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1 Journal of Korean Society of Oral Health Science 2018, September. 6(2): 53~58 ISSN (Print) ISSN (Online) 커피생콩추출물에의한안면부통증조절효과 이민경 1, 김희진 2, 박민경 3 동의대학교대학원보건의과학과부교수 1 동의대학교대학원보건의과학과석사과정 2 경운대학교치위생학과조교수 3 Regulation effects of orofacial pain by green coffee bean extracts in rats Min-Kyung Lee 1, Hee-Jin Kim 1, Min-Kyoung Park 2 1 Dept. of Biomedical Health Science, Dong-eui University 2 Dept. of Dental Hygiene, Kyungwoon University Correspondence to Park MK Tel: bukimin@hanmail.net Received Sep 24, 2018 Accepted Sep 29, 2018 ABSTRACT Green coffee bean (GCB) is a raw coffee bean that has not yet been roasted. Green coffee bean is the unroasted or immature robust coffee bean. It is mostly composed of Chlorogenic Acids (CGA), caffeine, trigonelline, and the diterpenes cafestol and kahweol. Chlorogenic Acids (CGA) have the anti-cancer effect of restraining free oxygen radicals. Even though experiments using Green Coffee Bean Exract (GCBE) have been done in various fields, experiments with regard to orofacial pain have been few. The aim of this study is to investigate whether administration of GCBE may be beneficial in pain modulation in inflammatory orofacial pain. We investigated by using GCBE in the development and modulation of orofacial pain in rats. Male, 7- to 8-week-old, Sprague-Dawley rats weighing g were used in this study. Experiments were carried out using a subcutaneous (SC) pain model caused by the injection of 5% formalin into the right vibrissa pad (SC, 50 μl). The amount of scratching or rubbing to the injection site was recorded for 9 consecutive 5-minute intervals following injection of formalin. The experimental subjects were separated into 5 groups (n=4); Naive, formalin(5%), formalin after distilled water (vehicle), formalin after GCBE (p.o.,concentrations of 30,60mg/mL). The number of behavioral reactions of scratching the facial region proximal to the injection site was recorded for 9 consecutive 5-minute intervals following injection of the formalin. As a result, we found that oral administration of GCBE (p.o., concentrations of 30, 60 mg/ml) has an effect of relieving the formalin-induced orofacial pain. In particular, high concentrations (60 mg/ml) of GCBE substantially decrease the nociceptive behavior. These results mean that GCBE may affect the occurrence of orofacial pain and modulation. Therefore, Green coffee bean extract may be a potential therapeutic treatment for orofacial pain. Key words : Green coffee bean, Orofacial pain, Formalin Ⅰ. 서론 현재의대한민국은커피전성시대라해도과언이아니라고 볼수있다. 도심속사람이모이는곳이면반드시커피전문점존재하고있고, 편의점에서판매되는커피브랜드만해도 50여종이넘는다. 커피전문점의맛을집에서도저렴하게즐 Copyright@ 2018 by the Korean Society of Oral Health Science (KOHS) 53

2 Journal of Korean Society of Oral Health Science Vol. 6 No. 2 September 2018 길수있는캡슐커피브랜드도다양해졌다 [1]. 이러한양상이급속도로확대되면서커피는이제없어서는안될대중적인기호음료로사랑받고있다 [2]. International Coffee Organization (ICO) 자료에의하면 2017년우리나라의커피소비량은유럽연합을제외한단일국가로는세계 6위의커피소비국가이다. 이는 2014년 1,873천 ( 단위 :60kg) 포대, 2015년 1,963천포대, 2016년 2,161천포대, 2017년 2,300천포대로해마다증가하고있다 (ICO, 2018). 이는우리나라인구 5,144만 (e-나라지표, 2017) 을기준으로할때평균 335잔 (1잔 8g기준 ) 을마시는것에해당하는양이다 [3]. 우리가마시는커피제조의과정으로는커피체리를수확한후이를커피콩으로가공해야하는데, 과육으로부터씨앗을분리해내고, 속껍질을벗겨내면이것이영어로 Green Coffee Bean, 일본에서는생두 ( 生豆 ), 우리말로커피생콩이된다 [4]. 커피원료인커피생콩은폴리페놀의일종인클로로겐산 (chlorogenic acid) 과카페인 (caffeine) 을포함한다양한생리활성물질이함유되어있다 [5]. 앞서말한바와같이커피의수요가증가함에따라커피의생리활성에관련된연구가활발히이루어지고있는데, 특히클로로겐산은폴리페놀화합물의일종으로대장암과피부노화억제효능이있는것으로알려져있으며발암단백질의활성화를줄여대장암세포의증식과전이과정을억제한다는사실이입증되기도하였고 [6], 납 (Pb) 에노출된마우스에서클로로겐산이체중감소를억제하고, 신장기능및구조를완화시킨다는것을입증하였으며 [7], 또한만성치주염을유발하는그람음성균종인 Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans 에대한항균활성측정연구에서만성치주염유발균을억제하는것을연구에서확인하였다 [8]. 클로로겐산은커피 1 L 당 500 mg에서 800 mg정도포함되어있고, 섭취된클로로겐산중최고 30% 가인체의소장에서흡수되어지며섭취후소변에서는미량만이회수되는것으로미루어보아흡수되지않은클로로겐산은모든위장관에걸쳐존재할수있으므로다양한생물학적효과를기대할수있으며대표적으로항산화물질로써작용한다고보고된바가있어 [6] 천연항산화, 항균제, 항암제등으로주목받고있다. 구강안면부위의통증으로는측두하악장애 (temporomandibular disorders, TMD) 외에두통이나경부통, 설통, 비정형치통, 구강작열감증후군, 편평태선등이있으며 [9], 이들을구강안면통증이라한다. 구강안면통증의치료법은크게약물치료, 물리치료, 장치요법, 심리치료로나누어지는데약물치료에는동통조절을위한진통제가가장일반적으로이용되어지고마취제, 근이완제, 항우울제, 항불안제, 항경련제, 항히스타민제등다양한계열의약물들이사용되기도한다 [10]. 하지만이런약물치료시에는부작용이뒤따르기도하는데약물의단기간복용시소화불량이나설사, 복부통증과같은위장관의부작용이가장흔하며, 장기간복용시위장관의궤양, 출혈, 천공을초래할수있다 [11]. 이러한부작용으로인공합성물질의안전성이거론되면서비교적안전성이확인된천연물에서같은기능을갖는천연물질을얻고자하는노력이집중적으로이루어지고있으며, 특히항산화성물질은인체내의노화억제, 항암등생리활성기능이입증되면서식품그자체보다도생리기능에더많은관심이집중되고있다 [12]. 커피생콩은항산화, 항암및항균등의다양한효능이입증되었으며, 다양한연구가이루어지고있지만구강안면통증에관여하는지에대한연구는거의전무한실정이다. 따라서본연구에서는천연물인커피생콩이안면부통증을유발한흰쥐에서염증성통증에대한경감효과가있는지를확인하고자한다. Ⅱ. 연구대상및방법 1. 실험동물 실험동물은효창사이언스 (Deagu, Korea) 에서 7-8주령의 Sprague-Dawley계수컷흰쥐 ( g) 를공급받아사용하였다 의일정한환경에서 12시간주 / 야순환주기하였고물과사료는자유로이공급하였다. 행동적인억압등에의한실험전스트레스를가능한최소화하였다. 본연구는의식이있는동물의실험에관한통증연구학회의윤리적규정을준수하고동의대학교동물실험윤리위원회의의승인 (C ) 을받아연구를시행하였다. 54

3 Regulation Effects of Orofacial Pain by Green Coffee Bean Extracts in Rats 2. 시약준비 Green Coffee Bean 추출물 (GCBE) 은 ( 주 )KBH한국생활건강에서판매하는 GREEN COFFEE BEAN 추출분말 ( 커피원두 100%, 인도 ) 을구입하여사용하였다. 실험을위한그룹은 Naive, 5% formalin, 대조군 (vehicle, D.W), GCBE 30 mg/ml 투여군, GCBE 60 mg/ml 투여군으로구분하였고, 약물은각각 1 ml 의용량으로경구투여하였고, 약물주입은안면부위통증유도 30분전에시행하였다. 실험동물의안면부피하에 formalin을주입하여유도한안면부통증모델에서 GCBE 경구투여로인한통증행위반응의결과는 <Fig.1> 과같다. 1차통증행위반응은 formalin 주입군, 대조군 (Veh+ F), GCBE (30 mg/ml, 60 mg/ml) 주입군간의유의한차이가없었으며, 2차통증행위반응에서는 formalin 주입군, 대조군에비해 GCBE 두가지농도주입군에서반응이유의하게감소되었으며, 특히 GCBE 60 mg/ml 에서농도의존적으로통증행위반응이감소함을나타내었다. 3. Formalin으로유도한안면부통증 formalin 으로유도한안면부통증반응은 Park[13] 등의연구에서사용된방법과동일하게수행하였다. 실험동물의스트레스를최소화하기위해플라스틱통에 10분이상적응시켰으며대조군 (n=4) 과실험군 (n=4) 은실험동물에각각 distilled water 1 ml 와 GCBE 1 mll 를경구투여하였고 30분경과시오른쪽안면부에 5% formalin(50 μl) 을인슐린주사기 (31 gauge) 를이용하여주입하였다. 주입직후부터 5분간격으로 45분동안통증행위반응을관찰하였으며약물이주입된안면부위를문지르거나긁는행위를관찰하였다. 4. 통계분석실험결과는 IBM SPSS Statistic ver. 22.0(IBM Co., Armonk, NY, USA) 을이용하여다중그룹에서일원배치분산분석을하였고, 사후분석은 LSD post-hoc test를이용하였다. Sigmaplot 2001 (SPSS Inc., Chicago, IL, USA) 을이용하여그래프를나타내었다. 모든결과는평균 ± 표준오차 (standard error of the mean) 로표시하였고통계적인비교를위하여유의수준은 0.05로설정하였다. Ⅲ. 결과 1. 통증행위반응에서 Green Coffee Bean 추출물의통증조절효과 Number of Scratches Naive + Saline Formalin (F) Veh + F GCBE 30 mg/ml + F GCBE 60 mg/ml + F 1st phase 2nd phase <Fig.1> The effects of GCBE on behavior responses following injection of formalin (5%, 50 μl) into vibrissa pad. GCBE reduced behavioral responses during the second phase compared with 5% formalin-treated group. p<0.05 vs Naive, p<0.05 vs F, p<0.05 vs vehicle (veh)+f. GCBE : Green Coffee Bean Extract 2. 시간흐름에서 GCBE 안면부통증조절효과 통증행위반응은시간의경과에따라변화를나타내었으며 GCBE 투여로인한통증행위반응의조절효과는 <Fig. 2> 과같다. formalin의주입으로인한통증행위반응은 20분이후부터증가하여 35분에가장높게나타났으며 40분까지지속되다가 45분에감소되었다. 농도별로보았을때는 GCBE 30 mg/ml 에서는 20분에통증행위반응이가장높았으며 25분이후에는점차감소하였다. GCBE 60 mg/ml 주입군의경구투여에서도 20분에서통증행위반응이가장높았으며이후점차감소함을나타내었다. 20~35분까지통증행위반응이증가하거나지속되는대조군에비하여 GCBE 투여군에서는두가지의농도에서모두통증행위반응이유의하게감소하였다. 55

4 Journal of Korean Society of Oral Health Science Vol. 6 No. 2 September 2018 Number of Scratches Naive + Saline Formalin (F) Vehicle + F GCBE 30 mg/ml + F GCBE 60 mg/ml + F Time <Fig.2> Time response curve for number of scratches in formalin after adminstration of GCBE. GCBE significantly reduced formalin-induced nociceptive response at min.(n=4 in each group). p<0.05 vs Naive, p<0.05 vs F, p<0.05 vs vehicle (veh)+f. Ⅳ. 고찰및결론 본연구는구강안면영역의통증을실험에적용하기위해실험모델의안면부피하에 formalin을주입한통증모델에서커피생콩추출물의통증조절에대한효과를확인하고자하였다. 치과질환중하나인구강안면통증은여러단계로환자한테영향을미친다. 안면부통증이일상생활이나운동활동및사회적활동에미치는영향은이미선행연구에서도밝혀졌으며, 안면부통증은삶의질과연관되어있다 [14]. 구강안면통증은두부, 안면모든구강내구조물의경조직연조직과관련된통증을포함하는용어로서, 치아질환을비롯하여측두하악장애뿐아니라삼차신경통같은신경병성통증까지다양한질환들이유사한형태의동통으로발되므로진단이어려우며두통, 근골격성통증, 신경성통증, 심인성통증, 암등의질환으로부터발생하는통증을모두포함한다 [10]. 이러한통증조절을위해적절한진통제를선택사용하는것은가장중요한일로서일반적으로질환이나통증의특성과관계없이통증의정도에따라비스테로이드소염제 (nonsteroidal antiinflammatory drug, NSAID) 및아편유사제가흔히사용되고있다 [15]. 비스테로이드소염제는진통, 소염, 해열에흔히사용되는약물이다. 1899년 Aspirin이처음판매되기시작한이래현재까지 NSAID는세계적으로가장많이처방되는약제로일부 NSAID는약국에서의사의별도처방없이구매할수있으며, 경구약, 주사제, 외용제등다양한제형으로일상에서널리사용되고있다. 1937년도처음위장관출혈및위궤양의부작용이보고되었으며, 이후소화기계, 심혈관계, 신요로계, 혈액학계에걸친다양한부작용이보고되고있고 [16], 혈액응고장애및혈소판감소증등, 출혈경향이있거나위궤양, 신기능저하, 천식등이있는환자에서는기저질환을악화시킬수있으므로사용을피한다 [17]. 이러한합성의약품사용으로인한부작용이심각히나타남으로써최근의연구방향은안전성이보장된식물, 미생물유래등천연자원을이용한기능성식품개발및의약품연구에관심이집중되고있다 [18]. 이에본연구에서는천연약물로써의다양한생리학적효능이있는커피생콩추출물이구강안면의염증성통증의조절에도효과적일것으로기대하였다. 커피생콩 (Green Coffee Bean) 은빨간열매중에있는종자에서외피를벗겨내면과육이있고그속에내과피와온피에싸여져 2개의종자가마주보며있고이종자를탈곡과건조등정제한것을말한다. 이러면커피원두는배전 (roasting) 과정을거쳐서비로소커피고유의향과맛을낸다 [19]. 커피원두에는 Chlorogenic acid, caffeine, melanoidin 등과같은항산화물질의존재가보고되어왔으며, 생체내활성산소종 (reactive oxygen species) 이증가해서나타나는산화적스트레스로인한노화나심장병과같은각종대사성질환은항산화제에의해예방되거나방어될수있다 [20]. 그러나커피생콩의성분중하나인 chlorogenic acid는원두의볶음과정중에거의소실된다고하여 [21], 최근에는 chlorogenic acid 의함량이높은커피생콩이주목받고있다. Kozuma 등의연구에서는경미한고혈압환자를무작위로추출한실험그룹을다기관또는이중맹검법을시행하여위약군과 3가지의커피생콩추출물 (GCE) 을 4주간투여한결과위약군과비교하여 GCE 투여군은혈압이농도의존적으로유의하게감소하였으며 GCE로인한부작용은관찰되지않았다고하였다. GCE 의일일섭취는고혈압환자의혈압을감소시키며, 뇌졸중과관상동맥질환예방에도움이될수있을것이라고시사하였으며 [22], Edward 등의연구 56

5 Regulation Effects of Orofacial Pain by Green Coffee Bean Extracts in Rats 에서는 40마리의암컷햄스터를두개의동등한그룹으로나누어그룹 I의햄스터는정상적인사료를먹었고, 그룹 II의햄스터에게는커피생콩 (20%) 가루가첨가된같은사료를주었다. 햄스터를식이요법에적응시킨후, 각그룹에서 16 마리의동물을무작위로선택하여햄스터의구강내오른쪽주머니로중금속오일에함유시킨 7,12-dimethylbenz(a) anthracene (DMBA) 0.5% 용액을매주 3회도포하여발암을유도하였다. 4주간관찰한결과커피생콩추출물을복용시킨그룹 II의햄스터는조직학적검사및시각적검사에서 DMBA에의한오른쪽주머니점막의발암발생에상당한지연을보인결과를나타내어 [23], 커피생콩이천연항암제로서의효과를기대하였다. 본연구에서는포르말린으로유도한실험동물의안면부통증에서 30, 60 mg/ml 의커피생콩추출물투여는통증행위반응을유의하게감소시켰다. 특히, 고농도인 60 mg/ml 에서농도의존적인효과를나타내었다. 이러한결과는선행연구에서입증되어진커피생콩추출물이가진항산화, 항균및항암효과를바탕으로염증발생및통증신호의전달물질을억제시키는효과에기인한것으로생각되며이와같은연구결과를기초로하여커피생콩추출물이구강안면부염증성통증조절에대한예방제또는천연치료제로활용이가능할것으로사료되며후속연구에서는커피생콩추출물의반복투여및다른천연물들과의병용요법으로인한상호작용에관한연구가필요하다고생각된다. 참고문헌 1. Yoon BK, Kim HK, Park YM: An Exploratory Study on Korea Green coffee bean Cultivation for the future. Jorunal of Photo Geography 21(3): , Chung JE, Lee JK, Kim JS: The Comparative Analysis of Major Chemical Constituents in Green Coffee Differentiated by Harvesting Time and Roasting Temperatures that Affect Coffee Quality. Journal of The Korea Society for Coffee Industry 4(1):48-68, Hong KO: Analysis on the Trends of Coffee Related Research in Korea and Future Research Direction. Journal of Tourism and Leisure Research 30(2): , Lee JK: The Comparative Analysis of Major Chemical Constituents in Green Coffee Differentiated by Harvesting Time and Roasting Temperatures that Affect Coffee Quality. Journal of The Korea Society for Coffee Industry 1(1):56-62, Shin JH, Ahn YG: Simulateous Determination for the Contents of Caffeine and Chlorogenic Acid in Coffee Beans. The Korean Society Of Community Living Science 24(1):5-12, Park KD: Draw Comparison of Chlorogenic Acid Content of the Dutch Extraction Method. Food Service Industry Journal 13(4): , T Zhang, S Chen, L Chen, L Zhang, F Meng, S Sha, C Ai, J Tai: Chlorogenic Acid Ameliorates Lead-Induced Renal Damage in Mice. Biological Trace Element Research 185(2):1-9, N Bharath, NK Sowmya, DS Mehta: Determination of antibacterial activity of green coffee bean extract on periodontogenic bacteria like Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans: An in vitro study. Contemporary Clinical Dentistry 6(2): , Jun SH, Jung MH: Patients who Visit to Dental Clinic Utilization Behavior, Dental Fear and Oral and Maxillofacial Pain. Journal of Dental Hygiene Science 9(3): , Choi SH, Kim KS, Kim ME, Lee DJ, Jin SB: Treatment Outcome and Prognosis of the Outpatients with Orofacial Pain. Korean Journal of Oral Medicine 31(2): , Suh BJ: 만성두개안면통증의약물치료 ( 영문없음 ). The Journal of The Korean Dental Association 39(4): , Shin DH: 천연물로부터항균및항산화물질의탐색과이용 ( 영문없음 ). Food Science and Industry 36(3):81-89, Park MK, Song HC, Yang KY, Ju JS, Ahn DK: Participation of Peripheral P2X Receptors in Orofacial 57

6 Journal of Korean Society of Oral Health Science Vol. 6 No. 2 September 2018 Inflammatory Nociception in Rats. International Journal of Oral Biology 36(3): , T Maulina, Yubiliana G, Rikmasar R: The Effectiveness of Orofacial Pain Therapy in Indonesia: A Cross-Sectional Study. Pain Research and Treatment Yoon DM: Analgesic therapy according to disease specific pathophysiolog. Journal of the Korean Medical Association 54(7): , Ahn GY, Bae SC: Strategies for the safe use of non-steroidal anti-inflammatory drugs. Journal of the Korean Medical Association 61(6): , Park JC, Choi YS, Kim JH: Current pharmacological management of chronic pain. Journal of the Korean Medical Association 53(9): , Choung MG, Sohn EH: Anti-tumor activity of saponin fraction of Platycodon gradiflourm through immunomodulatory effects associated with NO production in RAW cells. Korean Journal of Plant Resources 24(5): , Kim KJ, Park SK: Changes in Major Chemical Constituents of Green Coffee Beans during the Roasting. Korean Journal of Food Science and Technology 38(2): , Kim MJ, Park JE, Lee JH, Choi NR, Hong MH, Pyo YH: Antioxidant Capacity and Bioactive Composition of a Single Serving Size of Regular Coffee Varieties Commercially Available in Korea. Korean Journal of Food Science and Technology 45(3): , Rhi JW, Shin HS: Antioxidative Effect of Brown Materials Extracted from Roasted Coffee Beans. Korean Journal of Food Science and Technology 25(3): , Kozuma K, Tsuchiya S, Kohori J, Hase T, Tokimitsu I: Antihypertensive effect of green coffee bean extract on mildly hypertensive subjects. Hypertension research 28(9): , Miller EG, Formby WA, Rivera-Hidalgo F, Wright JM: Inhibition of hamster buccal pouch carcinogenesis by green coffee beans. Oral Surgery, Oral Medicine, Oral Pathology 65(6): ,

Lumbar spine

Lumbar spine CT 32 111 DOI : 10.3831/KPI.2010.13.2.111 Lumbar Spine CT 32 Received : 10. 05. 23 Revised : 10. 06. 04 Accepted : 10. 06. 11 Key Words: Disc herniation, CT scan, Clinical analysis The Clinical