고지방식이를 투여한 생쥐에서 마황과 향부자의 항비만 효능 비교 연구 The comparative studies on anti-obesity effects of Ephedrae Herba and Cyperi rhizoma in high fat diet fed mice원문보기
Objectives : This comparative study was to investigate on anti-obesity effects of Ephedrae Herba and Cyperi rhizoma in high fat diet(HFD) fed mice. Methods : Male C57BL/6J mice were fed a normal diet(normal group, N), high fat 45 cal% diet[HFD, control group, C), HFD with Ephedrae Herba(EH group) an...
Objectives : This comparative study was to investigate on anti-obesity effects of Ephedrae Herba and Cyperi rhizoma in high fat diet(HFD) fed mice. Methods : Male C57BL/6J mice were fed a normal diet(normal group, N), high fat 45 cal% diet[HFD, control group, C), HFD with Ephedrae Herba(EH group) and Cyperi rhizoma(CR group) extracts fed for 5 weeks. We were observed as follows : changes of body weight, amount of diet intake, weight of total visceral fats, levels of obesity-related hormones and blood lipids. Results : The change of body weight after EH and CR oral administration significantly more decreased in EH group than that of control group. The FFR(Food Efficiency Ratio) was decreased in EH group, but more increased in CR group than that of control group. The weight of periepididymal and perirenal fats were significantly decreased in EH and CR groups compared to the control group. The levels of serum leptin and insulin were significantly decreased in EH group, and the level of serum adiponectin was increased in EH group compared to control group. The levels of serum triglyceride and total cholesterol were significantly decreased in EH and CR groups, and HDL-cholesterol levels was significantly increased in EH group compared to control group. Conversely in CR group, its values showed the opposite effect. The staining density of lipid droplets within the hepatocytes was widely distributed in CR and control groups, but in EH group, its density was weakly stained. Conclusions : These experimental results suggest that Ephedrae Herba shows conspicuous anti-obesity effect, and Cyperi rhizoma shows weak anti-obesity effect.
Objectives : This comparative study was to investigate on anti-obesity effects of Ephedrae Herba and Cyperi rhizoma in high fat diet(HFD) fed mice. Methods : Male C57BL/6J mice were fed a normal diet(normal group, N), high fat 45 cal% diet[HFD, control group, C), HFD with Ephedrae Herba(EH group) and Cyperi rhizoma(CR group) extracts fed for 5 weeks. We were observed as follows : changes of body weight, amount of diet intake, weight of total visceral fats, levels of obesity-related hormones and blood lipids. Results : The change of body weight after EH and CR oral administration significantly more decreased in EH group than that of control group. The FFR(Food Efficiency Ratio) was decreased in EH group, but more increased in CR group than that of control group. The weight of periepididymal and perirenal fats were significantly decreased in EH and CR groups compared to the control group. The levels of serum leptin and insulin were significantly decreased in EH group, and the level of serum adiponectin was increased in EH group compared to control group. The levels of serum triglyceride and total cholesterol were significantly decreased in EH and CR groups, and HDL-cholesterol levels was significantly increased in EH group compared to control group. Conversely in CR group, its values showed the opposite effect. The staining density of lipid droplets within the hepatocytes was widely distributed in CR and control groups, but in EH group, its density was weakly stained. Conclusions : These experimental results suggest that Ephedrae Herba shows conspicuous anti-obesity effect, and Cyperi rhizoma shows weak anti-obesity effect.
麻黃은 發散之劑로 교감신경과 중추신경의 흥분을 유도하고 防風通聖散과 같은 여러 제제에서 비만 치료의 목적으로 사용되어 지고 있고, 香附子의 경우 理氣解鬱之劑로 부교감신경을 흥분시켜 香砂平胃散처럼 소화 흡수를 촉진하는 제제나 약물로 사용되어 지고 있고 일정정도 비만에 효과적인 것으로 알려져 있다. 이렇게 교감신경의 흥분과 부교감신경의 흥분이라는 다른 방향에서 작용하는 두가지 약물이 비만에서 어떻게 효과적으로 작용되는 지를 비교해보기 위하여 C57BL/6J계 생쥐에 고지방사료를 식이하여 비만을 유도하여 약물 투여 후 체중의 변화량 및 부고환과 신장주위 지방의 무게의 변화, 비만관련 혈청 내 지질과 호르몬의 농도 변화 중심으로 비만에 대한 마황과 향부자의 효능을 살펴보고자 하였다.
제안 방법
고지방사료를 5주간 식이한 후 마황과 향부자 추출물의 항비만 효과를 실험적으로 비교 관찰한 바 다음과 같은 결과를 얻었다.
실험동물은 각 군에 5 마리씩 배정하여 일반사료 급여군(정상군, normal group), 고지방사료 급여군(대조군, control group) 및 고지방사료 급여와 동시에 마황투여군(Ephedrae Herba group, EH group), 향부자투여군(Cyperi rhizoma group, CR group)으로 나누었다. 정상군은 기본사료인 AIN 93G purified rodent diet(FeedLab, Gu-ri, Korea)를 자유 급식 시켰다.
W. 용량으로 1일 1회 일정한 시간에 5주간 경구투여하였다.
실험동물은 각 군에 5 마리씩 배정하여 일반사료 급여군(정상군, normal group), 고지방사료 급여군(대조군, control group) 및 고지방사료 급여와 동시에 마황투여군(Ephedrae Herba group, EH group), 향부자투여군(Cyperi rhizoma group, CR group)으로 나누었다. 정상군은 기본사료인 AIN 93G purified rodent diet(FeedLab, Gu-ri, Korea)를 자유 급식 시켰다. 정상군을 제외한 모든 실험군은 고지방사료에 lard를 첨가하여 열량을 45 cal% fat을 증가시킨 high fat 45 cal% diet(FeedLab, Gu-ri, Korea)를 자유 급식시키면서 대조군에는 멸균수를, 실험군인 EH군은 회수한 마황 동결건조물 150 mg/Kg B.
정상군은 기본사료인 AIN 93G purified rodent diet(FeedLab, Gu-ri, Korea)를 자유 급식 시켰다. 정상군을 제외한 모든 실험군은 고지방사료에 lard를 첨가하여 열량을 45 cal% fat을 증가시킨 high fat 45 cal% diet(FeedLab, Gu-ri, Korea)를 자유 급식시키면서 대조군에는 멸균수를, 실험군인 EH군은 회수한 마황 동결건조물 150 mg/Kg B.W. 용량으로, CR군은 회수한 향부자 동결건조물 300 mg/Kg B.
대상 데이터
본 실험에 사용된 실험동물은 C57BL/6J계 생쥐(수컷, 7주령)는 ㈜샘타코에서 분양받아 1주일간 사육실에서 적응시킨 후 항온항습(22 ± 2 ℃, 65 ± 2 % RH)하에서 사육하였고, 기본사료인 AIN-93G와 고지방 사료인 HFD(high fat diet) 45 cal% diet는 피드랩(Gu-ri, Korea)에서 구입하였으며, 자유 식이하면서 물을 충분히 공급하며 실험에 사용하였다. 기본사료와 고지방사료의 배합비율은 다음과 같다(Table 1).
실험에 사용된 마황(Ephedrae Herba)과 향부자(Cyperi rhizoma)는 광명당제약(Ulsan, Korea)에서 구입하였다.
이론/모형
간조직은 20µm 두께로 frozen microtome(냉동절편기)으로 절단하였다. 간조직 절편은 free floating method를 이용하여 Oil red O 염색18)을 시행하여 광학현미경으로 관찰한 후 촬영하였다.
혈청 중 아디포넥틴 함량은 adiponectin kit (mouse/rat adiponectin ELISA kit, Shibayagi, Japan)를, 혈청 중 leptin 함량은 leptin kit (mouse leptin ELISA kit, KOMA Biotech, korea)를, 혈청 중 insulin 함량은 insulin kit (mouse insulin ELISA kit, Shibayagi, Japan)를 사용하여 Enavall과 Perlmann17)의 방법에 따라 측정하였다. ELISA microplate(96 well)에 anti-mouse adiponectin antibody(100 ㎕/well)로 4℃에서 하룻밤 코팅시킨 후 각 well을 wash buffer(300 ㎕/well)로 3회 세척하고, biotin conjugated anti adiponectin antibody(100㎕/well)를 첨가한 후 30분간 반응시켰다.
성능/효과
麻黃(EH)투여군에서는 대조군에 비해 체중, 식이섭취량 및 내장지방을 유의성 있게 감소하였다. Leptin, insulin의 농도 및 triglyceride와 cholesterol의 농도도도 유의성 있게 감소하였다. 간세포 내 지질입자 크기의 감소와 지질의 분포도 미약하게 관찰되었다.
發散之劑인 麻黃과 理氣解鬱하는 香附子가 비만에 대해서 어떻게 작용하는 지를 비교하기 위해 비만관련 혈청 내 지질과 호르몬의 농도변화 및 간조직의 지질의 침착 정도 등을 관찰한 바 유의한 결과를 얻었다.
香附子(CR)투여군에서는 내장 지방의 무게, triglyceride 및 cholesterol의 농도는 대조군에 비해 유의성 있게 감소하였고 adiponectin의 농도는 유의성 있게 증가하였다.
Leptin, insulin의 농도 및 triglyceride와 cholesterol의 농도도도 유의성 있게 감소하였다. 간세포 내 지질입자 크기의 감소와 지질의 분포도 미약하게 관찰되었다.
이상의 실험 결과를 종합하여 麻黃과 香附子 추출물의 항비만효과를 실험적으로 비교 관찰한 바 마황은 체중과 식이섭취량의 감소, 내장지방 무게의 감소, 혈중 leptin과 insulin 농도의 감소 및 혈중 triglyceride와 total cholesterol 농도의 감소 등에 의한 항비만 효과를 뚜렷하게 나타내었으나, 향부자는 대조적으로 일부 내장지방의 무게 감소, adiponectin의 농도 감소 및 혈청지질의 감소만을 초래하여 항비만 효능은 경미하였다.
참고문헌 (46)
Field AE, Coakley EH, Must A, Spadano JL, Laird N, Dietz WH, Rimm E, Colditz GA. Impact of overweight on the risk of developing common chronic diseases during a 10-year period. Arch Intern Med. 2001;161(13):1581-6.
Polesel J, Zucchetto A, Montella M, Dal Maso L, Crispo A, La Vecchia C, Serraino D, Franceschi S, Talamini R. The impact of obesity and diabetes mellitus on the risk of hepatocellular carcinoma. Ann Oncol. 2009;20(2):353-7.
Hu G, Jousilahti P, Nissinen A, Antikainen R, Kivipelto M, Tuomilehto J. Body mass index and the risk of Parkinson disease. Neurology. 2006;67(11):1955-9.
Whitmer RA, Gunderson EP, Quesenberry CP Jr, Zhou J, Yaffe K. Body mass index in midlife and risk of Alzheimer disease and vascular dementia. Curr Alzheimer Res. 2007;4(2):103-9.
Yang KS, Lee HJ. Pharmacological studies on the Cyperus rotundus. Report of SIHE. 1984;20:26-31.
Kim JG. Processing and manufacturing of herbal medicine. Seoul:Yakup Press. 1997:1057.
Im JP. Herbological pharmacognosy. Seoul: Shinilbooks. 2003:224-5.
Compilation committee of oriental pharmacology text book. Oriental pharmacology. Seoul:Shinilbooks. 2005:632-3.
Han JH, Kim KY. Oriental pharmacology. Seoul:Esdang. 2004:309-11
Enavall E, Perlmann P Enzyme-linked immunosorbent assay, Elisa.3. quantitation of specific antibodies by enzyme-labeled anti-immunoglobulin in antigen-coated tubes. J Immunol. 1972;109(1):129-35.
Bancroft JD, Stevens A, Turner DR. Theory and practice of histological techniques. 4th ed. Newyork:Churchil Livingstone. 1998:205.
Korean society for the study of obesity. Diagnosis and treatment of obesity. Seoul:Korea medical book publisher. 2003:83.
Grundy, SM. Multi-factorial causation of obesity(implications for prevention). Am J Clin Nutr. 1998;67(3):563-72.
Kim JY, Song YS. The study on the korean and western medical literatures obesity. J Oriental Rehab Med. 1993;3(1): 299-304.
Kim DW. A literature review on the obesity symptom. J of Oriental Med. 1992;18(3)
Lee YJ, Lee MJ. Effects of ephedra sinica on obese zucker rats' blood serum lipids and skeletal muscles fatty acid metabolism. J Oriental Rehab Med. 2005;15(3):99-111.
Malecka-Tendera E. Effect of ephedrine and theophylline on weight loss. resting energy expenditure and lipoprotein lioase activity in obese over-fed rats. International J Obesity. 1993;17(6):343-7.
Youn DH, Kang JD, Na CS. Effects of herbal acupuncture (Ephedra sinica and Green tea) at Umnungchon(SP9) and Pungnyung(ST40) in obese Rats induced by high fat diet. Korean J Meridian & Acupoint. 2004;21(1):51-60.
Buemann B, Marckmann P, Christensen NJ, Astrup A. The effect of ephedrine plus caffeine on plasma lipids and lipoproteins during a 4.3MK/day diet. International J Obesity. 1994;18(5):329-32.
Cho EJ, Ryu BH, Song BK, Lee TH, Suh PG, Ryu SH, Kim HS. Purification and Characterization of the Inhibitory Principle agianst Pancreatic Cholesterol Esterase from Ephedra herba. J Korean Soc Food Sci Nutr. 1999;28(4):816-21.
Lee HJ, Yang KS, Lee DH, Kim TH. Pharmacological studies on the Cyperus rotundus. Kor J Pharmacogn. 1985;16(1):49-50.
Jeong SJ, Miyamoto T, Inaqaki M, Kim YC, Higuchi R. Rotundines A-C, three novel sesquiterpene alkaloids from Cyperus rotundus. J Nat Prod. 2000;63(5): 673-675.
Gilani AH, Janbaz KH, Akhtar MS Selective protective effect of an extract from fumaria parviflora on paracetamol induced hepatotoxicity. General Pharmacology: The Vascular System. 1996;27(6):979-83.
Maffei M, Halas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S, Lallone R, Ranganathan S. Leptin levels in human and rodent : measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med. 1995;1(11):1155-61.
Hotta K, Funahasgi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maede K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y. Plasma concentrations of a novel, adipose-specificprotein, adiponectin, in type 2 diabetic patients. Arterioscl Throm Vas. 2000;20(6):1595-9.
Park S, Hong SM, Ahn IS. Long-term ICV infusion of insulin, but not glucose, modulates body weight and hepatic insulin sensitivity through modifying hypothalamic insulin signaling pathway in type 2 diabetic rats. Neuroendocrinology. 2009;89(4): 387-99.
Korean society for the study of obesity. Clinical obesity. Seoul:Korea medical book publisher. 2008:86-9, 260-3, 425-562.
Sacrpace PJ, Zhang Y. Leptin resistnace; a prediposing factor for diet-induced obesity. Am J Physiol Regul Integr Comp Physiol. 2009;296(3): R463-R500.
Kim SJ, Park KG, Kim HK, Kim MK, Lee SW, Hwang JS, Han SW, Hur SH, Lee IK. Serum adiponectin concentration according to visceral fat amount and its relationship of metabolic risk factors in premenopausal obese women. Korean J Med. 2004;66(3): 259-66.
Chai YH, Kim BS, Kim KH, Park HJ. A Study on the Relationship between Obesity Index and Examination Results Among Visitors of a Comprehensive Health Screening Center in Pusan. J. Korean Public Health Assoc. 1993;19(2):64-77.
Han KH. Dyslipidemia in metabolic syndrome. Cardiovascular update. 2003;5(4): 21-7.
Shon CM, Nho MR, Lee YH, Lim JH. The clinical and cost effectiveness of medical nutrition therapy in persons with hypercholesterolemia. J. Korean dietetic association. 2003;9(1):32-90.
Park YJ, Rhee CS, Lee YC. Distribution Patterns of Serum Lipids by Degree of Obesity and Blood Pressure in Korean Adults. J. Lipid Atheroscler. 1993;3(2):165-80.
Son HS. Etiology of dyslipidemia. Diabetes mellitus. 2004;5(2):40-2
Meisenberg G, Simons WH. Medical biochemistry. Seoul:Jungmunkag. 2005:407-67.
Kang HC, Kim SM, Yoon BB, Kook SR, Park YS, Ko YK, Lee DJ. Relationship of body fat, lipid, blood pressure, glucose in serum to waist-hip ratio between obese and normal body mass index group. J Korean Acad Fam Med. 1997;18(3):317-25.
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