ORIGINAL ARTICLE 87

Presystemic Metabolism of Anthraquinone Polyphenols in Rhubarb

1,2 _ . ~~ 3 ~ ~ 4 Ya-Tze Lin -'-, Pei-Hua ChangJ, Kuo-Ching Wen' , Chung-Ping YuJ,

) _. 0 Pei-Dawn Lee Chao5, Yu-Chi Hou

6, Su-Lan Hsiu5

lNational Laboratories of Food and Drugs, Department of Health, Executive Yuan, Taipei; 2Institute of ~ 4 Pharmaceutical Chemistry, Jlnstitute of Chinese Pharmaceutical Science, 'School of Cosmeceutics, ' School of

Pharmacy, 6School of Chinese Medicine, China Mecl ical Universi" Taichung, Taiwan, R.O.C

Objectives. Anthraqllinone polyphenols are bioactive constitllents which mainly present as glycosicles in rhllbarb, an herb widely used in clinical Chinese medicine. Most polyphenol glycosides are absorbed only after being hydrolyzed to their aglycones by enteral microflora. In the present study, we investigated the presystemic metabolism of fOllr anth raqllinone polyphenols inclllding aloe.emoc\ in, rhein, emodin , anc\ chrysophanol as well as their glycosides in rhllbarb decoction and in rat feces. Methods. Aloe-emoc\ in, rhein , emodin an c\ chrysophanol in rhubarb decoction and feces suspension were c\etermined by HPLC methods developed in this stlldy. The presystemic metabolism of these anthraqllinones by enteral microflora was investigated by separately incubating rhubarb c\ecoction and anthraquinone aglycones with rat feces suspension un c\ er anaerobic conditions Results. The contents of four anthraquinone aglycones in rhllbarb c\ ecoction significantly increased instantaneously upon mixing with feces suspension. Moreover, there was a rapid c\ecrease in all anthraquinone aglycones cluring incubation Conclusions. The anthraqllinone polyphenols in rh llbarb were presystemically metabolizec\ before absorption , inclll c\ ing hy c\ rolysis of glycosides and degraclation of ag lycones by enterobacteria. ( Mid Taiwan J Med 2004;9:87-95 )

Kewords anthraqllinones, feces, HPLC, metabolism, polyphenols, rhubarb

INTRODUCTION Anthraquinone polyphenols are a class of

naturally occurring plant constituents with antioxidation properties [1-3]. They have been reported to exhibit antifungus , anticancer, purgative and anti-in f1ammation activities [4-8]. Therefore, they are promising therapeutic agents against a variety of diseases. Rhubarb , the roots and rhizomes of Rheum palmatum Rcceivcd : 3 March 2004 Acceptcd . 23 April 200 1.

Rcviscd : 2 1 April 2004

Address rcprinl rcqucsts 10 : Su-Lan Hsiu, School of Pharl11acy, China Mcdical Univcrs i 9 1 Hsuch-Shih Road, Taichung 404, Taiwan, R.O.C.

(Polygonaceae) , contains a large number of anthraquinone polyphenols. Rhubarb decoction is widely prescribed in clinical Chinese medicine as a potent laxative, antibacteriocide, anticancer agent, antispasmodic and choleretic. 1n addition, rhubarb has also been reported to lower blood pressure [9,10] and cholesterol levels [11]. Recent studies reported that rhubarb inhibi ted reactive oxygen species and induced nitric oxide synthetase [12,13].

It has recently been shown that mo s t f1avonoid aglycones are absorbed directly by the gut wall, whereas glycosides are usually absorbed

ORIGINAL ARTICLE 87

Presystemic Metabolism of Anthraquinone Polyphenols in Rhubarb

1,2 _ . ~~ 3 ~ ~ 4 Ya-Tze Lin -'-, Pei-Hua ChangJ, Kuo-Ching Wen' , Chung-Ping YuJ,

) _. 0 Pei-Dawn Lee Chao5, Yu-Chi Hou

6, Su-Lan Hsiu5

lNational Laboratories of Food and Drugs, Department of Health, Executive Yuan, Taipei; 2Institute of ~ 4 Pharmaceutical Chemistry, Jlnstitute of Chinese Pharmaceutical Science, 'School of Cosmeceutics, ' School of

Pharmacy, 6School of Chinese Medicine, China Mecl ical Universi" Taichung, Taiwan, R.O.C

Objectives. Anthraqllinone polyphenols are bioactive constitllents which mainly present as glycosicles in rhllbarb, an herb widely used in clinical Chinese medicine. Most polyphenol glycosides are absorbed only after being hydrolyzed to their aglycones by enteral microflora. In the present study, we investigated the presystemic metabolism of fOllr anth raqllinone polyphenols inclllding aloe.emoc\ in, rhein, emodin , anc\ chrysophanol as well as their glycosides in rhllbarb decoction and in rat feces. Methods. Aloe-emoc\ in, rhein , emodin an c\ chrysophanol in rhubarb decoction and feces suspension were c\etermined by HPLC methods developed in this stlldy. The presystemic metabolism of these anthraqllinones by enteral microflora was investigated by separately incubating rhubarb c\ecoction and anthraquinone aglycones with rat feces suspension un c\ er anaerobic conditions Results. The contents of four anthraquinone aglycones in rhllbarb c\ ecoction significantly increased instantaneously upon mixing with feces suspension. Moreover, there was a rapid c\ecrease in all anthraquinone aglycones cluring incubation Conclusions. The anthraqllinone polyphenols in rh llbarb were presystemically metabolizec\ before absorption , inclll c\ ing hy c\ rolysis of glycosides and degraclation of ag lycones by enterobacteria. ( Mid Taiwan J Med 2004;9:87-95 )

Kewords anthraqllinones, feces, HPLC, metabolism, polyphenols, rhubarb

INTRODUCTION Anthraquinone polyphenols are a class of

naturally occurring plant constituents with antioxidation properties [1-3]. They have been reported to exhibit antifungus , anticancer, purgative and anti-in f1ammation activities [4-8]. Therefore, they are promising therapeutic agents against a variety of diseases. Rhubarb , the roots and rhizomes of Rheum palmatum Rcceivcd : 3 March 2004 Acceptcd . 23 April 200 1.

Rcviscd : 2 1 April 2004

Address rcprinl rcqucsts 10 : Su-Lan Hsiu, School of Pharl11acy, China Mcdical Univcrs i 9 1 Hsuch-Shih Road, Taichung 404, Taiwan, R.O.C.

(Polygonaceae) , contains a large number of anthraquinone polyphenols. Rhubarb decoction is widely prescribed in clinical Chinese medicine as a potent laxative, antibacteriocide, anticancer agent, antispasmodic and choleretic. 1n addition, rhubarb has also been reported to lower blood pressure [9,10] and cholesterol levels [11]. Recent studies reported that rhubarb inhibi ted reactive oxygen species and induced nitric oxide synthetase [12,13].

It has recently been shown that mo s t f1avonoid aglycones are absorbed directly by the gut wall, whereas glycosides are usually absorbed