title: Triptolide preserves cognitive function and reduces neuropathology in a mouse model of Alzheimer's disease.
abstract: Triptolide, a major bioactive ingredient of a widely used herbal medicine, has been shown to possess multiple pharmacological functions, including potential neuroprotective effects pertinent to Alzheimer's disease (AD) in vitro. However, the therapeutic potential of triptolide for AD in vivo has not been thoroughly evaluated. In the present study, we investigated the impact of peripherally administered triptolide on AD-related behavior and neuropathology in APPswe/PS1ΔE9 (APP/PS1) mice, an established model of AD. Our results showed that two-month treatment with triptolide rescued cognitive function in APP/PS1 mice. Immunohistochemical analyses indicated that triptolide treatment led to a significant decrease in amyloid-β (Aβ) deposition and neuroinflammation in treated mice. In contrast to previous findings in vitro, biochemical analyses showed that triptolide treatment did not significantly affect the production pathway of Aβ in vivo. Intriguingly, further analyses revealed that triptolide treatment upregulated the level of insulin-degrading enzyme, a major Aβ-degrading enzyme in the brain, indicating that triptolide treatment reduced Aβ pathology by enhancing the proteolytic degradation of Aβ. Our findings demonstrate that triptolide treatment ameliorates key behavioral and neuropathological changes found in AD, suggesting that triptolide may serve as a potential therapeutic agent for AD.
authors.affiliation: Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Shaowu
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: LeBlanc
authors.affiliation: Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects*; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology* / Q000627:therapeutic use*; D004852:Epoxy Compounds / Q000494:pharmacology / Q000627:therapeutic use; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D007249:Inflammation / Q000473:pathology; D008569:Memory Disorders / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D010616:Phenanthrenes / Q000494:pharmacology* / Q000627:therapeutic use*; D053764:Presenilin-1 / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016564:Amyloid beta-Protein Precursor; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; D053764:Presenilin-1; C001899:triptolide