Absorption, Disposition, and Pharmacokinetics of Saponins from Chinese Medicinal Herbs: What Do We Know and What Do We Need to Know More?

Abstract

Saponins are a group of amphiphilic glycosides containing one or more sugar chains linked to a nonpolar triterpene or steroid aglycone skeleton, which are believed to be responsible for the pharmacological activities of many Chinese medicinal herbs. The purpose of this paper is to summarize the contemporary knowledge of the absorption, disposition, and pharmacokinetics of some important saponins, including ginsenosides, licorice saponins, dioscorea saponins, astragalosides, and saikosaponins. Poor intestinal absorption of saponins is mainly due to their unfavorable physicochemical traits, such as large molecular mass ( > 500 Da), high hydrogen-bonding capacity ( > 12), and high molecular flexibility ( > 10), that underlie poor membrane permeability. Rapid and extensive biliary excretion is another primary factor that limits the oral bioavailability of most saponins. However, several saponins, including ginsenosides Ra3, Rb1, Rc, and Rd, and dioscin, are excreted slowly into the bile and in turn have significantly long elimination half lives (7-25 h in rats). These longcirculating saponins may be used as pharmacokinetic markers to substantiate systemic exposure to the ingested herb extracts. In addition to biliary excretion for elimination of most saponins unchanged, renal excretion may also be important for certain saponins. Saponins can be hydrolyzed by the colonic microflora. After absorption, the deglycosylated aglycones undergo phase I and/or II metabolism by the host. In line with the poor permeability, saponin concentrations in most rat tissues are lower than the concurrent plasma level and the brain level is usually very low. However, the liver concentrations of many saponins, as well as the kidney levels of certain saponins, can be quite high, which involves transporter-mediated uptake mechanisms. Repeated p.o. ingestion of glycyrrhizin appears to be able to induce CYP3A in rodents and humans, while several deglycosylated products of ginsenosides can moderately inhibit CYP activities in vitro with IC50 values of 10-50 μM. More research is required for elucidation of the absorption, disposition, and pharmacokinetics of multiple saponins to enhance understanding which saponins are most likely to exert pharmacological effects in vivo, as well as influence of complex herb matrix. In addition, research is also needed to characterize the microbiotal deglycosylation and the subsequent aglycone metabolism by the host for a broader range of saponins, as well as the hepatobiliary transporter phenotyping for and the interaction with saponins. Furthermore, in vitro and in vivo studies of saponin-based herb-drug interactions are also warranted.

The Hepatobiliary Disposition of Timosaponin B2 Is Highly Dependent on Influx/Efflux Transporters but Not Metabolism

“…This low passive permeability may prevent its absorption, and efflux transporters (Bcrp/Mrp2) may pump it back into the intestinal tract. The low passive permeability of TB-2 may result from its unfavorable physicochemical traits, including its large molecular mass (921, favorable value ,500 Da), high hydrogen-bonding capacity (31, favorable value ,12) and high molecular flexibility (25, favorable value ,10), which leads to poor membrane permeability and hinders intestinal absorption (Yu et al, 2012). Moreover, metabolism in the gastrointestinal tract may also impede TB-2 absorption, as the deglycosylation of many saponins occurs in the gastrointestinal tract via the action of colonic microflora (Hasegawa et al, 1996).…”

Consumption of Japanese Yam Improves Lipid Metabolism in High-Cholesterol Diet-Fed Rats

“…Orally administered dioscin is reportedly absorbed from the intestines, distributed to the liver, plasma, and other tissues, and is metabolized to Dio in the liver (27)(28)(29)(30). Since Jin contains both Dio and dioscin, the effects of Jin supplementation in rats may reflect both molecules.…”

Identification of Triterpenoids from Schefflera systyla, Odontadenia puncticulosa and Conostegia speciosa and In Depth Investigation of Their in vitro and in vivo Antifungal Activities

“…The absence of in vivo antifungal activity of 1 in G. mellonella could be explained by the poor membrane permeability of the triterpene glycosides due to its large molecular mass (> 500 Da), high hydrogen-bonding capacity (> 12) and high molecular flexibility (> 10). 53 Saponins are known to possess many biological activities such as haemolytic, antiviral, fungicidal, molluscicidal or cytotoxic activities, partially due to their interaction with the cell membrane. 50,54 Recently, some saponins have shown in vivo antifungal activity comparable to amphotericin B against Candida species in the C. elegans nematode assay.…”