...4 EHPL,2:1 6 1... 6 1.1.....6 1.2.. 6 1.3......6 2......7 2.1.. 7 2.1.1. 7 2.1.2. 7 2.2....7. 7 3......8 3.1....8 3.2...11 3.3...12 4... 13 (EHPL, 2:1). 13 1.....13 1.1....14 1.2....14 1.3...14 2....14 2.1..14 2.2..15 3....15 1
3.1...15 3.2 EHPL...17 4... 19....19 1.... 19 1.1....19 1.2....20 1.3......20 2....20 2.1.....20 2.2... 20 2.3......20 2.4... 21 2.5.......21 2.6......22 3....23 3.1.....23 3.2... 24 3.3......24 3.4... 24 3.5.......25 3.6......29 4.......35. 35 1... 35 1.1....35 1.2....35 1.3.. 35 2....35 2
2.1......35 2.2......36 2.3......36 3...37 3.1.... 37 3.2.... 38 3.3.... 38 4... 39.. 40.. 44 1:. 45 2:. 50.... 55.... 70.... 72.... 73 3
,Hypericum perforatum L HPL St. John s wort, SJW hypericin, hyperforin pseudohypericin, EHPL [1] [2][3] (Lysine hydrochloride) 1:1,2:1,1:2 1 Herpes simplex virus, HSV-1 (Varicella-Zoster virus, VZV) : 2:1( ) HSV-1 VZV VZV Post-herpetic trigeminal neuralgia,phn PHN Human immunodeficiency virus HIV [4] HIV [5] HIV PHN 4
5
EHPL,2:1 1. 1.1 Extract of Hypericum perforatum L, EHPL, 1605795 3 Lysine hydrochloride, 010605 01130 Indomethacin, 020730 Aspirin,, 0005564, carboxymethylcellulose sodium CMC-Na, 970826 20021209 990728 2:1, 0.25% CMC 0.25% CMC 0.25% CMC 1.2. ICR 18 22 g 20 2, 1 12 SCXK -0004 1.3. AB104-N Mettler-Toledo HH.BII420 50µl 6
2. 2.1 [6] 2.1.1 5 125mg/kg 250mg/kg 500mg/kg CMC 5mg/kg (ip) (ig) 7 7 7 1 0.92% ( )20µl 0 5 15 30 4 [7] 2.1.2 5 125mg/kg 250mg/kg 500mg/kg CMC 10mg/kg (ip) (ig) 7 7 30 l 6mm 2.2 [8][9][10] 5 125mg/kg 250mg/kg 500mg/kg CMC ( ) 300mg/kg (ig) 50mg/kg 2.7 2.8mg 6mm, 12 h 12h 7
60 24h mg( )/10g( ) s Excel-2000 t, p<0.05 3. 3. 1 Table 1 Analgesic effects of Laijinsi on the formaldehyde-induced nociceoptive response in mice ( s, n=10) group dose 0~5min 15~30min mg/kg/d Time(sec) Inhibition(%) Time(sec) Inhibition(%) 7d ig Vehicle (0.25%CMC) 27.24 13.55 43.31 21.54 Morphine 5 (ip) 1d 12.04 4.12 *** 55.80 5.59 4.82 *** 87.09 Laijinsi 125 18.66 15.45 31.50 23.07 19.65 * 46.73 250 19.12 10.51 29.81 17.71 21.50 * 59.11 500 18.25 7.51 33.00 8.10 12.53 ** 81.30 *p<0.05, **p<0.01 and ***p<0.001 vs vehicle; Student s t-test. 8
the time of licking the hind paw(sec) 70 60 50 40 30 20 10 0 cmc *** *** morphine5 Laijinsi125 * Laijinsi250 * Laijinsi500 ** 0~5min 15~30min group(mg/kg) *p<0.05,**p<0.01 and ***p<0.001,vs vehicle ;Student's t-test. Fig. 1 Analgesic effects of Laijinsi in formaldehyde-induced nocicepetive response in mice( s,n=10)., 125mg/kg, 250mg/kg, 500mg/kg 15~30 0~5 9
Table 2 Anti-inflammatory effects of Laijinsi on the formaldehyde-induced paw edema in mice ( s,n=10) group Dose(ig) Weight edema Inhibition(%) Vehicle (0.25%CMC) (mg/kg/d 7d) (mg) 34.29 14.86 morphine 5 (i.p) 1d 17.93 14.33 * 47.11 Laijinsi 125 16.08 14.85* 53.11 250 18.08 11.64* 47.27 500 14.75 6.17** 56.98 *p<0.05 and **p<0.01, vs vehicle; Student s t-test. 60 50 weight edema(mg) 40 30 20 * * * ** 10 0 cmc morphine5 125 250 500 group(mg/kg) *p<0.05 and **,p<0.01,vs vehicle ;Student's t-test. Figure 2. Anti-inflammatory effects of Laijinsi on the formaldehyde-induced paw edema in mice ( s,n=10) 10
2 2 125mg/kg, 250mg/kg, 500mg/kg 3.2 Table 3 Anti-inflammatory effects of Laijinsi on xylene-induced mice ear edema ( s, n=10) group Dose Weight edema inhibition mg/kg/d 7d ig mg Vehicle (0.25%CMC) 10.18 3.27 Indomethacin 10 (i.p) 1d 2.51 3.32*** 75.35 Laijinsi 125 6.49 1.81** 36.25 250 5.02 2.50*** 50.69 500 5.32 3.25** 47.74 **p<0.01and ***p<0.001, vs vehicle, Student s t-test 15 12 weight edema mg) 9 6 *** ** *** ** 3 0 cmc indo10 125 250 500 Laijinsi group(mg/kg) **p<0.01 and ***p<0.001, vs vehicle ;Student s t-test. 11
Fig. 3. Anti-inflammatory effects of Laijinsi on xylene-induced mice ear edema ( s, n=10). 3 3 CMC 125mg/kg 250mg/kg 500mg/kg 250mg/kg 50.69% ip (75.35%) 3.3 mice.( Table 4 Anti-inflammatory effects of Laijinsi on slip-induced granuloma in group s,n=10) Vehicle (0.25%CMC) dose (mg/kg/d 7d,ig) index of granuloma proliferation(mg/10g) 15.65 4.38 Aspirin 300 11.56 3.04* 26.14 Laijinsi * p<0.05 vs vehicle, Student s t-test. 125 11.09 4.34* 28.64 250 11.14 4.25* 28.81 500 11.17 2.89* 29.22 inhibition 25 index of granuloma proliferation(mg/10g) 20 15 10 5 * * * * 0 CMC aspirin300 Laijinsi125 Laijinsi250 Laijinsi500 group(mg/kg) *p<0.05 vs vehicle, Student s t-test 12
Fig. 4. Anti-inflammatory effects of Laijinsi on slip-induced granuloma in mice.( ±s,n=10) 4 4 CMC 500mg/kg 250mg/kg 125mg/kg LD 50 1.1g/kg [11] LD 50 (11.73g/kg) 4. (EHPL,2:1) 1. 1. 1 Extract of Hypericum perforatum L, EHPL, 1605795 3 Lysine hydrochloride,, 010605 Aspirin,, 0005564, carboxymethylcellulose sodium CMC-Na,,970826,Evan s, 20021209 910103, Sigma 2:1 0.25% CMC 0.25% CMC 0.25% CMC 13
1.2. ICR 18 22 g 20 2 1 12 SCXK -0004 1.3. 1mL AB104-N Mettler-Toledo TU-1800 721 Lingli LDZ5-2 2. [12][13] 2.1 5 125mg/kg 250mg/kg 500mg/kg CMC 300mg/kg (ig) 7 1h 1% Evan s 0.1mL/10g 0.6% 0.1mL/10g, 20min 6mL 3 0.1 ml 0.1N NaOH 10mL 2 h 721 590nm A A Evan s [14][15] 2.2 500mg/kg EHPL166mg/kg 333mg/kg 666mg/kg CMC 300mg/kg( ) ig 7 7 1 2% ( )50µl 4 2.5mL 1h 3000rpm/min 15min 0.5mL 0.5mol/L KOH- 2mL 50 20min 5mL UV-754 278nm A A PGE 2 14
s Excel-2000 t, p<0.05 3. 3 1 Table 5 Inhibitory effect of Laijinsi on acetic acid-induced increase of vascular permeability in mice.( s,n=10) group Dose capillarity inhibition % (mg/kg/d 7d, ig) permeability (A) Vehicle 0.134 0.041 (0.25%CMC) aspirin 300 0.073 0.018** 45.49 Laijinsi 125 0.101 0.030 24.18 250 0.094 0.036* 29.97 500 0.096 0.033* 28.20 *p<0.05 and **p<0.01,vs vehicle Student s t-test 15
0.2 capillarity permeability A 0.18 0.16 0.14 0.12 0.1 0.08 0.06 0.04 0.02 ** * * 0 cmc aspirin300 laijinsi125 group(mg/kg) laijinsi250 Laaijinsi500 *p<0.05 and **p<0.01 vs vehicle Student s t-test. Fig. 5. Inhibitory effect of Laijinsi on acetic acid-induced vascular permeability in mice.( s,n=10) 5 5 500mg/kg 250mg/kg therapeutic index TI (TI=LD 50( )/ED 50( )) 16