一、葛根素之腦血流測定
如圖四所示，葛根素經腹腔注射給與，僅在 50 mg/kg 劑量 下達到最高腦血流，時間為 30 分鐘。
Fig 4. Effects of puerarin (25 and 50 mg/kg, i.p.) on the changed cerebral blood flow rate of middle cerebral artery measured by laser Doppler flowmetry in rats. ∗∗∗ p< 0.001, compared with the vehicle group.
Time (min)
10 20 30 40 50 60
∆ cerebral blood flow rate (ml/min/100 g tissue)
-10 0 10 20 30
40 Vehicle
Puerarin 25 mg/kg Puerarin 50 mg/kg
*** *** ***
二、葛根素對誘發被動迴避學習反應障礙物質之影響
Fig 5. Effects of puerarin (PUR, 10, 25 and 50 mg/kg, i.p.) on scopolamine (SCOP, 1 mg/kg)-induced acquisition impairment of the passive avoidance response in rats. Each
Step through latency (sec)
0
Step through latency (sec)
0
column represents the medain, and the range inside 5th and 95th percentile.
如圖六所示，PUR(10、25、50 mg/kg)經腹腔注射給藥後，對 SCOP(0.5 mg/kg，i.p.) 誘發之大鼠學習獲得障礙，不具改善作用。
Fig 6. Effects of puerarin (PUR, 25 and 50 mg/kg, i.p.) on scopolamine (SCOP) at
subdose (0.5 mg/kg)-induced acquisition impairment of the passive avoidance response in rats.
Each column represents the medain, and the range inside 5th
Step through latency (sec)
0 100 200 300
(16)
(12) (12)
(12)
VEH VEH 25 50 PUR (mg/kg) SCOP 0.5 mg/kg
Step through latency (sec)
0 100 200 300
(16)
(12) (12)
(12)
VEH VEH 25 50 PUR (mg/kg) SCOP 0.5 mg/kg
and 95th percentile.
2、PUR 對 PCA 誘發被動迴避學習反應障礙之影響
如圖七所示，訓練前 30 分鐘給予 PCA(5 mg/kg，i.p.)，可縮短大鼠 在明室之滯留時間，誘發大鼠學習獲得障礙。PUR(10、25、50 mg/kg，) 經腹腔注射給藥後，僅於 25、50 mg/kg 劑量下，對 PCA(5 mg/kg，i.p.) 誘 發之大鼠學習獲得障礙，具改善作用(p<0.001)。
Fig 7. Effects of puerarin (PUR, 10, 25 and 50 mg/kg, i.p.) on p-chloroamphetamine
(PCA, 5 mg/kg)-induced consolidation impairment of the passive avoidance response in rats.
Each column represents the median, and the range inside the 5th and 95th percentile.
∗∗∗
Step through latency (sec)
0 100 200 300
(16)
(12) (12)
(14)
(16)
VEH VEH 10 25 50 PUR (mg/kg) PCA 5 mg/kg
***
***
p<0.001, compared with PCA/VEH group.
3、PUR 對 MK-801 誘發被動迴避學習反應障礙之影響
如圖八所示，訓練前 30 分鐘給予 MK-801(0.1 mg/kg，i.p.)
，可縮短大鼠在明室之滯留時間，誘發大鼠學習獲得障礙。PUR(10、25、
50 mg/kg)經腹腔注射給藥後，僅於 25、50mg/kg 劑量下，對 MK-801(0.1 mg/kg ，i.p.) 誘發之大鼠學習獲得障礙，具改善作用(p<0.05)，且於 50mg/kg 之劑量下作用較佳(p<0.01)。
Fig 8. Effects of puerarin (PUR, 10, 25 and 50 mg/kg, i.p.) on MK-801 (0.1 mg/kg)-induced
Step through latency (sec)
0 100 200 300
(16)
(10) (10)
(12)
(10)
VEH VEH 10 25 50 PUR (mg/kg) MK-801 0.1 mg/kg
*
**
acquisirion impairment of the passive avoidance in rats. Each column represents the median, and the range inside 5th and 95th percentile.
∗ p<0.05, ∗∗ p<0.01, compared with
MK-801/VEH group.4、PUR 對 MECA 誘發被動迴避學習反應障礙之影響
如圖九所示，訓練前 30 分鐘給予 MECA(10 mg/kg，i.p.)，可縮短大 鼠在明室內之滯留時間，誘發大鼠學習獲得障礙。PUR(10、25、50 mg/kg，) 經腹腔注射給藥後，對 MECA(5 mg/kg，i.p.) 誘發之大鼠學習獲得障礙，
具改善作用(p<o.oo1)。
Fig 9. Effects of puerarin (PUR, 10, 25 and 50 mg/kg, i.p.) on mecamylamine (MECA, 10
Step through latency (sec)
0 100 200 300
(16)
(14) (12)
(14)
(14)
VEH VEH 10 25 50 PUR (mg/kg) MECA 10 mg/kg
***
***
*
mg/kg)-induced acquisition impairment of the passive avoidance response in rats. Each column represents the median, and the range inside the 5th and 95th percentile. ∗∗∗ p<0.001, compared with CXM/VEH group.
5、PUR 對 CXM 誘發被動迴避學習反應障礙之影響
如圖十所示，訓練後立即給予 CXM(1.5 mg/kg，s.c.)，可縮短大鼠 在明室之滯留時間，誘發大鼠記憶鞏固障礙。PUR(10、25、50 mg/kg，) 經腹腔注射給藥後，僅於 25、50 mg/kg 劑量下，對 CXM(1.5 mg/kg，s.c.) 誘發之大鼠記憶鞏固障礙，具改善作用(p<0.001)。
Fig 10. Effects of puerarin (PUR, 10, 25 and 50 mg/kg, i.p.) on cycloheximide (CXM,
Step through latency (sec)
0
Fig 10. Effects of puerarin(PUR, 10, 25 and 50 mg/kg, i.p.) on cycloheximide (CXM, 1.5 mg/kg)-induced consolidation impairment of the passive avoidance response in rats. Each column represents the median, and the range inside the 5th and 95th percentile. *** p < 0 . 0 0 1 , c o m p a r e d w i t h C X M / V E H g r o u p .
***
***
Step through latency (sec)
0
Step through latency (sec)
0
1.5 mg/kg)-induced consolidation impairment of the passive avoidance response in rats. Each column represents the median, and the range inside the 5th and 95th percentile. ∗∗∗ p<0.001, compared with CXM/VEH group.
三、葛根素對 cycloheximide 誘發被動迴避學習反應障礙 物質之機轉
1、如圖十一所示，PUR(25 mg/kg)經腹腔注射給藥後，對 CXM (1.5 mg/kg，s.c.) 誘發大鼠記憶鞏固障礙之改善作用，可 被 SCOP(0.3 mg/kg，i.p.)部分拮抗(p<0.05)。
Fig 11. Effects of puerarin (PUR, 50 mg/kg, i.p.) plus scopolamine (SCOP, 0.3 mg/kg) on cycloheximide (CXM, 1.5 mg/kg)-induced consolidation impairment of the passive avoidance
Step through latency (sec)
0 100 200 300
(16)
(12) (14)
(10)
(10)
VEH SCOP VEH PUR PUR+SCOP CXM 1.5 mg/kg
***
**
a
reponse in rats. Each column represents the median, and the range inside 5th and 95th percentile.
∗∗ p<0.01, ∗∗∗ p<0.001, compared with CXM/VEH group. a p<0.05, compared with
PUR/CXM group.2、如圖十二所示，PUR(50 mg/kg)經腹腔注射給藥後，CXM (1.5 mg/kg，s.c.) 誘發大鼠記憶鞏固障礙之改善作用，
可被 MECA(3 mg/kg，i.p.)部分拮抗(p<0.01)。
Fig 12. Effects of puerarin (PUR, 50 mg/kg, i.p.) plus mecamylamine (MECA, 3
mg/kg) on cycloheximide (CXM, 1.5 mg/kg)-induced consolidation impairment of the passive avoidance response in rats. Each column represents the median, and the range inside the 5th and
Step through latency (sec)
0 100 200 300
(16)
(12) (14)
(10)
(10)
VEH MECA VEH PUR PUR+MECA CXM 1.5 mg/kg
***
**
aa
95th percentile.
∗∗ p<0.01, ∗∗∗ p<0.001, compared with CXM/ VEH group. aa p<0.01,
compared with PUR/CXM group.3、如圖十三所示，PUR(50 mg/kg)經腹腔注射給藥後，對 CXM (1.5 mg/kg，s.c.) 誘發大鼠記憶鞏固障礙之改善作用，
可被 PCA(1 mg/kg，i.p.)所拮抗(p<0.001)。
Fig 13. Effects of puerarin (PUR, 50 mg/kg, i.p.) plus p-chloroamphetamine (PCA, 1 mg/kg) on cycloheximide (CXM, 1.5 mg/kg)-induced consolidation impairment of the passive avoidance response in rats. Each column represents the median, and the range inside the 5th and 95th percentile. ∗∗∗ p<0.001, compared with CXM/VEH group. a p<0.005, compared with PUR/CXM group.
Step through latency (sec)
0 100 200 300
(16)
(12) (14)
(10)
(12)
VEH PCA VEH PUR PUR+PCA CXM 1.5 mg/kg
***
***
a
4、如圖十四所示，PUR(50 mg/kg)經腹腔注射給藥後，對 CXM
(1.5 mg/kg ， s.c.) 誘 發 大 鼠 記 憶 鞏 固 障 礙 之 改 善 作 用 ， 無 法 被 8-OH-DPAT(0.025 mg/kg，i.p.)所拮抗(p<0.01)。
Fig 14. Effects of puerarin (PUR, 50 mg/kg, i.p.) plus 8-OH-DPAT (DPAT, 0.025 mg/kg) on cycloheximide (CXM, 1.5 mg/kg)-induced consolidation impairment of the passive avoidance response in rats. Each column represents the median, and the range inside the 5th and 95th percentile. ∗∗∗ p<0.001, compared with CXM/VEH group.
Step through latency (sec)
0
Step through latency (sec) ***
0
5、如圖十五所示，PUR(50 mg/kg)經腹腔注射給藥後，對 CXM
(1.5 mg/kg，s.c.) 誘發大鼠記憶鞏固障礙之改善作用，可被 DOI(0.02 mg/kg，i.p.)所拮抗(p<0.01)。
Fig 15. Effects of puerarin (PUR, 50 mg/kg, i.p.) plus DOI (0.02 mg/kg) on cycloheximide
(CXM, 1.5 mg/kg)-induced consolidation impairment of the passive avoidance response in rats.
Each column represents the median, and the range inside the 5th and 95th percentile.
∗∗∗
p<0.001, compared with CXM/VEH group. aa p<0.01, compared with PUR/CXM group.
Step through latency (sec)
0 100 200 300
(16)
(12) (14)
(10)
(12)
VEH DOI VEH PUR PUR+DOI CXM 1.5 mg/kg
***
aa
6、如圖十六所示，PUR(50 mg/kg)經腹腔注射給藥後，對 CXM (1.5 mg/kg，s.c.) 誘發大鼠記憶鞏固障礙之改善作用，
可被 PRO(3 mg/kg，i.p.)所拮抗(p<0.01)。
Fig 16. Effects of puerarin (PUR, 50 mg/kg, i.p.) plus propranolol (PROP, 3 mg/kg) on cycloheximide (CXM, 1.5 mg/kg)-induced consolidation impairment of the passive avoidance reponse in rats. Each column represents the median, and the range inside the 5th and 95th percentile.
∗∗∗ p<0.001, compared with CXM/VEH group. aa p<0.01, compared with
PUR/CXM group.Step through latency (sec)
0 100 200 300
(16)
(12) (14)
(10)
(12)
VEH PROP VEH PUR PUR+PROP CXM 1.5 mg/kg
***
aa
7、如圖十七所示，PUR(50 mg/kg)經腹腔注射給藥後，對 CXM (1.5 mg/kg，s.c.) 誘發大鼠記憶鞏固障礙之改善作用，
可被 PHE(0.01 mg/kg，i.p.)所拮抗。
Fig 17. Effects of puerarin (PUR, 50 mg/kg, i.p.) plus phenoxybenzamine (PHE, 0.3 mg/kg) on cycloheximide (CXM, 1.5 mg/kg)-induced consolidation impairment of the passive avoidance response in rats. Each column represents the median, and the range inside the 5th and 95th percentile. ∗∗∗ p<0.001, compared with CXM/VEH group.
a p<0.05, compared with PUR/CXM group.
Step through latency (sec)
0 100 200 300
(16)
(12) (14)
(10) (16)
VEH PHE VEH PUR PUR+PHE CXM 1.5 mg/kg
***
a
五、 雙側腦部 Dorsal raph 區投與 serotonergic neurotoxin
Fig 18. Effects of puerarin (PUR, 1, 5, 10 and 25 µg/ 20µl, i.c.v.) on cycloheximide (CXM, 1.5 mg/kg)-induced consolidation impairment of the passive avoidance response in rats. Each column represents the median, and the range inside the 5th and 95th percentile.
∗∗ p<0.01, ∗∗∗
p<0.001, compared with CXM/VEH group.
如圖十九所示，PUR(5、10
µ
g/20µ
l)於腦室給藥，在 5,7-DHT(4µ
g/2µ
l/side)破壞 dorsal raphe 後，對 CXM(1.5 mg/kg，s.c.) 誘發大鼠記Fig 19. Effects of puerarin (PUR, 5 and 10 µg/20 µl, i.c.v.) on cycloheximide (CXM, 1.5 mg/kg)-induced consolidation impairment of the passive avoidance response in sham operated or dorsal raphe lesioned rats induced by 5,7-DHT (4 µg/2 µl/side). Each column represents the median, and the range of the 5th and 95th percentile. *** p < 0.001, compared with CXM/VEH group.
Step-through latency (sec)
五、雙側腦部 locus coeruleus 區投與 noradrenergic neurotoxin 6-OHDA 對葛根素改善學習記憶之影響
如圖二十所示，PUR(5、10
µg/20 µl)於腦室給藥，在 6-OHDA(4 µg/2 µ
l/side)破壞 locus coeruleus 後，對 CXM(1.5 mg/kg，s.c.) 誘發大鼠 記憶鞏固之障礙，只在 10µ
g 劑量下具改善作用(p<0.01)，但仍比假手術 組的改善作用明顯下降。Fig 20. Effects of puerarin (PUR, 5 and 10 µg/20 µl, i.c.v.) on cycloheximide (CXM, 1.5 mg/kg)-induced consolidation impairment of the passive avoidance response in sham operated or locus coeruleus (LC) lesioned rats induced by 6-OHDA (4 µg/2 µl/side). Each column represents the median, and the range inside the 5th and 95th percentile. ∗∗∗ p<0.001, compared with CXM/VEH group. aaa p<0.001, compared with PUR/CXM group.
Step-through latency (sec)
六、側腦室投與 cholinergic neurotoxin AF64A 對葛根素 改善學習記憶之影響
如圖二十一所示，於側腦室給予 AF64A(3 nmole/ml per brain)後可 誘發大鼠學習記憶障礙。PUR(5、10
µ
g/20µ
l)於腦室給藥後，對 AF64A(3 nmole/ml per brain)誘發之大鼠學習記憶障礙，僅於 10µ
g/2 0µ
l 劑量 下具改善作用(p<0.01)。Fig 21. Effects of puerarin (PUR, 5 and 10 µg/20 µl, i.c.v.) on AF64A (3 nmol/3 µl)-induced consolidation impairment of the passive avoidance response in rats. Each column represents the median, and the range inside the 5th and 95th percentile. ∗∗ p<0.01, compared with
AF64A/VEH group.
Step-through latency (sec)
0 200 400 600
(12)
(12)
(20)
(14)
VEH VEH 5 10 PUR (µg/20 µl, i.c.v.) AF64 A 3 nmol/3