中國醫藥大學機構典藏 China Medical University Repository, Taiwan:Item 310903500/25971

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(7) DE 123!0 12ghiJ}~ NE, DA {|. wA NE, DA, 5-HT {|34HIiJ}~A. Black and white chambers. 5-HT {|9.

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(9) . )*+,-)./+,012342 buspirone 56789 :;<=3>?@ A3. Abstract. B !"#$%&'(C 0.1. 0.5 g/kg DE3)*+, )./+,FGHI. In this study, we investigated the anxiolytic effect. &JCKLMNOPQEPRS)*T. of Coptis rhizome and berberine after acute and. UKNO VOKWX*Y34Z[\C. one-week administration by black/white test and. KLMNO9>

(10) . elevated plus-maze, the sedative effect of Coptis. ?@A3)*+,] )./+,]FGHI&J. rhizome and berberine after acute and one-week. C^_`LMNO TU^_`K*Y3Z[&. administration by hexobarbital-induced hypnosis and. JCab`LMNO TUa_`K*Y9. locomotor. . B &'(C 0.5 g/kg DE3)*+,. investigated the sedative mechanism of berberine by. )./+,FGHI hexobarbital cdefNO. combining APO, n -MT, LD+BEZ, PCPA and. ghiJjdQE9&'( 0.5 g/kg Gk0. 5-HTP, and the anxiolytic and sedative mechanisms. APO3LD+BEZ PCPA cdQEHIl4H. of the berberine by detecting the changes of. mn -MT 5-HTP cdQEZ[9. monoamines in the rats’ brain.. activity. detection.. Furthermore,. we.

(11) opqrstuviJwxyz{|<. In the black/white test, the methanol extract of. =3&'( 0.1 0.5 g/kg GghiJ}~ NE, DA. Coptis rhizome and berberine after acute and. {| wA NE, DA, 5-HT {|34HIiJ}. one-week administration prolonged the first time. ~A 5-HT {|9. entry, time spent in the white compartment and the. :;<=. B !". total changes between the two compartments, shorten. $%&'()*+, )./+,>hDE. the time spent in the black compartment. In the 1.

(12) elevated plus-maze test, the methanol extract of. )*+,-(./01234567. Coptis rhizome and berberine after acute and. 89*:;<=>?-()@ABCD1. one-week administration prolonged the entries and. EFG(/1HIJKLM NOPQ. time spent in the open arms. The methanol extract of. R36S9* LMT$UVW. Coptis rhizome and berberine at higher dose after. XY-Z[\6]^_(`a$. acute and one-week administration prolonged the. bc/deef$ghi&R-j. hexobarbital-induced sleeping time in mice and. k(1)$ lmn&,opqr

(13) . decreased the locomotor activity in the rats. The. (protoberberine type alkaloids; berberine,. hypermotilities induced by APO, LD+BEZ and PCPA. palmatine) (2)$stuvwxy %&. were. z (3) {D|(4) }~(5) . decreased. by. the. berberine. and. the. hypomotilities induced by HAL and 5-HTP were augumented. by. the. berberine.. The. (6) (7)PR$. berberine.

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(16) !|RK. NE, DA and 5-HT in the brain stem, and increased. D . the levels of 5-HT in the cortex. These results suggested that the methanol extract. D| D ¡&. of Coptis rhizome and berberine after acute and. ¢$

(17) &£R¤¥¦. one-week administration possessed anxiolytic and. §¨o©§ª«$¬&¢ _/d. sedative effects. The sedative mechanism of the. -.®/¯*k°!uR±. berberine was related to the decrease in the. ²³&´µ$¶·vw¸F¹Nº»Black. catecholaminergic system activity and the increase in. & White) ¼ { ½ ¾ ¿ À Á » Elevated. the serotonergic system activity. The anxiolytic. plus-mazeÂP¡. mechanism of the berberine was related to the. ÇÈÉÊ. decrease in the levels of NE, DA in the cortex and NE,. RBsÌÍÎÏR*. DA, 5-HT in the brain stem, and the increase in the. ÐÑ®-jÒÓÔÕ-jÒÓÖ{*ÒÓ. levels of 5-HT in the cortex.. ×Ø&ÙÚ<H*R3 diazepam?. yÃÄÅÆ´µ &,pË.

(18) *. ¶·vwÛ´µ ÇÈÉÊ Keywords: Coptis rhizome, Berberine,. pË. Antianxiety.

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(67) 0.10.5 g/kgÒÓ×!¥¦. ¦ NE DA * tumover rate Ï42?#. U®/wy*bø,i}õûp. locus coeruleus NE !=Øå. üÈÔ òÊ. raphe =!4344A ipsapirone.

(68) %&. (3 5-HT NE DA P). !Ó&1!p!¢Ý37$. Ø# 5-HT1A autoreceptors üÜ. *R$. = 5-HT ! turnover rateiAü raphe à locus coeruleus *© NE. ¶¹Nº¼yÅ¾¿½ÀÁkl * ¡j. =ê(disinhibition)R±. * ¡ ëhexobarbitalk. ¥¦ NE * turnover rate4546 ?B substantia. UÄÅ3¡ ij¡. . nigra ! DA =Ü raphe =!.

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(70) . DA * turnover rate Ü&¥¦*s. 0.1 g/kgÒÓ×ÐõÐQPà$Ul. $#·!á 5-HT NE DA P«. ¡Óhexobarbitalkl*Hø,½ú. ¬=g 7. Klt. ýC*ª®.

(71) !K-jÐ. n*!). medicinal herbs. Journal of. 38-4147. $ZIÏ "#$Pvw. Ethnopharmacology 1986; 15: 279-288.. õ;ôà NE DA *ýCüÜ. 4. Chen HC, Hsieh MT: Hemodynamic. NE DA % turnover rate ¥¦øá. effects of "san-huang-hsieh-hsin-tang" in. 5-HT NE DA *ýCüÜ 5-HT NE. patients with essential hypertension.. DA % turnover rate ¥¦øØÙÚ. American Journal of Chinese Medicine. R 48 $¶·vwiÐ&£R. 1986; 14: 51-58.. . ({Áû4»Â'()´µ. 5. Takase H, Imanishi K, Miura O, Yumioka.

(72) 0.10.5 g/kg àyÃ¡ àá. E: A possible mechanism for the gastric. «¬lt. mucosal protection by oren-gedoku-to. *ýCª*

(73) y. (OGT), a traditional herbal medicine.. ÃÒÓÈÔ

(74) 0.10.5 g/kg 2SPY. Japanese Journal of Pharmacology 1989;. 3!üÜàá4 NE DA *ýC. 51: 17-23.. á 5-HT *ýC±¥¦à 5-HT !. 6. Yamahara J: Behavioral pharmacology of. ýC$!)

(75) 0.1 g/kg ÒÓ×*. berberine-type alkaloids. (1) Central. R!¤ß$Uà NE, DA ýC. depressive action of Coptidis rhizoma and. á NE, DA, 5-HT ýC±¥¦$U. its constituents. Nippon Yakurigaku Zasshi. à 5-HT ýC&¢$. 1976; 72; 899-908.. *ùFÒÓÈÔ òÊ. 7. Kumazawa N, Ohta S, Tu SH,.

(76) 3% È*ÙÚR. Kamogawa A, Shinoda M: Protective. lR·!¤Kß$Uà NE, DA. effects of various methanol extracts of. ýCá NE, DA, 5-HT ýC±¥¦. crude drugs on experimental hepatic injury. $Uà 5-HT ýC&¢$. induced by alpha-naphthylisothiocyanate in rats YakugakuZasshi 1991; 111: 199-204.. . 8. Griebel G, Moreau JL, Jenck F, Misslin R, Martin JR Acute and chronic treatment. 1. Tang W, Eisenbrand G: Chinese Drugs of Plant Origin. Pp.362-371, Springer Verlag,. with 5-HT reuptake inhibitors differentially. Berlin, Heidelberg, New York, 1992.. modulate emotional responses in anxiety. 2. Lee MK, Kim HS: Inhibitory effects of. models in rodents. Psychopharmacology 1994; 113: 463-470.. protoberberine alkaloids from the roots of. 9. Ogawa N, Hara C, Takaki S: Anxiolytic. Coptis japonica on catecholamine biosynthesis in PC12 cells. Planta Medica. Activity of SC-48274 compared with those. 1996; 62: 31-34.. of buspirone and diazepam in experimental anxiety models. Japan J Pharmacol 1993;. 3. Franzblau SG, Cross C: Comparative in. 61: 115-21.. vitro antimicrobial activity of Chinese 8.

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(80) . 60. First time entry (sec.). *** 40. ***. ***. ** *. 20. 0. Control. 0.1. 0.5. CRMeOH ext.. 0.1. 0.5 (g/kg) 2 (mg/kg). Berberine. BUS. Fig 1. Effects of methanol extract of Coptis rhizome (CRMeOH ext.), berberine and buspirone (BUS) after acute treatment on the first time entry in black and white compartment in mice. *P < 0.05, **P < 0.01, ***P < 0.001 as compared with the control group (Kruskal-Wallis H following by Mann-Whitney U test).. 12.

(81) Time spent in white compartment (sec.). ***. 200. ***. *** ***. 150. ***. 100. 50. 0. Time spent in black compartment (sec.). 300. 250. ***. 200. *** 150. ***. ***. ***. 100. 50. 0. Control. 0.1. 0.5. CRMeOH ext.. . 0.1. 0.5 (g/kg) 2 (mg/kg). Berberine. BUS. Fig 2. Effects of methanol extract of Coptis rhizome (CRMeOH ext.) berberine, and buspirone (BUS) after acute treatment on the time spent in white and black compartments of black and 13 < 0.001 as compared with the white test in mice. ***P control group (Kruskal-Wallis H following by Mann-Whitney U test)..

(82) Total changes between two compartments (counts). ***. 60. 50. ***. **. 0.1. 0.5. ***. **. 40. 30. 20. 10. 0. Control. BUS. CRMeOH ext. 0.1. 0.5 (g/kg). Berberine. Fig 3. Effects of buspirone (BUS), methanol extract of Coptis rhizome (CRMeOH ext) and berberine on the total changes between two compartments in the Black & white test in mice. **P < 0.01, ***P < 0.001 as compared with the control group (Oneway ANOVA following by Scheffe test). . 14.

(83) 50. ***. First time entry (sec.). 40. ***. 30. ** *. 20. 10. 0. Control. 0.1. 0.5. CRMeOH ext.. 0.1. 0.5 (g/kg). Berberine. Fig 4. Effects of methanol extract of Coptis rhizome (CRMeOH ext.) and berberine after one-week administration on the first time entry from white to black in black & white test in mice. *P < 0.05, **P < 0.01, ***P < 0.001 as compared with the control group. (Kruskal-Wallis H following by Mann-Whitney U test). . 15.

(84) Time spent in white compartment (sec.). 250. 200. ***. ***. *** ***. 150. 100. 50. 0. Time spent in black compartment (sec.). 300. 250. 200. ***. 150. ***. ***. ***. 100. 50. 0. Control. 0.1. 0.5. CRMeOH ext.. . 0.1. 0.5 (g/kg). Berberine. Fig 5. Effects of methanol extract of Coptis rhizome (CRMeOH ext.) and berberine after one-week administration on the time spent in the white and black compartments in black & white test in mice. ***P < 0.001 as compared with the control group (Kruskal-Wallis H following by Mann16 Whitney U test)..

(85) Total changes between two compartments (counts). 60. ***. 50. **. **. **. 40. 30. 20. 10. 0. Control. 0.1. 0.5. CRMeOH ext.. 0.1. 0.5 (g/kg). Berberine. Fig 6. Effects of methanol extract of Coptis rhizome (CRMeOH ext.) and berberine after one week administration on the total changes between two compartments in black & white test. **P < 0.01, ***P < 0.001 as compared with the control group (One-way ANOVA following by Scheffe test). . 17.

(86) . ***. 80 70. Time spent Entries. ***. 30. **. 20 10. **. ***. 40. **. ***. 50. ***. ***. 60. ***. Time spent (sec.) and entries in open arms. 90. 0. Control. BUS. CRMeOH ext.. 0.1. CRMeOH ext. BER. 0.5. 0.1. BER. 0.5 (g/kg). Fig 7. Effects of buspirone (BUS, 2 mg/kg), methanol extract of Coptis rhizome (CRMeOH ext.) and berberine (BER) on the time spent and entries in open arms during 5 mins in mice. **P < 0.01, ***P < 0.001 as compared with the control group, respectively (One-way ANOVA following by Scheffe test).. 18.

(87) . **. 20. **. ***. 30. ***. ***. 40. ***. 50. **. 60. ***. Time spent Entries. ***. 70. ***. Time spent (sec.) and entries in open arms. 80. 10 0. Control. BUS. CRMeOH ext.. 0.1. CRMeOH ext. BER. 0.5. 0.1. BER. 0.5 (g/kg). Fig 8. Effects of buspirone (BUS, 2 mg/kg), methanol extract of Coptis rhizome (CRMeOH ext.) and berberine (BER) after one-week administration on the time spent and entries in open arms during 5 mins in mice. **P < 0.01, ***P < 0.001 as compared with the control group, respectively (One-way ANOVA following by Scheffe test).. 19.

(88) . 70 60. ***. Onset Duration. **. Time (mins). 50 40 30 20 10 0. Control. CRMeOH ext. CRMeOH ext. BER. 0.1. 0.5. 0.1. BER. 0.5 (g/kg). Fig 9. Effect of methanol extract of Coptis rhizome (CRMeOH ext.) and berberine (BER) on the hexobarbital-induced hypnosis in mice. **P < 0.01, ***P < 0.001 as compared with the control group. (One-way ANOVA following by Scheffe test).. 20.

(89) Onset 120. ***. ***. 140. Duration. Times (mins). 100 80 60 40 20 0. Control. CR MeOH ext CR MeOH ext. Ber. Ber. Fig 10. Effect of methanol extract of Coptis rhizome (CR MeOH ext) and berberine after one-week administration on the hexobarbital-induced hypnosis in mice. ***P < 0.001, as compared with the control group. (One-way ANOVA followed by Scheffe test). . 21.

(90) Acute One week. 2000. ***. 1500. 1000. ***. *** **. Locomotor activity counts /30 min. 2500. 500. 0. Control. CRMeOH ext CRMeOH ext. BER. 0.1. 0.5. 0.1. BER. 0.5 (g/kg). Fig 11. Effect of methanol extract of Coptis rhizome (CRMeOH ext.) and berberine (BER) after acute or one-week administration on the locomotor activity in rats. **P < 0.01, ***P < 0.001 as compared with the control group, respectively. (One-way ANOVA following by Scheffe test). . 22.

(91) Locomotor activity counts /30 min. ***. ***. 5000. 4000. 3000. 2000. ***. 1000. 0. Control. BER. APO APO/BER. AMT. AMT/BER LD+BEZ LD+BEZ/BER. Fig 12. Effects of berberine (BER, 0.5 g/kg) on the changes of apomorphine (APO, 3 mg/kg)-, α-methyl-p-tyrosine (AMT, 100 mg/kg)-, and l-dopa plus benserazide (LD+BEZ)induced locomotor activities. ***P < 0.001 as compared with the APO and AMT group, respectively. (One-way ANOVA following by Scheffe test). . 23.

(92) *** Locomotor activity counts /30min. 3500 3000 2500. ***. 2000 1500 1000 500 0. Control. BER. 5-HTP 5-HTP/BER PCPA. PCPA/BER. Fig 13.Effects of berberine (BER, 0.5 g/kg) on the changes of 5-hydroxytryptophan (5-HTP, 50 mg/kg)- and p-chlorophenylalanine (PCPA, 200 mg/kg)-induced locomotor activities in rats. ***P < 0.001 as compared with 5-HTP and PCPA group, respectively. (Oneway ANOVA following by Scheffe test).. 24.

(93) 4000. **. 2000. **. 2500. *** ***. 3000. *** ***. Control BER 0.1 g/kg BER 0.5 g/kg. *** ***. 500. ***. 1000. ***. 1500. * ***. Concentration (ng/g tissue). 3500. 0. NE. DA. 5-HT. Cerebral Cotrex. NE. DA. 5-HT. Brain stem. Fig 14. Effect of BERBERINE (0.1, 0.5 g/kg) on the monoamines' levels in the cortex and brain stem of rats. **P < 0.01, ***P < 0.001as compared with the control group, respectively. (unpaired Student's t-test).. 25.

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