Amyloid beta (A beta) 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 mu M and 15 mu M) significantly suppresses oligomeric A beta 42 (oA beta 42)induced expression of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF alpha) 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 A beta 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 oA beta 42-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. (C) 2016 Elsevier Inc. All rights reserved.