中國醫藥大學機構典藏 China Medical University Repository, Taiwan:Item 310903500/25899
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(3) ¨j©. NSC 88-2314-B-039-013- 87 8 1 88 7 31 !"#$%. ¤:¥ (1¦pT. ª«Z[¬®¯p °
(4) . &'()*+,. ±[²³´µ ¶. -./. 1 ·¸¹ºa. . bcdGHIJKLh@ 0 1 2 3 4 5Black and white chambers 6 ( 789:;<=5Elevated plus-maze6>?@ABCDEFGHIJ KL@(MNOPGHQRmagnolol)(. (MNPGHQ(SGHQTUV/. SGHQRhonokiol)TUV/STWV/. (TWV/XABYZ[MXAB. >XABYZ[\Z buspirone ]^_`a. YZ& ¡n NE, DA (. bcd[e234>?@ABCD. - NE, DA, 5-HT [\kln. fg-[GHIJKLh@(MNOP. - VMA ( HVA (- VMA,. GHQ(SGHQTUV/(TWV/. HVA S 5-HIAA ¢a. ijklmno34pqrstuv34 wTUxy24pst(z4tp{|U. GHuGHQRmagnolol£(SG. }[\~o24pqrstae78. HQRhonokiol£uXABYZ. 9:;<=>?@ABCDfg-[TU V/(TWV/ijklmno. Abstract. >qrst(xypU}[~ mno >qrst(xy . In. pU}[\jkl 5-HTP, PCPA, BUS (. anxiolytic. RIT o>qrst(xyp. honokiol and magnolol after acute and. U}[~mno >qrst(x. one-week administration by black/white test. y pU}a. and elevated plus-maze. Furthermore, we. this. study, we investigated the effect. of. Magnoliae. cortex,. 8n). investigated the anxiolytic mechanism of. cd[GHQ(SGHQjn. honokiol and magnolol by combining 5-HTP,. NE, DA (- NE, DA, 5-HT . PCPA, BUS and RIT and detecting the. [\kln- VMA ( HVA . changes of monoamines in the rats’ brain. In the black/white test, the methanol. (- VMA, HVA S 5-HIAA a. extract of Magnoliae cortex, honokiol and 1.
(5) one-week. MØABÙÚpÔÕaABÛÜÝtÜÞ. administration prolonged the first time entry,. ßàáâã[xäÇYåæ[çèé. time spent in the white chamber and the total.
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(8) >Tîa. magnolol. after. acute. and. the time spent in the black chamber. In the elevated plus-maze test, the methanol extract. ABï"ð_ñoîòTóôõÙÚ. of Magnoliae cortex, honokiol and magnolol. p]ö÷ø»CD[T§ù]ï-úÑ. after. administration. ¾ûü_ñoýÍþpTѾp. prolonged the arm entries and time spent in. [
(9) ûü(?Ñ. the open arms. The honokiol and magnolol. ¾päo-ú>ö÷AB. decreased the levels of NE and DA in the. >]orbitofrontal cortexR,]. cortex, the NE, DA and 5-HT in the brain. limbic frontal lobe £ [. stem, and increased the levels of VMA, HVA. system>ö÷ prefrontal. in the cortex and the levels of VMA, HVA. cortex>. and 5-HIAA in the brain stem.. ! cortex > ü " [ # . acute. or. one-week. limbic. äoorbitofrontal cortexÜ. These results suggested that the methanol. amygdala[amygdalaT§$,]%&AB-. extract of Magnoliae cortex, honokiol and. úRfear-anxiety center£[v'T(_. magnolol. ñ>ö÷[ä. after. acute. and. one-week. administration possessed anxiolytic effect.. >Ѿ]. basolateral amygdala[)P¾v*+,>. The anxiolytic mechanism of the honokiol. HACER(medial[
(10) -.Ѿ. and magnolol were related to the decrease in. (?Ѿ[ä ûü(ño/. the levels of NE, DA in the cortex and NE,. 0>(1)aäoѾ 1@>¢ï[. DA, 5-HT in the brain stem, and the increase. 2iù]-úbenzodiazepineþ34>5. in the levels of VMA, HVA in the cortex and the levels of VMA, HVA and 5-HIAA in the. 6 7 ] 8 9 o : > -[. brain stem.. benzodiazepineþ34>56;<!=[ ¼ i ù]benzodiazepineï¾v>*?. Keywords: Magnoliae cortex, Honokiol,. (downstream)>Ѿ 1@ä@A. Magnolol, Anxiolytic effect. ö÷>YZ[obenzodiazepineBCABD E[É»amygdala>serotoninѾN [FGo*?>Ѿ 1@-[Hù. . ]serotonin]8Io5-HT agonist> »¼½¾¿ÀÁÂx[à ÄvÅ. ûJ -[KLbuspirone>XABYZ. Æà 9]ÇÈà [ÇÈÆÉÊ[Ë. ï¾vraphe>5-HT1A autoreceptors[. ÌÍÎ[ϵÐÑÒÓÔÕ Ökl[× 2.
(11) serotonergic activity [ ä M ¾ v. GH Magnolia officinalis Rehd. Et Wils.p. benzodiazepine receptors(2-3)aFGABN. Ý[u[ ô>oåa. >Oá-ú& [#oe-úlimbic. B äÙ1 ôÙ[ Õ[¡uu3±Z[°. system - >amygdalaserotonin>ÛÜÙ. >GH¡a+.z¢£. ^Pþ[äbenzodiazepine;Øt. ¤…….u[r¥u ô¦[G§¨©a. ÜQRamygdalaserotonin>Nþ a. ü-.ªZeBCABN(5)(6)a. »¼STÏZ>XAB/@[ jP. »ì/« ¬fGH-úr. UðBenzodiazepineð¡. (7)cp®¯YZ[_ strychnineu picrotoxin ( pentylenetetrazol ±/@{. non-benzodiazepineð(4)Benzodiazepine. ÉpWX°ÎprYZ[\pr. ð]»¼STPZ>XAB/@[äo. ±²ÍNûü(*+,ÍNûü. STVXWXuYZÚ[(\. (8)[M"³ 0SGH-P´L. ]^_uBC`a±YZ[boZ< Cå[9cdefYZ[. magnocurarine µ¶·¸\YZ[. Õï. magnolol ( isomagnolol -ú\]. oBCgh*[PijYZ>YZ[. µ¶YZ[MYZ& . klumn(?opqQ±-úr>. Ør¹º. »¼ 1@ glycine pYZ[_. YZaMUonon-benzodiazepineð[j. GABA ;~YZ(6)_mn´á§G. PUmðbarbituratesð(5-HT. H½ggh¾»»¼YZ[ghl. agonistsðUðBarbituratesð>YZ¡. ; ]rYZ(7)GH_¿ÀbÁ9. benzodiazepineð:[9fYZ;. (0Í9zó¨ÃÄC9iX¨. benzodiazepineðest8[u YZu. ÃÄYZ(9)[GH 50%ÅJLL@_Æ. klumn(?opqQ±-úѾr. Ç-ÅJ{ɨÈÉÃÄcrY. YZñ[_evwìxy[®zØ. ZaMNP>T. cytochrome p-450ûü;{ÉYZaä. ] magnolol (. honokiol[GHQpXÃÄ(X¨ÇPÊ. 5-HT agonists®zØ5-HT1A agonists[]. YZØËÌ-úprYZþ@A(10). :!|º(É}>XAB/[FM~. (XÍ(11)±YZaMagnolol ( honokiol. benzodiazepineð-(>fYZa. ]GHp. »¼STÏZ>XAB/@[MfYZ(. ¬f magnolol -úrYZ(12)j. [b:É}>5-HT. QO-ú serotoninergic system N[r. agonists[9 Cåä>/. -ú serotonin >Î(13 )ØTóX. @صEpDa. mÏÐÑg[j~ thromboxane O. åP[»ì/« . (ÒpÓ?(14)j¾vÎÔ?p GH[e0¾[]@. ÎFÕ(endothelium-drived releasing 3.
(12) 2. ICR ûùmn[á8 18ñ25. factor[EDRF)(rÒÖy×Ø \än. úûR Black & White(. ?Ùµ¶(15)XÉÚY. Elevated plus-mazefgZ£a. Z(16)(17)(XÍYZ(18)aÛ¢GH u[ ô>ABN²p/«YZ\ ÜÝEFa. üufgDý <1>u_þ4âRLight/dark test£>Þ. F G 0 Þ 1 2 3 4 R Black &. ß. White £ ( 7 8 9 : ; < = R Elevated. þ4âÄZeð?@AB². plus-maze£±?@ABfgCD[ßEF. pâ[GÙfgÕ [. GHIJKàh@(MNP magnolol. ] ?[} phµ]
(13) s. ( honokiol >XABYZ[áZÞß-. ]j(19)aGvmÙ¹pzfg. úѾ 1@>/@(ân-). þ[Tfg36R27X27. [1EFGHIJKàh@(. cm£[IT26R27X18 cm£Uf. MNP magnolol ( honokiol XABY. gtv47cm8p[GT. Z¡-ú serotonergic system >¢ïa\1. R7X7 cm£[ófgiM. »¼STPZpXAB/@ buspirone ]. ¹m(6pjÓ?Ï[ÏZ. ^_`[1ãäMBCååa. L9X9cmÕaófg¶M ` þ[þ4Z100W3 R °. . !. 4400lux£[4Z40W [U . Tufg/æ>çè. ´Ï37cm8aó!?@"5P#[\e. 0fgþZ>GH>éêëâ°. ó!?@"$"Ï%&÷'[fg. *. ³*(z) *(ò)a. 1. GH]@GHMagnolia. fgPTUV/(T*V/[T. officinalis Rehd. Et Wils.pÝa. UV/eGHIJKàh@(MN. GH1IJìí>[o50î*ï. Pmagnolol(honokiol1Ù¹ghPz¾. ÖLhðñòU[óUôðms[á. v+/V¡mn"T*V/ó,V/. Lh[¾~õö÷õ"[øµGH. TU[-V.,[ew.,V/mnÙ. IJKàh@a. ¹ghGHIJKàh@(MNP magnolol(honokiol "[)mn0e1. zufg?@. ¸[mnE4[£¢mn2r. 0 þÏZ>?@]. oóT4p3stueþ4tp{|U. 1. Sprague-Dawley ûùn[á8. }uwTU4 ITfgpstue. 180ñ250 úûRHPLCfgfg. U45ÌRline crossings£pU}(19)a. Z£a 4.
(14) 0fg1buspirone(25 mg/kg[p.o.)Y^_. nEDhL DGF. `[eV/20P#"x"g(20)a\¡. 0eGH-I!JKaÛ". *6@PzáZ. FP cortex ¡ brain stem z PDo5ml 0.01N HCl¡500Ll 0.1M. <2> u _ 7 8 9 : ; < =. EDTA*1i& M>Dly4 g. (Elevated. NaClD\112 ml n-butanolLhD¾. plus-maze) {ÉAB>Þß 0fg. NO´ "Dhµ n-butanol D). Ø7Pellow8e1985 É. øZeãäABp(Elevated. ly17 ml n-heptan ¡400Ll. plus-maze)[ØØ9¦:;$ÏZp?@. 0.025N HClÇPNO>D;). ABCD[Mê«. ÓyÇQPa6Rr. Ø7 ð?@. n-heptane -1 200Ll 0.2M. <=8(>tp,(21)a0v. tris-Hcl STUPRpH8.5£N. U(40?10 cm)(U (40?. OLh\´ Djµ)ìx@. 10?40 cm)[-1>^DO (10?10 cm). (26). aP´þµ)RNE[DA[. Üa fgPTUV/(T*V/[T. 5-HT£(Mìx@RHVA[VMA[. UV/eGHIJKàh@(MN. 5-HIAA£[1ñABýâ>aÏ. Pmagnolol(honokiol1Ù¹ghPz+. Z8RHPLC model. /V¡n"T*V/ó,V/T. 440, Solvent Delivery system M45£. U[-V.,[ew.,V/nÙ¹. RWaters Associates£ (L. ghGHIJKàh@(MNP. RElectrochemical Detectors LC-4B£. magnolol(honokiol"[nyfg. RBioanalytical system Inc.£â. -@[fg?@E_M-T . >aP´þZColumn]Lichrospher. [£¢nxy( 3U. 100RRP-18 endcapped,4mm?125mm£ RE.Merck 50734£DÓ?]l. }uqr>st]ãäAB(22)a. PIC B7(Waters Associates)>. fgÕ- 5P#[ó!nCâ. methanol/water ,MÖ]2.0. TU[ó20!afgst³(¤) . ml/minaP´PL@EVïÏZ. *(ò)a0fg1buspirone(25mg/kg[. Data module M730 9£¢>a. p.o.)Y^_`[eV/20P#"x"ga. <4>uáZÞß-úѾ 1@>/. <3>u_n)(Mìx@>Þ. @EFGHIJKàh@>N. ß. Pmagnolol(honokiolXABY. GHIJKàh@>NP. Z¡-úserotonergic system>¢. magnolol(honokiolV/n"D 5.
(15) ï. oU4tp{|U}ó,V/TU[. GHIJKàh@(MNP. -V.,[_mno234-wTUvþ. magnolol(honokiolV/D)¡Þß-úÑ. 4\ 4pstu2roþ4psti. ¾ 1@serotonergic system>/@Pz. ]^pYZ[ö_o4pst[kl. áZD7¦ýRDý(2)£[xfgá. oU4tp{|U}a. Z/@°*serotonin precusor--5-HTP 2u_789:;<= (Elevated plus-maze). R5u50 mg/kg[i.p.£30P#¦V/(23). {ÉAB>Þß. serotonin synthesis inhibitor--. [òu[¥bcd[GHIJLh. p-ChlorophenylalanineR200 mg/kg[ i.p.£. @R0.5[1.0 g/kg£TUV/(TWV/. 24ms¦V/(23)5-HT1A receptor. i_mno789:;<=-xy. agonist—BuspironeR0.05 mg/kg[i.p.£30. U}(stiklpYZ[¢px. P#¦V/(24)5-HT2 receptor. yU}(sti~pYZa. antagonist--RitanserinR0.01 mg/kg[ i.p.£. [ .u[¤bcd[GHQ. 30P#¦V/(25)a. Rmagnolol£(SGHQRhonokiol£TU V/i_mno789:;<=-. <5> üP. xyU}(stiklpYZ[ . 0fgþµ>} [234fg(7. pxyU}(sti~pYZa. 89:;<=[;1 non-parameter ü[ ³1 Kruskal-Wallis )FÕW}PW }[)1 Mann-Whitney U-test âMtX. 3u_n)(Mìx@>Þ. W>c[Y P me 0.05 1*s[;. ß. ù ] ü º Z a HPLC f g } 1. °[`bcd[GHQRmagnolol£. one-way ANOVA P MW}[)1. (SGHQRhonokiol£ijn. Scheffe’s multiple range test â[ü\P. NE, DA (- NE, DA, 5-HT . MtXW>c[Y P me 0.05 1. [\kln(- VMA (. *s[;ù]üºZa. HVA [- 5-HIAA a. "#$. 4uáZÞß-úѾ 1@>/. 1u_þ4âRLight/dark test£>Þß. @EFGHIJKàh@>N. v[T [ðbcd[GHIJL. Pmagnolol(honokiolXABY. h @ [ G H Q R magnolol) ( S G H Q. Z¡-úserotonergic system>¢. Rhonokiol)_mno234-wTUvþ. ï. 4\ 4pstu2roþ4psti. [:ñ[:.bcd[GHQ. ]^pYZ[ö_o4pst[kl 6.
(16) Rmagnolol£(SGHQRhonokiol£e. (U4t{|U}[s~mne4>. : ; < = f g - i j k °. qrstaGb¡0 >^_`>. buspirone(BUS) [p-chlorophenylalanine. buspironeT [cdGHKLh@[GH. RPCPA£( ritenserin(RIT){Ép. QRmagnolol)(SGHQRhonokiol£0. xyU}(qrstkl[( . XAB>YZa. x y U } ( q r s t~\aX 5-hydroxytryptophan (5-HTP) {Ép. MU[o7D:;O<={ÉAB. xyU}(qrst~[( . CD>fg-[MontgomeryoM -K. xyU}(qrstkla. L[GfgØcZdn_¸o8pD (p>t[ noFä{ÉAB. %&'. äiLßpCD. Ò34Ó. aPellow±> É. b³[o234{ÉmnABCD>. »[7D:;O<=ØTp)sq. fg-[234ØcZdnoefþgî. [jZßâ/@~XABÝ AB. òs[M0à EhAîòpÔ?_. YZ[sGCD_mn(niYZ. äiLßpCD(27)aCrawley & Goodwin. Ò 35 Ó. > É»[vdnÙjksþgî. KL[1ãädne>xyU}(. òpl[FGmLdno234- {. qrst[ëYABYZpKA. ÉU4t{|U}~uwTUv34 . ¦oPellow±> ľ¬f7D:;. þ4pst_(2ro24pst3. O<=jZßâbenzodiazepineðpXA. 4^>E][;G]jZßëAB. BNäoRodgersSCole¹¯KL[V. aoPellowuLister(Rodgers±> Ò35-37Ó. Ò28Ó. a³. aÄ KLbenzodiazepine. /diazepam(benzodiazepine!áYZg[. ð[°chlordiazepoxide(diazepam ]^m. °chlordiazepoxide(bretazenil[jþckl. noþ4>qrstäXABN[. xyU}(]^oqrst. ãäKA. GboCrawley & GoodwinuCostall(. Ò38Ó. aäbuspironeoLee & Rodgers,. Onaivi&MartinuYoung&Johnson±> . Dunn,. Kostowski(Soderpalm±"> T É. Ò28-30Ó. aIñ[buspironeoCostallu »[jklmn2roqrst( CarliuLopez-RubalcavauMisslin(Sanchez xyU}[cdbuspironeo7D. -$¬f. ±> É»[dn2roþ4>qrs. :;O<=ABCDXABYZ. Ò39-42Ó. a. Ò31-33Ó. a GHKLh@[GHQRmagnolol)(SG 0 >^_`buspirone>fgbi HQRhonokiol)jklmno>qr. t]^[äo4qrst ö_. ¡ ³¦Crawley(Costall±> bT. st(xyU}[cdGHKLh@[G. aäGHKLh@(GHQRmagnolol). HQRmagnolol)(SGHQRhonokiol)0. (SGHQRhonokiol)j]^mnwTUv. XAB>YZa. þ4\ 4pstueþ4>qrst 7.
(17) veö÷¡*e-rsûüp. gbcdGHQRmagnolol£(SGHQ. Ѿ@(° 5-HTuNEuDA ±)(M. Rhonokiol£ijn NE, DA . Ò43Ó. ìx@pthuÙjPp¢ï. a$. (- NE, DA, 5-HT [\kl. vKL 5-HT ÛÜ|y- {ÉA. n(- VMA ( HVA [. B@A[ä~- 5-HT >; @. - 5-HIAA a j } G H Q. AXABYZÒ44-46ÓMU[- DA Ì. Rmagnolol£(SGHQRhonokiol£>X. eÝ locus coeruleus > NE Ѿ$Ns¨. ABYZ[jpn NE, DA . AB>@A. Ò 47 Ó. aGñ[1990 . (- NE, DA, 5-HT [\kln. Golembiowska KL ipsapirone >XABY. (- VMA ( HVA [-. Zؾv~ 5-HT p turnoverrate[kl. 5-HIAA a. NEuDA > tumover rate þ. Ò 48 Ó. . : ߢe?@]SBCABN. 5-HT1A. ÔÕp cd[serotonergic system on. autoreceptors ( ~ Ѿw 5-HT p. oSABö÷]pQR34T8>. turnover rate [ x ä~x raphe _ locus. 56a~ serotonergic system N[. coeruleus >>[ϵ NE Ѿyz@A. @AXABYZkl serotonergic. r (disinhibition) Y Z [ \kl NE >. system N; @AABYZ (53,54)a. turnover rateÒ49Ó substantia nigra -p. BerendsenuBroekkamp ( Sanchez ± . DA Ѿ¨! raphe Ѿ{p>[ëG>. cd[5-HT ¶ð9!á¡?@AB C. $ Ipsapirone rs[substa nigra -p. D-{ÉAB>]i¢(55)[FG[. DA Ѿyz¨ @ArYZ[s DA. 0 á Z. > turnover rate ¨kl>»|avGj}. R5-hydroxytryptophan; 5-HTP£[5-HT A. - 5-HTuNEuDA ±)Ѿ 1@. rgRp-chlorophenylalanine; PCPA£. ¡Mìx@>oABp@A¡. 5-HT1A åg (° buspirone; BUS)u. ipsapirone. ¾ v N . 5-HT. ¦ Ô @. Ò50ÓÒ51Ó. a)Õ[ 5-HT2 aXg (ritanserin; RIT) ± 5-HT ! 0þxþ~± KL[ë- á>aXgÝ åg[\1789:;< BC34T8>56. NEuDA >~( NEuDA turnover. =Y]{ÉmnABCD[xTEF. rate kls[- 5-HTuNEuDA >. 5-HT !áoGHQ(SGHQXABY. ~( 5-HTuNEuDA turnover rate. Zþ34>56[xTþMXABY. kls[ @AYZYZ. Ò52Ó. aFG[0. Z>YZ& a. xTcZA@Dý(8. bÛ 5-HT1 receptors P7:[9. ý)EFGHQRmagnolol£(S. ]oe{(dorsal raphe nucleus ). GHQRhonokiol£_fg?@(. 5-HT yzáÀ¦> 5-HT1A Ü!á. -)(Mìx@>>Þß[f. (5-HT1A presynaptic receptors) []Tó 8.
(18) autoreceptors. Ý , ]. somatodendritic. 5-HT2 receptors). oeou*. autoreceptors 5-HT1A À " Ü ! á. +,S{±¸aRIT ] 5-HT2 >aX. (5-HT1A postsynaptic receptors) ;ØÑ-. g[V/ 1 mg/kg s ]^mno34. o limbic system ( hippocampus S. >qrstäö_o24>qrst(59)a. (56,57). a N À ¦ 5-HT1A. 0 ÏZÙÞßmno24>qrst. autoreceptors jryz> firing rate[x. (34>qrst> RIT (0.01 mg/kg; i.p.). ä~ 5-HT pѾ 1/>[N. ¡GHQ(SGHQáZfgbc. À" 5-HT1A !á;. rsûü. d[GHQ(SGHQjk° RIT o. pѾNra. pqrst(xyU}[\ö_ . amygdala). pqrst(xyU}a j}[GH. Ä}À¦ 5-HT1A autoreceptors (. Q(SGHQ>XABYZ¡E 5-HT2. À"p 5-HT1A receptors ¡ 5-HT1A. !á>N¨¢a. ågÝ 5-HT1 aXgb"[ N. 1bcd[GHIJLh. Ą Gi protein [ä K Ë[. @(GHQ(SGHQÙ o234Ý7. ÏѾyzÉÌ7[xä~ 5-HT Ѿ. D:;O<={ÉmnAB±CD-i. ä c L X A B N (24) a BUS ]. þc>XABYZaGHQ(SGHQ. 5-HT1A > åg[ghs¡ 5-HT. YZ& jp¡NÀ¦ 5-HT1A !. ѾÀ¦> 5-HT1A autoreceptors b. á[À" 5-HT1A ( 5-HT2 !á>. "[ 5-HT Ѿ ~(rs. N[xä~- 5-HT > turnover. 5-HT ѾN[~ 5-HT >(. rate þa\¡n NE, DA . turnover rate[ä@AXABYZ(58)ave. (- NE, DA ¢a. Cosall ± KL BUS e 0.06ñ2.0 mg/kg (i.p.) sXABYZ(30)FG[0 ©. ()*+. ZÙÞßmno24(34qrst>g. 1.. h> BUS (0.05 mg/kg; i.p.)ßSGHQ(S. Robert B. Graham: Physiological psychology. Wadsworth Publishing. GHQáZfgbÉ»[GHQ(S. Company, Belmont, California, A. GHQjkl 5-HTP[BUS ( PCPA o. Division of Wadsworth, Inc.. pqrst(xyU}[\ö_ . 1990;517-24.. pqrst(xyU}acdGHQ(. 2.. SGHQ>XABYZjp¡ 5-HT >A. Meller E, Goldstein M, Bohmaker K: Receptor reserve for 5-hydroxytry. (»¼À¦SÀ" 5-HT1A !á. ptamine1A-mediated inhibition of. ¢a. serotonin synthesis: Possible relatioship. À"p 5-HT2 !á (Postsynaptic. to anxiolytic properties of 5-hydroxytryptamine1A agonists. Mole 9.
(19) 3.. Pharmacol 1990;37:231-7.. Yamamoto N, Yoshizaki M: Studies on. Carli M, Prontera C, Samanin R:. the active principles of magnolia bark.. Evidence that central. Centrally acting muscle relaxant activity. 5-hydroxytryptamine neurons are. of magnolol and honokiol. Jpn J. involved in anxiolytic activity of. Pharmacol 25(5):605-7, 1975.. buspirone. Br J Pharmacol Exp Ther 4.. 5.. 13. Tsai TH, Lee TF, Chen CF, Wang LC:. 1989;96:829-36.. Modulatory effects of magnolol on. Rang HP, Dale MM: Anxiolytic and. potassium-stimulated. hypnotic drugs. In: Pharmacology,. 5-hydroxytryptamine release from rat. Churchill Livingstone Inc., New. cortical and hippocampal slices. Neurosci. York,1991,628-41.. Let 186(1):49-52, 1995.. Wang JP, Ho TF, Chang LC, Chen CC:. 14. Teng CM, Chen CC, Ko FN, Lee LG,. Anti-inflammatory effect of magnolol,. Huang TF, Chen YP, Hsu HY: Two. isolated from Magnolia officinalis, on. antiplatelet agents from Magnolia. A23187-induced pleurisy in mice.. officinalis. Thrombosis Research.. Journal of Pharmacy & Pharmacology.. 50(6):757-65, 1988.. 47(10):857-60, 1995. 6. 7. 8.. 15. Teng CM, Yu SM, Chen CC, Huang YL,. rSGH(Pp/«a/. Huang TF: EDRF-release and. Ë20(9): 522-524[1985a. Ca+(+)-channel blockade by magnolol, an. â-/»ì ¡ST0Z[. antiplatelet agent isolated from Chinese. LÃ[[492-496[1993a. herb Magnolia officinalis, in rat thoracic. H: GHp ¡ST0Za--. aorta. Life Sci 16. Wang JP.. Hsu MF.. Raung SL.. £¤¥u¦§¨u©ª«u¬j§u. Chen CC.. Kuo JS.. Teng CM:. GH(M®¯°_nÂfg. Anti-inflammatory and analgesic effects. ¨ÃÄpYZa-±/22(11):. of magnolol. N-S Arch Pharmacol 346(6):. /¡¢ 15(8): 55-57[1990. 9.. 47(13):1153-61, 1990.. 707-12, 1992.. 509-510[1991a. 17. Wang JP, Raung SL, Chen CC, Kuo JS,. 10. rS±ñ.-.-/P². Teng CM: The inhibitory effect of. (1): 54[1981a. magnolol on cutaneous permeability in. 11. Namba T, Tsunezuka M, Hattori M:. mice. Dental caries prevention by traditional. is. probably. mediated. by. a. nonselective vascular hyporeactivity to. chinese medicine. J Med Plant res 44:. mediators. N-S Arch Pharmacol 348(6):. 100-106, 1982.. 663-9, 1993.. 12. Watanabe K, Watanabe HY, Goto Y,. 18. ³´µ-/åP/«¡0Za2 10.
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(23) DG: 5-HT1A agonists reduce 5-hydroxytryptamine release in rat Ti me spen t i n the wh it e (sec). 250. hippocampus in vivo as determined by brain microdialysis. Brit J Pharmacol 1989 ; 96: 283-290.. ***. 200. ***. 150. ** **. **. *** **. 100. 50. 59. Barnes NM, Cheng CH, Costall B, Ge J,. 0. Kelly ME, Naylor RJ: Profiles of Ti me spen t i n the bl ack (sec .). 300. interaction of R(+)/S(-)-zacopride and anxiolytic agents in a mouse model. Eur J Pharmacol 1992 ; 218: 91-100.. 250 200. ***. ***. **. **. 1000. 0.5. **. ***. 2.5. 1. **. 150 100 50 0. Control. BUS. 500. Ho pu. (A) 1 day. 5 (mg/kg) MAG. HO N. Fi rst time en try (sec.). 50. ***. ***. 40. ***. Fig 2. Effects of Hopu, magnolol (MAG) and honokiol (HOL) on the time spent in the white and black chambers of black and white test in mice. **P < 0.01,***P < 0.001 as compared with the control group (K rus kal-Wallis H followed by Mann-Whitney U test).. ***. ***. 30. **. 20 10 0. (B) 7 da ys. 60 50 40 30. ***. ***. ***. ***. ***. *** ***. 2 50. Time s pent in t he whi te (sec). First ti me e ntry (se c.). 70. 20 10 0. C ontrol BU S. 5 00. 1 000. H opu. 0.5. 2.5. HO N. 1.0. 5 .0 (mg/kg). MA G. **. 1 50. ***. ***. **. * **. 2 00. ** *. 1 00. 50. 0 300. Time spent in t he black (s ec.). Fig 1. Effects of Magnoliae cortex (Hopu), honokiol (HON ) and magnolol (MA G) after one day (A ) and seven days (B) adminis tration on the first time entry from white to black chambers in the black and w hite tes t. **P < 0.01, ***P < 0.001 as compared w ith the control group (Krus kallWallis H test follow ed by M ann-Whitney U -test).. 250 200. ** *. ** **. 150. * **. ***. ** *. 100 50 0. Control. BUS. 500. 1000. Hopu. 1. 5 MAG. 0.5. 2.5 (mg/kg). HOL. F ig 3. Effects of Hopu, honokiol (HON) and magnolol (MAG) after 7 days administration on the time spent in the white and black chambers of black and white test in mice. BUS: buspirone. **P < 0.01, ***P < 0.001 as compared with the control group (Kruskal-Wallis H followed by Mann-Whitney U test).. 14.
(24) 40 30. 10 0 80 60 40. ***. 50. 12 0. **. Ti me spent i n the cl ose da rms (se c). *** ***. *** ***. 60. **. 20. 10. ** *. 0. 20. 120. 0. Control. BUS. 500. 1000 Hopu. 0.5. 2.5. 1.0. HON. 5.0 (mg/kg). MAG. Fig 4. Effects of Magnoliae cortex (Hopu), honokiol (HON) and magnolol (MAG) after one day and seven days administration on thetotal changes between the two chambers in the black and white test. **P < 0.01,***P < 0.001 as compared with thecontrol group (Krus kallWallis H test followed by Mann-Whitney U-test).. 100. *. Ti me spent i n the ope na rms (se c). Total changes between two c ompart ments. 70. *** ** * *** ***. ** * * **. 1 day 7 days. 80 60 40 20 0. Control. 0.5. 1.0. 0.5. 1.0 (g/kg). HopuMeOH Acute. **. 100. C losed a rm Open a rm s. **. ***. 60. 40. ***. Cl osed a rm Open a rm s. 60. 20. 50. 0.5. 1.0 (g/kg ). Hop uMe OH Ac ut e. 7 days. 40. ***. 1.0. 30. *. 0.5. ***. Con tro l. **. 0. Arm entries. Arm entries. 80. 7 days. Fig 6. Effects of methanol extract of Magnoliae cortex (Hopu) on the time-spent in the open arms and closed arms of elevated-plus maze in mice. *P < 0.05, **P < 0.01, ***P < 0.001 as compared with the control group (Krus kall-Wallis H tes t followed by Mann-Whitney U test). 20. F ig 5 . Effects o f methanol extract of M agnoliae cortex (H opu) on the arm entries in the elevated-p lu s maze in mice. * *P < 0.01, * **P < 0.001 as compared w ith the co ntrol gr oup ( Onew ay A NO V A followed by Scheffe's test). 10. 0. C ontrol. 0.5. 2 .5 HON. 1.0. 5.0 (mg /k g) M AG. F ig 7 . Effects o f h onokiol (HO N ) and magno lo l (M AG ) on th e arm en tr ies in the elevated -plus maze in mice. * P < 0.05, * *P < 0.01, ***P < 0 .00 1 as compared w ith the con tr ol g roup (O neway A NO VA follo wed by S ch eff e's tes t). 15.
(25) 60. Closed arms Open arms. 300. 50. 200. **. ** *. 250. 20. * **. 50. ** *. 0. ***. 10. 40. 0. 30. Control. 5-H TP. 5-H TP+ H OL 5 -HTP +M A G. 20. F ig 10. Effects of honok io l (H ON ) and magn olol (M A G) on the 5 -HTP induced arm entries in th e elevated plus -maze in mice. ** *P < 0.001 as compared with th e control grou p (O new ay A NO V A followed by S ch effe's tes t).. 10 0. Control. 0.5. 2.5. 1.0. HO N. 5.0 (mg/kg) M AG. Fig 8. Effects of honokiol (HO N) and magnolol (MA G) on the time-spent in the closed arms and open arms of elevated-plus maze in mice. **P < 0.01,***P < 0.001 as compared with the control group (Oneway A NOVA follow ed by Scheffe's test) T ime spent in close d arms (s ec). 3 00 2 50 2 00 1 50. ***. T ime spent i n the ope na rms (sec ). 30. ***. 50. ***. Arm entries. 100. ***. 40. 150. 1 00. **. Time spe nt in the closed arms (sec). 350. 50. Control HON 2.5 mg/ kg M AG 5 mg/ kg. 500 0. *** ***. 0. NE. DA. 5-HT. NE. DA. 5-HT. Brai n stem. Ce rebral Co trex. 1 00. **. T ime spent in open a rm s (sec ). ** **. 100 0. *** ** *. 200 0. *** ***. 300 0. ***. 1 20. 400 0. ** **. Levels of monoamines (ng/g ti ssue). 0 600 0. 80 60 40 20. ***. Control. ** ** *. 150 0. 100 0 50 0 0. VMA. H VA. 5-HIAA. C erebral Co tre x. VMA. H VA. 5 -HTP. 5 -HTP +H ON. 5- HTP+ M AG. Fig 11. Effects of h onokiol (HO N) and mag nolol (M AG ) on the 5-H TPinduced time-s pent in the clo sed arms and open arms in the elevated plus -maze in mice. ** P < 0.01, *** P < 0.001 as compared with th e control g roup (K rus kall-Wallis H test followed by Mann- Whitney U test).. *. **. 200 0. *** ** *. 250 0. * ** ** *. Le vel s ofmonoamines's met aboli tes (ng/ gt issue). 0 300 0. 5-HIA A. Bra in ste m. Fig 9. Effects of magnolol (M AG) and honokiol (H ON) on the levels of monoamine and its metabolites in the cerebral cortex or brain stem of rats. *P < 0.05, **P < 0.01, ***P < 0.001 as compared with the control group, respectively (Oneway ANO VA follow ed by Scheffe's test).. 16.
(26) C lose d arms Open a rms. ***. 60. 30 20. 10. 10. **. **. 20. *. 30. 40. *. **. Arm entries. 40. **. 50. 50. Arm entries. ***. Cl ose d arms Ope n arms. 60. 0. Control. 0. Control. PC PA. HO N. B US +H ON. BU S+ M AG. MA G. Fig 12. Effects of honokiol (HO N) an d magnolol (M AG ) on the PCP Ainduced arm entries in the elev ated p lus -maze in mice. **P < 0.01, ** *P < 0.0 01 as compared w ith the control gro up (O neway AN OV A followed by Scheffe' s test).. Fig 14. Effects of honokiol (HO N) and magnolol (M A G) on the bus pironeindu ced arm entries in the elevated plus -maze in mice. * P < 0.05, **P < 0.0 1, ***P < 0.0 01 as compared with the control g roup (On ew ay AN OV A followed by Scheffe's test).. 30 0. 3 00. T ime spent in the c losed a rms (sec ). T ime spent in the c losed a rms (se c). BU S. 25 0 20 0 15 0. ***. 10 0. **. 50 0. 2 50 2 00 1 50. ***. **. 1 00 50 0. Time spe nt in the ope n arms (se c). 1 00. T ime spent in the open a rms (se c). 1 20. **. 1 00. **. 80 60 40. *** 80. **. 60. 40. 20. 0. 20. Control. 0. Control. P CPA. H ON. BU S. BUS + HO N. BU S+ M AG. F ig 15. Eff ects of honokiol (HO N) and mag nolol (M AG ) on the busp iro neind uced time-s pent in th e clo sed arms and open arms in the elevated plu s-maze in mice. **P < 0.05, ** *P < 0.01 as compared with the control gro up (Krus kall-Wallis H tes t followed by Mann- Wh itney U test).. M AG. Fig 13. Effects of h onokiol (H O N) and magnolol (MA G) on the P CPA indu ced time-sp en t in the clos ed arms and open arms in the elevated plus -maze in mice. ** P < 0.01, ***P < 0.00 1 as compared w ith the control group (K rus kall-Wallis H test follow ed b y M ann-Whitney U test).. 17.
(27) ***. 70. C lose d arms Open a rms. 60. Arm en tries. ***. 50 40 30 20. *. *. 10 0. Control. RIT. RIT+ HO N. RIT+ MA G. Fig 16. Effects of h onokiol (H O N) and magno lol (M AG ) on the r itanserininduced arm entries in the elevated plus-maze in mice. *P < 0.0 5, ***P < 0 .00 1 as compared w ith the con tro l group (O neway A NO VA follow ed by S ch eff e's test).. Ti me spent i n the cl osed a rms (sec ). 3 00 2 50 2 00. ***. 1 50. **. 1 00 50 0. Time spent in the open arms (se c). 10 0. **. 80. *. 60. 40. 20. 0. Control. RIT. RIT+HON. RIT+ MAG. F ig 17. Effects of honokiol (HON ) and magnolol (MAG ) on the ritanserininduced time-s pent in the clos ed arms and open arms in the elevated plus -maze in mice. *P < 0.05, **P < 0.01, ***P < 0.001 as compared with the control group (Kruskall-Wallis H test followed by M ann-Whitney U tes t).. 18.
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