Icariside II, a Phosphodiesterase-5 Inhibitor, Attenuates Beta-Amyloid-Induced Cognitive Deficits via BDNF/TrkB/CREB Signaling
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 (A...
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| Format: | Article |
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Cell Physiol Biochem Press GmbH & Co KG
2018-09-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | https://www.karger.com/Article/FullText/493232 |
| _version_ | 1818384079382380544 |
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| author | Shuang Liu Xiaohui Li Jianmei Gao Yuangui Liu Jingshan Shi Qihai Gong |
| author_facet | Shuang Liu Xiaohui Li Jianmei Gao Yuangui Liu Jingshan Shi Qihai Gong |
| author_sort | Shuang Liu |
| collection | DOAJ |
| description | 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 (Aβ25-35) 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 Aβ25-35-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 Aβ25-35 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 Aβ25-35-induced PC12 cell injury, and inhibited Aβ25-35-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 Aβ25-35-induced neuronal injury. Conclusion: ICS II mitigates Aβ25-35-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. |
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| id | doaj.art-ac9496ce7fe94a1d839b8f8c5f751815 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-14T03:16:33Z |
| publishDate | 2018-09-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
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| spelling | doaj.art-ac9496ce7fe94a1d839b8f8c5f7518152022-12-21T23:19:07ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-09-014931010102510.1159/000493232493232Icariside II, a Phosphodiesterase-5 Inhibitor, Attenuates Beta-Amyloid-Induced Cognitive Deficits via BDNF/TrkB/CREB SignalingShuang LiuXiaohui LiJianmei GaoYuangui LiuJingshan ShiQihai GongBackground/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 (Aβ25-35) 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 Aβ25-35-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 Aβ25-35 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 Aβ25-35-induced PC12 cell injury, and inhibited Aβ25-35-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 Aβ25-35-induced neuronal injury. Conclusion: ICS II mitigates Aβ25-35-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.https://www.karger.com/Article/FullText/493232Icariside IIAlzheimer’s diseaseBrain-derived neurotrophic factortyrosine receptor kinaseTyrosine receptor kinase BcAMP response element binding |
| spellingShingle | Shuang Liu Xiaohui Li Jianmei Gao Yuangui Liu Jingshan Shi Qihai Gong Icariside II, a Phosphodiesterase-5 Inhibitor, Attenuates Beta-Amyloid-Induced Cognitive Deficits via BDNF/TrkB/CREB Signaling Cellular Physiology and Biochemistry Icariside II Alzheimer’s disease Brain-derived neurotrophic factortyrosine receptor kinase Tyrosine receptor kinase B cAMP response element binding |
| title | Icariside II, a Phosphodiesterase-5 Inhibitor, Attenuates Beta-Amyloid-Induced Cognitive Deficits via BDNF/TrkB/CREB Signaling |
| title_full | Icariside II, a Phosphodiesterase-5 Inhibitor, Attenuates Beta-Amyloid-Induced Cognitive Deficits via BDNF/TrkB/CREB Signaling |
| title_fullStr | Icariside II, a Phosphodiesterase-5 Inhibitor, Attenuates Beta-Amyloid-Induced Cognitive Deficits via BDNF/TrkB/CREB Signaling |
| title_full_unstemmed | Icariside II, a Phosphodiesterase-5 Inhibitor, Attenuates Beta-Amyloid-Induced Cognitive Deficits via BDNF/TrkB/CREB Signaling |
| title_short | Icariside II, a Phosphodiesterase-5 Inhibitor, Attenuates Beta-Amyloid-Induced Cognitive Deficits via BDNF/TrkB/CREB Signaling |
| title_sort | icariside ii a phosphodiesterase 5 inhibitor attenuates beta amyloid induced cognitive deficits via bdnf trkb creb signaling |
| topic | Icariside II Alzheimer’s disease Brain-derived neurotrophic factortyrosine receptor kinase Tyrosine receptor kinase B cAMP response element binding |
| url | https://www.karger.com/Article/FullText/493232 |
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