化学応用部門

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化学応用部門

教授門田重利（薬学博士）

助教授畑中保丸（薬学博士）助手手塚康弘（薬学博士）技官長岡武馬（薬学修士）

。研究目的

本部門では，化学的手法を応用する和漢薬の基礎研究として，天然薬物を中心とする生理活性分子の医薬化学的及び生物有機化学的研究を行っている。即ち，天然薬物の成分単離，構造解析，

合成等の，和漢薬成分に関する化学的研究を行う。さらに，その過程で構造が明らかとなる天然薬物成分について，その構造・活性相関，構造・機能相関の化学的解明に取り組んでいる。本年度の主な研究課題は下記の通りである。

。研究概要

I.天然薬物成分の単離，構造解析，合成，作用 1）人参，丹参，草豆蓮，蒙麗等の和漢生薬

2 ）インドネシア，ベトナム，ミャンマー，ネパール等の薬用植物

3

）窮香から単離した新規成分ムスクライド類の合成及び誘導体化 4）肝臓病や骨粗軽症に有効な天然薬物成分の開発研究

II.薬物・生体高分子相互作用系の生物有機化学

1）構造・機能相関解析に有用な独自の化学的手法の開発

2

）機能性生体高分子の構造生物学

上記の研究課題によって得られた本年度の成果（原著及び学会報告）は下記の通りである。

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。原著

1 ) Xiong Q . , Hase K . , Tezuka Y . , Tani T . , Namba T . , and Kadota S . : H e p a t o p r o t e c t i v e A c t i v i t y o f Phenylethanoids from G i s t α n c h e d e s e r t i c o l a . Planta Medica, 6 4 : 1 2 0

^四

1 2 5 ,1 9 9 8 .

Abstract: Four p h e n y l e t h a n o i d s i s o l a t e d from t h e stems o f C i s t α n c h e d e s e r t i c o l a , v i z . a c t e o s i d e ( 1 ) , 2

−

a c e t y l a c t e o s i d e ( 2 ) , i s o a c t e o s i d e ( 3 ) and t u b u l o s i d e B ( 4 ) , s i g n i f i c a n t l y s u p ‑ p r e s s e d NADPH/CCL‑induced l i p i d p e r o x i d a t i o n i n r a t l i v e r m i c r o s o m e s . A d d i t i o n o f them t o primary c u l t u r e d r a t h e p a t o c y t e s e f f i c i e n t l y p r e v e n t e d c e l l damage i n d u c e d by e x p o s u r e t o CCL o r D ‑ g a l a c t o s a m i n e ( D ‑ G a l N ) . A c t e o s i d e ( 1 ) f u r t h e r showed p r o n o u n c e d a n t i

占

e p a t o t o x i c a c t i v i t y a g a i n s t CCL i n v i v o .

2 ) Tezuka Y . , Kasimu R . , L i J . X . , Basnet P . , Tanaka K . , Namba T . , and Kadota S . : C o n s t i t u e n t s o f Roots o f S α l v i a d e s e r t α S c t t A N G . (Xinjiang‑Danshen). Chem. Pharm.

B u l l . , 4 6 : 1 0 7 ‑ 1 1 2 , 1 9 9 8 .

Summary: S α l v i a d e s e r t α S c t t A N G . ( L a m i a c e a e ) i s a p l a n t grown i n X i n j i a n g p r o v i n c e i n C h i n a , and i t s d r i e d r o o t s a r e c a l l e d X i n j i a n g ‑ D a n s h e n . T h i s p l a n t has not b e e n u s e d a s a m e d i c i n e o r a f o o d , but r e c e n t l y i t was r e p o r t e d t h a t Xinjiang‑Danshen i s mixed i n Danshen

( r o o t s o f S . m i l t i o r h i z αBuNGE), a well‑known C h i n e s e c r u d e d r u g , a t X i n j i a n g p r o v i n c e when l a t t e r was i n s h o r t s u p p l y . We examined t h e c o n s t i t u e n t s o f t h e r o o t s o f S . d e s e r t α

( X i n j i a n g ‑ D a n s h e n ) and i d e n t i f i e d a new c a f f e i c a c i d t r i m e r [ s a l v i a n o l i c a c i d K ( 1 ) ] , along with two known c a f f e i c a c i d dimers [ s a l v i a f l a s i d e ( 2 ) , r o s m a r i n i c a c i d ( 3 ) ] , a known c a f f e i c a c i d t e t r a m e r [ l i t h o s p e r m i c a c i d B ( 4 ) ] , s e v e n known a b i e t a n e ‑ t y p e d i t e r p e n e s [ 6 , 7 ‑ dehydroroyleanone ( 5 ) , r o y l e a n o n e ( 6 ) , t a x o d i o n e ( 7 ) , f e r r u g i n o l ( 8 ) , 7‑0me thy lhorminone ( 9 ) , 7 ‑ 0 ‑ a c e t y l h o r m i n o n e ( 1 0 ) , horminone ( 1 1 ) ] , and a known s t e r o i d [ d a u c o s t e r o l ( 1 2 ) ] . F i v e o f t h e d i t e r p e n e s ( 5 , 6 , 9 ‑ 1 1 ) were r o y l e a n o n e s and t h e main c a f f e i c a c i d d e r i v a t i v e was t h e t r i m e r

1.

These d i f f e r e d from t h e c o n s t i t u e n t s o f r o o t s o f S . m i l t i o r h i z α

，

which c o n t a i n s t a n s h i n o n e s a s d i t e r p e n e s and magnesium l i t h o s p e r m a t e Bas t h e main c a f f e i c a c i d d e r i v a ‑ t i v e . Thus, t h e mixing o f Xinjiang‑Danshen with Danshen i s not a p p r o p r i a t e and two s h o u l d b e c o n s i d e r e d d i f f e r e n t d r u g s .

3 ) Kasimu R . , Tanaka K . , Tezuka Y . , Gong Z . ‑ N . , L i J . X . , Basnet P . , Namba T . , and Kadota S . : Comparative Study o f Seventeen S α l v i αPlants; Aldose Reductase I n h i b i t o r y A c t i v i t y o f Water and MeOH Extracts and Liquid Chromatography‑

Mass Spectrometry (LC‑MS) Analysis o f Water E x t r a c t s . Chem. Pharm. B u l l . , 4 6 : 5 0 0 ‑ 5 0 4 , 1 9 9 8 .

Summary : The dry r o o t and rhizome o f S α l v i α m i l t i o r h i z α

（

Lamiaceae) a r e u s e d a s a c r u d e

drug Danshen, w h i l e t h o s e o f S . d e s e r t α

（

X i n j i a n g ‑ D a n s h e n ) a r e mixed i n Danshen a t

X i n j i a n g p r o v i n c e when t h e former i s i n s h o r t s u p p l y . The water and MeOH e x t r a c t s o f

S.

d e s e r t αshowed s t r o n g a l d o s e r e d u c t a s e (AR) i n h i b i t o r y a c t i v i t y , and t h e i r a c t i v e c o n s t i t u ‑

e n t s were d e t e r m i n e d t o b e p o l a r compounds d i f f e r e n t from t a n s h i n o n e s o f S . m i l t i o r h i z α

，

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i . e . , l i t h o s p e r m i c a c i d B ( 1 ) , s a l v i a n o l i c a c i d K ( 2 ) , s a l v i a f l a s i d e ( 3 ) , and r o s m a r i n i c a c i d ( 4 ) ( I C 5 0 , 2 . 6 3 ‑ 3 . 9 1

μM).

We a l s o examined t h e AR i n h i b i t o r y a c t i v i t y o f w a t e r and MeOH e x ‑ t r a c t s o f s e v e n t e e n S αl v i α p l a n t s , i n c l u d i n g t e n s p e c i e s o f Danshen r e s o u r c e s C S . b o w l e y α n α

，

S . d e s e r t α

，

S . m i l t i o r h i z α

，

S m i l t i o r h i z αvar. m i l t i o r h i z αf.αl b a , S . pαr a m i l t i o r h i z a , S . p α r αm i l t i o r h i z αf. p u r p u r e o ‑ r u b r α

，

S przew α l s k i i , S . przew α l s k i i u α

れ

mαnd α r i n o r u m ,S . s i n i c α f . p u r p u r e α

，

S t r i j u g α

） ,

and t h e i r w a t e r e x t r a c t s were a l s o a n a l y z e d by l i q u i d chroma‑

t o g r a p h y ‑ m a s s s p e c t r o m e t r y (LC‑MS). The r e s u l t s i n d i c a t e d t h a t t h e r e were f o u r t y p e s w i t h r e g a r d t o t h e AR i n h i b i t o r y a c t i v i t y and t h r e e t y p e s w i t h r e g a r d t o t h e amount o f 1 . Ten s p e c i e s u s e d a s Danshen r e s o u r c e s showed good c o r r e l a t i o n b e t w e e n t h e AR i n h i b i t o r y a c t i v i t y and t h e m o r p h o l o g i c a l c l a s s i f i c a t i o n . H o w e v e r , t h e i n t e n s i t i e s o f t h e i r AR i n h i b i t o r y a c t i v i t y v a r i e d , and t h e y c o n t a i n e d 1 i n v a r y i n g a m o u n t s . T h e s e f a c t s s u g g e s t e d t h a t t h e t e n s p e c i e s w e r e n o t t h e s a m e , and t h u s t h e i r u s e a s a Danshen r e s o u r c e s h o u l d b e b a s e d on t h e i r a c t i v i t y and/or a c t i v e c o n s t i t u e n t s .

4 ) P r a s a i n J . K . , L i J . ‑ X . , Tezuka Y . , Tanaka K . , Basnet P . , Dong H . , Namba T . , and Kadota S . : Calyxin H, E p i c a l y x i n H, and B l e p h a r o c a l y x i n s A and B , Novel D i a r y l h e p t a n o i d s from t h e S e e d s o f A l p i n i a b l e p h a r o c a l y x : J . N a t . P r o d . , 6 1 : 2 1 2 ‑ 2 1 6 , 1 9 9 8 .

Summary : Four u n p r e c e d e n t e d d i a r y l h e p t a n o i d s , c a l y x i n H ( 1 ) and e p i c a l y x i n H ( 2 ) , p o s s e s s i n g a d i a r y l h e p t a n o i d u n i t and a c h a l c o n e m o i e t y , and b l e p h a r o c a l y x i n s A ( 3 ) and B ( 4 ) , p o s s e s s i n g two d i a r y l h e p t a n o i d u n i t s and a c h a l c o n e m o i e t y , were i s o l a t e d from t h e s e e d s o f A l p i n i a b l e p h α r o e α l y x . The s t r u c t u r e s o f 1 ‑ 4 , i n c l u d i n g a b s o l u t e s t e r e o c h e m i s t r y , were e l u c i

^岨

d a t e d by s p e c t r o s c o p i c means and a f t e r a c o n s i d e r a t i o n o f t h e i r b i o g e n e s i s .

5 ) P r a s a i n J . K . , Tezuka Y . , Hase K . , Basnet P . , Dong H . , Namba T . , and Kadota S . : I n h i b i t o r y E f f e c t o f D i a r y l h e p t a n o i d s on N i t r i c Oxide P r o d u c t i o n i n A c t i v a t e d Murine Macrophages. B i o l . Pharm. B u l l . , 2 1 : 3 7 1

^四

・ 3 7 4 ,1 9 9 8 .

Summary: T h i r t e e n n o v e l d i a r y l h e p t a n o i d s b e a r i n g a c h a l c o n e o r a f l a v a n o n e m o i e t y C l ‑

1 3 ) , a new c u r c u m i n d e r i v a t i v e , 1 , 2 ‑ d i h y d r o b i s ( d e ‑ O ‑ m e t h y l ) c u r c u m i n ( 1 4 ) , and two known

f l a v o n o i d s ( 1 5 and 1 6 ) i s o l a t e d from t h e s e e d s o f A l p i n i a b l e p h α r o e α l y x K . Schum. were

t e s t e d f o r t h e i r i n h i b i t o r y e f f e c t s on n i t r i c o x i d e (NO) p r o d u c t i o n i n l i p o p o l y s a c c a r i d e

( L P S ) ‑ a c t i v a t e d murine macrophages J 7 7 4 . 1 i n v i t r

・

o .A l l t h e t e s t e d compounds i n h i b i t e d NO

p r o d u c t i o n i n a c o n c e n t r a t i o n ‑ d e p e n d e n t manner C I C s o = 3 6 ‑ 5 6 8

μM).

Among t h e compounds

e x a m i n e d , b l e p h a r o c a l y x i n B ( 1 3 ) was t h e most p o t e n t i n h i b i t o r o f NO p r o d u c t i o n ( I C s o = 3 6

μM).

A n a l y s i s o f t h e s t r u c t u r e a c t i v i t y r e l a t i o n s h i p among t h e s e n o v e l d i a r y l h e p t a n o i d s l e d

t o t h e c o n c l u s i o n t h a t t h e p o s i t i o n o f a t t a c h m e n t o f a c h a l c o n e o r a f l a v a n o n e t o a

d i a r y l h e p t a n o i d d o e s n o t a f f e c t t h e i r i n h i b i t o r y p o t e n c y a l t h o u g h t h e i r p r e s e n c e i n a s s o c i a ‑

t i o n c a u s e s a s u b s t a n t i a l enhancement o f t h e i n h i b i t o r y a c t i v i t y . M o r e o v e r , a c o n j u g a t e d

d o u b l e bond i n a c h a l c o n e m o i e t y p o t e n t i a t e d t h e i n h i b i t o r y a c t i v i t y . On t h e o t h e r h a n d ,

h e x a m e t h o x y d e o x y c a l y x i n A ( 1 7 ) and p e n t a m e t h o x y c a l y x i n B ( 1 8 ) , a m e t h y l a t e d p r o d u c t

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o f c a l y x i n A ( 1 ) and an e p i m e r i c m i x t u r e o f c a l y x i n B , showed g r e a t l y r e d u c e d a c t i v i t y s u g ‑ g e s t i n g t h a t p h e n o l i c h y d r o x y l groups a r e i n v o l v e d i n t h e i n h i b i t o r y a c t i v i t y .

6 ) P r a s a i n J . K . , Tezuka Y . , L

i

J . ‑ X . , Tanaka K . , Basnet P . , Dong H . , Namba T . , and Kadota S . : Novel D i a r y l h e p t a n o i d s from t h e S e e d s o f A l p i n i a b l e p h a r o c 1 α l y x : R e v i s e d S t r u c t u r e o f Calyxin A . J . Chem. R e s . , ( S ) 2 2 ‑ 2 3 , (M) 2 6 5 ‑ 2 7 9 , 1 9 9 8 . Summary: C a l y x i n s A ( 1 ) , E ( 2 ) , F ( 3 ) , 6 ‑ h y d r o x y c a l y x i n F ( 4 ) , c a l y x i n G and e p i c a l y x i n G ( 5 and 6 ) , a s e r i e s o f s t e r e o c h e m i c a l l y c o m p l e x , n o v e l d i a r y l h e p t a n o i d s h a v i n g a c h a l c o n e o r a f l a v a n o n e m o i e t y , were i s o l a t e d from t h e s e e d s o f A l p i n i α b l e p h α r o e α l y x K . Schum. and t h e i r s t r u c t u r e s were e l u c i d a t e d by s p e c t r o s c o p i c m e t h o d s . The s t r u c t u r e o f c a l y x i n A ( 1 ) was r e v i s e d and i t s s t e r e o c h e m i s t r y was d e d u c e d by t h e NMR s p e c t r a l a n a l y s i s o f i t s MTPA e s t e r s .

7 ) Hasegawa H . , Suzuki R . , Wakabayashi C . , Murata J . , Tezuka Y . , S a i k i I . , and Kadota S . : S y n t h e s i s o f a B i o l o g i c a l l y A c t i v e F l u o r e s c e n t D e r i v a t i v e o f GMl, a Main Ginseng Saponin M e t a b o l i t e Formed by I n t e s t i n a l B a c t e r i a . B i o l . Pharm.

B u l l . , 2 1 : 5 1 3 ‑ 5 1 6 , 1 9 9 8 .

Summary: A f l u o r e s c e n t d e r i v a t i v e s o f GMl [ 2 0 ‑ 0 − β − D‑g 1 u c o p y r a n o s y 1 ‑ 2 0 ( S ) ‑ p r o t o p a n a ‑ x a d i o l ] , a main Ginseng s a p o n i n m e t a b o l i t e formed by i n t e s t i n a l b a c t e r i a , was o b t a i n e d from t h e c o n d e n s a t i o n o f i t s t r i s n o r ‑ a l d e h y d e d e r i v a t i v e w i t h d a n s y l h y d r a z i n e . The d a n s y l a t e d GMl f l u o r e s c e d s t r o n g l y and showed a l m o s t t h e same p r o p e r t i e s a s i t s p a r e n t compound i n l i p o p h i l i c i t y and b i o l o g i c a l a c t i v i t i e s , s o t h i s f l u o r e s c e n t compound might p r o v i d e an i n s i g h t i n t o t h e mechanism o f p h a r m a c o l o g i c a l a c t i v i t i e s o f GMl.

8 )

Li

J . ‑ X . , L i P . , Tezuka Y . , Namba T . , and Kadota S . : Three Phenylethanoid G l y c o s i d e s and An I r i d o i d G l y c o s i d e from P i c r o r h i z α s c r o p h u l a r i i f l o r a . Phytoche‑

m i s t r y , 4 7 : 5 3 7 ‑ 5 4 2 , 1 9 9 8 .

A b s t r a c t : T h r e e new p h e n y l e t h a n o i d g l y c o s i d e s , named s c r o s i d e s A‑C and a new i r i d o i d g l y c o s i d e , named p i c r o s i d e I V , h a v e b e e n i s o l a t e d from t h e underground p a r t o f P i c r o r h i z α s c r o p h u l a r i i f l o r α

，

t o g e t h e r w i t h 1 1 known compounds. T h e i r s t r u c t u r e s were e l u c i d a t e d by t h e means o f 2D NMR s p e c t r o s c o p y and c h e m i c a l m e t h o d .

9 ) L i H . , L i J . , P r a s a i n J . K . , Tezuka Y . , Namba T . , Miyahara T . , Tonami S . , S e t o H . , Tada T . , and Kadota S . : A n t i o s t e o p o r o t i c A c t i v i t y o f t h e Stems o f Sambucus s i e b o l d i α n α . B i o l . Pharm. B u l l . , 2 1 : 5 9 4 ‑ 5 9 8 , 1 9 9 8 .

A b s t r a c t : We p r e v i o u s l y found t h a t a m e t h a n o l i c e x t r a c t o f t h e s t e m s o f S α mbucus

s i e b o l d i α n α i n h i b i t e d bone r e s o r p t i o n i n organ c u l t u r e . I n t h i s s t u d y , we f u r t h e r f r a c t i o n a t e d

t h e methanol e x t r a c t g u i d e d by t h e a c t i v i t y t o w a r d s bone r e s o r p t i o n s t i m u l a t e d by p a r a t h y ‑

r o i d hormone (PTH) i n v i t r o . The e t h y l a c e t a t e f r a c t i o n (EtOAc F r . ) o f t h e m e t h a n o l i c e x ‑

t r a c t i n h i b i t e d P T H ‑ s t i m u l a t e d bone r e s o r p t i o n o f n e o n a t a l mouse b o n e s , and t h e i n h i b i t o r y

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a c t i v i t y was more p o t e n t than t h o s e o f o t h e r f r a c t i o n s . O r a l a d m i n i s t r a t i o n o f t h e EtOAc F r . ( 5 0 and 1 0 0 mg/kg/d) t o o v a r i e c t o m i z e d (OVX) r a t p r e v e n t e d t h e d e c r e a s e i n bone m i n e r a l d e n s i t y (BMD) o f t h e lumbar ( L 2 ‑ 4 ) v e r t e b r a , i n d i c a t i n g t h a t t h e EtOAc F r . i s e f f e c t i v e i n v i v o . F u r t h e r m o r e , t h e EtOAc F r . ( 5 0 , 1 0 0 and 1 5 0 mg/kg/d) d e c r e a s e d t h e serum c a l c i u m l e v e l e l e v a t e d i n low c a l c i u m d i e t a r y r a t s . The p h e n o l i c c o n s t i t u e n t s o f t h e EtOAc f r a c t i o n were examined f o r t h e i r i n h i b i t o r y e f f e c t on bone r e s o r p t i o n s t i m u l a t e d by PTH i n n e o n a t a l mouse b o n e . Among t h e m , v a n i l l i c a c i d , v a n i l l i n and c o n i f e r y l a l c o h o l showed s i g n i f i c a n t i n ‑ h i b i t o r y e f f e c t s on bone r e s o r p t i o n . Of t h e compounds e x a m i n e d , v a n i l l i c a c i d was found t o h a v e a s i g n i f i c a n t i n h i b i t o r y e f f e c t on t h e d e c r e a s e o f BMD i n OVX m i c e . T h e r e f o r e , t h e EtOAc F r . o f S . s i e b o l d i αnαshowed a s u p p r e s s i v e e f f e c t on bone r e s o r p t i o n i n v i t r o and i n v i v o . I n a d d i t i o n , t h e i n h i b i t o r y e f f e c t s o f t h e EtOAc F r . on bone r e s o r p t i o n may b e a t l e a s t p a r t l y d u e t o t h e i n h i b i t o r y a c t i o n o f v a n i l l i c a c i d .

1 0 ) Matsumoto K . , Kohno S . , Ojima K . , Tezuka Y . , Kadota S . , and Watanabe H.:

E f f e c t s o f M e t h y l e n e c h l o r i d e ‑ s o l u b l e F r a c t i o n o f Japanese A n g e l i c a Root E x t r a c t , L i g u s t i l i d e and B u t y l i d e n e p h t h a l i d e , on P e n t o b a r b i t a l S l e e p i n Group‑housed and S o c i a l l y I s o l a t e d M i c e . L i f e S c i . , 6 2 : 2 0 7 3 ‑ 2 0 8 2 , 1 9 9 8 .

Summary: We p r e v i o u s l y showed t h e e x t r a c t o f J a p a n e s e a n g e l i c a r o o t (JAR‑E) r e v e r s e d t h e d e c r e a s e i n p e n t o b a r b i t a l ( P B ) s l e e p i n d u c e d by i s o l a t i o n s t r e s s and yohimbine and methoxamine, s t i m u l a n t s o f c e n t r a l n o r a d r e n e r g i c s y s t e m s , i n m i c e . H e r e , we t e s t e d t h e e f ‑ f e c t s o f s e v e r a l f r a c t i o n s from JAR‑E and l i g u s t i l i d e and b u t y l i d e n e p h t h a l i d e , p h t h a l i d e components o f JAR‑E, on PB s l e e p i n i s o l a t e d m i c e t o e l u c i d a t e t h e mechanism o f t h e a c t i o n o f JAR‑E. M e t h a n o l ‑ s o l u b l e ( M e t ‑ S ) and ‑ i n s o l u b l e ( M e t ‑ I S ) f r a c t i o n s were o b t a i n e d from JAR‑E. M e t h y l e n e c h l o r i d e ‑ s o l u b l e (MC‑S) and ‑ i n s o l u b l e f r a c t i o n s (MC‑IS) were p r e p a r e d from M e t ‑ S . MC‑S ( 1 1 . 4 ‑ 7 6 mg/kg, p . o . ) r e v e r s e d t h e i s o l a t i o n s t r e s s ‑ i n d u c e d c e c r e a s e i n PB s l e e p , b u t n e i t h e r M e t ‑ I S ( 0 . 8 ‑ 2 . 4 g / k g , p

・

o . )nor MC‑IS ( 0 . 7 ‑ 2 g / k g , p

・

o . )had t h e same e f ‑ f e c t . The i . p . a d m i n i s t r a t i o n o f MC‑S e x h i b i t e d a s i m i l a r a c t i v i t y t o t h a t o b s e r v e d a f t e r t h e p . o . a d m i n i s t r a t i o n o f t h e same f r a c t i o n . L i g u s t i l i d e ( 5 ‑ 2 0 mg/kg, i . p . ) and b u t y l i d e n e p h ‑ t h a l i d e ( 1 0 ‑ 3 0 mg/kg, i . p . ) r e v e r s e d PB s l e e e p d e c r e a s e i n i s o l a t e d m i c e . Both compounds ( 2 0 mg/kg, i . p . ) a t t e n u a t e d t h e s u p p r e s s i v e e f f e c t s o f yohimbine ( 3 0 n m o l , i . c . v . ) , methoxamine ( 2 0 0 n m o l , i . c . v . ) and a b e n z o d i a z e p i n e i n v e r s e a g o n i s t FG7142 ( 1 0 mg/kg, i . p . ) on PB s l e e p i n g r o u p ‑ h o u s e d m i c e . T h e s e r e s u l t s s u g g e s t t h e c o n t r i b u t i o n o f l i g u s t i l i d e and b u t y l i d e ‑ n e p h t h a l i d e t o t h e e f f e c t o f JAR‑E on PB s l e e p i n i s o l a t e d m i c e , and i m p l i c a t e c e n t r a l n o r a d r e n e r g i c and/or GABAA s y s t e m s i n t h e e f f e c t s o f t h e s e c o m p o n e n t s .

1 1 ) Banskota A . H . , Tezuka Y . , P r a s a i n J . K . , Matsushige K . , S a i k i I . , and Kadota S . : Chemical C o n s t i t u e n t s o f B r a z i l i a n P r o p o l i s and T h e i r C y t o t o x i c A c t i v i t i e s . J . N a t . P r o d . , 6 1 : 8 9 6 ‑ 9 0 0 , 1 9 9 8 .

A b s t r a c t : The e t h y l a c e t a t e s o l u b l e f r a c t i o n o f t h e m e t h a n o l i c e x t r a c t o f p r o p o l i s a f f o r d e d

a new p r e n y l a t e d chromane d e r i v a t i v e , 3 ‑ h y d r o x y ‑ 2 , 2 ‑ d i m e t h y l

^耐

8 ‑ p r e n yl c h r o m a n e ‑ 6 ‑

(6)

p r o p e n o i c a c i d ( 1 ) , a l o n g w i t h twenty two known compounds 2 ‑ 2 3 . Of t h e known compounds, 4 , 7 , 1 2 ‑ 1 9 and 2 2 were i s o l a t e d f o r t h e f i r s t t i m e from p r o p o l i s and t h e a b s o l u t e c o n f i g u r a ‑ t i o n o f 2 3 was e s t a b l i s h e d a s 2 S , 3 R . I n v e s t i g a t i o n s u g g e s t e d t h a t B α c c h α r i s s p p . a r e a s i g n i f i ‑ c a n t s o u r c e o f t r o p i c a l B r a z i l i a n p r o p o l i s , i n a d d i t i o n t o C l u s i α m i n o r , C . m α j o r and Ar α UC α r i α h e t e r o p h y l l α . A l l t h e compounds were t e s t e d f o r t h e i r c y t o t o x i c i t y t o w a r d s human HT‑1080 f i b r o s a r c o m a and murine c o l o n 2 6 ‑ 1 5 c a r c i n o m a c e l l s . Among t h e s e com

^・

p o u n d s , 9 and 1 9 ‑ 2 1 showed p o t e n t c y t o t o x i c i t y , h a v i n g ED50 v a l u e s e q u a l t o o r l e s s than 1 0

μg/mL.

1 2 ) Zhao W . , Guo Y . , Tezuka Y . , and Kikuchi T . : I s o l a t i o n and S t r u c t u r e Determina

^幽

t i o n o f Aurantiamide A c e t a t e from V e r α

，

trum nigrum

L. v

a r . u s s u r i e n s e N a k a i .

中国中薬雑誌，

2 3: 4 1 , 1 9 9 8 .

A b s t r a c t : A m o d i f i e d d i p e p t i d e h a s b e e n i s o l a t e d from V e r α trum nigrum v a r . u s s u r i e n s e f o r t h e f i r s t t i m e and c o n f i r m e d t o b e a u r a n t i a m i d e a c e t a t e by s p e c t r o s c o p i c a n a l y s i s .

1 3 ) Zhao W . , Guo Y . , Tezuka Y . , and Kikuchi T . : Chemical Research on t h e S t i l b e n e s from V e r α

，

trum nigrum L . v a r . u s s u r i e n s e N a k a i . C h i n e s e Journal o f M e d i c i n a l C h e m i s t r y , 8 : 3 5 ‑ 3 7 , 1 9 9 8 .

A b s t r a c t : A new s t i l b e n e named v e r u s s u s t i l b e n e and two known s t i l b e n e s h a v e b e e n i s o l a t e d from V e r a t r u m n i g r u m L . v a r . u s s u r i e n s e N a k a i . The s t r u c t u r e o f v e r u s s u s t i l b e n e ( I I I ) was d e t e r m i n e d by t h e u s e o f t w o ‑ d i m e n s i o n a l n u c l e a r m a g n e t i c r e s o n a n c e ( 2

^時

DNMR) t e c h ‑ n i q u e , and two o t h e r s t i l b e n e s were i d e n t i f i e d a s r e s v e r a t r o l ( I ) and 2 , 3 ' , 4 , 5

岨

t e t r a h y d r o x y s t i l b e n e ( I I ) .

1 4 ) Peungvicha P . , T e m s i r i r i k k u l R . , P r a s a i n J . K . , Tezuka Y . , Kadota S . , Thirawara

・

pan S . S . , and Watanabe H.

：

ιHydroxybenzoic A c i d : a Hypoglycemic C o n s t i t u e n t o f Aqueous E x t r a c t o f P α nd α n u s o d o r u s R o o t . J . Ethnopharmacol., 6 2 : 7 9 ‑ 8 4 , 1 9 9 8 . A b s t r a c t : Hypoglycemic a c t i v i t y ‑ g u i d e d f r a c t i o n l e d t o t h e i s o l a t i o n o f t h e known com‑

p o u n d , 4 ‑ h y d r o x y b e n z o i c a c i d , from P α nd α n u s o d o r u s R i d l . ( T h a i name: T o e i ‑ h o m , P a n d a n a c e a e ) . T h i s compound showed a h y p o g l y c e m i c e f f e c t i n normal r a t s a f t e r t h e o r a l a d m i n i s t r a t i o n o f 5 mg/kg. A d d i t i o n a l l y , t h e compound i n c r e a s e d serum i n s u l i n l e v e l s and l i v e r g l y c o g e n c o n t e n t i n normal r a t s .

1 5 ) Kasimu R . , Tezuka Y . , Tanaka K . , Gong Z . ‑ N . , L i J . ‑ X . , Basnet P . , Namba T . , and Kadota S . : L i q u i d Chromatography‑Mass Spectrometry A n a l y s i s o f D i t e r p e n o i d C o n s t i t u e n t s o f S e v e n t e e n S α l v i α P l a n t s . J . T r a d . M e d . , 1 5 : 1 0 9 ‑ 1 1 5 , 1 9 9 8 .

A b s t r a c t : The MeOH e x t r a c t s o f t h e s e v e n t e e n S α l v i a p l a n t s , i n c l u d i n g t e n s p e c i e s u s e d a s

r e s o u r c e s o f C h i n e s e c r u d e d r u g , Dan‑shen （丹参， RadixS a l v i a e m i l t i o r h i z a e , T a n ‑ j i n i n

J a p a n e s e ) , were c o m p a r a t i v e l y examined by t h e l i q u i d chromatography‑mass s p e c t r o m e t r y

(LC‑MS) method u s i n g t h i r t e e n d i t e r p e n o i d s a s s t a n d a r d s . The p r i n c i p l e component a n a l y s i s

(7)

(PCA) on t h e r e l a t i v e i n t e n s i t y o f t h e p r o t o n a t e d m o l e c u l a r i o n o f s t a n d a r d d i t e r p e n o i d s i n LC‑MS showed t h e p r e s e n c e o f s e v e r a l g r o u p s i n g e n u s s a l v i αwith r e g a r d t o t h e d i t e r p e n o i d s , which means t h a t t h e t e n s p e c i e s u s e d a s D a n ‑ s h e n r e s o u r c e s w e r e n o t t h e s a m e . T h e i r u s e a s a Dan‑shen r e s o u r c e , t h u s , s h o u l d b e b a s e d on t h e i r a c t i v i t y a n d / o r a c t i v e c o n s t i t u e n t s .

1 6 ) Tezuka Y . , Kikuchi T . , Zhao W . , Chen J . , and Guo Y . : Two New S t e r o i d a l A l k a l o i d s , 2 0 ‑ I s o v e r a t r a m i n e and V e r a p a t u l i n e , from t h e Roots and Rhizomes o f

V e r a t r z

Summary : Roots and r h i z o m e s o f V e r α trum p αtul u m L . ( L i l i a c e a e ) , u s e d a s a s o u r c e o f t h e C h i n e s e c r u d e drug L i ‑ l u ，＇ h a v e y i e l d e d two new s t e r o i d a l a l k a l o i d s , 2 0 ‑ i s o v e r a t r a m i n e ( 1 ) and v e r a p a t u l i n e ( 2 ) , a l o n g w i t h t h r e e known a l k a l o i d s , v e r a t r a m i n e ( 3 ) , v e r a t r o s i n e ( 4 ) , and j e r v i n e ( 5 ) . S t r u c t u r e s o f t h e new a l k a l o i d s , 1 and 2 , were d e t e r m i n e d t o b e a C ‑ 2 0 e p i m e r o f 3 and N ‑ ( m e t h o x y c a r b o n y l ) j e r v i n e , r e s p e c t i v e l y , by t h e u s e o f s p e c t r a l d a t a i n c l u d i n g 2D NMR.

1 7 ) Tezuka Y . , Kudoh M . , Hatanaka Y . , Kadota S . , and K i k u c h i T . : S y n t h e s i s o f M u s c l i d e ‑ A l D i a s t e r e o m e r s ; C o n f i r m a t i o n o f A b s o l u t e S t e r e o c h e m i s t r y . J . T r a d . M e d . , 1 5 : 1 6 8 ‑ 1 7 5 , 1 9 9 8 .

A b s t r a c t : ( 2 R , 5 R ) ‑ M u s c l i d e

^田

Aland ( 2 S , 5 R ) ‑ m u s c l i d e ‑ A l w e r e s y n t h e s i z e d from L ‑ v a l i n e and t h e i r d i a s t e r e o m e r s from D ‑ v a l i n e i n o r d e r t o d e t e r m i n e t h e s t r u c t u r e o f n a t u r a l m u s c l i d e ‑ A l i s o l a t e d from musk. Comparisons o f s p e c t r a l d a t a o f s y n t h e t i c , n a t u r a l , and p r e v i o u s l y s y n t h e s i z e d m u s c l i d e ‑ A l c o n f i r m e d t h e s t r u c t u r e s u g g e s t e d p r e v i o u s l y ; i . e . , n a t u ‑ r a l m u s c l i d e ‑ A l i s a m i x t u r e o f ( 2 R ) ‑ h y d r o x y ‑ 6 ‑ m e t h y l ‑ ( 5 R ) ‑ h e p t y l hydrogen s u l f a t e and ( 2 R

ト

h y d r o x y ‑ 6 ‑ m e t h y l ‑ ( 5 8 ) ‑ h e p t y lhydrogen s u l f a t e .

1 8 ) L i J .

・

X . ,S h i Q . , Xiong Q . ‑ B . , P r a s a i n J . K . , Tezuka Y . , Hareyama T . , Wang Z . ‑ T . , Tanaka K . , Namba T . , and Kadota S . : T r i b u l u s a m i d e A and B , New Hepatop1 ・ o

・

t e c t i v e Lignanamides from t h e F r u i t s o f T r i b u l u s t e r r e s t r i s : I n d i c a t i o n s o f C y t o p r o t e c t i v e A c t i v i t y i n Murine H e p a t o c y t e C u l t u r e . P l a n t a M e d i c a , 6 4 : 6 2

ト

6 3 1 , 1 9 9 8 .

A b s t r a c t : T r i b u l u s a m i d e s A ( 1 ) and B ( 2 ) , new l i g n a n a m i d e s e m b r a c i n g two c i n n a m i c amide p a r t s j o i n e d i n a c i s c o n f i g u r a t i o n , w e r e i s o l a t e d from t h e f r u i t s o f T r i b u l u s t e r r e s t r i s , t o g e t h e r w i t h f o u r known c o m p o u n d s , N ‑ t r α n s

イ

e r u l o y l t y r a m i n e( 3 ) , t e r r e s t r i a m i d e ( 4 ) , N‑

t r α

，

n s ‑ c o u m a r o y l t y r a m i n e ( 5 ) , and β − s i t o s t e r o l . The s t r u c t u r e s w e r e e l u c i d a t e d by 2D‑NMR

s p e c t r o s c o p y . A d d i t i o n o f compounds 1 ‑ 5 , e s p e c i a l l y 1 and 2 , t o primary c u l t u r e d mouse

h e p a t o c y t e s s i g n i f i c a n t l y p r e v e n t e d c e l l d e a t h i n d u c e d by D ‑ g a l a c t o s a m i n e ( D ‑ G a l N ) /tumor

n e c r o s i s f a c t o r α

（

TNF

−

α

．）

(8)

1 9 ) Tezuka Y . , Kikuchi T . , Zhao W . , Chen J . , and Guo Y . :

（＋）ー

V e r u s s u r i n e ,a New S t e r o i d a l A l k a l o i d from t h e Roots and Rhizomes o f Veratrum nigrum v a r . u s s u r i e n s e and S t r u c t u r e R e v i s i o n o f

（＋）圃

Verabenzoamine. J . N a t . P r o d . , 6 1 : 1 3 9 7 ‑ 1 3 9 9 , 1 9 9 8 .

Summary: Two minor s t e r o i d a l a l k a l o i d s , 1 and 2 , h a v e b e e n i s o l a t e d from t h e r o o t s and r h i z o m e s o f V e r α trum nigrum v a r . u s s u r i e n s e . T h e i r s t r u c t u r e s h a v e b e e n d e t e r m i n e d by t h e u s e o f s p e c t r a l d a t a a s 7 ‑ 0

^乱

c e t y l ‑ 1 5 ・ 0

ベ

2 ・ m e t h y l b u t y r o y 0 ‑ 3 ‑ 0 ‑ v e r a t r o y l g e r m i n e ( 1 ) and 1 5 ‑ 0

（開

2 ‑ m e t h y l b u t y r o y l ) ‑ 3 ‑ 0 ・ v e r a t r o y l g e r m i n e ( 2 ) . By s p e c t r a l d a t a c o m p a r i s o n w i t h v e r a b e n z o a m i n e , t h e s t r u c t u r e o f t h e l a t t e r compound h a s b e e n r e v i s e d from t h e p r e v i o u s l y r e p o r t e d 7

・

0

・

a c e t y l ‑ 1 5

^司

0

（・

2 ‑ m e t h y l b u t y r o y l )

・

3 ‑ 0 ‑ v e r a t r o y l g e r m i n e ( 1 ) t o 1 5

聞

O

（聞

2 ‑ m e t h y l ‑ b u t y r o y l ) ‑ 3 ‑ 0 ‑ v e r a t r o y l g e r m i n e ( 2 ) . A c c o r d i n g l y , a l k a l o i d 1 [ 7

・

O ‑ a c e t y l ‑ 1 5 ‑ 0 ‑ ( 2 ‑ m e t h y l b u t ‑ y r o y l ) ‑ 3 ‑ 0 ・ v e r a t r o y l g e r m i n e ]must b e n e w , and i t was g i v e n t h e t r i v i a l name v e r u s s u r i n e .

2 0 ) Banskota A.H., Tezuka Y . , Phung L . K . , Tran K . Q . , S a i k i I . , Miwa Y . , Taga T . , and Kadota S . : C y t o t o x i c C y c l o a r t a n e ‑ t y p e T r i t e r p e n e s from Combretum qu α drangu

・

l a r e . B i o o r g . Med. Chem. L e t t . , 8 : 3 5 1 9 ‑ 3 5 2 4 , 1 9 9 8 .

A b s t r a c t : S e v e n n o v e l c y c l o a r t a n e ‑ t y p e t r i t e r p e n e s were i s o l a t e d from Combretum qu α d r α n g u l α r e , and t h e i r s t r u c t u r e s were e l u c i d a t e d on t h e b a s i s o f s p e c t r a l a n a l y s i s . A l l t h e s e compounds were t e s t e d f o r t h e i r c y t o t o x i c i t y a g a i n s t murine c o l o n 2 6 ‑ 1 5 c a r c i n o m a c e l l s . Methyl q u a d r a n g u l a r a t e B ( 2 ) and methyl q u a d r a n g u l a r a t e D ( 4 ) e x h i b i t e d p o t e n t c y t o t o x i c i t y h a v i n g ED50 v a l u e s 9 . 5 4 and 5 . 4 2 μM, r e s p e c t i v e l y .

2 1 ) E l

^開

MekkawyS . , Meselhy M. R . , Nakamura N . , Tezuka Y . , H a t t o r i M . , Kakiuchi N . , Shimotohno K . , Kawahata T . , and Otaka T . : Anti‑HIV‑1 and A n t i ‑ H I V ‑ 1 ‑ p r o t e a s e S u b s t a n c e s from Ganoderm α l u c i d u m . P h y t o c h e m i s t r y , 4 9 : 1 6 5 1 ‑ 1 6 5 7 , 1 9 9 8 .

A b s t r a c t : A new h i g h l y o x y g e n a t e d t r i t e r p e n e named g a n o d e r i c a c i d αhas b e e n i s o l a t e d from a methanol e x t r a c t o f t h e f r u i t i n g b o d i e s o f G α n o d e rm α l u c i d u m t o g e t h e r w i t h t w e l v e known c o m p o u n d s . The s t r u c t u r e s o f t h e i s o l a t e d compounds were d e t e r m i n e d by s p e c t r a ‑ s c o p i c means i n c l u d i n g 2DNMR. G a n o d e r i o l F and g a n o d e r m a n o n t r i o l were f o u n d t o b e a c

^幽

t i v e a s a n t i ‑ H I V ‑ 1 a g e n t s w i t h an i n h i b i t o r y c o n c e n t r a t i o n o f 7 . 8 μg m l ‑ 1 f o r b o t h , and g a n o d e r i c a c i d B , g a n o d e r i o l B , g a n o d e r i c a c i d C l , 3 β

，

5 α

−

d i h y d r o x y ‑ 6 β

−

m e t h o x y e r g o s t a ‑ 7 , 2 2 ‑ d i e n e , g a n o d e r i c a c i d A , g a n o d e r i c a c i d Hand g a n o d e r i o l A were m o d e r a t e l y a c t i v e i n h i b i ‑ t o r s a g a i n s t HIV‑1PRwitha50% i n h i b i t o r y c o n c e n t r a t i o n o f 0 . 1 7 ‑ 0 . 2 3 mM.

2 2 ) Shang M . , C a i S . , Han J . , L i J . , Zhao Y . , Zheng J . , Namba T . , Kadota S . , Tezuka Y . , and Fan W . : S t u d i e s on F l a v o n o i d s from Fenugreek ( T r i g o n e l l a foenumgraecum L

ふ中国中薬雑誌，

2 3 :6 1 4 " ' . " ' 6 1 6 , 1 9 9 8 .

A b s t r a c t : O b j e c t i v e : To s t u d y t h e f l a v o n o i d s i n f e n u g r e e k ( T r i g o n e l l a foenumgr α e c u m )

p r o d u c e d i n C h i n a . Method: The f l a v o n o i d s were i s o l a t e d w i t h s i l i c a g e l , p o l y a m i d e and

Sephadex LH‑20 c h r o m a t o g r a p h y , and t h e i r s t r u c t u r e s were i d e n t i f i e d by p h y s i c a l , c h e m i c a l

(9)

p r o p e r t i e s and s p e c t r a l a n a l y s i s . R e s u l t : F i v e f l a v o n o i d compounds were i s o l a t e d from f e n u ‑ g r e e k s e e d s and i d e n t i f i e d a s v i t e x i n , t r i c i n , n a r i n g e n i n , q u e r c e t i n and t r i c i n ‑ 7 ‑ 0 − β −

D‑

g l u c o p y r a n o s i d e . Conclusion : Three f l a v o n o i d s , t r i c i n , n a t i n g e n i n and t r i c i n ‑7‑0

−

β

−

D‑

g l u c o p y r a n o s i d e , were i s o l a t e d from f e n u g r e e k a s w e l l a s from t h e p l a n t s o f T r i g o n e l l a f o r t h e f i r s t t i m e .

2 3 ) Shang M . , Cai S . , L i J . , Kadota S . , Tezuka Y . , Fan W . , and Namba T . : S t u d i e s on T r i t e r p e n o i d s from Common Fenugreek ( T r i g o n e l l a foenum

す

raecum

）.中草薬，

2 9 : 6 5 5 ‑ 6 5 7 ' 1 9 9 8 .

A b s t r a c t : S e v e n t r i t e r p e n o i d s were i s o l a t e d f o r t h e f i r s t t i m e from t h e e t h a n o l e x t r a c t o f s e e d o f T r i g o n e l l α f o e n u m ‑ g r α ecum L . , s i x o f them were i d e n t i f i e d a s l u p e o l , 3 1 ‑ n o r c y c l o a r t a n o l , b e t u l l i n , b e t u l i n i c a c i d , s o y a s a p o n i n I , and s o y a s a p o n i n I methyl e s t e r by p h y s i c o ‑ c h e m i c a l p r o p e r t i e s and s p e c t r a l a n a l y s i s .

2 4 ) L i H . , Miyahara T . , Tezuka Y . , Namba T . , Nemoto N . , Tonami S . , S e t o H . , Tada T . , and Kadota S . : The E f f e c t o f Kampo Formulae on Bone Resorption i n V i t r o and i n V i v o .

I.

A c t i v e C o n s t i t u e n t s o f Tsu‑kar

ト

g a n .B i o l . Pharm. B u l l . , 2 1 : 1 3 2 2 ‑ 1 3 2 6 , 1 9 9 8 . A b s t r a c t : Four water e x t r a c t s o f Kampo f o r m u l a e ( Y i ‑ k k a n ‑ s e n , D a i ‑ h o ‑ i n ‑ g a n , Ni c h i ‑ g a n , T s u ‑ k a n ‑ g a n ) were s c r e e n e d f o r t h e i r i n h i b i t o r y a c t i v i t i e s on bone r e s o r p t i o n i n d u c e d by p a r a t h y r o i d hormone (PTH) i n organ c u l t u r e u s i n g n e o n a t a l mouse p a r i e t a l b o n e s . Among t h e Kampo f o r m u l a e , Tsu‑kan‑gan (TKG) showed t h e most p o t e n t i n h i b i t o r y a c t i v ‑ i t y . We f u r t h e r f r a c t i o n a t e d t h e TKG water e x t r a c t by monitoring t h e i n h i b i t o r y a c t i v i t y on bone r e s o r p t i o n s t i m u l a t e d by PTH i n v i t r o . The MeOH f r a c t i o n o f t h e water e x t r a c t i n h i b ‑ i t e d PTH‑stimulated bone r e s o r p t i o n , and i t s i n h i b i t o r y a c t i v i t y was more p o t e n t than t h o s e o f o t h e r f r a c t i o n s . The MeOH f r a c t i o n was t h e n s u b j e c t e d t o Sephadex LH‑20 column c h r o ‑ matography t o g i v e f r a c t i o n s I , I I and I I I , which were examined f o r bone r e s o r p t i o n a c t i v i t y . F r a c t i o n I i n h i b i t e d PTH‑stimulated bone r e s o r p t i o n , and i t s i n h i b i t o r y a c t i v i t y was more p o t e n t than t h o s e o f t h e o t h e r f r a c t i o n s . Upon o r a l a d m i n i s t r a t i o n o f t h e t h r e e f r a c t i o n s ( 1 0 0 mg/kg/d) t o o v a r i e c t o m i z e d (OVX) m i c e , f r a c t i o n s I and I I I p r e v e n t e d t h e d e c r e a s e o f bone m i n e r a l d e n s i t y (BMD) o f t h e lumbar v e r t e b r a . E l e v e n compounds i s o l a t e d from t h e MeOH f r a c t i o n were examined f o r t h e i r i n h i b i t o r y e f f e c t on PTH‑stimulated bone r e s o r p t i o n . Among t h e m , b e r b e r i n e ( 1 ) , s y r i n g i n ( 3 ) , l i m o n i n ( 4 ) and mangif e r i n ( 1 0 ) showed a s i g n i f i ‑ c a n t i n h i b i t o r y e f f e c t on bone r e s o r p t i o n . I n t h e f o r m a t i o n a s s a y o f o s t e o c l a s t ‑ l i k e c e l l s , t h e s e compounds d e c r e a s e d t h e number o f t a r t r a t e ‑ r e s i s t a n t a c i d p h o s p h a t a s e (TRAP)‑

p o s i t i v e m u l t i n u c l e a t e d c e l l s (MN C s ) . The i n h i b i t o r y e f f e c t o f TKG on bone r e s o r p t i o n may b e a t l e a s t p a r t l y due t o t h e i n h i b i t o r y a c t i o n o f t h e s e compounds.

2 5 ) Ma J . ‑ Y . , Wang Z . ‑ T . , Xu L . ‑ S . , Xu G . ‑ J . , Kadota S . , and Namba T . : S e s q u i t e r p e n e Lactones from I x e r i s s o n c h i f o l i α . Phytochemistry, 4 8 : 2 0 1 ‑ 2 0 3 , 1 9 9 8 .

A b s t r a c t : The whole p l a n t o f I x e r i s s o n c h i f o l α a f f o r d e d two new g u a i a n o l i d e s e s q u i t e r p e n e

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l a c t o n e s named 8 ‑ d s o x y a r t e l i n [ 3 ‑ h y d r o x y ‑ l ( 1 0 ) , 3 ‑ g u a i a d i e n e ‑ 1 2 , 6 ‑ o l i d e2 ‑ o n e ] and i x e r i n Z [ 1 ( 1 0 ) , 3 , 1 1 ( 1 3 ) ‑ g u a i a t r i e n e ‑ 1 2 , 6

^司

o l i d e ‑ 2 ‑ o n e ‑ 3 ‑ 0 ‑ g l u c o p y r a n o s i d e ] , a l o n g w i t h t h e known compound 9 α ^， h y d r o x y z a l u z a l i n C , whose s t r u c t u r e and s t e r e o c h e m i s t r y wee d e t e r m i n e d by s p e c t r o s c o p i c m e t h o d s .

2 6 ) Hayakawa Y . , F u j i i H . , Hase K . , Ohnishi Y . , Sakukawa R . , Kadota S . , Namba T . , and S a i k i

I.:

A n t i ‑ m e t a s t a t i c and Immunomodulating P r o p e r t i e s o f t h e Water E x t r a c t from C e l o s i α a r g e n t e s S e e d s . B i o l . Pharm. B u l l . , 2 1 : 1 1 5 4 ‑ 1 1 5 9 , 1 9 9 8 .

A b s t r a c t : We h a v e i n v e s t i g a t e d t h e a n t i ‑ m e t a s t a t i c e f f e c t o f C e l o s i α α r g e n t e αseed e x t r a c t s (CAE), which h a v e t r a d i t i o n a l l y b e e n u s e d a s a t h e r a p e u t i c drug f o r e y e and h e p a t i c d i s e a s e s i n China and J a p a n . I n t r a p e r i t o n e a l C i . p . ) a d m i n i s t r a t i o n o f CAE f o r 7 d b e f o r e tumor i n o c u ‑ l a t i o n s i g n i f i c a n t l y i n h i b i t e d l i v e r m e t a s t a s i s c a u s e d by i n t r a p o r t a l i n j e c t i o n o f c o l o n 2 6 ‑ 1 5 c a r c i n o m a c e l l s i n a d o s e ‑ d e p e n d e n t manner. CAE a l s o showed c o n c e n t r a t i o n d e p e n d e n t m i t o g e n i c a c t i v i t y on BALB/c whole s p l e n o c y t e s , whereas i n c u b a t i o n o f t h e n o n ‑ a d h e r e n t f r a c t i o n o f s p l e n o c y t e s w i t h CAE d i d n o t i n d u c e t h i s a c t i v i t y . CAE h a s t h e a b i l i t y t o i n d u c e i n t e r l e u k i n ( I L ) ‑ 1 2 p r o d u c t i o n from macrophages i n v i t r o . F o l l o w i n g i . p . a d m i n i s t r a t i o n o f CAE t h e maximal l e v e l s o f I L ‑ 1 2 and i n t e r f e r o n CIFN

−）

γproduction i n serum were a c h i e v e d a t 2 ‑ 3 and 6 h , r e s p e c t i v e l y . Experiments u s i n g macrophage‑o r NK c e l l

^句

d e f i c i e n tm i c e r e ‑ v e a l e d t h a t CAE‑induced I L ‑ 1 2 i n serum was n o t m e d i a t e d by macrophages and t h a t IFN

−

γ p r o d u c t i o n was mainly d e p e n d e n t on n a t u r a l k i l l e r (NK) c e l l s . S i n c e CAE was i n a c t i v e when t h e c o n t r i b u t i o n s o f macrophages were removed i n our s y s t e m , i t s i n h i b i t o r y mechanism i s l i k e l y t o b e mainly a s s o c i a t e d w i t h t h e a c t i v a t i o n o f macrophages t o an a n t i ‑ m e t a s t a t i c s t a t e r a t h e r than NK c e l l s . CAE a d m i n i s t r a t i o n r e s u l t e d i n i n c r e a s e d p r o d u c t i o n o f I L ‑ 2 , IFN

−

γ and d e c r e a s e d p r o d u c t i o n o f a Th2 c y t o k i n e C I L ‑ 4 ) from s p l e n o c y t e s s t i m u l a t e d by PMA and A 2 3 1 8 7 . T h u s , t h e a n t i ‑ m e t a s t a t i c e f f e c t by CAE i s b a s e d on i t s immunomodulating p r o p e r ‑ t i e s i n c l u d i n g i n d u c t i o n o f c y t o k i n e s s u c h a s I L ‑ 1 2 , I L ‑ 2 and IFNγleading t o a Thl d o m i ‑ nant immune s t a t e and a c t i v a t i n g macrophages t o t h e t u m o r i c i d a l s t a t e . T h i s may p r o v i d e a b a s i s f o r t h e i n h i b i t i o n o f c a n c e r m e t a s t a s i s .

2 7 ) Matsuse

I.

T . , Goto W . , S h i r a k i K . , Yin D . , Kadota S . , and Namba T . : E f f e c t o f Shuang Huang Lian

（双黄連）

on H e p a t i t i s B Virus S u r f a c e Antigen S e c r e t i o n . J . T r a d . M e d . , 1 5 : 5 2 ‑ 5 6 , 1 9 9 8 .

A b s t r a c t : Shuang Huang L i a n

（双黄連，

SHL)i s o n e o f t h e C h i n e s e t r a d i t i o n a l m e d i c i n e s

composed o f t h e e x t r a c t s o f L o n i c e r a e F l o s , S c u t e l l a r i a e R a d i x , and F o r s y t h i a e F r u c t u s and

h a s b e e n u s e d f o r t h e t r e a t m e n t o f v a r i o u s c h r o n i c and a c u t e d i s e a s e s i n c l u d i n g v i r a l h e p a t i ‑

t i s .

It a

l s o h a s shown e f f i c a c y i n i n f e c t i o n s c a u s e d by a n t i b i o t i c ‑ r e s i s t a n t b a c t e r i a . SHL and

t h e e x t r a c t s o f e a c h c o n s t i t u e n t p l a n t m e d i c i n e were t e s t e d f o r s u p p r e s s i o n o f h e p a t i t i s B

v i r u s s u r f a c e a n t i g e n (HBsAg) s e c r e t i o n i n an e x p e r i m e n t a l model f o r c h r o n i c HBV i n f e c ‑

t i o n u s i n g t h e PLC/PRF / 5 c e l l l i n e . As a r e s u l t , SHL a s w e l l a s t h e e x t r a c t s o f L o n i c e r a e F l o s

and S c u t e l l a r i a e Radix s u p p r e s s e d t h e s e c r e t i o n o f HBsAg w i t h o u t c y t o t o x i c i t y .

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2 8 ) Hatanaka Y. and Kanaoka Y . : B i o t i n y l D i a z i r i n e Photophor: An Approach t o High

^幽

R e s o l u t i o n P h o t o a f f i n i t y L a b e l i n g f o r Probing Receptor‑Ligand I n t e r f a c e . H e t e r o ‑ c y c l e s , 4 7 : 6 2 5 ‑ 6 3 2 , 1 9 9 8 .

A b s t r a c t : The t e c h n i q u e o f p h o t o a f f i n i t y l a b e l i n g h a s become i n c r e a s i n g l y a p p r e c i a t e d a s a p o w e r f u l c h e m i c a l methodology f o r t h e d e t a i l e d s t r u c t u r a l a n a l y s i s o f l i g a n d b i n d i n g d o ‑ m a i n s . T h i s r e v i e w d e s c r i b e s our r e c e n t a p p r o a c h t o t h e d e v e l o p m e n t o f new p h e n y l d i a z i r i n e f a m i l y , t h e d e s i g n o f b i o t i n y l p h o t o p r o b e s , and t h e i r a p p l i c a t i o n i n t h e f i e l d o f g l y c o b i o l o g y .

2 9 ) Hatanaka Y . , Hashimoto H . , and Kanaoka Y . : A Rapid and E f f i c i e n t Method f o r I d e n t i f y i n g P h o t o a f f i n i t y B i o t i n y l a t e d S i t e s w i t h i n P r o t e i n s . J . Am. Chem. S o c . , 1 2 0 : 4 5 3 ‑ 4 5 4 , 1 9 9 8 .

A b s t r a c t : A r a p i d and e f f i c i e n t s t r a t e g y h a s b e e n d e v e l o p e d f o r i d e n t i f i c a t i o n o f p h o t o a f f i n i t y l a b e l e d p e p t i d e s . The s t r a t e g y i n v o l v e s a r a d i o i s o t o p e ‑ f r e e a p p r o a c h i n which t h e p h o t o a f f i n i t y l a b e l i s b i o t i n y l a t e d . The method t h e n u t i l i z e s a n o v e l d e r i v a t i z a t i o n o f PVDF membrane f o r i d e n t i f i c a t i o n and a n a l y s i s o f p e p t i d e fragments d e r i v e d from t h e p h o t o a f f i n i t y l a b e l e d b i n d i n g s i t e i n a s i m p l e d o t b l o t a s s a y . I n t h e p r e s e n t s t u d y , t h e method h a s b e e n a p p l i e d t o i d e n t i f i c a t i o n o f t h e b i n d i n g s i t e r e g i o n o f β1, 4 ‑ g a l a c t o s y 1 t r a n s f e r a s e ( G a l T ) . S e q u e n c e a n a l y s i s h a s r e v e a l e d t h a t t h e b i o t i n y l a t e d p h o t o p r o b e i s l o c a l i z e d i n a t r y p t i c GalT fragment ( Y 1 9 7 ‑ R 2 0 8 ) . T h e s e d a t a a r e c o n s i s t e n t w i t h p r e v i o u s s u g g e s t i o n s c o n c e r n i n g t h e GalT a c c e p t o r s i t e and c l e a r l y d e m o n s t r a t e t h e e f f e c t i v e n e s s o f our a p p r o a c h f o r r a p i d i d e n t i f i c a t i o n o f p h o t o l a b e l e d p e p t i d e s .

3 0 ) Koumanov F . , Yang J . , Jones A. E . , Hatanaka Y . , and Holman G.D.: C e l l S u r f a c e B i o t i n y l a t i o n o f GLUT4 Using Bis‑mannose P h o t o l a b e l e s , Biochem. J . , 3 3 0 : 1 2 0 9 1 2 1 5 , 1 9 9 8 .

A b s t r a c t : New c e l l impermeant b i s ‑ m a n n o s e p h o t o l a b e l s h a v e b e e n d e v e l o p e d which h a v e b i o t i n y l g r o u p s a t t a c h e d t o 4 ‑ C l ‑ a z i ‑ 2 , 2 , 2 ‑ t r i f l u o r o e t h y l )

^帥

b e n z o y l ‑ 1 , 3 ‑ b i s ( D ‑ m a n n o s ‑ 4 ‑ y l o x y) ‑ 2

^・

p r o p y l a m i n e(ATB‑BMPA) by e i t h e r a p o l y e t h o x y s p a c e r (Bio‑ATB‑BMPA) o r an a d d i ‑ t i o n a l h e x a n o i c a c i d s p a c e r (Bio‑LC‑ATB‑BMPA). The h a l f ‑ m a x i m a l i n h i b i t i o n c o n s t a n t s , Ki v a l u e s , f o r i n h i b i t i o n o f g l u c o s e t r a n s p o r t a c t i v i t y i n i n s u l i n

^『

s t i m u l a t e dr a t a d i p o c y t e s a r e 3 5 9

±

1 0 μMand 2 7 3

±

2 8

μM

f o r Bio‑ATB‑BMPA and Bio‑LC‑ATB‑BMPA, r e s p e c ‑ t i v e l y . T h e s e v a l u e s a r e s i m i l a r t o t h o s e p r e v i o u s l y r e p o r t e d f o r t h e n o n ‑ b i o t i n y l a t e d com‑

pound ATB‑BMPA. F o l l o w i n g u v ‑ i r r a d i a t i o n i n d u c e d c r o s s l i n k i n g o f t h e b i o t i n y l a t e d

p h o t o l a b e l s t o r a t a d i p o c y t e s , t h e b i o t i n y l a t e d GLUT4 c a n b e d e t e c t e d by n o n ‑ r a d i o a c t i v e and

r a d i o a c t i v e methods t h a t u t i l i s e t h e i n t e r a c t i o n w i t h s t r e p t a v i d i n . B i o t i n y l a t e d GLUT4 from

1 ‑ 2 μg o f a d i p o s e c e l l membranes, p r e c i p i t a t e d o n t o magnetic s t r e p t a v i d i n b e a d s , c a n b e s e n ‑

s i t i v e l y and q u a n t i t a t i v e l y d e t e c t e d u s i n g an e l e c t r o c h e m i l u m i n e s c e n t a s s a y m e t h o d . T h i s

u t i l i s e s a r u t h e n i u m ‑ t a g g e d anti‑GLUT4 a n t i b o d y t h a t on e x c i t a t i o n a t an e l e c t r o d e g e n e r ‑

a t e s a e l e c t r o c h e m i l u m i n e s c e n t s i g n a l i n an Origen a n a l y s e r . A l t e r n a t i v e l y , s u r f a c e ‑

b i o t i n y l a t e d GLUT4 c a n b e e a s i l y , b u t l e s s s e n s i t i v e l y , d e t e c t e d i n s t r e p t a v i d i n a g a r o s e

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p r e c i p i t a t e s which a r e a n a l y s e d by c o n v e n t i o n a l GLUT4 Western b l o t t i n g . Data o b t a i n e d u s i n g t h e n o n ‑ r a d i o a c t i v e methods compare f a v o u r a b l y w i t h t h o s e u s i n g t r i t i a t e d v e r s i o n s o f t h e b i o t i n y l a t e d p r o b e s . I n s u l i n t r e a t m e n t o f a d i p o c y t e s i n c r e a s e s t h e l e v e l s o f s i g n a l s from s u r f a c e ‑ b i o t i n y l a t e d GLUT4 by " " " 1 0

^帽

f o l do r " " " 2 0 ‑ f o l d r e s p e c t i v e l y when t h e e l e c t r o c h e m i l u ‑ m i n e s c e n t o r t h e Western b l o t d e t e c t i o n methods a r e u s e d and t h e s e s i g n a l s a r e b l o c k e d by c y t o c h a l a s i n

B.

3 1 ) Kempin U . , Kanaoka Y . , and Hatanaka Y . : A New C l e a v a b l e Carbene‑Generating Reagent with 3‑Phenyl3 ・ t r i f l u o r o m e t h y l d i a z i r i n ePhotophore. H e t e r o c y c l e s , 4 9 : 4 6 5

四

' 4 6 8 ,1 9 9 8 .

A b s t r a c t : S y n t h e s i s o f a 3 ‑ p h e n y l ‑ 3 ‑ t r i f l u o r o m e t h y l d i a z i r i n e d e r i v a t i v e h a v i n g a c l e a v a b l e 1 , 2 ‑ d i o l moiety f o r p h o t o c r o s s ‑ l i n k i n g t e c h n i q u e i s d e s c r i b e d . An e s t e r o f c i n n a m i c a c i d d e ‑ r i v a t i v e was p r e p a r e d by t h e W i t t i g r e a c t i o n o f 2 ‑ m e t h o x y ‑ 4 ‑ [ 3 ‑ t r i f l u o r o m e t h y l ‑ 3 H ‑ d i a z i r i n ‑ 3 ‑ y l ] b e n z a l d e h y d e w h i c h c a n b e r e a d i l y p r e p a r e d by t h e F r i e d e l

^曲

C r a f t sr e a c t i o n o f c o r r e s p o n d i n g p h e n y l d i a z i r i n e . The osmium o x i d a t i o n o f t h e o l e f i n i c bond g a v e t h e d e s i r e d d i o l d e r i v a t i v e , e t h y l 2 , 3 ‑ d i h y d r o x y ‑ 3 ‑ [ 2 ‑ m e t h o x y ‑ 4 ‑ ( 3 ‑ t r i f l u o r o m e t h y l ‑ 3 H ‑ d i a z i r i n ‑ 3

ぅ

r l ) p h e n y l ] p r o p i o n a t e , i n a h i g h y i e l d . The c l e a v a b i l i t y o f t h e d i o l group was c o n f i r m e d by t h e c o n v e n t i o n a l p e r i o d a t e o x i d a t i o n t o g i v e t h e s t a r t i n g a l d e h y d e .

3 2 ) Kempin U . and Hatanaka Y . : A n a l y s i s o f Carbohydrate‑Protein I n t e r a c t i n g Systems by P h o t o c r o s s l i n k i n g T e c h n i q u e , Photomedicine and P h o t o b i o l o g y , i n p r e s s , 1 9 9 8 .

A b s t r a c t : We h a v e d e v e l o p e d a s i m p l e method f o r t h e p r e p a r a t i o n o f p h o t o r e a c t i v e mem‑

b r a n e c a r r y i n g c a r b o h y d r a t e l i g a n d s on i t s s u r f a c e . F i r s t l y , a p o l y v i n y l i d e n e d i f l u o r i d e (PVDF) membrane was p h o t o c h e m i c a l l y m o d i f i e d w i t h two c a r b e n e ‑ g e n e r a t i n g d i a z i r i n e d e ‑ r i v a t i v e s f o r t h e c o n s t r u c t i o n o f two c h e m i c a l l y d i f f e r e n t amino f u c t i o n a l groups on t h e membrane s u r f a c e , a l i p h a t i c and a r o m a t i c a m i n e s , r e s p e c t i v e l y . A p h o t o r e a c t i v e benzophenone c a r b o x y l i c a c i d was t h e n s e l e c t i v e l y c o u p l e d t o t h e a l i p h a t i c amine s i t e . The r e ‑ maining a r o m a t i c amine was d i a z o t i z e d and s u b j e c t e d t o t h e d i a z o c o u p l i n g r e a c t i o n w i t h t h e p y r i d y l a m i n o d e r i v a t i v e o f N ‑ a c e t y l n e u r a m i n e l a c t o s e . To e v a l u a t e t h e a b i l i t y o f t h i s p h o t o r e a c t i v e a f f i n i t y membrane, p h o t o c r o s s l i n k i n g o f a s i a l i c a c i d b i n d i n g l e c t i n e from Maackiaαm u r e n s i s was e x a m i n e d .

。総説

1

）畑中保丸：構造生物学的有機化学：光アフィニティーラベルによる蛋白質機能構造のプロービング．有機合成化学協会誌，

5 6: 5 8 1 5 9 0 , 1 9 9 8

2）畑中保丸：光アフィニティーラベル：プロープ設計と蛋白質機能構造解析への応用．ファルマシア，

3 4: 8 2 0 8 2 4 , 1 9 9 8

3

）手塚康弘：ガン細胞を兵糧攻め：血管新生阻害剤フマギリンの標的蛋白見つかる．ファルマシア，

3 4: 1 6 4 1 6 5 , 1 9 9 8

(13)

4

）難波恒雄，黒川昌彦，門田重利，白木公康：伝統薬物を用いた抗ウイルス薬の開発．薬学雑誌，

1 1 8 :3 8 3 4 0 0 , 1 9 9 8

く〉学会報告

1 ) Banskota A . H . , Tezuka Y . , P r a s a i n J .

K., S

a i k i I

.,

Matsushige

K., and Kadota S

. : C h e m i c a l C o n s t i t u e n t s o f B r a z i l i a n P r o p o l i s and T h e i r C y t o t o x i c A c t i v i t i e s .

日本薬学会第1

1 8

年会，

1 9 9 8 , 3 / 3 1 ‑ 4 / 2

，京都．

2 )

関谷幸治，手塚康弘，難波恒雄，門田重利，片山和憲，小泉保，前田正敏，近藤隆，

田中謙：

But y l i d e n e p h t h a l i d e

の経皮適用による体内動態，日本薬学会第

1 1 8

年会，

1 9 9 8 , 3 / 3 1 ‑ 4 / 2

，京都．

3 )

畑中保丸，橋本誠：光アフィニティービオチン化による蛋白質機能構造の迅速解析，日本薬学会第

1 1 8

年会，

1 9 9 8 , 3 / 3 1 ‑ 4 / 2

，京都．

4 ) Hatanaka Y

.,

Hashimoto M . , and Kanaoka

Y.:

A Rapid and E f f i c i e n t Method o f P h o t o a f f i n i t y L a b e l i n g . The 1 3 t h F r e n c h ‑ J a p a n e s e Symposium on M e d i c i n a l and F i n e C h e m i s t r y , 1 9 9 8 , 5 / 2 5 2 8 , Hayama, J a p a n .

5 ) Kempin

U.，畑中保丸：光クロスリンキングを利用する糖鎖蛋白質相互作用系の解析．

第2

0

回日本光医学・光生物学会，

1 9 9 8 , 7 / 1 8 ‑ 1 9

，熊本．

6 )

活文哲，手塚康弘，難波恒雄，小松かっ子，門田重利：紅景天（

R h o d i o l a s αe r αS. H .

FUの地下部）のプロリルエンドベプチダーゼ阻害活性成分に関する研究．第

1 5

回和漢医薬学会大会，

1 9 9 8 , 8 / 2 9 3 0

，富山．

7 )

多田貴広，下村健次，手塚康弘，山辺幸久，門田重利：

Conyzaf i l a g i n o i d e s H i e r o n .

（全草）中のチロシナーゼ阻害活性成分に関する研究．第

1 5

1 9 9 8 , 8 / 2 9 ‑ 3 0

，富山．

8 )

金子卓嗣，入川志保，加藤佳樹，長谷耕二，熊泉波，手塚康弘，門田重利：マクロファージからの

NO

産生を抑制する生薬の探索．第1

5 1 9 9 8 , 8 / 2 9 ‑ 3 0

，富山．

9 )

木村郁子，水本淳，手塚康弘，越偉傑：蒙童エキスの含有成分

g e r m i d i n e ,g e r m e r i n e

のマウス摘出心房に対する陽性変時・変力作用．第

1 5

1 9 9 8 , 8 / 2 9 ‑ 3 0

，富山．

10）李慧英，手塚康弘，門田重利，難波恒雄，宮原龍郎，鈴木貴幸，堂脇理沙，根本信雄，

利波修一，瀬戸光，多国貴広：漢方方剤による抗骨粗慈活性成分の研究（I)一通関丸について．第1

5 1 9 9 8 , 8 / 2 9 3 0

，富山．

1 1 )

李建新，宮原龍郎，李慧英，鈴木貴幸，渡辺誠，五明幸夫，手塚康弘，門田重利，

根本信雄：午膝のエキス及びその成分の骨吸収抑制作用．第1

6

回日本骨代謝学会，

1 9 9 8 , 8 / 5 8

，東京．

1 2 ) Banskota A . H . , Tezuka

Y., P

r a s a i n J .

K., Matsushige K., S

a i k i I

.,

and Kadota S . : C h e m i c a l C o n s t i t u e n t s and P h a r m a c o l o g i c a l A c t i v i t i e s o f B r a z i l i a n P r o p o l i s . 8 t h I n t e r n a t i o n a l Symposium on A p i t h e r a p y , 1 9 9 8 , 9 / 1 7 1 9 , P o r t o r o s e , S l o v e n i a .

1 3

）浜崎憲夫，石井栄次，手塚康弘，長岡武馬，門田重利，富永和作，樋口和秀，荒川哲男，

矢野郁也：

H e l i c o b

α

c t e rp y l o r i

に対する呉莱英の抗菌活性とその活性成分．第5

1

回日本細

(14)

菌学会関西支部総会，

1 9 9 8 , 1 1 / 7

，西宮．

1 4

）窪田真，手塚康弘，門田重利，畑中保丸：人参サポニンの

TL C

プロッティング．第

2 7

回生薬分析シンポジウム，

1 9 9 8 , 1 1 / 1 3

，大阪．

1 5

）畑中保丸：基質特異性を担う構造情報の化学的解読：新規光反応性プロープの開発と糖転移酵素への応用．第

2 4

回日本応用酵素協会研究発表会，

1 9 9 8 , 1 1 / 1 6

，大阪．

く〉その他

1

）門田重利：第

7

回国際伝統医薬シンポジウム・富山

( 1 9 9 8

）「ベトナム，ミャンマーの伝統薬物の調査，研究」，

1 9 9 8 , 8 / 2 7 2 8

，富山．

2）手塚康弘：漢薬丹参の化学的研究ーアルドース還元酵素限害活性成分について一．

1 9 9 8 , 1 0 / 5

，中国・議陽薬科大学．

3

）手塚鹿弘：

NewD i a r y l h e p t a n o i d s o f A l p i n i a b l e p h a r o c a l y x (Yunnan‑Caodoukou).

1 9 9 8 , 1 0 / 6

，中国・藩陽薬科大学．

。海外調査

1）門田重利：ベトナム，タイ，ミャンマーにおける伝統医学，並びに天然薬物資源の調査研究，

1 9 9 8 , 3 / 1 1 2 6

，ベトナム，タイ，ミャンマー．

2 ）門田重利：ベトナム，タイ，ミャンマーにおける伝統医学，並びに天然薬物資源の調査研究，

1 9 9 8 , 1 1 / 1 9 ‑ 1 2 / 1 0

，ベトナム，タイ，ミャンマー．

。共同研究

1

）宮原龍郎：富山医科薬科大学薬学部，「骨粗転症に有効な漢方方剤の開発研究」，

1 9 9 8 ,

4

〜

2

）中村薫：京都大学化学研究所，「生体触媒を使ったキナ酸誘導体の合成研究」，

1 9 9 8 , 4 〜 3

）古賀大三：山口大学農学部，「植物性体防御におけるキチナーゼ誘導とキチン・キトサン

の糖鎖組成との関連性」，

1 9 9 8 , 4 〜

4）山形達也：日本皮革研究所，「FJB骨肉腫細胞の運動能点細胞一基質接着性・転移能を調節するガングリオシド

GD l a

，」

1 9 9 8 , 4

〜

5

）挑新生：中国・藩陽薬科大学「和漢薬人参の化学的研究」，

1 9 9 8 , 4 〜

。研究費取得状況

1

）平成

1 0

年度富山県受託研究：和漢薬・バイオテクノロジー研究（第

3

年度），（分担：門田重利）「癌転移を抑制する伝承薬物に関する研究」，

3 7

万

5

千

2 ）文部省科学研究費，国際学術研究（平成9

〜1 0

年度増額分），（代表：門田重利）「ベトナム，タイ，ミャンマーにおける伝統医学，並びに天然薬物資源の調査研究」，

2 0 0

万

3

）文部省科学研究費，国際学術研究（平成

1 0

年度），（代表：門田重利）「ベトナム，タイ，

ミャンマーにおける伝統医学，並びに天然薬物資源の調査研究」，

3 0 0

万

4

）文部省科学研究費，基盤研究

Al

（分担：門田重利）「新規高次神経変性疾患モデル動物，

細胞の開発，神経変性機序の解析と薬物評価法の確立」，

5 0

万

5)

（財）東京生化学研究会国際共同研究助成（代表：門田重利）「マクロファージからのNO

化 学 応 用 部 門