(19) 대한민국특허청 (KR) (12) 공개특허공보 (A) (51) 국제특허분류 (Int. Cl.) A23L 1/29 (2006.01) A23L 2/38 (2006.01) A23P 1/02 (2006.01) A23P 1/06 (2006.01) (21) 출원번호 10-2010-0085320 (22) 출원일자 2010 년 09 월 01 일 심사청구일자 2010 년 09 월 01 일 (11) 공개번호 10-2012-0022134 (43) 공개일자 2012년03월12일 (71) 출원인 권오진 경상북도경주시양정로 114-4 ( 성동동 ) (72) 발명자 권오진 경상북도경주시양정로 114-4 ( 성동동 ) 전체청구항수 : 총 2 항 (54) 발명의명칭한약재를이용한피로회복식품 (57) 요약 본발명은피로회복또는자양강장에효과가있는조성물제조방법에관한것으로황기, 당삼, 동충하초, 당귀, 하수오, 사삼, 숙지황, 백작약, 복령, 대추, 맥아, 맥문동, 두충, 생강, 구기자, 감초, 천연꿀등여러실험과논문으로그효능이밝혀진건강강장약재들과그약재들을일정한배합비로혼합하여최고의효과를거두는동시에맛에서도거부감없이누구나편하게음용할수있도록조합한것이다. 이발명은음과양기와혈모두를고려하여각부분별로조화로울수있게고루양생시킬수있는약재들을선별하여제조한것으로현대학업에지친학생들, 업무에시달리는직장인들, 나이드신노년층에이르기까지누구나가편하게음용하면서건강한삶을유지시킬수있다는데그의의가있는유용한발명이다. - 1 -
특허청구의범위청구항 1 황기, 당삼, 동충하초, 당귀, 하수오, 사삼, 숙지황, 백작약, 복령, 대추, 맥아, 맥문동, 두충, 생강, 구기자, 감초, 천연꿀로부터추출한한방피로회복용식품. 청구항 2 제 1항에있어서추출물은음료, 제환 ( 丸 ), 현탁액, 유제품, 주사제, 갤, 크림, 로션, 비누, 파운데이션, 클렌징, 스프레이중에서선택된제형을갖는한약추출조성물. 명세서 [0001] 기술분야 본발명은피로회복에효과가있는약재선별및배합, 가공기술에관한것이다. [0002] 배경기술 피로증상 [0003] [0004] 피로감은주위에서흔히볼수있는증상으로여러가지원인에의해발생할수있다그중선천적으로타고난체질의약함, 정신적육체적노동에의해오장 ( 五腸 ) 이손상받거나혹은무분별한음식의섭취로인한위장과비장의기능손상, 혹은큰병을앓았거나만성질환을앓으며몸의균형이깨진경우라고한의학에서는생각한다. 이상의각종원인, 몸의허함으로인한증상, 질병으로인한피로와허함, 만성병으로인한몸의정기가회복되지못함, 또는여러가지질병을제때치료하지못한경우, 잘못된치료를통한신체의균형실조등으로자주발생한다. 만성피로의주요성질은기와, 혈, 음, 양의손상이다. 그질환의상관장기는오장이지만그중에서도특히비장과신장에관련된경우가많다. 또여러가지원인으로발생한피로증은장기서로간에영향을미쳐어느한쪽이허하면점차다른장기에게까지영향을미쳐다른장기까지허하게하며그증상은점차심해지게된다. 피로감을해소하는주요원칙으론장기를보양하면서그특성에따라기를보하고혈을양생하며음을자양하고양기를돋우는방법을적절히배가시켜야한다. [0005] 본발명자는현대인들이겪고있는피로증상을해소하기위해우리몸의음양기혈의조화와오장육부의관계를자세히따져서로상호보완이될수있도록표준화시켜배합한것을특징으로하며, 연구한결과황기, 당삼 ( 만삼 ), 당귀, 하수오, 사삼, 숙지황, 백작약, 복령, 대추, 맥아, 맥문동, 두충, 동충하초, 감초, 구기자, 생강, 천연꿀의조합과그양을적절히배합함으로써피로회복에탁월한효과가있음을알게되어본발명을완성하게되었다. 여기서사용된모든한약재는식약청에서일반인들이복용하기에위험성이없거나적어식품으로사용허가가난것들이며, 그중대추는한약의약성을부드럽게하는특징이있으며감초는여러약들을조화롭게하는특징이있어적절히배합했다. 또안정성을더높이기위해한약추출물과대추추출물을적절히다시섞음으로해서복용에안정성을높였으며맛또한거부감이없도록조성한것을특징으로한다. 발명의내용 [0006] 해결하려는과제 피로에지친현대인들에게기력을회복하게하고면역력을증강하게하는조성물을제공하는것이다. - 2 -
[0007] 과제의해결수단본발명은황기, 당삼 ( 만삼 ), 당귀, 하수오, 사삼, 숙지황, 백작약, 복령, 대추, 맥아, 맥문동, 두충, 동충하초, 구기자, 감초, 생강, 천연꿀을유효성분으로포함하는만성피로회복용한약추출물을제공한다 [0008] [0009] [0010] 1. 하수오 보간신 ( 輔肝腎 ), 익정혈 ( 益精血 ), 윤장통변 ( 潤腸通便 ), 해창독 ( 解瘡毒 ) 의효능이있다 [0011] [0012] [0013] 하수오에서 분리한 stilbene glucoside의 하나인 (E)-2,3,5,4`-tetrahydroxy stilbene-2-o-beta-dglucopyranoside를 이용하여항산화작용을검토한결과중등도의효과가있음이보고되었다 (1). 한편, anthraquinone을함유하는하수오의추출물은심장의허혈-재관류에의한산화적스트레스상태에서보호 작용을보인다 (2). 하수오의에탄올추출물은동맥경화예방효과를나타낸다 (3). 질병의예방뿐만아니라항 노화효과 (4), 세포생존시간연장및면역조절, 내장과신진대사기능이있다 (5). 쥐를이용한실험에서 하수오는 cholinergic 신경계에대하여보호작용이있다고확인되었다 (6). 노화를가속시킨생쥐를이용한 실험에서하수오는인지력이향상되는효과를나타내었다 (7). 기타 hippocampus에미치는영향등을통해하 수오가학습능력및기억력향상에기여함이밝혀졌다 (8). [0014] [0015] [0016] [0017] [0018] [0019] [0020] [0021] [0022] 참고문헌 (1).Ryu G, Ju JH, Park YJ, Ryu SY, Choi BW, Lee BH. The radical scavenging effects of stilbene glucosides from Polygonum multiflorum. Arch Pharm Res. 2002; 25:636-9. (2).Yim TK, Wu WK,Mak DH, Ko KM. Myocardial protective effect of an anthraquinone-containing extract of Polygonum multiflorum ex vivo. Planta Med. 1998; 64:607-11. (3)Wang W, Zhong Xi Yi Jie He Za Zhi. Effect of alcoholic extract of prepared radix Polygoni multiflori on preventing atherosclerosis in Japanese quail, 1984; 4: 748-50. (4)Xiao PG, Xing ST, Wang LW. Immunological aspects of Chinese medicinal plants as antiageing drugs. J Ethnopharmacol 1993; 38: 167-75. (5)Chen K,Li C. Recent advances in studies on traditional Chinese anti-aging materia medica J Tradit Chin Med. 1993; 13: 223-6. (6)Li M, Du XP, Ye H. Protective effect of polygonum multiflorum thunb on the cerebral cholinergic neurofibers in rats Hunan Yi Ke Da Xue Xue Bao. 2003; 28: 361-4. (7)Chan YC, Wang MF, Chang HC. Polygonum multiflorum extracts improve cognitive performance in senescence accelerated mice. Am J Chin Med. 2003; 31: 171-9 (8)Chan YC, Cheng FC, Wang MF. Beneficial effects of different Polygonum multiflorum Thunb. extracts on memory and hippocampus morphology. J Nutr Sci Vitaminol (Tokyo). 2002; 48: 491-7. [0023] [0024] 2. 황기 - 3 -
[0025] 보기승양 ( 補氣升揚 ), 고표지한 ( 固表止汗 ), 탁독배농 ( 托毒排膿 ) 의효능이있다. [0026] [0027] [0028] ` 면역계에대한작용수용성부분중다당 Aps-11과 Aps-2는동물실험에서비장과간장의 RNA합성을증대시키는것등을참작할때황기의다당질은면역부활작용. immunomodulator로서의활성과대사조절기능이있음이인정된다 (1). 실험적으로황기를쥐에투여시흉선의무게증가, 식균작용및과산화물의생성증가작용이있다 (2). 또한황기는말초혈액단구세포증식을통해암세포에대한식균작용을향상시키고말초혈액 B세포의 IgG 생성능을증가시키는작용이있다 (3,4). 화학요법제를투여받는악성종양환자에게정맥주사로황기를투여한결과대조군에비해말초백혈구및혈소판의감소가적고, IgG과 IgM의레벨이증가하였다 (5). 성장기수컷 ICR 생쥐에게강제로운동을시키며황기를투여한결과경골근육및흉선의무게가증가하고세망내피계 (reticuloendothelial) 의식기능이강화되었으며복강대식세포의인산가수분해효소 (Phosphatase) 활성도증가되었다. 또한 ConA에의해유도된비장세포의증식도촉진되었다 (6). 황기추출물을정상쥐또는 cyclophosphamide나방사선, 노화등에의해면역력이저하된쥐에투여했을때 T 세포의존성항원에대한항체반응이증진된다 (7). 황기의일부분획 (F3) 은 13명의암환자로부터얻은단핵구를이용한실험에서 cycolphosphamide 투약에의해약화된면역력을복구하는데우수한효과를나타내었다 (8). [0029] [0030] [0031] `항암작용쥐를이용하여 diethylnitrosamine (DEN) 에의해유도되는간세포의발암에대한황기의효과를조사한결과 glutathione S - transferase placenta (GST-P) 의형성이현저하게저하되었다. 이는황기의간암세포억제효과를암시한다 (9). 신세포암종 (Renca) 을이식한 BALB/c 생쥐에황기를포함한혼합물을투여했을때좋은치료율을보였다. Renca를처리한생쥐의비장세포는 IL-2에대한반응성이떨어졌으나황기등을처리했을때이들의기능이회복되었다 (10). 말초혈액단구 (PBMC) 에황기를처리했을때종양괴사인자-α (TNF-α) 의분비가증가되는효과도있다 (11). [0032] [0033] `기타작용 Herpes simplex virus 에대한억제작용 (12,13), HSV-1 F (14), HBV(15,16), coxsackie virus(17) 등에대한항바이러스작용이있다. 난소가절제된쥐에서황기는뼈의손실을방어하는작용이있다 (18). 백혈구와혈소판의기능에작용한황기의항염증작용 (19), 항염증작용과관련한핵전사인자및접착분자에미치는영향등도보고되었다 (20). [0034] [0035] [0036] [0037] [0038] [0039] @ 참고문헌 (1).Wanger H, Hikino H, Farmworth NR : Immunostimulatory drugs of Fungi and Higher Plants in Economics and Medicinal Research., 1985; 113 (2).Sugiura H,Nishida H, Inaba R, Iwata H : Effects of exercise in the growing stage in mice and of Astragalus membranaceus on immune functions. Nippon Eiseigaku Zasshi. 1993; 47: 1021-31. (3).Wang RT, Shan BE, Li QX : Extracorporeal experimental study on immuno-modulatory activity of Astragalus memhranaceus extract. Zhongguo Zhong Xi Yi Jie He Za Zhi.2002; 22: 453-6. (4).Lau BH,Ruckle HC, Botolazzo T, Lui PD : Chinese medicinal herbs inhibit growth of murine renal cell carcinoma. Cancer Biother. 1994; 9: 153-61. (5).Duan P, Wang ZM. Clinical study on effect of Astragalus in efficacy enhancing and toxicity reducing of chemotherapy in patients of malignant tumor Zhongguo Zhong Xi Yi Jie He Za Zhi.2002; 22:515-7. - 4 -
[0040] [0041] [0042] [0043] [0044] [0045] [0046] [0047] [0048] [0049] [0050] [0051] [0052] [0053] [0054] (6).Sugiura H, Nishida H, Inaba R, Iwata H. Effects of exercise in the growing stage in mice and of Astragalus membranaceus on immune functions. Nippon Eiseigaku Zasshi. 1993; 47: 1021-31. (7).Zhao KS, Mancini C, Doria G, Enhancement of the immune response in mice by Astragalus membranaceus extracts. Immunopharmacology. 1990; 20: 225-33. (8).Chu DT, Sun Y,Lin JR. Immune restoration of local xenogeneic graft-versus-host reaction in cancer patients in vitro and reversal of cyclophosphamide-induced immune suppression in the rat in vivo by fractionated Astragalus membranaceus. Zhong Xi Yi Jie He Za Zhi. 1989; 9: 351-4. (9).Cui R, He J, Wang B, Zhang F, Chen G, Yin S, Shen H. Suppressive effect of Astragalus membranaceus Bunge on chemical hepatocarcinogenesis in rats. Cancer Chemother Pharmacol. 2003; 51: 75-80. (10).Lau BH,Ruckle HC, Botolazzo T,Lui PD. Chinese medicinal herbs inhibit growth of murine renal cell carcinoma. Cancer Biother. 1994; 9:153-61. (11).Zhao KW, Kong HY. Effect of Astragalan on secretion of tumor necrosis factors in human peripheral blood mononuclear cells Zhongguo Zhong Xi Yi Jie He Za Zhi. 1993; 13: 263-5. (12).Di Yi Jun Yi Da Xue Xue Bao. Experimental study of the effect of Astragalus membranaceus against herpes simplex virus type 1. Sun Y, Yang J.2004; 24: 57-8. (13).Zhang L, Liu Y, Yu Z. Study on the anti-herpes simplex virus activity of a suppository or ointment from of Astragalus membranaceus combined with interferon alpha 2b in human diploid cell culture. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 1998; 12: 269-71. (14).Wang Z, Cheng Z, Fang X. Antiviral action of combined use of rhizoma Polygoni cuspidati and radix Astragali on HSV-1 strain Zhongguo Zhong Yao Za Zhi. 1999; 24: 176-80, 192. (15).Wu L, Liu H, Xue P, Lu ZG, Du KF. Influence of a triplex superimposed treatment on HBV replication and mutation during treating chronic hepatitis B Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2001; 15: 236-8. (16).Xiong D,Yang Y, Su Y. Experimental study on treatment of viral myocarditis in mice by integrated traditional Chinese and Western Medicine Zhongguo Zhong Xi Yi Jie He Za Zhi. 1998; 18: 480-2. (17).Lu S, Zhang J,Yang D. Effects of Astragaloside in treating myocardial injury and myocardial Sarco/Endoplasmic CA(2+)-ATPase of viral myocarditis mice. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1999; 19: 672-4. (18).Kim C, Ha H, Lee JH, Kim JS, Song K, Park SW. Herbal extract prevents bone loss in ovariectomized rats. Arch Pharm Res. 2003; 26: 917-24. (19).Prieto JM, Recio MC, Giner RM, Manez S, Giner-Larza EM, Rios JL. Influence of traditional Chinese anti-inflammatory medicinal plants on leukocyte and platelet functions. J Pharm Pharmacol. 2003; 55: 1275-82. (20).Prieto JM, Recio MC, Giner RM, Manez S, Giner-Larza EM, Rios JL. Influence of traditional Chinese anti-inflammatory medicinal plants on leukocyte and platelet functions. J Pharm Pharmacol. 2003; 55: 1275-82. [0055] [0056] [0057] 3. 구기자 자신보간명목 ( 滋腎補肝明目 ), 윤폐지해 ( 潤肺止咳 ) 등의효능이있다 - 5 -
[0058] [0059] [0060] [0061] `간보호작용 Betaine은 choline의분해산물로서 S-adenosyl methionine (SAM) 의함량을증가시켜간보호활성을갖는다고알려져있는데, 이를이용한간보호활성에대한연구는동물을이용한연구에서부터임상까지많은연구가이루어져있다. CCl4로유도한간손상동물모델에서 betaine을경구투여한결과 (830mg/kg,7일) 간손상이현저히억제된다고보고되어있으며, ethanol로유도한간손상에대해서도현저히억제한다고보고되어있다 (6,7). 뿐만아니라임상연구에서도 betaine은비알콜성지방성간염 (nonalcoholic steatohepatitis; NASH) 환자에 betaine(10g, bid) 을 12개월간투여한결과조직학적소견의개선및혈청 aminotransferase의활성저하등의 NASH가현저히개선된다고보고되어있다 (8). Kim 등은구기자에서분리한 zeaxanthin이랫드의간세포 1차배양에서 CCl4로유도한간세포독성을현저히억제하는데, 이러한효과는 silybin과필적할정도라고보고하고있다 (2). 뿐만아니라 cerebroside의일종인 LCC 역시 galactosamine으로유도한간세포독성을현저히억제하는데이러한작용은 lipid peroxidation의억제및 glutathione level 의유지에의해간장보호효과가나타난다고보고하고있다 (3). 또한 pyrrole 유도체들도 CCl4 로유도한간세포독성을현저히억제한다고보고되어있다 (4). 한편, 담도폐쇄모델랫드에서발생하는간섬유화는만성적인 alcohol의섭취로유발되는만성간손상의모델로이용되고있다. 이러한동물모델에서 zeaxanthin di-palmitate를 25mg/kg의용량으로 6주간투여한결과, 혈중에서증가하는 aspar-tate transaminase 및 alkaline phosphatase의활성이현저히억제된다고보고되어있는데이러한작용은 zeaxanthin dipalmitate의항산화활성에기인된것이라고생각된다 (9). [0062] [0063] `호흡기계에대한작용기도의점막층은화학물질이나먼지입자, 각종미생물등의공격으로부터방어벽역할을하고있다. 이러한방어벽으로서의역할은주로끈적끈적한당단백이나 mucin에의한다. 따라서 mucin의상태에이상이발생되었을경우다양한호흡기계질환이발생된다고알려져있다. 일반적으로항염증약물의경우는 mucin분비를증가시키는데 glucocorticoid의경우는 mucin분비를억제한다. 최근 Lee 등의보고에의하면구기자에많은양으로함유되어있는 betaine의경우 mucin 을분비하는세포에직접작용하여 mucin분비를촉진한다는것을보고하고있다 (10). 이러한작용은 betaine이거담약물로서가능성이있음을의미하는것이며, 구기자의윤폐지해 ( 潤肺止咳 ) 효능을뒷받침하는것으로생각된다. [0064] [0065] [0066] `기타작용 L. barbarum에서분리한다당체를마우스에경구투여한결과현저한면력증강작용을나타내는데이러한작용은주로 IL-2수용체의발현증가에기인된것으로생각된다 (1). 또한세포성면역기능증강작용및조혈기능, 특히 leukocyte의증가작용이있다고알려져있으며, 이외에도혈당저하작용등도알려져있다 (1). 구기자의수용성분획이혈압저하작용을나타내는데이러한작용은 atropine에의해차단된다. 또한구기자엑스가 atropine과유사한부교감신경차단작용도가지고있다고알려져있다 (5). [0067] [0068] [0069] [0070] [0071] @ 참고문헌 (1)Zhu YP. Chinese Materia Medica Chemistry, Pharmacology and Applications. Harwood Academic Publishers, The Netherlands, pp642-646. 1998. (2)Kim SY, Kim HP, Huh H, Kim YJ. Antihepatotoxic zeaxanthins from the fruits of Lycium chinese. Arch Pharm Res. 1997; 20: 529-532. (3)Kim SY, Lee EJ,Kim HP,Lee HS, Kim YC. LCC, a cerebroside from Lycium chinense, protects primary cultured rat hepatocytes exposed to galactosamine. Phytother Res. 2000; 14: 448-51. (4)Chin YW, Lim SW,Kim SH, Shin DY, Suh YG, Kim YB, Kim YC, Kim J. Hepatoprotective pyrrole derivatives of Lycium chinense fruits. Bioorg Med Chem Lett. 2003; 13: 79-81. - 6 -
[0072] [0073] [0074] [0075] [0076] [0077] (5) 木村正康, 漢方藥理學, 1997, 南山堂, 東京. pp324-325. (6)Junnila M, Rahko T, Sukura A, Lindberg LA. Reduction of carbon tetrachloride-induced hepatotoxic effects by oral administration of betaine in made Han-Wistar rats: a morphometric histological study.vet Pathol. 2000; 37: 231-8. (7)Kanbak G, Inal M,Baycu C. Ethanol-induced hepatotoxicity and protective effect betaine. Cell Biochem Funct. 2001; 19: 281-5. (8)Yu AS, Keeffe EB. Nonalcoholic fatty liver disease. Rev Gastroenterol Disord. 2002; 2: 11-9. (9)Kim HP, Lee EJ, Kim YC, Kim J, Kim HK, Park JH, Kim SY, Kim YC. Zeaxanthin dipalmitate from Lycium chinense fruit reduces experimentally induced hepatic fibrosis in rats. Biol Pharm Bull. 2002; 25: 390-2. (10)Lee CJ, Lee JH, Seok JH,Hur GM, Park Js J, Bae S, Lim JH, Park YC. Effects of betaine, coumarin and flavonoids on much release from cultured hamster tracheal surface epithelial cells. Phytother Res. 2004; 18: 301-5. [0078] 4. 사삼 [0079] [0080] 자폐양음거담 ( 滋肺養陰祛痰 ) 및익위생진 ( 益胃生津 ) 하는효능이있다. [0081] [0082] 사삼에대한약리작용은알려진바가많지않다. 사삼에함유되어있는 saponin은거담작용을가지며그작용시간은 4시간이상인것으로알려져있다 (1). 한편, 사삼에함유되어있는 6-C-butyl-DMDP의경우 β- glucosidase에강력한억제작용을가지며 (IC50 = 68 γm), α-1-c-ethyl-fagomine의경우도 β-galactosidase 의활성을억제하는것으로알려져있다 (2). 다른연구에의하며사삼과같은속식물의뿌리에서분리된물질이 α-glucosidase에대하여강력한억제활성을가진다고보고하고있다 (3). 많은 glucosidase에억제활성을가지는물질이항바이러스, 항암및항당뇨효능을가진다고알려져있으며, 특히 α-glucosidase에억제활성을가지는물질은당뇨병치료약물로서개발가치가충분히있는것으로보고되어있다. 따라서사삼으로부터분리된성분의경우에도이러한효능이있을것으로추측이가능하다고할것이다. 한편, Lee 등은사삼의 ethylacetate 분획이위암에대한 chemopreventive agent로서가능성이있음을보고하고있어사삼의응용분야가기대된다 (4). [0083] [0084] [0085] [0086] [0087] @ 참고문헌 (1). Huang KC. The Pharmacology of Chinese Herbs (2nd Ed). CRC Press, Boca Raton, FL, pp287, 1999. (2).Asano N, Nishida M, Miyauchi M, Ikeda K, Yamamoto M, Kizu H, Kameda Y, Watson AA, Nash RJ, Fleet GW. Polyhydroxylated pyrrolidine and piperidine alkaloids from Adenophora triphylla var. japonica(campanulaceae). Phytochemistry. 2000; 53: 379-82. (3).Jiang P, Gao Z. Chemical constituents of Adenophora stricta Miq. Zhongguo Zhong Yao Za Zhi. 1990; 15: 486-7, 512. (4).Lee IS. Yang EJ, Kim HS, Chung SK, Furukawa F, Nishikawa A. Suppressive effects of Adenophora triphylla extracts on in vitro tumor cell growth and in vivo gastric epithelial proliferation. Anticancer Res. 2000; 20: 3227-31. - 7 -
[0088] 5. 두충 [0089] [0090] 보간신강근골 ( 補肝腎强筋骨 ) 및안태 ( 安胎 ) 의효능이있다. [0091] [0092] [0093] [0094] `실험관계에대한작용두충의추출물은항고혈압작용이있다고알려져있다. 항고혈압작용에대한연구에의하면두충에함유되어있는 genipin이중등도의작용이있다고보고되어있으며, 두충엽의추출물도랫드및임상에서항고혈압작용이있다고알려져있다 (2). 특히일본의후생성에서는고혈압의예방을위한건강기능식품으로서두충을인정하고있으며, 주작용성분은 geniposidic acid로보인다 (2). 그런데또다른보고에의하면두충의항고혈압작용은혈관평활근에대한직접적인이완작용에기인하며주활성성분은 pinoresinol diglucoside로보고하고있다 (3). 한편, 고지방식이섭취랫드에서두충엽추출물의투여는혈액중의총콜레스테롤함량, 혈장 triglyceride 및간 triacyglycerol을저하시킨다 (3). 그러나간세포에서의총콜레스테롤함량의변화는가져오지않는다. [0095] [0096] [0097] `항산화작용 Free radical은불포화지방산을공격하여 peroxide를생성시키며결과적으로세포막의 fluidity 저하를초래하며, 효소나수용체의활성을저하시키게된다. 또한 free radical이 DNA를공격하여암화를촉진시킨다. 따라서항산화약물의 free radical 소거작용은 peroxide로야기되는많은질환들, 예를들면심장질환, 뇌질환및암등을예방할수있게된다. 두충엽과수피및초 ( 炒 ) 한수피의물추출물을이용한항산화작용에서용량의존적으로항산화작용이우수하다고알려져있다 (4). 항산화작용은상기의두충에함유되어있는 protocatechuic acid에의한것인데, 그함량은두충엽에가장많고다음으로초 ( 炒 ) 한수피, 초 ( 炒 ) 하지않은수피순으로함유되어있다. 유사한연구결과가많이있는데이러한사실로부터두충차또는두충엽차의경우암의예방에매우유효할것으로보인다 (5). [0098] [0099] `항피로및스트레스완화작용두충의스트레스완화작용은이미잘알려져있다. 두충에서분리한 geniposidic acid가구속수침스트레스에서나타나는위궤양작용을억제한다고알려져있다 (2). 한편, 운동시에나타나는피로작용에대해두충엽추출물의투여시근육세포에서관찰되는 lactate dehydrogenase의활성이현저히증가되어있으며, 이효소의활성증가는운동시에생성되는피로물질인 lactate의분해를촉진시킨다 (6). 따라서두충의경우항피로및스트레스완화작용이있다고생각된다. [0100] [0101] `피부에대한작용노화의진행으로피부의 collagen 합성은감소된다. 저단백식이랫드의경우 collagen 합성이감소되는데 collagen 합성이감소된랫드모델에서두충엽추출물의투여는 collagen 합성을개선시킨다고알려져있다 (1). 두충엽중에는 geniposidic acid, aucubin 및 geniposide가주활성성분으로보고있다. 또한상처치유과정에서필수적인 granulation을두충엽이활성화시킨다. [0102] ` 기타작용 - 8 -
[0103] [0104] [0105] 두충은임상에서주로포제 ( 製 ) 하여사용하며포제의방법으로는초탄법 ( 炒炭法 ), 염자법 ( 鹽炙法 ) 및염수반윤증법 ( 鹽水半潤蒸法 ) 등이알려져있다 (7). 포제의방법에따라약리작용에서차이를보이는데, 임신한마우스에서분리한자궁조직에 acetylcholine의투여로나타나는경련성수축을염두충 ( 鹽杜 ) 이길항작용을가진다고알려져있다 (8). 즉, 동물의이체자궁에두충을투여하면수축이억제되고자궁수축제의작용을억제시키는해경 ( 解痙 ) 작용이있으며, 염제품은생품 ( 生品 ) 보다그작용이강하다. 이것은임상에서두충, 특히염두충 ( 鹽杜 ) 을태동불안 ( 胎動不安 ) 의치료에사용하는것과일치한다고알려져있다 (7). 두충의장기투여는부신및정소중량을증가시키며, 간에서 vitamin B1 및 E 의증가작용및 glycogen 함량증가작용이있다. 또한두충수피는학습행동의저하및성행동의저하를억제한다 (9). 최근두충의수피로부터항곰팡이작용이있는 peptide가분리보고되어있다 (10). 이외에도두충은이뇨작용, 면역증강작용, 진정및진통작용등이알려져있다 (9). [0106] [0107] [0108] [0109] [0110] [0111] [0112] [0113] [0114] [0115] [0116] @ 참고문헌 (1).Li Y, Kamo S, Metori K, Koike K, Che QM, Takahashi S. The promoting effect of eucommiol from Eucommiae cortex on collagen synthesis. Biol Pharm Bull. 2000 ; 23 : 54-9. (2).Deyama T, Nishibe S, Nakazawa Y. Constituents and pharmacological effects of Eucommia and Siberian ginseng. Acta Pharmacol Sin. 2001; 22: 1057-70. (3).Zhu YP. Chinese Materia Medica Chemistry, Pharmacology and Applications. Harwood Academic Publishers, The Netherlands, pp459-463, 1998. (4).Yen GC, Hsieh CL. Reactive oxygen species scavenging activity of Du-zhong (Eucommia ulmoides oliv.) and its active compounds. J Agric Food Chem. 2000 ; 48 : 3431-6. (5).Hsieh CL, Yen GC. Antioxidant actions of du-zhong (Eucommia ulmoides Oliv.) toward oxidative damage in biomolecules. Life Sci. 2000 ; 66 : 1387-400. (6).Li Y, Koike K, Che Q, Yamaguchi M, Takahashi S. Changs in lactate dehydrogenase and 3- hydroxyacetyl-coa dehydrogenase activies in rat skeletal muscle by the administration of Eucommia ulmoides OLIVER leaf with spontaneous running-training. Biol Pharm Bull. 1999 ; 22 : 941-6. (7). 김기준, 송호준. 한약포제학, 신일상사, 서울. 2002. pp324-329 (8).Wang Q, Li XP, Liu ST, Guan XJ. Experimental studies on the significance of processing Eucommia ulmoides Oliv. Zhongguo Zhong Yao Za Zhi. 1989 ; 14 :661-3, 702. (9). 木村正康, 心血管血液系疾患生藥, 漢方藥理學, 木村正康편, 1997, 南山堂, 東京. pp248. (10).Huang RH, Xiang Y, Liu XZ, Zhang Y, Hu Z, Wang DC. Two novel antifungal peptides distinct with a five-disulfide motif from the bark of Eucommia ulmoides Oliv. FEBS Lett. 2002 ; 521 : 87-90. [0117] 6. 숙지황 [0118] [0119] 자음보혈 ( 滋陰補血 ), 익정전수 ( 益精塡水 ) 의효능이있다. [0120] [0121] [0122] `항염증효과쥐의뇌에있는성상세포를분리해 substance P 와 lipopolysaccharide를투여해세포를자극한후숙지황추출물을투여했을때염증유도물질인종양괴사인자 - α와 (TNF-α), 인터루킨 -1의생성을억제시켰다 (1). - 9 -
[0123] [0124] `항알레르기효과숙지황추출물을투여후 compound 48/80으로전신적인알레르기반응을유도했을때숙지황추출물은농도의존적으로알레르기반응을억제하였다. 또한혈중 his-tamine의농도도억제되는것을알수있었다. antidinitrophenyl (DNP) IgE로피부알레르기를유발했을때에도숙지황은이를억제하였다 (2). [0125] @ 참고문헌 [0126] [0127] (1).Kim HM, An CS, Jung KY, Choo YK, Park JK, Nam SY. Rehmannia glutinosa inhibits tumour necrosis factor-alpha and interleukin-1 secretion from mouse astrocytes. Pharmacol Res. 1999 Aug;40(2): 171-6. (2).Kim HM, Lee EH, Lee S, Shin TY,Kim Y, Kim J. Effect of Rehmannia glutinosa on immediate type allergic reaction. Int J Immunopharmacol. 1998 Apr-May;20(4-5):231-40. [0128] [0129] [0130] 7. 맥문동 양음윤폐 ( 養陰潤肺 ), 청심제번 ( 淸心除煩 ), 익위생진 ( 益胃生津 ) 및윤장통변 ( 潤腸通便 ) 등의효능이있다 [0131] [0132] [0133] `호흡기계에대한작용기관지세척액에서단백질의양과 fucose의양이증가되는경우호흡곤란등이야기되는데 human neutrophil elastase의처리에의해증가된단백질의양이맥문동의처리로유의적으로감소한다고보고되어있으며, 맥문동의물추출물이기관지점액의분비촉진및기관지섬모운동을촉진시킨다고보고되어있다 (2). 이러한현상은맥문동탕에서도동일하게관찰된다. 뿐만아니라 SO2로야기된기도상피조직손상모델에서감소하는섬모운동을맥문동의물추출물이완전히개선시킨다고보고되어있다 (3). 이러한사실들은맥문동의양음윤폐 ( 養陰潤肺 ) 의효능을뒷받침하는것으로생각된다. [0134] [0135] ` 심장에대한작용 Chloroform-epinephrine 이나 BaCl2 또는 aconitine 으로유도된심부정맥을맥문동으로부터분리한총 saponin 이억제한다고보고되어있다 (4). 이러한작용은생맥산 ( 生脈散 ) 의심기능개선과관련되는것으로보인다. [0136] [0137] `신경계에대한작용맥문동을메탄올로추출한후나눈부탄올분획이신경교세포 (astrocyte) 에서의 nerve growth factor (NGF) 분비증가작용을나타낸다 (5). NGF는다양한신경계질환에관여하고있는데문제는단백질인관계로작용부위로의이동이문제가된다. 만약 NGF를분비시키는약물이있다면신경계질환에효과적일수있다. [0138] [0139] `항균작용 Gram-positive 박테리아에는 sortase라는 transpeptidase가광범위하게분포하고있으며 sortase의억제는 Gram-positive 박테리아의감염을억제할수있다고알려져있는데이러한약물로는 vancomycin이나 moenomycin 이있지만그활성의정도는약하다 (6). 따라서 sortase를억제할수있는항생물질이향후새로운항생물질로각광을받을수있을것으로보인다. 맥문동의 sortase 억제활성을검토한결과 IC50 가 7.96 μg/ml 정도 - 10 -
로활성이우수하다 (7). [0140] [0141] ` 기타작용 면역증강작용및혈당저하작용등이알려져있는데모두 polysaccharide 에의한것으로보인다 (1). [0142] @ 참고문헌 [0143] [0144] [0145] [0146] [0147] [0148] [0149] (1).Zhu YP. Chinese Materia Medica Chemistry, Pharmacology and Applications. Harwood Academic Publishers, The Netherlands, pp629-632. 1998. (2).Tai S, Sun F, O'Brien DW, Lee MS,Zayas JG, King M. Evaluation of a mucoactive herbal drug, radix ophiopogonis, in a pathogenic quail model. J Herb Pharmcother. 2002; 2: 49-56. (3).O'Brien DW,Morri MI, Lee MS, Tai S, King M. Ophiopogon root (Radix Ophiopogonis) prevents ultrastructural damage by SO2 in an epithelial injury model for studies of mucociliary transport. Life Sci. 2004; 74: 2413-22. (4).Chen M, Yang ZW,Zhu JT, Xiao ZY, Xiao R. Anti-arrhythmic effects and electrophysiological properties of Ophiopogon total saponins. Zhongguo Yao Li Xue Bao. 1990; 11:161-5. (5).Hur J, Lee P, Kim J, Kim AJ, Kim H, Kim SY. Induction of nerve growth factor by butanol fraction of Liriope platyphylla in C6 and primary astrocyte cells. Biol Pharm BUull. 2004; 27: 1257-60. (6).Supuran CT,Scozzafava A, Clare BW. Bacterial protease inhibitors. Med Res Rev. 2002; 22:329-72. (7).Kim SW, Chang IM, Oh KB. Inhibition of the bacterial surface protein anchoring transpeptidase sortase by medicinal plants. Biosci Biotechnol Biochem. 2002; 66: 2751-4. [0150] 8. 대추 [0151] [0152] 보중익기 ( 補中益氣 ), 양혈안신 ( 養血安神 ), 및완화약성 ( 緩和藥性 ) 등의효능이있다. [0153] [0154] [0155] `항염증및항알러지작용대추의 50% methanol 냉침추출물이항궤양작용을가진다고알려져있다. 또한물추출물이 IgE 항체에의한 psssive cutaneous anaphylaxis 및접촉성피부염을억제하며,IgE 항체자극에의한 LTD4의유리도억제한다고알려져있다 (1). [0156] [0157] [0158] `신경계에대한작용대추에서도산조인보다는약하지만진정작용이있는데, 이는산조인에서단리한물질인 nuciferine 의가열로생성되는물질인 aprophine형알칼로이드인 lysicamine에의한작용이다 (4). 최근 Hoe 등은 50여종의한약물에대하여 cholinergic 신경계에대한활성을검토한결과대추의 methanol 추출물이가장우수하였으며, 주활성성분은 oleamide임이확인되어있다 (3). - 11 -
[0159] [0160] `기타작용대추에많은양으로함유되어있는 betulinic acid는항 HIV작용, 강력한종양억제작용이있다고알려져있다 (5,6). 그러나최근에보고에의하면암세포에대한세포독성의측면에서 3-O-cis-p-coumaroylalphitolic acid 나 3-O-trans-p-coumar-oylalphitolic acid가오히려 betulinic acid보다더강력하다고보고되어있다 (2). [0161] [0162] [0163] [0164] [0165] [0166] [0167] @ 참고문헌 (1). 木村正康, 漢方藥理學硏究動向, 漢方藥理學, 木村正康편,1997, 南山堂, 東京. pp136-137. (2).Lee SM, Min BS,Lee CG, Kim KS, Kho YH. Cytotoxic triterpenoids from the fruits of Zizyphus jujuba. Planta Med. 2003; 69:1051-4. (3).Heo HJ, Park YJ, Suh YM, Choi SJ, Kim MJ, Cho HY, Chang YJ, Hong B, Kim HK, Kim E, Kim CJ, Kim BG, Shin DH. Effects of oleamide on choline acetyltransferase and cognitive activities. Biosci Biotechnol Biochem. 2003; 67: 1284-91. (4). 한병훈, 박명환, 한용남. 산조인및대추, 대추나무로부터단리한아포르핀과환상펩티드알칼로이드의생쥐에대한진정작용, 약학회지. 1993; 37 : 143-148. (5).Eiznhamer DA, Xu ZQ. Betulinic acid : a promising anticancer candidate. IDrugs. 2004; 7: 359-73. (6).Kai H, Koine T, Baba M, Okuyama T. Pharmacological effects of Daphne genkwa and Chinese medical prescription, " Jyu-So-To". Yakugaku Zasshi. 2004; 124: 349-54. [0168] 9. 맥아 [0169] [0170] 소식화중 ( 消食和中 ), 하기 ( 下氣 ) 등의효능이있다. [0171] [0172] [0173] `소화작용이약에는당분해효소등음식물을소화시킬수있는소화효소를함유하고있어탄수화물이나단백질식이의소화를돕는다. 이약의 amylase는열에불안정하므로이약의추출물이나가온하는것은약효를감소시킨다. 이약의물추출물은위산및, pepsin의분비를촉진한다. [0174] [0175] `혈당강하효과이약의물추출물은토끼및정상인의혈당을감소시킨다. 이작용은 7시간동안지속되었다. Hordenine은 epineprine과유사한교감신경흥분효과를갖고있다. 이약은혈관을수축하고기관지를이완시키며장관운동을억제한다. 그러나이약에는이 hordenine 이극미량들어있어이와같은효과를기대하기는어렵다. [0176] [0177] [0178] @ 참고문헌 1. Wang, Y.S., Pharmacology and Applications of Chinese Materia Medica, pp.473-476, Beijing People's Health Publisher (1983). 2.Namba T., The Encylopedia of Wakan-Yaku With color pictures, 1995; (1) 226 Hoikusha press. - 12 -
[0179] 10. 당삼 [0180] [0181] 보중익기 ( 補中益氣 ), 생진양혈 ( 生津養血 ) 등의효능이있다. 보기 ( 補氣 ) 작용이인삼과비슷하여일반적으로보기 ( 補氣 ) 와건비 ( 健脾 ) 의방제 ( 方劑 ) 에인삼의대체약물로많이사용된다. 다만보 ( 補 ) 하는작용이인삼과비교하여약하다고알려져있다 (1). [0182] [0183] [0184] `면역계에대한작용당삼은 polysaccharide의함량이매우높은약물이다. 당삼으로부터분리한 poly-saccharide를이용한연구에서초기에는비장세포의분화를억제하지만장기간투여에의해분화가촉진된다고보고되어있다 (3). 또한당삼은세포성면역과체액성면역두가지를모두증가시킨다고알려져있다 (2). 세포성면역의측면에서보면 cytotoxic T-cell을활성화시키지만 natural killer-cell의활성화에는영향이없다는보고도있다 (4). [0185] [0186] [0187] `위장관에대한작용 Stress로유도한위궤양모델, acetic acid로유도한위궤양모델, indomethacin으로유도한위궤양모델, 0.2N NaOH로유도한위궤양모델등다양한위궤양모델에서당삼의추출물이위궤양을억제한다고알려져있다 (5). 특히스트레스및 acetic acid로유도한위궤양모델에서이러한효과는더욱현저한데, 이러한궤양은사람에서관찰되는궤양과매우유사하다고알려져있다. PGE2가위산의분비를억제한다고알려져있는데당삼의항궤양효과가 PGE2의분비증가와관련되어있는지는아직확인되어있지않다. 한편, 당삼의추출물이위장관의운동을촉진한다고알려져있는데이는당삼을비위허한 ( 脾胃虛寒 ) 에사용한다는전통적인지식와일치하는것으로생각된다 (6). 이러한당삼의효과는 muscarinic receptor 또는 nicotinic receptor를경유한것으로보인다. [0188] [0189] `신경계에대한작용당삼과은행엽의혼합물 ( 당삼의 total glycosides 75mg 과은행엽추출물 40mg으로구성 ) 을 60명의환자에게시험한경과 ( 이중맹검시험 ), 은행엽단독보다는복합물이유의적으로인지개선능력을보인다고보고되어있다 (7). 또다른연구에의하면당삼의총 alkaloid가 PC12 cell에서 NGF(nerve growth factor) 에의해유도되는신경성장에대하여증강작용이있다고보고하고있어뇌신경활성화에대한당삼의작용이기대된다 (8). [0190] [0191] [0192] `기타작용마우스에경구투여시산소소비량의감소를유도하여저산소상태에서마우스의생존연장의효과를나타낸다 (2). 또한부탄올분획에서약물이나스트레스에의한궤양의형성을억제한다고알려져있다 (2). 한편, peroxy radical에의해적혈구의용혈이발생되는데, 당삼추출물이적혈구의용혈을현저히억제한다고보고되어있다 (9). [0193] @ 참고문헌 [0194] [0195] (1). 서부일, 최호영. 임상한방본초학. 영림사, 서울, 한국, pp767-770, 2004. (2).Zhu YP.Chinese Meteria Medica Chemistry, Pharmacology and Applocations. Harwood Academic publishers, The Netherlands, pp557-560. 1998. - 13 -
[0196] [0197] [0198] [0199] [0200] [0201] [0202] (3).Wang ZT, Ng TB, Yeung HW, Xu GJ. Immunomodulatory effect of a polysaccharide-enriched preparation of Codonopsis pilosula roots. Gen Pharmacol. 1996; 27:1347-50. (4).Shan BE, Yoshida Y, Sugiura T, Yamashita U. Stimulating activity of Chinese medicinal herbs on human lymphocytes in vitro. Int J Immunopharmacol. 1999; 21:149-59. (5).Wang ZT, Du Q, Xu GJ, Wang RJ,Fu DZ, Ng TB. Investigations on the protective action of Condonopsis pilosula (Dangshen) extract on experimentally-induced gastric ulcer in rats. Gen Pharmacol. 1997; 28: 469-73. (6).Zheng TZ, Li W, Qu SY, Ma YM, Ding YH, Wei YL.Effects of Dangshen on isolated gastic muscle strips in rats. World J Gastroenterol. 1998; 4:354-356. (7).Singh B, Song H, Liu XD, Hardy M, Liu GZ, Vinjamury SP, Martirosian CD. Dangshen( Condonopsis pilosula) and Bai guo (Gingko biloba) enhance learning and memory. Altern Ther Health Med. 2004; 10: 52-6. (8).Liu JH, Bao YM, Song JJ, An LJ. Condonopsis pilosula(franch) Nannf total alkaloids potentiate neurite outgrowth induced by nerve growth factor in PC12 cells. Acta Pharmacol Sin. 2003; 24: 913-7. (9). Ng TB, Liu F,Wang HX. The antioxidant effects of aqueous and organic extracts of Panax quinquefolium, Panax notoginseng, Codonopsis pilosula, Pseudostellaria heterophylla and Glehnia littoralis. J Ethnopharmacol. 2004; 93: 285-8. [0203] 11. 당귀 [0204] [0205] 보혈 ( 補血 ), 활혈조경 ( 活血調經 ) 및윤장통변 ( 潤腸通便 ) 하는효능이있다. [0206] [0207] [0208] `혈액에대한작용예로부터당귀의사용은보혈제로또는활혈조경하는약물로사용되어왔다. 최근 Wang 등은당귀가미소순환의개선에효과적이라고보고하고있다 (3). 정상 RBC에당귀의추출물을 60분간가한후응집과변형및삼투압에의한용혈에대한영향을조사한결과, 당귀추출물이 RBC의응집속도를감소시키고적혈구의변형능감소를억제하며, 삼투압에의한용혈을현저히감소시킨다는사실을확인하였다. 이러한사실은당귀가적혈구의유동성에긍정적으로작용하며심혈관계에도유효함을의미한다고할수있을것이다. 저자등의연구에의해서도이러한사실은뒷받침된다 (4). 또다른보고에의하면당귀에함유되어있는 ferulic acid가혈소판응집및 serotonin의유리를억제한다고보고하고있다 (2). [0209] [0210] `심혈관계에대한작용당귀의추출물및정유성분은적출심장에대하여수축력을저하시키며, 항부정맥효과도있다 (2). 한편, 관상동맥의저항성을감소시키며순환량을증가시킨다. 뿐만아니라총말초저항을감소시키며심근의산소소비량을감소시킨다. 결과적으로심근의순환을촉진시키며혈압을저하시킨다고볼수있다 (2). 그런데이러한심박수감소, 혈관확장및혈압강하작용은심장에직접적인작용이아니라당귀의중추작용에의한것으로추론된다 (1). 뿐만아니라토끼를이용한동맥경화증모델에서경동맥의비후정도가당귀투여군에서유의적으로억제되었으며, 혈장의 lipid 및 trigly-ceride 함량이감소되었다. 그러나총콜레스테롤함량및 HDL 및 LDL의함량에는영향이없었다 (5). - 14 -
[0211] [0212] `기억력개선작용 Kang 등의보고에의하면당귀에함유되어있는 decursin이 scopolamine으로유도된건망증동물모델에서유의적으로기억력개선의효과를가진다는사실을알수있다 (6). 이러한작용은 acetylcholine esterase(ach E) 활성의억제에기인하는것으로보인다. 그런데 ACh E의저해정도의연구에의하면 decursin 보다는 decursinol이더효과적으로 ACh E를억제한다고알려져있다 (7). [0213] [0214] `면역계에대한작용 10 kda의폴리다당체인 angelan은 macrophage를활설화시켜 IL-2, IL-4, IL-6 및 interferone-감마등의 cytokine 유리를증가시킨다 (8). 이러한비특이적면역활성이일차적으로일어나고이차적으로 helper T- cell 의활성화와 B cell의생성증가를가져온다. 이러한 angelan 의효능으로부터항암제또는항암의보조요법제로개발가능성을시사하고있다. 한편, 중국당귀와 ferulic acid 는 macrophage의식작용에대한증강작용이있다고알려져있다 (9). [0215] [0216] `위장관에대한작용위장관에대한작용은주로중국당귀를이용한연구결과이다. 최근 Ye 등은중국당귀에서분리한 polysaccharide가정상적인위상피세포의증식을촉진시킨다로보고하고있다. (10). Acetic acid 로유발된위궤양모델에서주로 polysaccharide로구성된당귀의추출물을 25 또는 50 mg/kg으로투여한결과대조군보다현저한궤양면적의감소와위점막두께의증가가관찰되었다. 그러나중국당귀에서분리한 poly-saccharide와참당귀에서분리한 angelan이동일한지의여부는확인되어있지않다. [0217] [0218] `자궁근에대한작용홍화와당귀및익모초로구성된처방의추출물이마우스의자궁근을자극한다고알려져있다 (11). 홍화와익모초의경우는 H1 및 α-adrenergic receptor에작용하며당귀의경우는 H1 수용체에작용하여자궁근을자극한다. 그러나 ferulic acid의경우는자궁근수축억제작용이있다고알려져있다 (12). 그런데다른보고에의하면정유성분은자궁근에대하여억제적으로작용하며비휘발성성분의경우는자궁근을수축한다는사실을확인할수있다 (2). [0219] [0220] [0221] `기타작용당귀의진통및항염증작용이알려져있는데, 당귀및성분중의하나인 ferulic acid는 carrageenin으로유도된부종을유의성있게억제하며 acetic acid로유도된모세혈관의투과성증대를억제한다 (13). 한편, 정유성분의하나인 ligustilide는 guinea pig 에서 acetylcholine 및 hista-mine으로야기된천식을억제하며, in vitro에서 ligustilide는진경작용이있다고알려져있다 (2). [0222] [0223] `약물상호작용토끼에서 warfarin의대사등에미치는당귀의효능을확인한결과, 당귀그자체에의해서는혈액응고의지표인 prothrombin time (PT) 에아무런영향을미치지않지만 Warfarin 투여후당귀의투여에의해서는 PT가연장된다 (14). 그러나당귀투여는 Warfarin의 steady 상태에서의농도에는아무런영향을미치지않는다. 따라서만성적으로 warfarin을투여하는경우당귀의사용에는주의를할필요가있다. [0224] @ 참고문헌 [0225] (1).Kang SY, Lee KY, Sung SH, Park MJ, Kim YC. Coumarins isolated from Angelica gigas inhibit - 15 -
acetylcholinesterase: structure-activity relationships. J Nat Prod. 2001; 64: 683-5. [0226] [0227] [0228] [0229] [0230] [0231] [0232] [0233] [0234] [0235] [0236] [0237] [0238] (2). 木村正康, 漢方藥理學硏究動向, 漢方藥理學, 木村正康편,1997, 南山堂, 東京. pp370-372. (3).Wang X, Wei L, Ouyang JP, Muller S, Gentils M, Cauchois G, Stoltz JF. Effects of an angelica extract on human erythrocyte aggregation, deformation and osmotic fragility. Clin Hemorheol Microcirc. 2001; 24: 201-5. (4).Ryu JH,Yook CS.The effects of Sa-Mul-Tang (Si-Wu-Tang), a traditional chinese medicine, on phenylhydrazine-induced anemic rats. J. Appl. Pharmacol., 2001; 9:1-6. (5).Zhui Y, Jing-Ping OY, Yongming L, Lei W, Shuzheng T, Hailu Y, Hanqiao Z, Xiaohong Y. Experimental study of the antiatherogenesis effect of Chinese medicine angelica and its mechanisms. Clin Hemorheol Microcirc. 2000; 22: 305-10. (6).Kang SY, Lee KY, Park MJ, Kim YC, Markelonis GJ, Oh TH, Kim YC. Decursin from Angelica gigas mitigates amnesia induced by scopolamine in mice. Neurobiol Learn Mem. 2003; 79: 11-8. (7).Kang SY,Lee KY, SUNG sh, Park MJ, Kim YC. Coumarins isolated from Angelica gigas inhibit acetylcholinesterase: structure-activity relationships. J Nat Prod. 2001; 64: 683-5. (8).Han SB, Kim YH, Lee CW, Park SM, Lee HY, Ahn KS, Kim IH, Kim HM. Characteristic immunostimulation by angelan isolated from Angelica gigas Nakai. Immunopharmacology.1998; 40: 39-48. (9).Xu LN, Ouyang R, Yin ZZ, Zhang LY, Ji LX. The effect of Dang-Gui(Angelica sinensis) and its constituent ferulic acid on phagocytosis in mice (author's transl). Yao Xue Xue Bao. 1981; 16: 411-4. (10).Ye YN, So HL, Liu ES, Shin VY, Cho CH. Effect of polysaccharides from Angelica sinensis on gastric ulcer healing. Life Sci. 2003; 72: 925-32. (11).Shi M, Chang L, He G. Stimulating action of Carthamus tinctoriusl., Angelica sinensis (Oliv.) Diels and Leonurus sibiricus L. on the uterus. Zhongguo Zhong Yao Za Zhi. 1995; 20: 173-5, 192. (12).Ozaki Y, Ma JP. Inhibitory effects of tetramethylpyrazine and ferulic acid on spontaneous movement of rat uterus in situ.chem Pharm Bull(Tokyo). 1990; 38: 1620-3. (13).Ozaki Y. Antiinflammatory effect of tetramethylpyrazine and ferulic acid.chem Pharm Bull (Tokyo). 1992; 40: 954-6. (14).Lo AC, Chan K, Yeung JH, Woo KS. Danggui (Angelica sinensis) affects the pharmacodynamics but not the pharmacokinetics of warfarin in rabbits. Eur J Drug Metab Pharmacokinet. 1995; 20: 55-60. [0239] 12. 백작약 [0240] [0241] 유간지통 ( 柔肝止痛 ), 양혈염음 ( 養血斂陰 ), 평억간양 ( 平抑肝陽 ) 등의효능이있다. [0242] [0243] [0244] [0245] `내분비계에대한작용 Paeoniflorin과 8-debenzoylpaeoniflorin은 streptozotocin으로당뇨를유발한쥐에서혈당을내리는효과가있다. 이러한혈당억제효과는 1mg/kg 농도로투여한정상혈당쥐에서도확인하였다. 8-debenzoylpaeoniflorin 은작약보다혈당억제효과가낮다. 혈장인슐린의농도는변화가없는것으로보아인슐린비의존적효과인것으로보이며 paeoniflorin에의한글루코스사용능이증가한것으로생각할수있다 (1). Prolyl endopeptidase (PEP) 는 vasopressin, substance P, thyrotropin 분비호르몬 (TRH) 과같은기억과학습 - 16 -
에관여하는 proline 을함유하는뉴런단백질의대사에중요한역할을하는효소이다. PEP 특이적인억제제는기 억력개선효과를기대할수있다. 작약의메탄올추출물은 PEP 를억제하며 IC50 은 2.4 μg/ml 이었다 (2). [0246] [0247] `혈관확장작용 Prostaglandin F2a로수축시킨쥐대동맥에작약을처리했을때혈관이확장되었으며내피세포를제거했을때는혈관확장효과가없었다. NG-nitro-1-arginine methyl ester 처리로인해혈관확장작용이억제되었다. 주성분인 Paeoniflorin 과 paeonol에서는혈관확장효과가없었다. 작약추출물인 Pentagalloylglucose, hexagalloylglucose, heptagalloylglucose, octagalloylglucose은내피세포가있을경우혈관확장을보였으나내피세포가없을때에는이러한효과가없었다. 이러한결과들을통해작약의 gallotannin이내피세포의존적인혈관확장에중요한역할을할것으로추정된다 (3). [0248] [0249] `동맥경화억제효과콜레스테롤을식이시킨토끼에게 nifedipine, diltiazem( 칼슘길항제 ) 또는작약을투여하고혈중지질과산화물 (LPO), TXB2, 6-keto-PGF1a를측정하였다. ni-fedipine (15mg/kg/day), diltiazem(30 mg/kg/day), 작약 (5g/kg/day) 은각각동맥경화를 60.8%, 45.2%, 74.2% 감소시키는효능을나타내었다. 혈중 LPO, TXB2, cholesterol, phospholipid, calcium은약물을복용시킨군에서모두대조군 ( 콜레스테롤단독투여군 ) 에비해낮았지만 6-keto-PGF1a는증가하였다 (4). 이러한결과는작약이동맥경화를억제하는작용이있음을설명한다. [0250] [0251] `혈압상승효과 Guanethidine으로유도한저혈압생쥐에 paeoniflorin을혈관주사하였을때저혈압증상을억제하는것을확인하였다. Adenosine A1 수용체억제제 8-cyclo-pentyl-1,3-dipropylxanthine을전처리했을때이러한효과를억제하였다. 즉작약주성분의하나인 paeoniflorin은 guanethidine으로생쥐뇌에있는 adenosine A1 수용체의활성을경유한저혈압을억제하는작용이있음을알수있다 (5). [0252] [0253] `고콜레스테롤혈증억제효과고지방식이를시킨쥐에작약을투여한후내피세포기능과적혈구의 superoxide dismutase(sod) 활성능을측정하였다. 작약을투여한군은내피세포에의한혈관확장과 SOD의활성이증가하는현상을보였다, 고콜레스테롤혈증은내피세포의기능저하를초래하는데작약은내피세포를보호해고콜레스테롤혈증을억제하는효능이있을것으로보인다 (6). [0254] [0255] `항산화효과 Fenton-type 반응으로수산화지질을발생시켜 2-deoxyribose의분해와쥐간의마이크로솜지질과산화를유도한후항산화효과를확인하였다. 백작약의씨에있는 stilbene계열중 trans-3-viniferin과 gnetin H은 2- deoxyribose의분해와지질과산화를억제하였다. Cis-3-Viniferin, suffruticosol A,B도완만한항산화효과를보였다 (7). [0256] [0257] [0258] `항암효과인간간암세포주인 HepG2와 Hep3B에백작약물추출물을처리했을때 HepG2와 Hep3B의증식을억제하였으며 DNA의절편현상과염색체의응집, 세포주기가 sub-g1 단계에머무는세포사멸 (apoptosis) 현상을확인하였다. Hep3B 세포는 p53이결여된세포이므로백작약에의한세포사멸은 p52경로와독립된경로로보인다 (8). 5종의암세포에서항암성과 Salmonella typhimurium TA100에서 N-methyl-N -nitro-nnitrosoguanidine(mnng) 의돌연변이성을확인하였다. 백작약의씨에있는 6종의 stilbene 계열물질은농도의존 - 17 -
적인세포독성을보였으며생쥐신경교종암세포인 C6 는 IC50 이 8.2 에서 20.5 ug/ml 으로가장강력한독성을 보였다. [0259] Trans-Resveratrol는간암세포주인 HepG2와대장암세포주인 HT-29세포에서가장강력한독성을보였다. 반대로 trans-3-viniferin, cis-vinifrin 및 gnetin H는경부암세포주인 Hela와유방암세포주인 MCF-7에서가장강한독성을보였다. Suffruticosol A와 B는 C6를제외하고는약한독성을나타내었다. 6종의 stilbene계열물질은항돌연변이원성을보였다. 특히 trans-resveratrol은가장강한항돌연변이원성을보였다 (9). [0260] [0261] ` 관절염치료효과 관절염생쥐에작약, 부자, 작약과부자혼합추출물을투여했을때작약과부자혼합추출물에서관절염예 방효과가가장우수하였다 (10). [0262] [0263] [0264] [0265] [0266] [0267] [0268] [0269] [0270] [0271] [0272] @ 참고문헌 (1) Hsu FL,Lai CW, Cheng JT. Antihyperglycemic effects of paeoniflorin and 8- debenzoylpaeoniflorin, glucosides from the root of Paeonia lactiflora. Planta Med. 1997 Aug; 63(4): 323-5. (2) Tezuka Y, Fan W, Kasimu R,Kadota S. Screening of crude drug extracts for prolyl endopeptidase inhibitory activity. Phytomedicine. 1999 Jul; 6(3) : 197-203. (3) Goto H, Shimada Y,Akechi Y, Kohta K, Hattori M, Terasawa K. Endothelium-dependent vasodilator effect of extract prepared from the roots of Paeonia lactiflora on isolated rat aorta. Planta Med. 1996 Oct; 62(5): 436-9. (4) Zhang Y.The effects of nifedipine, diltiazem, and Paeonia lactiflora Pall. on atherogenesis in rabbits. Zhonghua Xin Xue Guan Bing Za Zhi. 1991 Apr; 19(2): 100-3. (5) Cheng JT, Wang CJ, Hsu FL. Paeoniflorin reverses guanethidine-induced hypotension via activation of central adenosine A1receptors in Wistar rats. Clin Exp Pharmacol Physiol. 1999 Oct; 26(10): 815-6. (6) Goto H, Shimada Y, Tanaka N, Tanigawa K, Itoh T, Terasawa K, Effect of extract prepared from the roots of Paeonia lactiflora on endothelium-dependent relaxation and antioxidant enzyme activity in rats administered high-fat diet. Phytother Res. 1999 Sep; 13(6): 526-8. (7) Kim HJ, Chang EJ, Cho SH,Chung SK, Park HD, Choi SW. Antioxidantive activity of resveratrol and its derivatives isolated from seeds of Paeonia lactiflora. Biosci Biotechnol Biochem. 2002 Sep; 66(9): 1990-3. (8) Lee SM, Li ML, Tse YC, Leung SC, Lee MM, Tsui SK, Fung KP, Lee CY, Waye MM. Paeoniae independent pathway. Life Sci. 2002 Sep 27;71(19): 2267-77. (9) Kim HJ, Chang EJ, Bae SJ, Shim SM, Park HD, Rhee CH, Park JH, Choi SW. Cytotoxic and antimutagenic stilbenes from seeds of Paeonia lactiflora. Arch Pharm Res. 2002 Jun; 25(3): 293-9. (10)Xue L, Zhang HY, Qin L, Wang XC, Wang L. Effect of chuanwu and baishao used separately or in combination on adjuvant arthritis in rats. Zhongguo Zhong Yao Za ZHI. 2000 Mar;25(3): 175-8. [0273] 13. 복령 [0274] - 18 -
[0275] 이수삼습 ( 利水渗濕 ), 건비 ( 健脾 ) 및영심안신 ( 寧心安神 ) 의효능이있다. [0276] [0277] 복령은이뇨, 진정효과및강장효과가있다고알려져있는약물이다. [0278] [0279] ` 진정수면작용 Caffeine 으로유도된흥분을억제하며, hexobarbital 로유도된수면을연장시키는작용이있다 (2). [0280] [0281] [0282] `항산화, 항염증작용적혈구세포막에 free radical의생성을야기하는물질인 2.2-azo-bis(2-amidinopropane) dihydrochloride (AAPH) 을사용하여적혈구세포막의용혈을유도한다음복령을처리한경우농도의존적으로적혈구의용혈을억제하는데, pachymic acid, polyporenic acid등의 triterpene carboxylic acid가활성성분이다 (3). 아울러 free radical 생성시스템을이용한 in vitro 실험에서도활성산소소거작용이매우우수하였다 (4). 한편, triterpene 유도체인 3-β-hydroxybenzoyldehydrotumulosic acid의경우 TPA로유발시킨염증반응을현저히억제함을확인하였다 (5). [0283] [0284] `면역증강작용복령의 50% 에탄올추출물은단핵구세포배양 (human peripheral blood monocyte) 에서 IL-1베타, IL-6 및 tumor necrosis factor-α (TNF-α) 의분비를촉진시키며, 이러한작용은용량의존적이다 (6). 한편,transforming growth factor-β (TGF-β) 의분비는억제하였다. 이러한효과로부터복령은면역증강작용이있을것이라는추론이가능하다. [0285] [0286] ` 항당뇨효과 Sato 등은고혈당마우스인 db/db 마우스에복령에서분비된 dehydrotrametenolic acid 를투여한결과현저한 혈당저하작용을관찰하였다 (7). [0287] [0288] [0289] `이뇨작용 25% 알코올추출물을 5일동안 0.5g/kg의용량으로투여했을때 (i.p.). 토끼에서현저한이뇨작용이관찰되었다. 이뇨작용은 0.1mg/kg salyrgan 의근육투여와유사했다. 알코올추출물을랫드에투여했을때도 (p.o.) 이뇨작용이관찰되었다. 그러나토끼의경우경구투여시이뇨작용이나타나지않았다. 한편, orginal-type anti-gbm( glomerular basement membrane) 으로유도한신염랫드에복령에서분리한 pachyman을투여하여조직병리학적검사를실시한결과, 현저한신염억제작용이관찰되었으며, 이러한 pachyman의항신염효과는사구체에 C3의침착저해에의한작용이라고제안하고있다 (8). [0290] [0291] [0292] [0293] @ 참고문헌 (2).Chung KF, Lee CK. Over-the-counter sleeping pills: a survey of use in Hong Kong and a review of their constituents. Gen Hosp Psychiatry. 2002; 24: 430-5. (3).Sekiya N, Goto H, Shimada Y, Endo Y, Sakakibara I, Terasawa K. Inhibitory effects of triterpenes isolated from Hoelen on free radical-induced lysis of red blood cells. Phytother Res. 2003; 17: 160-2. (4).Schinella GR, Tournier HA, Prieto JM, Mordujovich D, Rios JL. Antioxidant activity of anti- - 19 -
inflammatory plant extracts.life Sci. 2002; 70: 1023-33. [0294] [0295] [0296] [0297] (5)Yasukawa K, Kaminaga T, Kitanaka S, Tai T, Nunoura Y, Natori S, Takido M. 3beta-phydroxybenzoyldehydrotumulosic acid from Poria cocos, and its anti-inflammatory effect. Phytochemistry. 1998; 48: 1357-60. (6).Yu SH, Tseng J. Fu-Ling, a Chinese herbal drug, modulates cytokine secretion by human peripheral blood monocytes. Int J Immunopharmacol. 1996; 18: 37-44. (7).Sato M, Tai T, Nunoura Y, Yajima Y, Kawashima S, Tanaka K. Dehydrotrametenolic acid induces preadipocyte differentiation and sensitizes animal models of noninsulin-dependent diabetes mellitus to insulin. Biol Pharm Bull. 2002; 25: 81-6. (8).Hattori T, Hayashi K, Nagao T, Furuta K, Ito M, Suzuki Y. Studies on antinephritic effects of plant components(3): Effect of pachyman, a main component of Poria cocos Wolf on original-type anti- GBM nephritis in rats and its mechanisms. Jpn J Pharmacol. 1992; 59: 89-96. [0298] [0299] 14. 감초 [0300] [0301] 청열해독 ( 淸熱解毒 ), 윤폐지해 ( 潤肺止咳 ), 보비익기 ( 補脾益氣 ), 조화제약 ( 調和諸藥 ) 등의효능이있다. [0302] [0303] [0304] [0305] `항염증작용감초에서분리한 18α-glycyrrhetinic acid 는일반쥐및부신을제거한쥐에서항육아종성작용을보이며당질코르티코이드와유사한항염증성작용을나타낸다. 반면입체이성체인 18β-glycyrrhetinic acid 정상쥐에서는비슷한효과를보이지만부신을제거한쥐에서는작용을나타내지못한다 (1). Percolation 방법에의한감초추출물을 gel 형태로제형화하여아토피성피부염환자를대상으로한임상실험에서효과가확인되었다 (2). 신장염등의신장질환에대한감초의작용이알려져있다. Glycyrrhiza glabra에서분리된 pyranoisoflavan 인 glabridin, Glycyrrhiza ur-alensis에서분리한 licochalcone A 등은신장염 (nephritis) 에대한개선작용이있음이보고되었다 (3,4). 사염화탄소로유도한간손상에대해감초의성분중 18β-glycyrrhetinic acid는 cytochrome P450 2E1의발현억제를통하여간보호효과를나타낸다 (5). [0306] [0307] [0308] [0309] `항암작용생쥐를이용한실험에서감초는자궁에서 estradiol-17베타에의해유도된 c-fos/jun의발현을억제하며 N- methyl-n-nitrosourea 및 estradiol-17베타에의한자궁내막의발암을억제한다 (6,7). Ames bioassay를통한실험에서감초조추출물은항돌연변이원성이있음이확인되었다 (8). Glycyrrhizic acid는 aflatoxin에의해유도된산화적스트레스를억제하고이효과는항발암원성으로서의효능을기대하게한다 (9). 플라보노이드계열의성분인 isoliquiritigenin은전립선암의성장을억제하는효능이있는것으로알려졌다 (10). Glycyrrhiza uralensis의추출물은위암세포주인 MGC-803 세포에서세포고사를유도한다 (11). 감초에서분리된 licocoumarone은인간단핵구백혈병세포주인 U937세포에대해세포고사를유도한다 (12). 감초의 chalcone 계열화합물인 isoliquiritigenin은신장암의폐전이를억제하는작용이알려졌다 (13). - 20 -
[0310] [0311] `해독에미치는작용 Acetaminophen의대사에미치는감초의영향이밝혀졌다. Acetaminophen을투여한수컷 Sprague-Dawley 쥐에감초 methanol 추출물을 6일간전처리한결과 acetaminophen-glucuronide 포합체의담즙과소변을통한누적배설량이유의성있게증가하였다. 이러한결과는감초또는 glycyrrhizin이글루쿠론산화를촉진했다고볼수있으며이작용은실험쥐의간에서이물질에대한해독에감초가영향을미치는것으로해석된다 (14). 부자와생강등의혼합물에감초의배합비율을바꾸며전탕했을때감초의양이증가함에따라 aconitin의양이감호한다 (15). [0312] [0313] `항산화작용감초는심근세포막에서의지질과산화를억제하고산소라디칼을소거하는기능이있다 (16,17). 감초의메탄올추출물은쉽게산화가일어나는물질에대한천연항산화제로서의효과가기대된다 (18). 항산화효과를확인하는다른예로서감초를구강투여한토끼에게진동스트레스를부가할때말초혈중 catalase의활성을감소시키고진동스트레스에대한저항성을증가시킨다는보고가있다 (19). [0314] [0315] `순환기계에대한작용감초에서분리한 aldose 환원효소억제제인 isoliquiritigenin은 in vitro에서아스피린과유사한수준의혈소판응집억제효과를나타낸다 (20,21). Streptozotocin으로유도한당뇨병쥐의좌골신경에서증가된 sorbitol의함량은 isoliquirigenin과같은 aldose reductase 억제제에의해유의성있게억제된다. 그리고당뇨병쥐에서현저하게저하된 PGI2의합성은 aldose reductase 억제제에의해회복된다 (22). [0316] [0317] `항미생물작용 Glycyrrizic acid는 in vitro에서 Epstein- Barr virus의복제를억제하는효과가있다 (23). 감초의성분인 glycyrrhizin을 SARS환자로부터채취한코로나바이러스인 FFM-1과 FFM-2에처리했을때이바이러스들의복제를억제하는효과가확인되었다 (24). 한편 HIV양성환자에서얻은말초혈액단구세포를배양할때 gly-cyrrhizin은 HIV의복제를억제하는효과가있다 (25). [0318] [0319] `기타작용감초의에탄올추출물분획중 liquilitin apioside는말초및중추신경계에작용하여진해작용을나타낸다 (26). 감초의물추출물과 glycyrrhizin 그리고 3-glycyrrhetinic monodesmoside는허혈에의한손상개선및신기능개선효과가있다 (27). 감초는쥐에서표면 mucin의함량을증가시키며에탄올에의한위점막손상을방지한다 (28). 면역계에대한작용으로서감초는면역억제생쥐에대한보호작용이있다. 대식세포의수, 대식세포의화학주성, 그리고림프구세포의배생성반응을회복시키거나증진시킨다 (29). 감초성분 glycyrrhizin의 aglycon인 glycyrrhetinic acid는 puromycin aminonucleoside 신증 (nephrosis) 에효과가있다. 이물질은소변중단백질의양을감소시키고혈청콜레스테롤증가및단백질감소를억제한다 (30). Estrogen과 progestin 같은난소스테로이드호르몬은세로토닌 re-uptake를억제하여세로토닌신경계의기능에영향을미친다. 감초의성분중 isoflavans 계열화합물의일부는 estradiol과유사하게세로토닌 re-uptake를억제하고세로토닌신경계기능을조절하는작용이있다. 이러한작용은월경전후여성의우울증을완화하는데유효할것으로기대된다 (31). 감초의주요성분인 glycyrin 및에탄올추출물은유전적으로당뇨를유발한 KK-Ay mouse에서혈당치를유의성있게저하시킨다 (32). [0320] [0321] @ 참고문헌 (1).Amagaya S,Sugishita E, Ogihara Y,Ogawa S,Okada K, Aizawa T. Comparative studies of the - 21 -
stereoisomers of glycyrrhetinic acid on anti-inflammatory activities. J Pharmacobiodyn. 1984; 7: 923-8. [0322] [0323] [0324] [0325] [0326] [0327] [0328] [0329] [0330] [0331] [0332] [0333] [0334] [0335] [0336] [0337] [0338] (2).Saeedi M, Morteza-Semnani K,Ghoreishi MR. The treatment of atopic dermatitis with licorice gel. J Dermatolog Treat. 2003; 14:153-7. (3).Fukai T, Satoh K, Nomura T, Sakagami H. Preliminary evaluation of antinephritis and radical scavenging activities of glabridin from Glycyrrhiza glabra. Fitoterapia. 2003; 74: 624-9. (4).Fukai T, Satoh K, Nomura T, Sakagami H. Antinephritis and radical scavenging activity of prenylflavonoids. Fitoterapia. 2003; 74: 720-4. (5).Jeong HG, You HJ, Park SJ, Moon AR, Chung YC, Kang SK, Chun HK. Hepatoprotective effects of 18 beta-glycyrrhetinic acid on carbon tetrachloride-induced liver injury: inhibition of cytochrome P450 2E1 expression. Pharmacol Res. 2002; 46: 221-7. (6).Mori H, Niwa K, Zheng Q,Yamada Y, Sakata K,Yoshimi N. Cell proliferation in cancer prevention: effects of preventive agents on estrogen-related endometrial carcinogenesis model and on an in vitro model in human colorectal cells. Mutat Res. 2001; 480-481 : 201-7. (7).Niwa K, Hashimoto M, Morishita S, Yokoyama Y, Mori H, Tamaya T. Preventive effects of Glycyrrhizae radix extract on estrogen-related endometrial carcinogenesis in mice. Jpn J Cancer Res. 1999; 90: 726-32. (8).Sakai Y, Nagase H, Ose Y, Sato T, Yamada A, Hibi M, Yamada F. Anitimutagenicity of extracts from crude drugs in Chinese medicines. Mutat Res. 1986; 174: 1-4. (9).Chan HT, Chan C, Ho JW. Inhibition of glycyrrhizic acid on aflatoxin B1-induced cytotoxicity in hepatoma cells. Toxicology. 2003; 188: 211-7. (10).Kanazawa M, Satomi Y, Mizutani Y, Ukimura O, Kawauchi A, Sakai T, Baba M, Okuyama T, Nishino H, Miki T, Isoliquiritigenin inhibits the growth of prostate cancer. Eur Urol. 2003 May; 43(5): 580-6. (11).Ma J, Fu NY, Pang DB, Wu WY, Xu AL. Apoptosis induced by isoliquiritigenin in human gastric cancer MGC-803 cells. Planta Med. 2001; 67: 754-7. (12).Watanabe M, Hayakawa S, Isemura M, Kumazawa S, Nakayama T, Mori C, Kawakami T. dentification of licocoumarone as an apoptosis-inducing component in licorice. Biol Pharm Bull. 2002; 25: 1388-90. (13).Yamazaki S, Morita T, Endo H, Hamamoto T, Baba M, Joichi Y, Kaneko S, Okada Y, Okuyama T, Nishino H, Tokue A. Isoliquiritigenin suppresses pulmonary metastasis of mouse renal cell carcinoma. Cancer Lett. 2002; 183: 23-30. (14).Moon A, Kim SH. Effect of Glycyrrhiza glabra roots and glycyrrhizin on the glucuronidation in rats. Planta Med. 1997; 63: 115-9. (15).Pei M, Wang S, Li J. Correlativity analysis of detoxicating effect of radix Glycyrrhizae on radix Aconiti preparata in sini decoction. Zhongguo Zhong Yao Za Zhi. 1996; 21: 50-2, inside back cover. (16).Wu W, Luo H, Hou C. In vitro experiment on scavenging oxy-radical and suppressing myocardial lipid peroxidation with sini decoction. Zhongguo Zhong Yao Za Zhi. 1995; 20: 690-1, 701, inside backcover. (17).Wu W, Hou C, Luo H, Jin W, Luo C. Anti-lipid peroxidation effects of sini decoction and its components on ischemic myocardium and the dose- and time-effects. Zhongguo Zhong Yao Za Zhi. 1995; 20: 235-7, 254. (18).Morteza-Semnani K, Saeedi M, Shahnavaz B, Comparison of antioxidant activity of extract from roots of licorice (Glycyrrhiza glabra L.) to commercial antioxidants in 2% hydroquinone cream. J Cosmet Sci. 2003; 54: 551-8. - 22 -
[0339] [0340] [0341] [0342] [0343] [0344] [0345] [0346] [0347] [0348] [0349] [0350] [0351] [0352] [0353] (19).Oganesyan KR. Antioxidant effect of licorice root on blood catalase activity in vibration stress. Bull Exp Biol Med. 2002; 134: 135-6. (20).Tawata M, Aida K, Noguchi T, Ozaki Y, Kume S, Sasaki H, Chin M, Onaya T. Anti-platelet action of isoliquiritigenin, an aldose reductase inhibitor in licorice. Eur J Pharmacol. 1992; 212: 87-92. (21).Tawata M, Yoda Y, Aida K, Shindo H, Sasaki H, Chin M, Onaya T. Anti-platelet action of GU-7, a 3- arylcoumarin derivative, purified from glycyrrhizae radix. Planta Med. 1990; 56: 259-63. (22).Wakasugi M, Noguchi T, Inoue M, Tawata M, Shindo H, Onaya T. Effects of aldose reductase inhibitors on prostacyclin (PGI2)synthesis by aortic rings from rats with streptozotocin-induced diabetes. Prostaglandins Leukot Essent Fatty Acids. 1991; 44: 233-6. (23).Lin JC. Mechanism of action of glycyrrhizic acid in inhibition of Epstein-Barr virus replication in vitro. Antiviral Res. 2003 Jun; 59(1): 41-7. (24).Cinatl J, Morgenstern B, Bauer G, Chandra P, Rabenau H, Doerr HW. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet. 2003; 361: 2045-6. (25).Sasaki H, Takei M, Kobayashi M, Pollard RB, Suzuki F, Effect of glycyrrhizin, an active component of licorice roots, on HIV replication in cultures of peripheral blood mononuclear cells from HIV-seropositive patients. Pathobiology. 2002-2003; 70:229-36. (26).Kamei J, Nakamura R,Ichiki H, Kubo M. Antitussive principles of Glycyrrhizae radix, a main component of the Kampo preparations Bakumondo-to (Mai-men-dong-tang). Eur J Pharmacol. 2003;469:159-63. (27).Yokozawa T, Liu ZW,Chen CP. Protective effrcts of Glycyrrhizae radix extract and its compounds in a renal hypoxia (ischemia)-reoxygenation (reperfusion) model. Phytomedicine. 2000; 6: 439-45. (28).Goso Y, Ogata Y, Ishihara K, Hotta K. Effects of traditional herbal medicine on gastric musin against ethanol-induced gastric injury in rats. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1996; 113: 17-21. (29).Jin R, Wan LL, Mitsuishi T, Kodama K, Kurashige S. Immunomodulative effects of Chinese herbs in mice treated with anti-tumor agent cyclophosphamide. Yakugaku Zasshi. 1994; 114: 533-8. (30).Guoji Y, Orita M, Tashiro K, Abe H. Effects of glycyrrhetinic acid on aminonucleoside nephrosis in rats. Naunyn Schmiedebergs Arch Pharmacol. 1994; 349: 318-23. (31).Ofir R, Tamir S, Khatib S, Vaya J. Inhibition of serotonin re-uptake by licorice constisuents. J Mol Neurosci. 2003; 20: 135-40. (32).Kuroda M, Mimaki Y, Sashida Y, Mae T, Kishida H, Nishiyama T, Tsukagawa M, Konishi E, Takahashi K, Kawada T, Nakagawa K, Kitahara M. Phenolics with PPAR-gamma ligand-binding activity obtained from licorice (Glycyrrhiza uralensis roots) and ameliorative effects of glycyrin on genetically diabetic KK-A(y) mice. Bioorg Med Chem Lett. 2003; 13: 4267-72. 15. 생강 [0354] [0355] 생강은해표산한 ( 解表散寒 ), 온중지구 ( 溫中止嘔 ) 의효능이있다. [0356] [0357] ` 소화작용 - 23 -
[0358] 이약추출물을투여했을때위산과위액의분비가처음에는억제되었으나나중에는촉진하는효과를나타냈다. 근육주사를했을때 24시간동안위액분비가촉진되었다. 개실험에서도이약의추출물은위액및위산분비는촉진하였으며, lipase 활성은변화하지않았으나 pepsin 활성은감소하였다. 6-shogaol 과 6-gingerol 은위수축운동을저해하였다. Gingerol 과 shogaol 들은사염화탄소또는갈락토사민에의한간장해를보호하였다.(1). [0359] [0360] `항구토효과이약의추출물은황산동으로유도한개에서구토증상을억제하였으나, 중추신경을통한구토유도물질인 apomorphine 이나디기탈리스로유도한동물에서는구토를억제하지는못했다. Shogaol 과 zingerone 은항구토물질이다. 이약의가루는동요병에 dimenhydrinate 보다우수하며, 특히구토와배멀미에유효하다 (2). [0361] [0362] `중추신경계효과 6-shogaol 과 6-gingerol 를경구혹은정맥투여시자발적동요병을억제한다. 그리고진경진통작용이있으며 hexobarbital 수면효과를증강시킨다. 6-shogaol 은 6-gingerol 보다강하다. 6-shogaol 은 dihydrocodeine phosphate 에필적할만한진해작용을갖고있다. 생강으로만든주상액은알부민이나포르말린으로유도한흰쥐의관절염에유효했다. [0363] [0364] `심혈과효과건강한사람에게생강을씹게하면혈압이상승하였으며, 수축기혈압뿐만아니라이완기혈압도상승시켰다. 생강과이약의주성분인 gingerol 은기니아피그의적출동맥의근수축력을보였다. 강심효과는 8-gingerol 이가장강하고 10-generol, 6-gingerol 순이였다 (3). [0365] [0366] ` 항균활성및항염작용 생강은항균력이있으며 prostaglandin 의생합성과정을억제하여항염효과를나타낸다 (4). [0367] @ 참고문헌 [0368] [0369] [0370] [0371] (1).Hikino, H., Kino, Y., Kato, N., Hamada, Y., Shioiri, T., Aiyama, R., Antihepatotoxic actions of gingerols and diaryhepatanoids, Journal of Ethnophamacology, 1985; 14, 31-39. (2).Kawai, T., Kinoshita, K oyama, K., Takahashi, K., Anti-rmrtic principles of Magnololia obovata bark and Zingiber officinala rhizome, Planta Medica, 1984; 60, 17-20. (3).Shoji, N., Iwasa, A., Takemoto, T.,Ishida, Y., Ohizumi, Y., Cardiotonic principles of gingiber, Journal of Phamaceutical Sciences, 1982; 71, 1174-1175. (4).Kiuchi F., Shibuya, M., Sankawa, U., Inhibitors of prostaglandin biosynthesis from gingiber, Chemical and Pharmaceutical Bulletin, 1982; 30, 754-757. [0372] 16. 동충하초 [0373] 동충하초란곤충을기주로자실체를형성하는곤충기생균의일종으로전세계적으로 300 여종이보고되고있다. 동충하초는거의모든곤충의유충, 번데기, 성충등전생육단계에걸쳐기주의외비를통하여침입하며균사 는춘체내의모든기관이소비될때까지생장을지속한후단단하게응축되는데자실체를형성하는대표적인동 - 24 -
충하초속으로는자냥균류의맥각균목, 동충하초과에속하는코디셉스속이있으며이밖에도불완전균류의페실로 마이세스속등여러가지속이있다. [0374] [0375] [0376] 동충하초는보폐 ( 保肺 ), 익신 ( 益腎 ), 보정수 ( 補精髓 ), 지혈화담 ( 止血化痰 ) 의효능이있다. [0377] [0378] ` 남성의강정효과 ( 면역력증강작용 ) [0379] [0380] - 면역기능을강화, 기력촉진, 감기, 폐결핵, 만성기침, 천식, 빈혈, 발작 - 자양강장효과를증진시켜남성의성기능장애, 고혈압등에좋은치료약 [0381] [0382] ` 당뇨병과동충하초 -1993 년 pharmaceutical bulletin 학술지에의하면동충하초추출물을당뇨병에걸린쥐의복강내에투여한결 과 3~6 시간후혈당치가 40% 저하됨 [0383] [0384] ` 항암작용및항피로 - 종양억제율 83% 의높은항암성분으로항암효과가높고특히폐암, 간암, 유방암의치료와예방에뛰어난효과 가있어서환자들이상황버섯과더불어병용하여복용하고있다. [0385] [0386] ` 항균작용 - 결핵균, 폐렴구균, 저출혈성패혈증간균등에대한억제작용 [0387] [0388] [0389] ` 중추신경계통작용 - 효율적인수면유도, 중추신경의흥분을억제하는진정작용 - 항경련작용, 체온저하작용 [0390] [0391] [0392] [0393] 17. 천연꿀 @. 천연꿀의효능 `피로회복, 숙취제거 ' 에아주좋은효과가있다. 설탕은분해과정에서비타민이나무기질류를필요로하지만꿀에들어있는당분 ( 포도당, 과당 ) 은체내에서더이상분해될필요가없는단당체로되어있어체내흡수가빠르고아주빨리그리고완벽하게되며영양의밸러스를깨트리지않고곧바로에너지로활용된다. 그래서좋은꿀을먹음으로해서피로회복과숙취제거효과를얻을수있다. [0394] [0395] ` 꿀은위를편안하게해주고특히변비에효과적이다. 벌꿀은장의연동운동을도와정장작용을해주고비피더스균을증식시키고창자속에장균을억제 - 25 -