amyloid β injection mouse model of Alzheimer's disease by suppressing MKL1.
Amyloid β (Aβ) provokes severe inflammation response in the central nervous system, which is a key risk factor for the progression of Alzheimer's disease (AD). Anti-inflammation medications shed light on treating AD. In this study, we found hypericin is a potent anti-AD constituent through anti-inflammation. Pretreatment with hypericin (5 μM and 15 μM) significantly suppresses oligomeric Aβ42 (oAβ42)-induced expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNF α) and inducible nitric oxide synthase (iNOS) and production of NO in microglia without cytotoxicity. We further found that hypericin ameliorates inflammatory response by suppressing MKL1, which is the essential cofactor of p65 during the transcription process. In an Aβ injection AD mouse model, animals orally administrated hypericin (50 mg/kg) for seven days significantly decreased pro-inflammatory cytokines expression and NO production in hippocampus, meanwhile, hypericin improved oAβ42-induced learning and memory impairment in mice in the Morris water maze test. Therefore, hypericin could be considered as a potential candidate for treating AD.
State Key Laboratory of Nature Medicine, China Pharmaceutical University, Nanjing, Jiangsu, China.
Mu
M
Zhang
State Key Laboratory of Nature Medicine, China Pharmaceutical University, Nanjing, Jiangsu, China.
Yanyan
Y
Wang
State Key Laboratory of Nature Medicine, China Pharmaceutical University, Nanjing, Jiangsu, China.
Fei
F
Qian
State Key Laboratory of Nature Medicine, China Pharmaceutical University, Nanjing, Jiangsu, China. Electronic address: liping2004@126.com.
Ping
P
Li
State Key Laboratory of Nature Medicine, China Pharmaceutical University, Nanjing, Jiangsu, China. Electronic address: xiaojunxu2000@163.com.
Xiaojun
X
Xu
D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D016229:Amyloid beta-Peptides; D000818:Animals; D000873:Anthracenes; D002460:Cell Line; D003071:Cognition; D003072:Cognition Disorders / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000276:immunology*; D010446:Peptide Fragments; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D015534:Trans-Activators / Q000276:immunology*; D016896:Treatment Outcome
D016229:Amyloid beta-Peptides; D000873:Anthracenes; C511173:Mrtfa protein, mouse; D010446:Peptide Fragments; D015534:Trans-Activators; C075222:amyloid beta-protein (1-42); D010569:Perylene; C004965:hypericin
Alzheimer's disease; Hypericin; Inflammation; MKL1; NF-κB