期刊文献+

红景天苷衍生物对抗抑郁及促学习记忆作用的影响 被引量:1

The antidepressive and ameliorating cognitive impairment effects of a salidroside amide derivative
原文传递
导出
摘要 目的通过大、小鼠体内药动学研究,寻找成药性较好的红景天苷衍生物,并采用动物体内药效模型初步评价该化合物改善学习记忆及抗抑郁的作用。方法设计并合成了一系列红景天苷酰胺衍生物(5a^5e),通过大鼠体内药代动力学研究,找到入脑迅速目标化合物(5c),后续以东莨菪碱造成大鼠记忆获得障碍模型,研究不同剂量5c(20、5、1.25 mg/kg)和红景天苷(20、5、1.25 mg/kg)对该模型大鼠学习记忆改善作用;以小鼠悬尾实验中小鼠不动时间,研究不同剂量5c(50、25、12.5 mg/kg)及红景天苷(25 mg/kg)的抗抑郁作用。结果大鼠药代动力学的成药性评价显示,单次口服给予25 mg/kg 5c后,约1.4 h达峰,生物利用度为33.3%(优于红景天苷21.8%),口服吸收后可入脑,脑/血组织中的浓度为比为2.5。在大鼠记忆获得障碍模型Morris水迷宫撤台实验测试中,5c高剂量组(20 mg/kg)及盐酸多奈哌齐组大鼠第一次上台潜伏期及第一次穿台路程较模型对照组缩短,差异具有统计学意义(P <0.05)。大鼠脑部SOD活性测定结果显示,5c高剂量组(20 mg/kg)大鼠脑部SOD活性高于空白对照组,差异具有统计学意义(P <0.05),在小鼠悬尾实验中,在给药2 h的测试时间点,5c高剂量组小鼠悬尾不动时间较空白对照组缩短,差异具有统计学意义(P <0.05)。结论通过对红景天苷进行结构改造,得到了具有良好透过血脑屏障的能力红景天苷衍生物5c,体内药效学评价结果显示:该化合物具有抗抑郁及改善学习记忆的作用,且效果优于红景天苷。 Objective A rat pharmacokinetics study was done to search for salidroside amide derivatives with better pharmaceutical properties.The effects of the screened derivatives on improving cognition and antidepression were preliminarily evaluated by animal pharmacodynamics model.Methods A series of salidroside amide derivatives were designed and synthesized(5 a^5 e).Pharmacokinetics study of the rats was used to found target compound(5 c)that can enter into brain quickly.Thereafter,a rat model of memory acquisition disorder induced by scopolamine was established to study the effects of different doses of 5 c(20,5 and 1.25 mg/kg)and salidroside(20,5 and 1.25 mg/kg)on learning and memory of the model rats.The antidepressant effects of different doses of 5 c(50,25 and 12.5 mg/kg)and salidroside(25 mg/kg)on mice were studied in tail suspension test measured as immobilization time.Results The pharmaceutical property of pharmacokinetic evaluation showed that after oral administration of 25 mg/kg 5 c,blood level reached peak at about 1.4 h,the bioavailability of salidroside was 33.3%(higher than 21.8%of salidroside).After oral administration,salidroside can be absorbed into brain and the concentration ratio of brain/blood was 2.5.In Morris water maze withdrawal test of rat model,the first incubation period and the first crossing distance of rats in high dose 5 c group(20 mg/kg)and donepezil hydrochloride group were shorter than those in model control group,and the differences were statistically significant(P<0.05).The measurement of rat brain SOD activity showed that activity of SOD in brain of rats in 5 c high dose group(20 mg/kg)was higher than that in blank control group,and the differences were statistically significant(P<0.05).In the tail suspension test of mice,two hours after administration,the tail suspension immobilization time of mice in5 c high dose group was shorter than that in blank control group,and the differences were statistically significant(P<0.05).Conclusion Salidroside has been reconstructed to develop the derivatives 5 c,that had better ability to go though bloodbrain barrier.In vivo pharmacokinetic evaluation shown that this chemical had antidepressant and ameliorating cognitive impairment effects and the efficacy was better than salidroside.
作者 李云飞 张瑱 许忻 LI Yun-fei;ZHANG Zhen;Xu Xin(Shanghai Synergy Pharmaceutical Sciences CO.,LTD,Shanghai 201203,China)
出处 《世界临床药物》 CAS 2019年第7期479-485,共7页 World Clinical Drug
关键词 红景天苷衍生物 学习记忆 抑郁 salidroside derivative cognitive depressive
  • 相关文献

参考文献6

二级参考文献88

  • 1徐建民,俞海燕.不同剂量的东莨菪碱对大鼠学习记忆能力的影响[J].苏州大学学报(医学版),2006,26(1):53-54. 被引量:14
  • 2张烨,单良,娄向新,袁崇刚.甘丙肽提高离体海马神经细胞在过氧化氢损伤中的存活率[J].分子细胞生物学报,2006,39(5):391-398. 被引量:7
  • 3袁瑜,张良,李玉锋.红景天活性成分及药理作用[J].食品与药品,2007,9(05A):54-57. 被引量:49
  • 4江湧,方永奇,邹衍衍.β-细辛醚对痴呆小鼠学习记忆能力及SOD、GSH-Px和MDA水平的影响[J].中国老年学杂志,2007,27(12):1126-1127. 被引量:30
  • 5Darbinyan V,Kteyan A,Panossian A,et al.Rhodiola rosea in stress induced fatigue-a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty[J].Phytomedicine,2000,7(5):365.
  • 6Song EK,Kim JH,Kim JS,et al.Hepatoprotective phenolic constituents of Rhodiola sachalinensis on tacrineinduced cytotoxicity in Hep G2 cells[J].Phytother Res,2003,17 (5):563.
  • 7Kucinskaite A,Briedis V,Savickas A.Experimental analysis of therapeutic properties of Rhodiola rosea L.and its possible application in medicine[J].Medicina (Kaunas),2004,40(7):614.
  • 8Mattioli L,Funari C,Perfumi M.Effects of Rhodiola rosea L.extract on behavioural and physiological alterations induced by chronic mild stress in female rats[J].J Psychopharmacol,2009,23:130.
  • 9Mattioli L,Perfumi M.Rhodiola rosea L.extract reduces stress-and CRFinduced anorexia in rats[J].J Psychopharmacol,2007,21 (7):742.
  • 10Perfumi M,Mattioli L.Adaptogenic and central nervous system effects of single doses of 3% rosavin and 1% salidroside Rhodiola rosea L.extract in mice[J].Phytother Res,2007,21 (1):37.

共引文献49

同被引文献20

引证文献1

二级引证文献16

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部