**2.2 ADME of ginsenosides**

Absorption, distribution, metabolism and excretion (ADME) describe the pharmacokinetics and pharmacodynamics of a single or more compounds in an organism such as human, mouse etc. The knowledge of pharmacokinetics of ginsenoside and its metabolites is very imperative in designing an optimal dosage regimen and minimizing the adverse effect that may result from ginseng-drugs interaction. The polar ginsenosides include Rg1, Re, Rb1, Rc, Rb2, Rb3, and Rd., while less polar ginsenosides include Rg2, Rg3, Rg5, Rh2, Rk1, and Rs4 [15, 16]. Protopanaxadiol ginsenosides are metabolized to ginsenoside compound K by the intestinal microflora in humans. Ginsenoside compound K (20-*O*-β-D-glucopyranosyl-20(S) protopanaxadiol), is found in the blood stream of humans as an active metabolite after oral administration of protopanaxadiol ginsenosides Rb1, Rb2, Rc, and Rd., and has significantly higher mean maximum plasma concentration and significantly lower half-life when compare to the ginsenoside Rb1 [17].

According to Qi et al., [18], the ginseng saponins have low absorption rate and characterized by extensive metabolism in the gastrointestinal tract, poor membrane permeability, and low solubility of deglycosylated products; and with less than 5% dose bioavailability of the protopanaxadiol (PPD) group of saponins (ginsenosides Ra3, Rb1, Rd., Rg3, and Rh2) and of the protopanaxatriol (PPT) group of saponins (ginsenosides Rg1, Re, Rh1, and R1) were less than 5%. However, PPT saponins have better bioavailability than PPD saponins, which may be due to the fact that PPD saponins degrade faster than PPT saponins. Study on ginseng absorption by HPLC analysis, showed that Rb1 (4.35%) and Rg1 (18.40%) were absorbed, respectively [19].

Study on the effect of American ginseng and Asian ginseng extracts on gene expression of the hepatic cytochrome P450 enzyme in elderly humans, has shown that protopanaxadiol (PPD), protopanaxatriol (PPT) and their metabolites, moderately inhibited CYP2C9 activity and strongly inhibited CYP3A4 activity [20, 21]. Henderson et al., [22] have studied the effects of seven naturally occurring ginsenosides Rb1, Rb2, Rc, Rd., Re, Rf, and Rg1 and eleutherosides B and


#### **Table 1.**

*Chemical constituents of* P. ginseng.


**Table 2.**

*The molecular mechanism of ginsenosides pharmacological activities.*

E (active components of the ginseng root) on the catalytic activity of *c*DNA expressed CYPs (CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) in *in vitro* experiments. They found that the ginsenosides and eleutherosides tested are not likely to inhibit the metabolism of co-administered medications in which the primary route of elimination is via cytochrome P450 [22]. Comprehensive review of the ginseng active compounds pharmacokinetics, drug–drug interaction, and influence of cytochrome P450 has been published [23]. Chemical constituents of *P. ginseng* and mechanisms of selected ginseng compounds are shown in **Tables 1** and **2** respectively.

### **3. Bioinformatics analyses of ginsenosides**

A study has proposed a novel method to explore underlying mechanisms of multiple actions of multiple constituents of Ginseng (*Panax ginseng*) against cancers, and the bioinformatics analyses was initiated with proteins regulated by ginsenoside rb1/re/rg1, using standard tools such as ChEMBL, STRING, DAVID and KEGG [43].

In the study conducted by Yan et al. [44] to identify immunomodulatory biomarkers in an immune cell induced by ginseng, microarray assays were carried out to identify differentially expressed genes associated with American ginseng (*Panax quinquefolius*) exposure to 4 groups of Murine splenic cells from adult male C57BL/6 (B6) mice which were isolated to mimic 4 basic pathophysiological states. The microarray data obtained was analyzed with Partek Genomics Suite software while DAVID Bioinformatics Resources 6.7 was used for functional annotation clustering. The effect of American ginseng on the interferon gamma signaling functions was obtained by the use of Interferome software [44].

In their study, Zhu et al. [8], have reported two major *Panax ginseng* glycoprotein (PGG-1 and PGG-2) obtained by high performance liquid chromatography, with

*Bioinformatics Exploration of Ginseng: A Review DOI: http://dx.doi.org/10.5772/intechopen.96167*

the molecular weights of 1.5 KDa and 8.2 KDa respectively calculated by gel permeation chromatography. The ginseng samples were analyzed by LC–MS using a nanoflow RP-HPLC online-coupled to a Q Exactive mass spectrophotometer operating in the positive ion mode. The raw MS files were analyzed and searched against the UniProt ginseng protein sequence database using Byonic software (Version 2.3.5). The computed parameters of PGG determined by MS include theoretical isoelectric point (pI), instability index, aliphatic index and grand average of hydropathicity (GRAVY). The aliphatic index of PGG-1 ranged from 0 to 130, with an average of 48.23; the aliphatic index of PGG-2 ranged from 61.25 to 195.71, with an average of 129.41 [8].

Bioinformatics network analysis has been used to analyzed a combination of ginseng and arginine regimen, ginseng and lingzhi as well as ginseng and gingko regimens [45, 46], in order to understand potential impact of drug–drug interaction (agonism or antagonism) based on common pathways.
