牡丹皮中丹皮酚的抗焦虑作用

Anxiolytic-like Effect of Active Phenolic Components from Moutan Cortex in Kunming Mice Animal Models

目的:探讨中药牡丹皮抗焦虑作用物质基础。方法:80只成年雄性昆明种小鼠随机分为空白组(Control),阳性药组(地西泮,BZ,1 mg·kg-1),牡丹皮水蒸气蒸馏馏分低、中、高剂量组(Px,50,100,200 mg·kg-1),牡丹皮蒸馏剩余药渣水提物低、中、高剂量组(Wx,100,200,400 mg·kg-1);实验依次进行自由探索模型实验(FEP)、旷场实验(OFT)、高架十字迷宫实验(EPM)、高架〇迷宫实验(EZM)和明暗箱实验(LDB);FEP实验参数包括陌生区时间百分率(Ntime%)、陌生区水平运动百分率(Ncross%)、陌生区垂直运动百分率(Nrear%)、总水平运动(Cross)和总垂直运动(Rear);OFT实验参数包括中央区时间百分率(Ctime%)、中央区水平运动百分率(Ccross%)、总水平运动(Cross)和总垂直运动(Rear);EPM和EZM实验参数包括开臂时间百分率(Otime%)、开臂进入次数百分率(Oentries%)和两臂总进入次数(Entries);LDB实验参数包括明区停留时间百分率(Ltime%)、明区水平运动百分率(Lcross%)、明区垂直运动百分率(Lrear%)、穿梭次数(Transition)、总水平运动(Cross)和总垂直运动(Rear)。结果:与Control组比较,BZ及Px低、中、高剂量可显著增加FEP_Ntime%,FEP_Ncross%,FEP_Nrear%,OFT_Ctime%,OFT_Ccross%,EPM_Otime%,EPM_Oentries%,EZM_Otime%,EZM_Oentries%,LDB_Ltime%,LDB_Lcross%,LDB_Lrear%(P<0.05);Wx仅高剂量可显著增加OFT_Ccross%,EZM_Otime%,LDB_Lrear(P<0.05);BZ及Px,Wx低、中、高剂量对FEP_Cross,FEP_Rear,OFT_Cross,OFT_Rear,EPM/EZM_Entries,LDB_Transition,LDB_Cross,LDB_Rear实验参数影响均无统计学差异。结论:牡丹皮抗焦虑作用有效部位是水蒸气蒸馏馏分(Px),即丹皮酚类成分,其可能的作用靶点是γ-氨基丁酸A受体(GABAAR)。

Objective：To explore the anxiolytic-like effect of extracts from a Chinese traditional herb,Moutan Cortex.Method：Eighty male Kunming mice were divided into eight groups：the vehicle-treated group（Control）,the diazepam-treated group（BZ,1 mg·kg-1,ip）,three phenolic component-treated groups（Px,10,20,40 mg·kg-1,ig） and three aqueous extract-treated groups（Wx,50,100,200 mg·kg-1,ig）.Behavior of mice from each group in free exploratory paradigm（FEP）,open field test（OFT）,elevated plus maze（EPM）,elevated zero maze（EZM） and light/dark box（LDB） was recorded by sequence,with a less-than twenty-second interval.The following parameters were evaluated：percentage of time spent in the FEP novel compartment（Ntime%）;percentage of number of units visited in the FEP novel area（Ncross%）;percentage of number of rears in the FEP novel area（Nrear%）;the total number of units visited in FEP（Cross）;the total number of rears in FEP（Rear）;percentage of time spent in the OFT central area（Ctime%）;percentage of number of squares visited in the OFT central area（Ccross%）;the total number of horizontal squares in OFT（Cross）;the total number of rears in OFT（Rear）;percentage of time spent in the EPM or EZM open arms（Otime%）;percentage of number of entries into the EPM or EZM open arms（Oentries%）;the total number of entries into the EPM or EZM open and closed arms（Entries）;percentage of time exploring in the LDB light area（Ltime%）;percentage of number of squares crossing in the LDB light area（Lcross%）;percentage of rears in the LDB light area（Lrear%）;the total number of transition in LDB（Transition）;the total number of horizontal squares in LDB（Cross）;the total number of rears in LDB（Rear）.Result：Compared with control group,both 1 mg·kg-1 BZ and various doses of Px treatment obviously increased the percentage of exploratory and locomotor activity in FEP novel area,such as Ntime%,Ncross%,Nrear%;in OFT central area,such as Ctime%,Ccross%;in EPM and EZM open arms,such as Otime%,Oentries%;in LDB light area,such as Ltime%,Lcross%,Lrear%.However,only 200 mg·kg-1 Wx made an enhancement in OFT Ccross%,EZM Otime % and LDB Lrear%.Meanwhile,both BZ and various doses of Px and Wx showed no effect on the total locomotor and exploratory activity,such as Cross,Rear,Entries and Transition parameters in FEP,OFT,EPM,EZM or LDB.Conclusion：The phenolic components,such as paeonol and its analogues and metabolism,from Moutan Cortex,are the major active ingredients for the anxiolytic-like effect,and they may exhibit positive allosteric effect by targeting on GABAA receptor.