PMID- 30196289 OWN - NLM STAT- MEDLINE DCOM- 20181012 LR - 20190212 IS - 1421-9778 (Electronic) IS - 1015-8987 (Linking) VI - 49 IP - 3 DP - 2018 TI - Icariside II, a Phosphodiesterase-5 Inhibitor, Attenuates Beta-Amyloid-Induced Cognitive Deficits via BDNF/TrkB/CREB Signaling. PG - 985 LID - 10.1159/000493232 [doi] AB - BACKGROUND/AIMS: Icariside II (ICS II) is an active component from Epimedium brevicornum, a Chinese medicine extensively used in China. Our previous study has proved that ICS II protects against learning and memory impairments and neuronal apoptosis in the hippocampus induced by beta-amyloid25-35 (Abeta25-35) in rats. However, its in-depth underlying mechanisms remain still unclear. Hence this study was designed to explore the potential underlying mechanisms of ICS II by experiments with an in vivo model of Abeta25-35-induced cognitive deficits in rats combined with a neuronal-like PC12 cells injury in vitro model. METHODS: The cognitive deficits was measured using Morris water maze test, and apoptosis, intracellular reactive oxygen species (ROS) and mitochondrial ROS levels were detected by TUNEL, DCFH-DA and Mito-SOX staining, respectively. Expression of Bcl-2, Bax, brain derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB), and cAMP response element binding (p-CREB) and active-Caspase 3 levels were evaluated by Western blot. RESULTS: It was found that ICS II, a phosphodiesterase-5 inhibitor, significantly attenuated cognitive deficits caused by Abeta25-35 injection in rats, and ICS II not only significantly enhanced the expression of BDNF and TrkB, but also activated CREB. Furthermore, ICS II also significantly abrogated Abeta25-35-induced PC12 cell injury, and inhibited Abeta25-35-induced intracellular reactive oxygen species (ROS) overproduction, as well as mitochondrial ROS levels. In addition, ICS II up-regulated the expressions of BDNF and TrkB consistent with the findings in vivo. ANA-12, a TrkB inhibitor, blocked the neuroprotective effect of ICS II on Abeta25-35-induced neuronal injury. CONCLUSION: ICS II mitigates Abeta25-35-induced cognitive deficits and neuronal cell injury by upregulating the BDNF/TrkB/CREB signaling, suggesting that ICS II can be used as a potential therapeutic agent for dementia, such as Alzheimer's disease. CI - (c) 2018 The Author(s). Published by S. Karger AG, Basel. FAU - Liu, Shuang AU - Liu S AD - Department of Pharmacology, Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China. FAU - Li, Xiaohui AU - Li X AD - Department of Pharmacology, Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China. FAU - Gao, Jianmei AU - Gao J AD - Department of Clinical Pharmacotherapeutics, School of Pharmacy, Zunyi Medical University, Zunyi, China. FAU - Liu, Yuangui AU - Liu Y AD - Department of Pharmacology, Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China. FAU - Shi, Jingshan AU - Shi J AD - Department of Pharmacology, Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China. FAU - Gong, Qihai AU - Gong Q AD - Department of Pharmacology, Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China. AD - Department of Clinical Pharmacotherapeutics, School of Pharmacy, Zunyi Medical University, Zunyi, China. LA - eng PT - Journal Article DEP - 20180907 PL - Germany TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (Amyloid beta-Peptides) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Flavonoids) RN - 0 (Peptide Fragments) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Reactive Oxygen Species) RN - 0 (amyloid beta-protein (25-35)) RN - 113558-15-9 (baohuoside I) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 3.1.4.35 (Cyclic Nucleotide Phosphodiesterases, Type 5) RN - EC 3.4.22.- (Caspase 3) RN - H2D2X058MU (Cyclic GMP) SB - IM MH - Alzheimer Disease/etiology/metabolism/*prevention & control MH - Amyloid beta-Peptides/toxicity MH - Animals MH - Apoptosis/drug effects MH - Brain-Derived Neurotrophic Factor/metabolism MH - Caspase 3/metabolism MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - Cyclic GMP/metabolism MH - Cyclic Nucleotide Phosphodiesterases, Type 5/chemistry/*metabolism MH - Flavonoids/*pharmacology MH - Hippocampus/drug effects/metabolism MH - Male MH - Maze Learning/drug effects MH - PC12 Cells MH - Peptide Fragments/toxicity MH - Proto-Oncogene Proteins c-bcl-2/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Reactive Oxygen Species/metabolism MH - Receptor, trkB/metabolism MH - Signal Transduction/*drug effects OTO - NOTNLM OT - Alzheimer's disease OT - Brain-derived neurotrophic factortyrosine receptor kinase OT - Icariside II OT - Tyrosine receptor kinase B OT - cAMP response element binding EDAT- 2018/09/10 06:00 MHDA- 2018/10/13 06:00 CRDT- 2018/09/10 06:00 PHST- 2018/01/13 00:00 [received] PHST- 2018/08/27 00:00 [accepted] PHST- 2018/09/10 06:00 [pubmed] PHST- 2018/10/13 06:00 [medline] PHST- 2018/09/10 06:00 [entrez] AID - 000493232 [pii] AID - 10.1159/000493232 [doi] PST - ppublish SO - Cell Physiol Biochem. 2018;49(3):985. doi: 10.1159/000493232. Epub 2018 Sep 7.