• 약학회지
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• 제51권6호
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• pp.495-499
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• 2007

Seven epoxy- and hydroxyandrostane derivatives ($DH-1{\sim}DH-7$) and nine epoxy- and hydroxycholestane derivatives ($CH-1{\sim}CH-9$) with unsaturation in ring A and ring B were synthesized from DHEA and cholesterol, respectively. The antinociceptive effects of all synthesized compounds were measured by hot plate method. Most of androstane derivatives except $1{\alpha},2{\alpha}$-epoxy-4,6-androstadiene-3,17-dione (DH-3), and CH-6, CH-7 and CH-9 exhibited antinociceptive effect. 1,4-Androstadiene-$3{\beta},17{\beta}$-diol (DH-5, 100 mg/kg, $35.8{\pm}7.39$), $6{\alpha},7{\alpha}$-epoxy-1,4-androstadiene-3,17-dione (DH-4, 100 mg/kg, $32.6{\pm}5.50$) and $5{\alpha},6{\alpha}$-epoxy-17-oxo-androstan-$3{\beta}$-ol (DH-1, 100 mg/kg, $32.5{\pm}2.98$) were more effective than morphine (10 mg/kg, $30.6{\pm}0.5$). The analgesic effects of androstane derivatives on acetic acid writhing in mice were lower than aspirin. The androstane derivatives were less effective than ibuprofen at inhibiting effects on the carrageenin induced paw oedema. 4,6-Cholestadien-$3{\beta}$-ol (CH-5), $1{\alpha},2{\alpha}$-epoxy-4,6-cholestadien-$3{\beta}$-ol (CH-7) and $7{\alpha}$-hydroxy4-cholesten-3-one (CH-9) showed the decrease of serum triglyceride and total cholesterol levels in poloxamer P-407 injected rat.

• 한국수산과학회지
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• 제31권4호
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• pp.508-515
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• 1998

대표적인 양식 해조류 종인 김 (Polphyra yezoensis) 추출물을 쥐에 복강주사하여 항고콜레스테롤 효과를 조사하였다. 고콜레스테롤혈증은 Triton WR-1339 (600$\mu$g/ g-체중)를 복강주사하여 유도시켰다. 이때 혈중 콜레스테롤은 Triton 주사후 20시간만에 최대치로 상승되었다. 김 추출물 (30$\mu$g/g-체중)을 Triton과 동시에 복강 오른쪽과 왼쪽에 주사하였을 때 총콜레스테롤 및 저밀도지질단백은 Triton만의 주사 경우에 비하여 $37\%$ 및 $24\%$ 정도로 감소되었다. 그리고 조직화학적 변화를 보기 위하여 쥐의 간 조직을 Triton 및 김 추출물을 주사한 후 40시간째에 fromol-calcium 용액에 고정시켰다. Triton 주사 후간조직에서 나타난 일반적인 형태변화는 그물구조의 세포질을 가진 간세포가 간엽 전체에서 관찰되었고, 간세포 손상으로 인한 간세포판은 사라졌다. 그러나 김 추출물 투여군에서는 그물구조의 세포질을 가진 간세포가 줄었으며, 간세포내에 침착되어 있던 지방 입자와 콜레스테롤입자의 수와 크기도 감소하였다. 따라서 김 추출물은 Triton 주사로 인한 지방대사장애로 초래되는 고콜레스테롤혈증의 감소에 유의한 작용을 하는 것으로 사료된다.

• Journal of Microbiology and Biotechnology
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• 제12권2호
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• pp.222-227
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• 2002

Squalene synthase catalyzes the reductive dimerization of two molecules of farnesyl diphosphate to form squalene at the final branch point of the cholesterol biosynthetic pathway. Due to the unique position of this enzyme in the pathway, its inhibitors may have advantages as antihypercholesterolemic agents. Therefore, selective inhibitors of squalene synthase do not prevent the formation of the essential branch products of the isoprene pathway, such as dolichol, coenzyme-Q, and prenylated proteins, as might be expected for inhibitors of enzymes earlier in the pathway; for example, lovastatin and mevalotin. The current study reports that CJ90002, a pentagalloylglucose isolated from Paeonia moutan SIM (Paeoniaceae), which is an important Chinese crude drug used in many traditional prescriptions, was a potent inhibitor of rat microsomal squalene synthase, and also a potent inhibitor of cholesterol biosynthesis in vitro. In addition, the intraperitoneal and oral administration of CJ90002 had a significant lowering effect on plasma cholesterol levels in hamsters.

• 약학회지
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• 제51권1호
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• pp.56-62
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• 2007

Twelve epoxy and hydroxydiosgenin derivatives (DI-1${\sim}$DI-12) were synthesized from diosgenin (25(R)-5-spirosten-3${\beta}$-ol). Diosgenin was epoxidized with m-chloroperoxybenzoic acid (mCPBA) to oxidize 25(R)-4${\alpha}$,5${\alpha}$-epoxyspirostane (DI-1). Diosgenin was reacted with DDQ to form 25(R)-1,4,6-spirostatrien-3-one (DI-2), which was treated with 30% H$_2$O$_2$ to give 25(R)-1${\alpha}$,2${\alpha}$-epoxy-4,6-spirostadien-3-one (DI-3) and treated with mCPBA to form 25(R)-6${\alpha}$,7${\alpha}$-epoxy-1,4-spirostadien-3-one (DI-7), respectively. DI-3 was reduced with NaBH$_4$ to afford 25(R) -1${\alpha}$,2 ${\alpha}$-epoxy-4,6-spirostadien-3${\beta}$-ol(DI-4) and reacted with Li metal in absolute ethanol to form 25(R)-2-ethoxy-1,4,6-spirostatrien-3-one (DI-5). DI-7 was reduced with NaBH$_4$ to produce 25(R)-3${\beta}$,7${\alpha}$-dihydroxy-4-spirostene (DI-8) and treated with Li metal in liquid ammonia to produce 25(R)-7${\alpha}$-hydroxy-4-spirosten-3-one (DI-9). DI-2 was reduced with NaBH$_4$ to form 25(R) -4,6-spirestadien-3${\beta}$-ol(DI-10), which was stirred with 30% H$_2$O$_2$ to synthesize 25(R)-4,6-spirostadien-3-one (DI-11) and reacted with mCPBA to give 25(R)-4${\beta}$,5${\beta}$ -epoxy-6-spirosten-3${\beta}$-ol (DI-12), respectively. The antinociceptive effects of synthesiz ed compounds were measured by hot plate method and compound DI-7 signifcantly exhibited antinociceptive effect. DI-2 decreased the serum triglyceride and total cholesterol levels in poloxamer P-407 injected rat.