公开(公告)号：US20120029010A1

公开(公告)日：2012-02-02

申请号：US13253958

申请日：2011-10-05

申请人： Mark T. Hamann ,  Anna J. Kochanowska ,  Abir El-Alfy ,  Rae R. Matsumoto ,  Angelo Boujos

发明人： Mark T. Hamann ,  Anna J. Kochanowska ,  Abir El-Alfy ,  Rae R. Matsumoto ,  Angelo Boujos

IPC分类号： A61K31/4375 ,  A61P25/22 ,  A61K31/137 ,  A61P25/24 ,  C07D471/04 ,  A61K31/4045

CPC分类号： A61K31/135 ,  A61K31/404 ,  A61K31/4745

摘要： The sponges were collected from a variety of locations in the Florida Keys and separated based on morphology and color. The samples were identified as three species, two of which are well known: V. rigida (Esper, 1794) (order Verongida, family Aplysinidae) and S. aurea (Hyatt, 1875) (order Dictyoceratida, family Thorectidae), and a third S. cerebriformis (Duchassaing & Michelotti, 1864), is less common and separated based on subtle differences of morphology and coloration, from the other two species. Several compounds were isolated and were evaluated in established animal models predictive of neurological related drug function, namely, the rodent FST and the chick anxiety-depression model.

摘要翻译： 从佛罗里达群岛的各种地点收集海绵，并根据形态和颜色进行分离。 样品被鉴定为三种，其中两种是众所周知的：其中两种是知名的：V. rigida（Esper，1794）（Veriantida，Aplysinidae）和S.Aurea（Hyatt，1875）（Dictyoceratida，Thorectidae） 基于形态学和着色的微妙差异，其他两个物种的脑血管病（Duchassaing＆Michelotti，1864）较不常见和分离。 分离出几种化合物，并在建立的动物模型中进行评估，预测神经相关药物功能，即啮齿动物FST和小鸡焦虑抑郁模型。

公开(公告)号：US20090093513A1

公开(公告)日：2009-04-09

申请号：US12248234

申请日：2008-10-09

申请人： Mark T. Hamann ,  Anna J. Kochanowska ,  Abir El-Alfy ,  Rae R. Matsumoto ,  Angelo Boujos

发明人： Mark T. Hamann ,  Anna J. Kochanowska ,  Abir El-Alfy ,  Rae R. Matsumoto ,  Angelo Boujos

IPC分类号： A61K31/4745 ,  A61K31/404 ,  A61K31/135 ,  A61P25/00

CPC分类号： A61K31/135 ,  A61K31/404 ,  A61K31/4745

摘要： The sponges were collected from a variety of locations in the Florida Keys and separated based on morphology and color. The samples were identified as three species, two of which are well known: V. rigida (Esper, 1794) (order Verongida, family Aplysinidae) and S. aurea (Hyatt, 1875) (order Dictyoceratida, family Thorectidae), and a third S. cerebriformis (Duchassaing & Michelotti, 1864), is less common and separated based on subtle differences of morphology and coloration, from the other two species. Several compounds were isolated and were evaluated in established animal models predictive of neurological related drug function, namely, the rodent FST and the chick anxiety-depression model.

摘要翻译： 从佛罗里达群岛的各种地点收集海绵，并根据形态和颜色进行分离。 样品被鉴定为三种，其中两种是众所周知的：其中两种是知名的：V. rigida（Esper，1794）（Veriantida，Aplysinidae）和S.Aurea（Hyatt，1875）（Dictyoceratida，Thorectidae） 基于形态学和着色的微妙差异，其他两个物种的脑血管病（Duchassaing＆Michelotti，1864）较不常见和分离。 分离出几种化合物，并在建立的动物模型中进行评估，预测神经相关药物功能，即啮齿动物FST和小鸡焦虑抑郁模型。

公开(公告)号：US09439875B2

公开(公告)日：2016-09-13

申请号：US13105470

申请日：2011-05-11

申请人： Agnes M. Rimando ,  Abir El-Alfy ,  Md Al Rahim

发明人： Agnes M. Rimando ,  Abir El-Alfy ,  Md Al Rahim

IPC分类号： A61K31/09 ,  A61P25/22 ,  A61K31/075 ,  A61K31/045

CPC分类号： A61K31/075 ,  A61K31/045

摘要： We report for the first time that pterostilbene, a natural analog of resveratrol, shows anxiolytic-like action by downregulating phosphorylated levels of ERKs in the hippocampus of mice. Mice administered pterostilbene (1-10 mg/kg BW) by oral gavage were subjected to the Elevated-plus maze (EPM) test. Pterostilbene manifested anxiolytic activity at 1 and 2 mg/kg doses, demonstrated by an increase in percent permanence time and number of entries in open arms, critical determinants correlated with anxiety. This anxiolytic activity of pterostilbene was comparable to that of diazepam at 1 and 2 mg/kg in the EPM. The percent traveled distance and the percent permanence time in the enclosed arms were decreased with the 1 and 2 mg/kg doses. The 5 and 10 mg/kg doses did not show any anxiolytic effect. Locomotor activity was unaffected in all doses. Western blot analysis corroborated the observed behaviors in the EPM, revealing a decrease in both ERK1 and ERK2 phosphorylation in hippocampal homogenates from mice treated with 1 and 2 mg/kg doses; the 5 and 10 mg/kg doses showed no significant effect on the phosphorylation of ERKs. Pterostilbene was detected in serum and brain tissue following a single oral administration, demonstrating that the compound can cross the blood-brain barrier to reach the brain regions, including hippocampus, and thereby exert its anxiolytic effect. Resveratrol, the parent molecule of pterostilbene, did not have any anxiolytic effect.

摘要翻译： 我们首次报道，天冬氨酸萜烯是白藜芦醇的天然类似物，通过下调小鼠海马中ERKs的磷酸化水平显示抗焦虑样作用。 通过口服管饲法施用ter芪烯（1-10mg / kg BW）的小鼠进行升高加迷宫（EPM）试验。 Pterostilbene以1和2mg / kg剂量表现出抗焦虑活性，通过持续时间百分比增加和开放臂中的入选数量增加，与焦虑相关的关键决定因素表现出抗焦虑活性。 在EPM中，ter il烯的抗焦虑活性与1mg / kg剂量的地西泮相当。 随着1和2mg / kg剂量，随机携带的距离百分比和持久时间百分比下降。 5和10mg / kg剂量没有显示任何抗焦虑作用。 所有剂量的运动活动均不受影响。 Western印迹分析证实EPM中观察到的行为，揭示了用1和2mg / kg剂量处理的小鼠的海马匀浆中ERK1和ERK2磷酸化的降低; 5和10mg / kg剂量对ERK的磷酸化没有显着影响。 在单次口服给药后，在血清和脑组织中检测到P芪烯，表明化合物可以穿过血脑屏障到达脑区域，包括海马，从而发挥其抗焦虑作用。 白藜芦醇是ter il烯的母体分子，没有任何抗焦虑作用。

公开(公告)号：US20160067192A1

公开(公告)日：2016-03-10

申请号：US13105470

申请日：2011-05-11

申请人： Agnes M. Rimando ,  Abir El-Alfy ,  Md Al Rahim

发明人： Agnes M. Rimando ,  Abir El-Alfy ,  Md Al Rahim

IPC分类号： A61K31/09 ,  A61P25/22

CPC分类号： A61K31/075 ,  A61K31/045

摘要： We report for the first time that pterostilbene, a natural analog of resveratrol, shows anxiolytic-like action by downregulating phosphorylated levels of ERKs in the hippocampus of mice. Mice administered pterostilbene (1-10 mg/kg BW) by oral gavage were subjected to the Elevated-plus maze (EPM) test. Pterostilbene manifested anxiolytic activity at 1 and 2 mg/kg doses, demonstrated by an increase in percent permanence time and number of entries in open arms, critical determinants correlated with anxiety. This anxiolytic activity of pterostilbene was comparable to that of diazepam at 1 and 2 mg/kg in the EPM. The percent traveled distance and the percent permanence time in the enclosed arms were decreased with the 1 and 2 mg/kg doses. The 5 and 10 mg/kg doses did not show any anxiolytic effect. Locomotor activity was unaffected in all doses. Western blot analysis corroborated the observed behaviors in the EPM, revealing a decrease in both ERK1 and ERK2 phosphorylation in hippocampal homogenates from mice treated with 1 and 2 mg/kg doses; the 5 and 10 mg/kg doses showed no significant effect on the phosphorylation of ERKs. Pterostilbene was detected in serum and brain tissue following a single oral administration, demonstrating that the compound can cross the blood-brain barrier to reach the brain regions, including hippocampus, and thereby exert its anxiolytic effect. Resveratrol, the parent molecule of pterostilbene, did not have any anxiolytic effect.

摘要翻译： 我们首次报道，天冬氨酸萜烯是白藜芦醇的天然类似物，通过下调小鼠海马中ERKs的磷酸化水平显示抗焦虑样作用。 通过口服管饲法施用ter芪烯（1-10mg / kg BW）的小鼠进行升高加迷宫（EPM）试验。 Pterostilbene以1和2mg / kg剂量表现出抗焦虑活性，通过持续时间百分比增加和开放臂中的进入数量增加，与焦虑相关的关键决定因素表现出抗焦虑活性。 在EPM中，ter il烯的抗焦虑活性与1mg / kg剂量的地西泮相当。 随着1和2mg / kg剂量，随机携带的距离百分比和持久时间百分比下降。 5和10mg / kg剂量没有显示任何抗焦虑作用。 所有剂量的运动活动均不受影响。 Western印迹分析证实EPM中观察到的行为，揭示了用1和2mg / kg剂量处理的小鼠的海马匀浆中ERK1和ERK2磷酸化的降低; 5和10mg / kg剂量对ERK的磷酸化没有显着影响。 在单次口服给药后，在血清和脑组织中检测到P芪烯，表明化合物可以穿过血脑屏障到达脑区域，包括海马，从而发挥其抗焦虑作用。 白藜芦醇是ter il烯的母体分子，没有任何抗焦虑作用。

公开(公告)号：US08268856B2

公开(公告)日：2012-09-18

申请号：US13253958

申请日：2011-10-05

申请人： Mark T. Hamann ,  Anna J. Kochanowska ,  Abir El-Alfy ,  Rae R. Matsumoto ,  Angelo Boujos

发明人： Mark T. Hamann ,  Anna J. Kochanowska ,  Abir El-Alfy ,  Rae R. Matsumoto ,  Angelo Boujos

IPC分类号： A61K31/4375 ,  A61K31/4045 ,  A61K31/137 ,  C07D471/04 ,  A61P25/24 ,  A61P25/22

CPC分类号： A61K31/135 ,  A61K31/404 ,  A61K31/4745

摘要： The sponges were collected from a variety of locations in the Florida Keys and separated based on morphology and color. The samples were identified as three species, two of which are well known: V. rigida (Esper, 1794) (order Verongida, family Aplysinidae) and S. aurea (Hyatt, 1875) (order Dictyoceratida, family Thorectidae), and a third S. cerebriformis (Duchassaing & Michelotti, 1864), is less common and separated based on subtle differences of morphology and coloration, from the other two species. Several compounds were isolated and were evaluated in established animal models predictive of neurological related drug function, namely, the rodent FST and the chick anxiety-depression model.

摘要翻译： 从佛罗里达群岛的各种地点收集海绵，并根据形态和颜色进行分离。 样品被鉴定为三种，其中两种是众所周知的：其中两种是知名的：V. rigida（Esper，1794）（Veriantida，Aplysinidae）和S.Aurea（Hyatt，1875）（Dictyoceratida，Thorectidae） 基于形态学和着色的微妙差异，其他两个物种，脑血管病（Duchassaing＆Michelotti，1864）较不常见和分离。 分离出几种化合物，并在建立的动物模型中进行评估，预测神经相关药物功能，即啮齿动物FST和小鸡焦虑抑郁模型。