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1 대한한방내과학회지제 27 권 1 호 (2006 년 3 월 ) Korean J.Orient.Int. Med. 2006:27(1): Effect of Sojukgunbihwan granule on Gastric Motility in Rats Jong-hee Hong, Sang-hyub Yoon, Jin-sung Kim, Bong-ha Ryu Background & Objective : The herbal medicine Sojukgunbihwan granule has been used for the treatment of functional dyspepsia, generally categorized as a gastric dysmotility disease. However, its mechanisms are not yet well known. Therefore, the effects of Sojukgunbihwan granules on gastric motility in rats was investigated. Methods : The myoelectrical activity of the gastric smooth muscle was recorded by a bipolar electrode placed at the gastric antrum of rats. The contractile waves were measured for 30 minutes before and after intragastric administration of each solution(normal saline, Pyungwisan 40 /, Sojukgunbihwan granules 60 / ) and expressed as the motility index. Gastric emptying was measured by the number of glass beads expelled from the stomach(containing one hundred 1 glass beads) within an hour after glass beads and test drugs(normal saline, Pyungwisan 40 /, Pyungwisan 120 /, Sojukgunbihwan granules 60 /, Sojukgunbihwan granules 180 / ) were administered. In another series of experiments to evaluate the mechanisms of Sojukgunbihwan granules under delayed conditions, the rats were treated with atropine sulfate(1 /, s.c.), cisplatin(10 /, i.p.), and NAME(N G -nitro-l-arginine methyl ester, /, s.c.) respectively. Results : Intragastric administration of Sojukgunbihwan granules increased the myoelectrical activity significantly, gastric motility index rose 25%, and gastric emptying of glass beads was significantly enhanced over a period of 60minutes. Under the delayed gastric emptying induced by atropine sulfate, cisplatin, and NAME, Sojukgunbihwan granules aggravated gastric emptying in the atropine sulfate(5.71±3.45 vs 3.71±4.42) and cisplatin(13.86±3.53 vs 5.14±5.05, p<0.01) treated groups, but enhanced gastric emptying in the NAME treated group(5.00±3.21 vs 11.71±5.65, p<0.05). Conclusions : Results suggest that Sojukgunbihwan granules stimulate gastric motility through cholinergic and 5-hydroxytryptamine 3 receptors. Results are indicative of Sojukgunbihwan as an especially effective remedy in dysmotility-like functional dyspepsia with impaired reservoir functions such as gastric adaptive relaxation.,,, , 1 3 (Tel , Fax sandrock58@nate.com),.,,,,,,,,,, 2.,. 3, 4, 5, 6

2 , 7,8. (succussion splash), 9. 25%,, (,,,,,, ) 10,11.,, 12.,,, 13-6, 17,18.,..,. 1) g ( ). (, Co.) 12. 2),. Table 1, 2, 1 (SJ ) 3.g, (PW ) 2.5g. atropine sulfate, N G - nitro-l-arginine methyl ester(name) Sigma, cisplatin. 1) protocol ( 60 /, 40 / ) 1, , (NS), 1 (PW-1), 1 (SJ-1) , 60 2 section. (NS), 1 (PW-1), 3 (PW-3), 1 (SJ-1), 3 (SJ-3). 2) Gastric myoelectrical activity 24, sodium pentobarbital(30 / ). Bipolar electrodespylorus

3 Herbal name Drug name Scientific name Dosage(g) Red Sandalwood Cyperi Rhizoma Puerariae Radix Atractylodies Rhizoma Magnoliae Cortex Auratii nobilis Pericarpium Pogostemonis Herba Zingiberis Rhizoma Alpiniae Officinarum Rhizoma Cinnamomi Cortex Crataegii Fructus Aucklandiae Radix Glycyrrhizae Radix Sparganii Rhizoma Zedoariae Rhizoma Citri Reticulatae Viride Pericarpium Massa Medicata Fermentata Hordei Fructus Germinatus Aurantii Fructus Arecae Semen Amomi Fructus Tsaoko Fructus Caryophylli Flos Amomi Rotundus Fructus Piperis Nigri Fructus Piperis Longi Fructus Pterocarpus santalinus Lignum Cyperus rotundus L. Pueraria thunbergiana BENTH. Atractylodes japonica Koidzumi Magnolia officinalis REHD. et WILS Citrus nobilis Makino Pogostemon cablin BENTH. Zingiber officinale ROSCOE Alpinia officinarum HANCE Cinnamomum cassia PRESL Crataegus pinnatifida BGE. Aucklandia lappa DECNE. Glycyrrhiza uralensis FISCH Sparganium stoloniferum BUCH.-HAM. Curcuma zedoaria ROSC. Citrus unshiu MARKOVICH Tricticum sativum Linne Hordeum vulgare Linne Citrus aurantum L. Areca catechu L. Amomum xanthioides WALL. Amonum tsaoko CREVOST et LEM. Eugenia caryophyllata THUNB Amomum kravanh PIERRE ex CAGNEP. Piper nigrum L. Piper longum L Total amount Herbal name Drug name Scientific name Dosage(g) Atractylodies Rhizoma Auratii nobilis Pericarpium Magnoliae Cortex Glycyrrhizae Radix Atractylodes japonica Koidzumi Citrus nobilis Makino Magnolia officinalis REHD. et WILS Glycyrrhiza uralensis FISCH Total amount 20 5antrumserosal surface 7-0. Electrode 20 polyethylene tube(id 0.28, OD 0.61, Becton Dickinson and Company) stainless steel epoxy

4 (Fig. 1). silicon tube(id 0.58, OD ). 2 electrode tube 19. Myoelectrical activitypolygraph( GRASS Model 79E.). cutoff frequency low 0.15, high 35. 5, 24. artifact 1 urethane 500 / Restrainer baseline recording, 30(Figure 2). Motility index PowerLab(Chart version 4.11, ADInstruments) 30 (volts/s). Motility index(%) = 100 3) Gastric emptying Gastric emptyingmiyata glass bead( 1 ) 100 nelaton catheter30 60 glass bead. glass bead. atropine sulfate(1 /, ), cisplatin(10 /, ), NAME(N G -nitro-l-arginine methyl ester, /, ). atropine sulfatename, cisplatin 30glass bead. ±(mean±s.e.), SPSS 10.0 for windows. one-way analysis of variance(anova), Mann-Whitney U-Test. test p<0.05. Gastric myoelectrical activity, 1 (SJ-1) 20 normal saline(ns) 1 (PW-1) (Fig. 3). Gastric motility index(%) ±8.32% (P<0.05). Normal saline 7.98 ±13.06%, ±6.35% motility (Fig. 4).

5 mv NS PW SJ min Fasting Treatment Gastric motility index(%) NS PW-1 SJ-1 * 1) 30.,, ±6.29, ±7.57, ±4.86, ±3.45, normal saline 6.71±5.02 (Fig. 5).

6 Gastric emptying (Glass beads expelled for 30min) r NS PW-1 PW-3 SJ-1 SJ (p<0.05)., normal saline, ±13.05, ±16.46, normal saline 12.43±5.06, ±2.67, ±11.18 (Fig. 6). 2) 1 atropine sulfate, cisplatin, NAME(N G -nitro-l-arginine methyl ester). Atropine sulfate NAME 5.71±3.45, 5.00±3.21, cisplatin13.86± atropine sulfate Gastric emptying (Glass beads expelled for 60 min) r Atropine+NS Atropine+SJ Gastric emptying (Glass beads expelled for 60min) r NS PW-1 PW-3 SJ-1 SJ-3 * Gastric emptying (Glass beads expelled for 60min) r Cisplatin+NS ** Cisplatin+SJ

7 (5.71±3.45vs 3.71±4.42 ), cisplatin (13.86±3.53 vs 5.14±5.05, p<0.01), NAME (5.00±3.21 vs 11.71±5.65, p<0.05)(fig. 7, 8, 9). Gastric emptying (Glass beads expelled for 60 min) r NAME+NS * NAME+SJ ,23. 25%,,, 10,11., 4-8.,,.,,.,,.,,,, 24,25.,, pepsin,, 13-6, 26..,.,, , 3.

8 ... 1,. 1., vagus nerve. Vagus nerve acetylcholine. Atropinevagus nerve acetylcholine, atropine. 1 atropine., 28. vagus nerve., 5-HT 3 receptor cancer chemotherapy cisplatin. 5-HT 3 receptor enterochromaffin cell serotonin,,,,, Cisplatin 5-HT 3 receptor, mouse rat gastric emptying. 5-HT 3 receptor antagonist cisplatin Cancer chemotherapy,, receptor 33,36. (Zingiber officinale)acetone ethanol 5-HT 3 receptor antagonist ondansetron 37. cisplatin 10 / gastric emptying 37. 2% cellulose normal saline. cisplatin 1 normal saline. 5-HT 3 receptor cisplatin, cisplatindm. 5-HT 3 receptor., nonadrenergic noncholinergic(nanc) nerve. NANC nerve fundus receptive

9 relaxation., 38., 39. NANC nerve NO NAME(N G -nitro-l-arginine methyl ester). Nitric oxide(no) NANC nerve, mucosa, smooth muscle cell, neuron. NO 38. NO fundusresting tension, gastric emptying 40. L- NAME 41, NO. L- arginine, NOtonic effect 42. L-arginine, N G -nitro-l-arginine. NAME.., NANC nerve,. choline5-ht 3 receptor, ada- ptive relaxation., vagus nerveacetylcholine atropine sulfate, 5-HT 3 receptor cisplatin, NO(nitric oxide) NAME(N G - nitro-l-arginine methyl ester) (p<0.05) (p<0.05) NAME (p<0.05), cisplatin (p<0.01), atropine sulfate.. choline 5-HT 3 receptor, : ; 2000, p ,,,.. : ; 2000, p.51-8, 65-74, 83-8,

10 3.,,,,, ;22(3): ,,, ;24(2): Haraswa S. Multicenter cooperative post-marketing clinical trial of TJ-43 Rikkunshi-to in dysmotility-like dyspepsia. J of Clini. and Expert. med. 1998;187(3): ,,,,, ;23 (2): Ouyang H, Yin J, Wang Z, Pasricha PJ, Chen JD. Electroacupuncture accelerates gastric emptying in association with changes in vagal activity. Am J Physiol Gastrointest Liver Physiol. 2002;282(2):G Chang CS, Ko CW, Wu CY, Chen GH. Effect of electrical stimulation on acupuncture points in diabetic patients with gastric dysrhythmia: a pilot study. Digestion. 2001;64(3): Parkman HP, Hasler WL, Fisher RS. American Gastroenterological Association technical review on the diagnosis and treatment of gastroparesis. Gastroenterology. 2004;127(5): ;6: ;6: Jan Tack, K. J. Lee. Pathophysiology and Treatment of Functional Dyspepsia. J Clin Gastroenterol. 2005;39(supp. 3):S ,. HCl Pepsin ;2: ,., ;13: ,,,., ;22(1): ,,,,., ;6(1): , ;18(1): ,, ;18(1): Kazuo Nishiyama, Makoto Katori, Akinori Ueno, Takashi Ohno, Katsunori Saigenji. Suppression of Myoelectrical Activity of Gastric Smooth Muscle by Endogenous Gastric Prostaglandin E 2. Dig Dis Sci. 1992;37(7); Suzuki Y, Harada Y, Ueno A, Katori M, Okabe H. Release of endogenous prostaglandins by mild hyperosmotic saline inhibit tetragastrin-stimulated gastric acid secretion in rats. Prostaglandins. 1986;32: Keiji Miyata, Mayumi Yamano, Takeshi Kamato and Shinobu Akuzawa. Effect of Serotonin (5- HT) 3-Receptor Antagonists YM060, YM114(KAE- 393), Ondansetron and Granisetron on 5-HT 4 Receptors and Gastric Emptying in Rodents. Jpn. J. Pharmacol. 1995;68: Thompson WG. Non-ulcer dyspepsia. Can Med Assoc J. 1984;130: Lennard-Jones JE. Functional gastrointestinal disorders. N Engl J Med. 1983;308: : ; 1991, p.

11 220-1, : ; 2000, p ,,,. LESSON. : ; 2001, p : ; 1994, p Shibata C, Sasaki I, Naito H, Ueno T, Matsuno S. The herbal medicine Dai-Kenchu-Tou stimulates upper gut motility through cholinergic and 5-hydroxytryptamine 3 receptors in conscious dogs. Surgery. 1999;126: Yamano M, Kamato T, Miyata K. Participation of a cholinergic mechanism in 5-hydroxytryptamine (5-HT) 3 and 5-HT 4 receptor-mediated stimulation of gastric emptying in rats. Arzneimittelforschung. 1997;47(11): Ozaki A, Sukamoto T. Improvement of cisplatininduced emesis and delayed gastric emptying by KB-R6933, a novel 5-HT 3 receptor antagonist. Gen Pharmacol. 1999;33(3): Nagakura Y, Kiso T, Ito H, Miyata K, Yamaguchi T. The role of 5-hydroxytryptamine3 and 5-hydroxytryptamine4 receptors in the regulation of gut motility in the ferret. Life Sci. 2000;66 (24):PL Aapro M, Blower P. 5-hydroxytryptamine type-3 receptor antagonists for chemotherapy-induced and radiotherapy-induced nausea and emesis: can we safely reduce the dose of administered agents? Cancer. 2005;104(1): Yoshida N, Omoya H, Ito T. DAT-582, a novel serotonin receptor-3 antagonist is a potent long lasting antiemetic agent in the ferret and dogs. Journal of Experimental Pharmacology and Therapeutics. 1992;260: Eeckhout C, Vedder A. 5-HT 3 antagonists reverse the cisplatin induced slowing of gastric emptying in fed rats. Gastroenterology. 1988;94:A Kishibayashi N, Ichikawa S, Yokohama T, Ishii A, Karasawa A. Pharmacological properties of KF18259, a novel 5-HT 3 receptor antagonist, in rats: inhibition of the distal colonic function. Japanese Journal of Pharmacology. 1993;63: Visnovsky P. The effect of cyclophosphamide and methotrexate on gastric emptying and secretion in rats. Bratislavske Lekarske Listy. 1992; 93: Sharma S.S., Gupta Y.K.. Reversal of cisplatininduced delay in gastric emptying in rats by ginger(zingiber officinale). Journal of Ethnophamacology. 1998;62: Abrahamsson H. Non-adrenergic non-cholinergic nervous control of gastrointestinal motility patterns. Arch Int Pharmacodyn Thér. 1986;280 (suppl): Tack J. Functional Dyspepsia: Impaired Fundic Accommodation. Curr Treat Options Gastroenterol. 2000;3(4): Plourde V, Quintero E, Suto G, Coimbra C, Tache Y. Delayed gastric emptying induced by inhibitors of nitric oxide synthase in rats. Eur J Pharmacol. 1994;256: Lefebvre RA, Baert E, Barbier AJ. Influence of L-N G -nitro-l-arginine on non-adrenergic noncholinergic relaxation in the guinea-pig gastric fundus. Br J Pharmacol. 1992;106: A. Ḉorak, T. Coşkun, İ. Alican, H. Kurtel, B. Ḉ. Yeğen. The Effect of Nitic Oxide Synthase Blockade and Indometacin on Gastric Emptying and Gastric Contractility. Pharmacology. 1997; 54: Kido T, Nakai Y, Kase Y, Sakakibara I, Nomura M, Takeda S et al. Effects of Rikkunshi-to, a Traditional Japanese Medicine, on the Delay of

12 Gastic Emptying Induced by N(G)-Nitro-L-arginine. J Pharmacol Sci. 2005;98(2): Nakai Y, Kido T, Hashimoto K, Kase Y, Sakakibara I, Higuchi M et al. Effect of the rhizo- mes of Atractylodes lancea and its constituents on the delay of gastric emptying. J Ethnopharmacol. 2003;84(1):51-5.

달생산이 초산모 분만시간에 미치는 영향 Ⅰ. 서 론 Ⅱ. 연구대상 및 방법 達 은 23) 의 丹溪 에 최초로 기 재된 처방으로, 에 복용하면 한 다하여 난산의 예방과 및, 등에 널리 활용되어 왔다. 達 은 이 毒 하고 는 甘苦 하여 氣, 氣寬,, 結 의 효능이 있

달생산이 초산모 분만시간에 미치는 영향 Ⅰ. 서 론 Ⅱ. 연구대상 및 방법 達 은 23) 의 丹溪 에 최초로 기 재된 처방으로, 에 복용하면 한 다하여 난산의 예방과 및, 등에 널리 활용되어 왔다. 達 은 이 毒 하고 는 甘苦 하여 氣, 氣寬,, 結 의 효능이 있 대한한방부인과학회지 THE JOURNAL OF ORIENTAL OBSTETRICS & GYNECOLOGY VOL.17, NO.2 : 115-122 (2004) 달생산이 초산모 분만시간에 미치는 영향 * 북경한의원, ** 윤산부인과의원, *** 최은림산부인과의원, 상지대학교 한의과대학 부인과학교실 ****, 경희대학교 동서의학대학원 김성준 *****, 윤왕준