Chapter 16
Bioavailability, Metabolism, and Pharmacokinetics of Glycosides in Chinese Herbs 1
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Pei-Dawn Lee Chao , Su-Lan Hsiu , and Yu-Chi Hou Downloaded by UNIV OF GUELPH LIBRARY on July 7, 2012 | http://pubs.acs.org Publication Date: January 12, 2006 | doi: 10.1021/bk-2006-0925.ch016
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Schools of Pharmacy and Chinese Medicine, China Medical University, Taichung, Taiwan 404, Republic of China
Glycosides are a group of natural products in Chinese herbs. In preparing decoctions of traditional Chinese medicine, glycosides are soluble in hot water. However, due to their hydrophilic nature, the biological fate of glycosides is of great interest. After oral administration of glycosides to rats, rabbits or humans, serum or urine samples collected at specific time points were analyzed by H P L C prior to and after hydrolysis by sulfatase and glucuronidase. The results indicated that the glycosides of flavonoids and monoterpenes were not present as their parent forms in the circulation. Moreover, the aglycones were negligibly present in the circulation except paeoniflorgenin, a monoterpene. The predominant metabolites of flavonoid glycosides circulating in the blood are the sulfate and glucuronide conjugates of their aglycones, which often reside in the body for prolonged time due to enteric recycling. In contrast, a triterpene glycoside glycyrrhizin and its aglycone glycyrrhetic acid were both present in the blood stream. In conclusion, glycosides are often subject to deglycosylation in the intestine prior to absorption and phenolic aglycones are further sulfated/glucuronidated by gut and/or liver. Therefore, the in vitro bioactivities of alcoholic aglycones and conjugated metabolites of phenolic aglycones should be more predictive for the in vivo efficacy of glycosides in Chinese herbs.
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© 2006 American Chemical Society
In Herbs: Challenges in Chemistry and Biology; Wang, M., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2006.
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Introduction Glycosides are a group of natural products widely distributed in Chinese herbs, fruits and vegetables. The structure of a glycoside consists of a sugar moiety and an aglycone that is mainly a phenol or an alcohol. In preparing decoctions of traditional Chinese medicine, glycosides are quite soluble in the hot water. However, due to their hydrophilic nature, the biological fates and bioactivities of glycosides are of great interest. There has recently been a proliferation of in vitro studies on herbal components, concerning mainly effects on cell signaling pathways. These studies are largely focused on commercially available compounds including various glycosides and aglycones. However, in recent years, there is an increasing recognition that flavonoid glycosides are generally not absorbed per se and most flavonoid aglycones are not present in the circulation, whereas their conjugated metabolites predominate (/). Therefore, whether the in vitro effects produced by glycosides and aglycones can be extrapolated to the in vivo bioactivities still remains unclear and needs to be clarified. This review would deal with the bioavailability, metabolism and pharmacokinetics of naturally occurring glycosides of flavonoids and terpenes in Chinese herbs.
Bioavailabilities of Glycosides The definition of bioavailability for a drug is the fraction of an oral dose that reaches the systemic circulation in its parent form. In terms of glycosides, the presence of sugar moiety confers the hydrophilic property that makes them soluble in hot water. However, based on drug absorption theory, glycosides are generally too lipophobic to be absorbed through enterocytes via transcellular diffusion (2). Most of flavonoid glycosides (e.g. rutin, naringin, hesperidin, baicalin, daidazin and phellamurin whose structures are shown in Figure 1) are hydrophilic and thus may not be transported across the phospholipid bilayers of cell membranes by passive diffusion. Naringin and hesperidin are flavanone glycoside constituents in many Citrus herbs like the fruits of C. aurantium, C. grandis and C. reticulata. The bioavailabilities of naringin and hesperidin after oral administration were investigated in rabbits. The results showed that naringin and hesperidin were not absorbed per se (3,4). Another flavanone glycoside phellamurin, a major constituent of Phellodendron wilsoni, was orally
In Herbs: Challenges in Chemistry and Biology; Wang, M., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2006.
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OH
Hesperidin
Baicalin
Daidzin
Phellamurin
CH OH 2
CH
