羅氏鹽膚木，學名Rhus semialata var. roxburghii，全台及全

世界各地皆有分布。屬漆樹科 (Anacardiaceae) 漆樹屬，為落葉灌

木或小喬木。五倍子為五倍子蚜蟲(Melaphis chinensis Bell) 寄生

在羅氏鹽膚木時，所形成的蟲癭。五倍子為民間常用之中草藥，具有

清熱、解毒、抗發炎及消腫等效果，這些效果可能跟人體免疫調節或

抗腫瘤等生物活性有所關聯，因此藉由各類層析方法，去發掘五倍子

當中生物有效成份為何，是本篇論文的首要研究方向。而以生物活性

試驗為導引，經由各種分離法及衍生物合成法，我們得到十二個純化

合物，包括有一個水解型單寧： 1,2,3,4,6-penta-O-galloyl-β-D-

glucose ( 1 )；二個類單黃酮類：quercetin ( 2 )、quercetin-

3,7-3’,4’-tetramethyl ether ( 3 )；三個有機酸類：gallic

acid ( 4 )、methyl gallate ( 5 ) 、p-anisic acid ( 6 )；四個

類三萜類：lupeol ( 7 )、betulonic acid ( 8 )、moronic acid

( 9 )、semimoronic aicd ( 10 ) ；一個類固醇類：β-

sitosterol ( 11 )；一個芳香族：bis-(2-methylhexyl)

phthalate ( 12 )。此外，另以具不同位置羥基取代之1,4-

naphthoquinone為起始物，進行乙醯基化及苯甲基化反應得到衍生

物：2-acetoxy-1,4-naphthoquinone ( 13 )、5-acetoxy-1,4-

naphthoquinone ( 14 )、2-benzloxy-1,4-naphthoquinone (15 )。

在生物活性試驗方面，所得到的數據資料顯示，化合物 2、13、

14、15對於口腔表皮癌細胞 (KB cells)、子宮頸癌細胞 (HeLa

cells) 具有細胞毒殺效果；此外，我們發現化合物1 ( 1,2,3,4,6-

pneta-O-galloy-β-D-glucose, 5GG ) ，可抑制周邊血液免疫細胞

的活化 ( PBMCs)、且能抑制嗜中性球與單核細胞分泌活性氧屬

(reactive oxygen species, ROS) 及可能對口腔上皮癌細胞之細胞

週期具調控作用。以PI為染劑利用DNA單染法 (DNA Hypoploidy) 經

流式細胞儀分析，以及進行催化性 DNA Topoisomerase I activity

抑制試驗，進一步分析化合物 quercetin 和三個化學結構相似的

1,4-naphthquinone衍生物可能的抗癌機制，其結果顯示此類化合物

能抑制DNA Topoisomerase I 的催化活性，並可能經由對口腔上皮癌

細胞之細胞周期具有調控作用而誘導細胞進行細胞凋亡。

Rhus semialata var roxburghii is defoliate tree (Rhus

L., Anacardiaceae) and is distributed all over the Taiwan

and world. Rhus chinensis Mill is formed as a gall by the

period when Melaphis chinensis lives in the R. semialata.

R. chinensis Mill is a folk medicine using for heat

cleansing effect, antidotal action, anti-inflammation and

detumescene. Some of these effects may be related to immune

regulation and anti-tumor in some literatures. To

investigate the effective components from Rhus chinensis

Mill is our first aim of this thesis by various

chromatographic techniques. Bioassay-directed

fractionations and derivative reactions led to twelve pure

compounds: one hydrolyzable tannin: 1,2,3,4,6-penta-O-

galloyl-β-D-glucose ( 1 ); two monomeric flavonoids:

quercetin ( 2 ), quercetin-3,7,3’,4’-tetra-methyl ether (

3 ); three organic acids: gallic acid ( 4 ), methyl gallate

( 5 ), p-anisic acid ( 6 ); four triterpenoids: lupeol (

7 ), betulonic acid ( 8 ), moronic acid ( 9 ), semimoronic

acid ( 10 ); one steroids:β-sitosterol ( 11 ); one

aromatic compound: bis-(2-methylhexyl) phthalate ( 12 ).

All above twelve pure compounds were isolated from R.

chinensis. To further study the structures and activities

relationships (SAR), we took 1,4-naphthoquinones with

different regiochemistric hydroxy substitutions as starting

materials to prepare three derivatives : 2-acetoxy-1,4-

naphthquinone ( 13 ), 5-acetoxy-1,4 naphthquinone ( 14 ),

and 2-benzoxy-1,4-naphthoquinone ( 15 ). Structures of all

acquired compounds were confirmed by spectral elucidations

including NMR, MS, FT-IR etc.

Bioassay data revealed that compound 2, 13, 14, 15

exhibited cytotoxic effects against cancer cells ( KB, and

HeLa cell lines); moreover, we found that compound 1 (

1,2,3,4,6-pneta-O-galloy-β-D-glucose, 5GG ) showed some

biologically inhibitory effects, such as inhibiting the

activation of peripheral blood mononuclear cells (PBMCs),

and production of reactive oxygen species (ROS) from

neutrophils and mononuclear cells. And it might probably

regulate cell cycle of KB cells. Quercetin and three 1,4-

naphthoquinone derivatives were further investigated their

anticancer mechanism by using DNA Hypoploidy analysis with

flow cytometry and catalytic DNA topoisomerase I inhibition

assay. We inferred that both synthetic 1,4- naphthoquinone

analogues and quercetin had inhibition against DNA

topoisomerase I activity and might induce apoptosis through

mediating cell cycle of KB cells.

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