저밀도 지방단백질 수용체(Low Density Lipoprotein Receptor)의 생합성에 관한 연구 : (II) Ginsenoside의 간 Cholesterol 대사촉진작용

주충노,최주영,이용우,Joo, Chung-No,Choi, Joo-Young,Lee, Yong-Woo 생화학분자생물학회 1987 한국생화학회지 Vol.20 No.4

It was demonstrated that liver cholesterol level of high cholesterol diet and ginsenoside administered rat (test group) was considerably lower than that of control group (high cholesterol diet fed rat). Acyl-coenzyme A: cholesterol acyltransferase(ACAT) activity of the test group was found stimulated. The effect of ginsenoside on the biosynthesis of bile acid from cholesterol by rat liver homogenate was also investigated in vitro and found that ginsenoside stimulated the biosyntehsis. It was also observed the effects several amphiphiles such as sodium dodecyl sulfate. Triton X-100, Lubrol-wx as well as ginsenoside mixture or purified ginsenosides on ACAT and found that all of them stimulated the ACAT activity considerably when they were present in an adequate amount respectively suggesting that nonspecific enzyme stimulating effect of the ginsenoside might be due to the surface activity of ginsenoside. From the above experimental results, it seemed that hypocholesterolemic activity of ginsenosides might be due to the lowered liver cholesterol level by enhanced ACAT activity as well as rapid bile acid biosynthesis from cholesterol. Low cholesterol level might also prevent the LDL receptor biosynthesis inhibition induced by high cholesterol diet resulting in a rapid removal of raised palsma LDL level. Ginsenoside의 고cholesterol혈증 억제작용메카니즘을 규명하기 위해 cholesterol 대사에 미치는 ginsenoside혼합물과 정제된 ginsenoside $Rb_1$, $-Rb_2$, -Re, $-Rg_1$ 의 영향을 조사하였다. 고cholesterol식이와 ginsenoside을 함께 투여한 시험군의 간cholesterol농도는 고cholesterol식이만으로 사육한 대조군에 비하여 현저히 낮았으며, acyl-coenzyme A: cholesterol acyltransferase(ACAT)활성은 시험군의 경우 대조군보다 불과 10% 정도 증가하였으나, 간세포의 미크로좀분획을 이용한 ACAT활성에 미치는 ginsenoside의 in vitro 영향은 ginsenoside의 농도가 $1{\times}10^{-4}{\sim}10^{-5}%$ 일 때 크게 증가하였다. 또한 간 파쇄액을 효소원으로 사용하여 cholesterol로부터의 담즙산 합성에 미치는 gisenoside의 영향을 in vitro에서 관찰한 결과 반응 혼합물에서의 ginsenoside의 농도가 $1{\times}10^{-3}%{\sim}10^{-4}%$ 일때 담즙산 합성이 현저히 증가하였다. 이상의 실험결과로부터 ginsenoside는 간에서의 cholesterol 대사를 촉진하여 간세포내 cholesterol농도를 효과적으로 낮춤으로써 cholesterol로 인한 LDL수용체합성억제를 완화하므로써 고cholesterol식이로 인한 고cholesterol혈증유발을 억제하는 것으로 생각된다.

동물체에서의 황대사에 관한 연구

주충노,이용우,이수영 ( Chung No Joo,Yong Woo Lee,Soo Young Lee ) 생화학분자생물학회 1988 BMB Reports Vol.21 No.1

Absorption of elemental sulfur in rat was investigated. The purified sulfur (powder) containing radioactive crystalline rhombic elemental sulfur(S-35) was administered orally and found that considerable amounts of radioactivities were recovered from liver, jejunum, testis, and cartilage and also from blood, suggesting that elemental sulfur was absorbed in the animal body. It was also found that the radioactivity of sulfate in the blood, liver and cartilage was significantly high, indicating that the elemental sulfur was oxidized to sulfate. Analysis of acid mucopolysaccharides showed that a significant portion of the sulfate was incorporated into mucopolysaccharide sulfate in both liver and cartilage. From the above results, it is likely that absorbed elemental sulfur was converted to sulfate, which might be then incorporated into acid mucopolysaccharides.

동물체에서의 황대사에 관한 연구

주충노,이용우,이수영,Joo, Chung-No,Lee, Yong-Woo,Lee, Soo-Young 생화학분자생물학회 1988 한국생화학회지 Vol.21 No.1

쥐에게 $^{35}S$-원소를 함유한 정제된 황분말을 경구투여한 후 각 조직을 분석한 결과, 간, 공장(jejunum), 정소, 연골 등에서 상당량의 방사능이 회수되었고, 혈청에서도 방사능이 회수되었다. 이것은 고체황이 장기에 흡수되었음을 의미하는 것이다. 고체황의 황산으로의 전환을 검토한 결과, 간의 경우 흡수된 방사능의 약 28%, 연골의 경우는 약 45%가 황산염으로 확인 되었다. 혈청의 경우는 약 70%가 황산염으로 존재함을 관찰하였다. 한편 산성 무코다당류를 분석한 결과, 간의 경우 약 20%, 연골의 경우는 약 31%가 편입된 것으로 추정되었다. 이와같은 실험결과로부터 고체황은 체내에 흡수되어 항산으로 전환된 후 그 일부가 산성 무코다당류로 편입된 것으로 생각된다. Absorption of elemental sulfur in rat was investigated. The purified sulfur (powder) containing radioactive crystalline rhombic elemental sulfur(S-35) was administered orally and found that considerable amounts of radioactivities were recovered from liver, jejunum, testis, and cartilage and also from blood, suggesting that elemental sulfur was absorbed in the animal body. It was also found that the radioactivity of sulfate in the blood, liver and cartilage was significantly high, indicating that the elemental sulfur was oxidized to sulfate. Analysis of acid mucopolysaccharides showed that a significant portion of the sulfate was incorporated into mucopolysaccharide sulfate in both liver and cartilage. From the above results, it is likely that absorbed elemental sulfur was converted to sulfate, which might be then incorporated into acid mucopolysaccharides.

( 2 ) Ginsenoside 의 간 Cholesterol 대사 촉진작용

주충노,최주영,이용우 ( Joo Young Choi,Yong Woo Lee,Chung No Joo ) 생화학분자생물학회 1987 BMB Reports Vol.20 No.4

It was demonstrated that liver cholesterol level of high cholesterol diet and ginsenoside administered rat (test group) was considerably lower than that of control group (high cholesterol diet fed rat). Acyl-coenzyme A: cholesterol acyltransferase(ACAT) activity of the test group was found stimulated. The effect of ginsenoside on the biosynthesis of bile acid from cholesterol by rat liver homogenate was also investigated in vitro and found that ginsenoside stimulated the biosyntehsis. It was also observed the effects several amphiphiles such as sodium dodecyl sulfate, Triton X-100, Lubrol-wx as well as ginsenoside mixture or purified ginsenosides on ACAT and found that all of them stimulated the ACAT activity considerably when they were present in an adequate amount respectively suggesting that nonspecific enzyme stimulating effect of the ginsenoside might be due to the surface activity of ginsenoside. From the above experimental results, it seemed that hypocholesterolemic activity of ginsenosides might be due to the lowered liver cholesterol level by enhanced ACAT activity as well as rapid bile acid biosynthesis from cholesterol. Low cholesterol level might also prevent the LDL receptor biosynthesis inhibition induced by high cholesterol diet resulting in a rapid removal of raised palsma LDL level.

( 1 ) 저밀도 지방단백질 수용체 생합성 억제완화에 미치는 Gisenoside 의 영향

이용우,구자현,주충노 ( Yong Woo Lee,Ja Hyun Koo,Chung No Joo ) 생화학분자생물학회 1987 BMB Reports Vol.20 No.4

The effect of saponin fraction from Panax ginseng C. A. Meyer and the purified ginsenosides-Rb₁, -Rb₂, -Re, -Rg₁ on LDL receptor biosynthesis in high cholesterol fed rat has been investigated. The cholesterol level of blood serum of high cholesterol diet-ginsenoside administered rat was greatly lower than that of high cholesterol diet administered rat (control) suggesting that the ginsenosides have hypocholesterolemic action. Analysis of LDL receptor from various organs such as liver, kidney, adrenal cortex and testis showed that the population of LDL receptors were significantly increased in the above organs suggesting that the hypocholesterolemic action might be brought about by the increase of LDL receptor.

저밀도 지방단백질 수용체(Low Density Lipoprotein Receptor)의 생합성에 관한 연구 : (I) 저밀도 지방단백질 수용체 생합성 억제완화에 미치는 Ginsenoside의 영향

이용우,구자현,주충노,Lee, Yong-Woo,Koo, Ja-Hyun,Joo, Chung-No 생화학분자생물학회 1987 한국생화학회지 Vol.20 No.4

Ginsenoside의 고cholesterol혈증 억제작용 메카니즘을 규명하기 위해 고 cholesterol식이를 투여한 쥐의 low density lipoprotein(LDC) 수용체생 합성에 미치는 인삼 (Panax ginseng C.A. Meyer)의 사포닌 분획과 정제된 ginsenoside-$Rh_1$, $-Rb_2$, -Re, $-Rg_1$의 영향을 조사하여 다음과 같은 결과를 얻었다. 고cholesterol식이와 ginsenoside을 함께 투여한 쥐(시험군)의 혈청 cholesterol농도는 고cholesterol식이만으로는 사육한 쥐(대조군)에 비해 현저히 낮았다. 또한, 각 장기 (간, 신장, 정소, 부신피질)의 cholesterol 농도를 조사한 경우에도 위와같은 결과를 얻었다. 쥐 간의 $^{125}I$-LDL에 대한 LDL수용체의 결합활성은 시험군이 대조군에 비해 크게 증가되었으며, 다른 장기 (신장, 정소, 부신피질)의 경우에도 간의 경우와 유사하였다. 이것은 ginsenoside의 혈중 cholosterol 농도저하작용으로 인하여 고농도의 cholesterol에 의한 LDL 수용체의 생합성억제가 완화된 것으로 생각한다. The effect of saponin fraction from Panax ginseng C. A, Meyer and the purified ginsenoside-$Rh_1$, $-Rb_2$, -Re, $-Rg_1$ on LDL receptor biosynthesis in high cholesterol fed rat has been investigated, The cholesterol level of blood serum of high cholesterol diet-ginsenoside administered rat was greatly lower than that of high cholesterol diet administered rat (control) suggesting tbat the ginsenosides have hypocholesterolemic action, Analysis of LDL receptor from various organs such as liver. kidney, adrenal cortex and testis showed that the population of LDL receptors were significantly increased in the above organs suggesting that the hypocholesterolemic action might be brought about by the increase of LDL receptor.