Degradation of Ginsenosides in Humans After Oral Administration

Abstract

This article is available online at http://dmd.aspetjournals.org ABSTRACT:Even though the degradation of ginsenosides has been thoroughly studied in animals and in vitro using acids, enzymes, and intestinal bacteria, knowledge concerning the systemic availability of ginsenosides and their degradation products in humans is generally lacking. Therefore, the attention in this article is focused on the identification of ginsenosides and their hydrolysis products reaching the systemic circulation in man. This is of great importance in understanding clinical effects, preventing herb-drug interactions, and optimizing the biopharmaceutical properties of ginseng preparations. Using a sensitive mass spectrometric method, which is specific for the identification of ginsenosides in complex biological matrices, the degradation pathway of ginsenosides in the gastrointestinal tract of humans could be elucidated following the oral administration of ginseng. Within the frame of a pilot study, human plasma and urine samples of two subjects were screened for ginsenosides and their possible degradation products. In general, the urine data coincided well with the plasma data. In both volunteers the same hydrolysis products, which are not originally present in the Ginsana extract (Pharmaton S.A., Lugano, Switzerland) ingested, were identified in plasma and urine. It was shown that two hydrolysis products of the protopanaxatriol ginsenosides, namely G-Rh 1 and G-F 1 may reach the systemic circulation. In addition, compound-K, the main intestinal bacterial metabolite of the protopanaxadiol ginsenosides, was detected in plasma and urine. These products are probably responsible for the action of ginseng in humans. In opposition to previous reports, G-Rb 1 was identified in plasma and urine of one subject.

Simultaneous Enrichment of Deglycosylated Ginsenosides and Monacolin K in Red Ginseng by Fermentation withMonascus pilosus

“…13) Generally, deglycosylated ginsenosides are more easily absorbed by the human body and have more productive bioactive functions. 3,14,15) For example, ginsenosides Rg 3 , Rh 1 , Rh 2 and compound K are known to have excellent pharmacological effects. 14,16) Many people cannot fully benefit from the health effects of red ginseng due to limited ability to absorb ginsenosides.…”

Metabolite 1 of Protopanaxadiol-Type Saponins, an Axonal Regenerative Factor, Stimulates Teneurin-2 Linked by PI3-Kinase Cascade

“…major C.Y.WU et FENG) in human neuroblastoma SK-N-SH cells, and found that protopanaxadiol-type (ppd-type) saponins (ginsenoside Rb 1 , ginsenoside Rb 3 , notoginsenoside R 4 and notoginsenoside Fa) were the active compounds (Tohda et al, 2002). Ppd-type saponins are known to be completely metabolized into 20-O-b-D-glucopyranosyl-20(S)-protopanaxadiol (M1) by intestinal bacteria when taken orally (Odani et al, 1983;Tawab et al, 2003). Our previous report showed that M1 had axonal extension activity in degenerated neurons, and ameliorated memory disorder and synaptic loss in an Alzheimer's mouse model induced by (Tohda et al, 2004).…”

Active ingredients in Chinese medicines promoting blood circulation as Na+/K+-ATPase inhibitors

“…MLB, a polyphenolic compound, is metabolized within a few hours after consumption [87] . In contrast, it takes a couple of days to metabolize the steroid-like ginsenosides in human body [88,89] . In light of our recent studies, we rationalize that the combinational usage of danshen and sanqi for the treatment of cardiovascular diseases takes the advantages of the non-toxic and yet strong Na + /K + -ATPase inhibitory potency of MLB to relieve the symptoms promptly and the moderate Na + /K + -ATPase inhibitory potency of ginsenosides to provide a relatively long-term basal therapeutic effect.…”

“…Nevertheless, ginsenosides might act as prodrugs, as they tend to be metabolized to their active forms by intestinal bacterial deglycosylation after oral administration [84] . Generally, the metabolites, easily absorbed by the intestines due to an increase of hydrophobicity after deglycosylation, might display the same or different pharmacological actions in comparison with their parent compounds [85] . Therefore, the cardiac therapeutic effects of ginseng and sanqi could very possibly be attributed to the effective inhibition of Na + /K + -ATPase by the metabolized ginsenosides, with sugar moieties attached only to the C-3 position of the steroid-like structure.…”