Bioavailability, metabolism, and pharmacokinetics of glycosides in Chinese herbs

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 HPLC 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.