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Aqueous Extracts of Jibaekjihwang-tang Ameliorate Ovariectomy-induced Climacterium Symptoms in Mouse

난소적출 마우스에서 지백지황탕 열수 추출물의 갱년기 장애 개선 효과 평가

  • Lee, Seung-Hye (Dept. of Obstetrics & Gynecology, College of Korean Medicine, Daegu Haany University) ;
  • Kim, Dong-Chul (Dept. of Obstetrics & Gynecology, College of Korean Medicine, Daegu Haany University)
  • 이승혜 (대구한의대학교 한의과대학 부인과교실) ;
  • 김동철 (대구한의대학교 한의과대학 부인과교실)
  • Received : 2017.04.24
  • Accepted : 2017.05.22
  • Published : 2017.05.26

Abstract

Objectives: The purpose of this study was to evaluate the anti-climacterium effects of Jibaekjihwang-tang (JBJHT), especially on estrogenic, anti-obesity, hypolipidemic, hepatoprotective against fatty liver and anti-osteoporotic effects by Ovariectomy (OVX) mice. Methods: In order to evaluate anti-climacterium effects of JBJHT, we used bilateral OVX female ddY mice. In this study, six groups were used; sham control, OVX control, estradiol, JBJHT 500, 250 and 125 mg/kg treated groups. Since 28 days after OVX surgery, JBJHT extracts were orally treated, and $17{\beta}$-estradiol $0.03{\mu}g/head$ were subcutaneously injected for 84 days, once a day. And then, we observed anti-climacterium effects classified into five categories; estrogenic, anti-obesity, hypolipidemic, hepatoprotective against fatty liver and anti-osteoporotic effects. The results were compared with $17{\beta}$-estradiol $0.03{\mu}g/head$/day subcutaneous treated OVX mice. Results: OVX control mice showed noticeable hypertrophic changes of adipocytes in abdominal fat pads, fatty liver, uterine atrophic changes, decreases of bone strength were also observed in OVX control. However, these estrogen-deficient climacterium symptoms were significantly and dose-dependently inhibited by JBJHT 500, 250 and 125 mg/kg treatment. Moreover, JBJHT 500 mg/kg showed comparable inhibitory effects as compared to those of estradiol $0.03{\mu}g/head$/day subcutaneous treatment. Conclusions: The results suggest that oral administration of JBJHT 500, 250 and 125 mg/kg has clear dose-dependent anti-climacterium effects in OVX mice.

목 적: 본 연구에서는 지백지황탕 열수추출물(수율=19.76%)의 갱년기 장애 개선 효과를 확인하기 위해 난소적출(Ovariectomy, OVX) 마우스 모델을 이용하여 estrogen 유사 효과, 항비만 효과, 고지혈증 억제 효과, 지방간에 대한 보호 효과 및 골다공증 억제 효과의 5가지 생리활성 효과로 구분하여 평가하였다. 방 법: 본 연구에서는 지백지황탕의 갱년기 장애 개선 효과를 평가하기 위해 사람의 다양한 갱년기 장애와 유사한 증상을 나타내는 난소적출 마우스모델을 활용하였다. 총 6개의 실험군에서 각 8마리의 마우스를 사용하여 위수술 sham 대조군, OVX 대조군, Estradiol 대조 약물군, 지백지황탕 500, 250, 125 mg/kg 투약 실험군으로 나누어 실험하였다. OVX 수술 28일 후부터 지백지황탕 추출물을 각각 500, 250 and 125 mg/kg으로 매일 1 회씩 84일 동안 경구투여하고, $17{\beta}$-estradiol $0.03{\mu}g/head/day$ 피하 투여군과 비교 하여 estrogen 유사 효과, 항비만 효과, 고지혈증 억제 효과, 지방간에 대한 보호 효과 및 골다공증 억제효과로 구분하여 평가 하였다. 본 실험결과는 $17{\beta}$-estradiol $0.03{\mu}g/head/day$ 피하 투여 마우스에서의 결과와 비교 평가 하였다. 결 과: 본 실험의 결과, OVX 대조군에서는 위수술 매체 대조군에 비해 현저한 체중 및 증체량, 체지방 및 복부 축적 지방량, 복부 축적 지방 중량, 혈청 중 AST, ALT, TC, LDL, TG 및 osteocalcin 함량의 증가가 자궁, 간 및 대퇴골 중량, 혈중 bALP 및 estradiol 함량, 평균 total body 골밀도 및 대퇴골 골밀도의 감소와 함께 인정되었으며, 현저한 복부 축적 지방 두께의 증가 및 지방세포의 비대, 간의 지방병증, 자궁의 불용성 위축, 대퇴골의 골량 감소 소견이 각각 인정되었다. 한편 이러한 OVX에 의해 유발된 estrogen 결핍성 폐경기 관련 갱년기 장애 소견이 지백지황탕 추출물 500, 250 및 125 mg/kg의 84일에 걸친 연속 투여에 의해 투여 용량 의존적으로 현저히 억제되었으며, 특히 지백지황탕 500 mg/kg은 estradiol $0.03{\mu}g/head/day$ 피하투여군과 유사한 갱년기 장애 개선 효과를 OVX 마우스에서 나타내었다. 결 론: 이상의 결과에서, 지백지황탕 500, 250 및 125 mg/kg의 경구투여는 OVX 마우스에서 estrogen 결핍성 폐경기 관련 갱년기 장애(비만, 고지혈증, 간 지방병증 및 골다공증) 개선 효과를 투여 용량 의존적으로 나타내었다. 그러나 지백지황탕은 총 8종의 약제로 구성되어 있고, 각각 수많은 생리활성 물질을 함유하고 있어, 향후 생리활성을 나타내는 화학성분의 검색과 더불어 다양한 방면으로 기전적인 연구가 체계적으로 수행되어야 할 것으로 판단된다.

Keywords

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