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Sprague Dawley 흰쥐에서 테스토스테론에 의하여 유발된 전립선 비대증에 미치는 산수유 추출물의 영향

Effects of Corni Fructus on Testosterone-induced Benign Prostatic Hyperplasia in Sprague Dawley Rats

  • 권다혜 (동의대학교 항노화연구소) ;
  • 황보현 (동의대학교 항노화연구소) ;
  • 최은옥 (동의대학교 항노화연구소) ;
  • 김민영 (동의대학교 항노화연구소) ;
  • 지선영 (동의대학교 항노화연구소) ;
  • 김경일 (구례산수유영농조합법인) ;
  • 박노진 (구례산수유영농조합법인) ;
  • 김성옥 (경성대학교 식품응용공학부) ;
  • 홍수현 (동의대학교 항노화연구소) ;
  • 박철 (동의대학교 분자생물학과) ;
  • 황혜진 (동의대학교 식품영양학과) ;
  • 정지숙 (구례산수유영농조합법인) ;
  • 최영현 (동의대학교 항노화연구소)
  • Kwon, Da He (Anti-Aging Research Center, Dongeui University) ;
  • Hwangbo, Hyun (Anti-Aging Research Center, Dongeui University) ;
  • Choi, Eun Ok (Anti-Aging Research Center, Dongeui University) ;
  • Kim, Min Yeong (Anti-Aging Research Center, Dongeui University) ;
  • Ji, Seon Yeong (Anti-Aging Research Center, Dongeui University) ;
  • Kim, Kyung-Il (Gurye Sansooyu Farming Association Corporation) ;
  • Park, No-Jin (Gurye Sansooyu Farming Association Corporation) ;
  • Kim, Sung Ok (Department of Food Science and Biotechnology, College of Engineering, Kyungsung University) ;
  • Hong, Su-Hyun (Anti-Aging Research Center, Dongeui University) ;
  • Park, Cheo (Department of Molecular Biology, College of Natural Sciences, Dongeui University) ;
  • Hwang, Hye-Jin (Department of Food and Nutrition, College of Nursing, Healthcare Sciences & Human Ecology, Dongeui University) ;
  • Jeong, Ji-Suk (Gurye Sansooyu Farming Association Corporation) ;
  • Choi, Yung Hyun (Anti-Aging Research Center, Dongeui University)
  • 투고 : 2018.06.27
  • 심사 : 2018.08.05
  • 발행 : 2018.12.30

초록

노년기 비뇨기 계통에 가장 흔한 증상의 하나인 전립선 비대증은 요도를 둘러싼 전립선의 주위의 평활근과 상피세포의 과다 증식에 의한 것이다. 산수유는 강력한 항산화 효과로 인하여 다양한 질병의 예방 및 치료에 효과적이라고 보고되었지만 전립선 비대증에 대한 효능은 아직 알려지지 않았다. 본 연구에서는 산수유 열수 추출물이 testosterone에 의하여 유도되는 전립선 비대증에 미치는 영향을 조사하였다. 실험동물 내재성 testosterone의 영향을 배제하기 위해 거세를 하였으며, 전립선 비대증을 유도하기 위해, testosterone propionate (TP)를 피하 주사하였다. 산수유 추출물은 TP 주입과 함께 매일 경구 투여하였고, $5{\alpha}$-reductase type 2의 선택적 억제제인 finasteride를 양성 대조군으로 사용하였다. 본 연구의 결과에 의하면, 산수유 추출물 투여군에서는 finasteride 처리군에서와 마찬가지로 혈청 내 dihydrotestosterone 농도가 억제되었으며 전립선 무게 증가와 조직병리학적 변화가 유의하게 감소되었다. 산수유 추출물은 또한 전립선 조직 및 혈청에서 각각 TP에 의해 증가된 $5{\alpha}$-reductase type 2의 발현 및 농도를 유의적으로 억제하였다. 아울러 산수유 추출물은 TP에 의하여 유도된 AR, AR의 co-activator 및 세포증식 마커 단백질들의 발현 증가뿐 만 아니라 prostate-specific antigen의 수치와 발현도 감소시켰다. 결론적으로 산수유 추출물은 전립선 비대억제를 위한 식의약 소재로서의 개발 가능성이 매우 높음을 의미한다.

Benign prostatic hyperplasia (BPH) is characterized by prostatic hypertrophy mainly in the elderly. Corni Fructus is reportedly effective in the prevention and treatment of various diseases, but its efficacy on BPH has not been previously studied. In the present study, we investigated whether or not a Corni Fructus water extract (CF) could prevent testosterone-induced prostatic hyperplasia in rats. To induce BPH, castrated rats were subcutaneously injected with testosterone propionate (TP). CF was administered daily by oral gavage, along with the TP injections, and finasteride, a selective inhibitor of $5{\alpha}$-reductase type 2, was used as a positive control. The results show that CF significantly reduces prostate weight and histopathologic changes while also decreasing levels of serum dihydrotestosterone, similar to the finasteride-treated group. CF also suppresses TP-induced $5{\alpha}$-reductase expression and concentration in prostate tissue and serum, respectively. Furthermore, CF markedly inhibited TP-induced expression of the androgen receptor (AR) and the steroid receptor coactivator 1, an AR coactivator, which was associated with a decrease in prostate-specific antigen levels in both serum and prostate tissue. In conclusion, the results of this study indicate that CF weakens BPH status by inactivation of $5{\alpha}$-reductase and AR.

키워드

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Fig. 1. Effects of CF administration on prostate weights in TP-induced BPH rats.

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Fig. 2. Effects of CF administration on the histological changes in the prostate tissues and DHT in serum of TP-induced BPH rats.

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Fig. 3. Effects of CF administration on 5α-reductase type 2 in TP-induced BPH rats.

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Fig. 4. Effects of CF administration on the expression of AR, SRC1, PCNA and cyclins in TP-induced BPH rats.

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Fig. 5. Effects of CF administration on PSA in TP-induced BPH rats.

Table 1. Classification of experiment groups

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Table 2. Effects of CF treatment on the several organ weights of TP-induced BHP rats

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Table 3. Effects of CF treatment on the serum biochemical parameters for the liver and kidney functions of TP-induced BHP rats

SMGHBM_2018_v28n12_1507_t0003.png 이미지

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