Saponin phytosome: A solution to enhance bioavailability of saponin

JOURNAL OF MILITARY PHARMACO-MEDICINE N07-2016

SAPONIN PHYTOSOME: A SOLUTION TO ENHANCE
BIOAVAILABILITY OF SAPONIN (A REVIEW)
Nguyen Van Long*; Dang Truong Giang*; Vu Tuan Anh*
Nguyen Thi Lan Huong*; Nguyen Thi Thu Hoai*
SUMMARY
Saponin is a group of compounds occurring naturally in plants and animals. These
compounds may own important biological effects. However, one of the factors reducing their
pharmacological effect in vivo of these compounds is poor bioavailability. There are many
factors affecting the bioavailability of saponins including solubility, stability and permeability.
Phytosomal technology is able to improve the bioavailability of saponins in vivo by increasing
solubility, stability and permeability of these compounds. This study aims to review the
advances of this modern technology to enhance bioavailability of saponin.
* Key words: Saponin; Bioavailability; Phosphatidylcholine; Phytosomal technology.

INTRODUCTION
Saponin is a class of glycosides found
abundantly in various plant species. In
terms of chemical structure, saponin can
be divided into two groups: triterpenoid
saponins and steroidal saponins. In general,
saponins have many pharmacological
effects as expectorant, anti-inflammatory,
antihypertensive, immuno-modulatory,
hypoglycemia, antifungal, antiparasitic
effects, etc…) [1].
However, the major challenge in
developing saponins as clinically useful
drugs is their poor bioavailability. The poor
bioavailability of saponins was caused by

the physicochemical properties of its (e.g.
solubility, stability) and the ability of saponins
to permeate a biological membrane [7].
There were few reports about the
pharmaceutical formulation study to enhance
the oral bioavailability of saponins such as
nanoparticles, liposome, phytosome….
This report aims to review some factors
affect the bioavailability of saponins and

phytosomal technology
bioavailability of saponins.

to

enhance

BIOAVAILABILITY OF SAPONINS
Some recent studies showed that the
bioavailability of some saponins is low.
Studies of oral bioavailability of ginsenoside
Rh2, a secondary ginsenoside with anticancer effects, is lower than 1% in mice
A/J after oral administration of 5 mg/kg or
20 mg/kg Rh2 [8].
An oral administration of glycyrrhizin
(oleane type) in mice at a dose of 200
mg/kg body weight, the oral bioavailability
was appoximately 4%. In Beagle dogs,
the bioavailability of orally glycyrrhizin was
3.24% [6].

Astragaloside IV is another types of
saponins which has bioactivities against
cancer cell lines such as epithelial liver
cells. Pharmacokinetic studies have shown
that the oral bioavailability of astragaloside
IV in Sprague Dawley rats (at doses of 20
mg/kg) was 3.7% or 7.4% in Beagle dogs
(at doses of 10 mg/kg) [5].

* Military Medical University
Corresponding author: Dang Truong Giang ()

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JOURNAL OF MILITARY PHARMACO-MEDICINE N07-2016

Bioavailability is therefore an important
concern for saponins if they were to be
developed as viable drug candidates.
Pharmaceutical companies usually do not
develop drugs whose oral bioavailability
is lower than 30%. Thus, enhancing
bioavailability of saponins is necessary
[7].
SOME FACTORS AFFECT
BIOAVAILABILITY OF SAPONINS
Bioavailability of saponins is dramatically
affected by some factors such as solubility,
stability and permeability [7].

1. Solubility.
The solubility of saponins depends on
the number of sugar units in its chemical
structure. Aqueous solubility of aglycones
is lower than their corresponding glycosides.
It was reported that the aqueous solubility
of oleanolic acid and betulinic acid, two of
the saponin triterpene aglycones were
approximately 0.02 µg/mL [7]. However,
the increase in solubility of the drug does
not necessarily lead to an increased
absorption. This is due to the fact that
drug absorption is a complicated process
that is affected by different factors. Although
the presence of sugar units can enhance
solubility of saponin, other factors such as
high molecular weight, hydrophilicity, and
the large number of hydrogen bonds
reduce the permeability of the saponin,
which ultimately leads to poor absorption
of saponins [7].
2. Stability.
The complicated chemical structure of
saponins can be changed during storage
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or processing which leads to the
transformation of their physicochemical
properties and/or biological activities.
Glycosidic bonds (between sugar chains

and aglycones), and inter-glycosidic bonds
between sugar residues can be hydrolyzed
in acid or base environment [7].
The presence of the free carboxylic
group of saponins can be the reason for
releasing the corresponding ester as
storing in alcohol. Since free carboxylic
groups from saponins are able to create
enough acidity in alcohol, it catalyzes the
formation of the corresponding ester
which is the main reason of saponin
instability [7].
3. Permeability.
The ability of a drug to permeate a
biological membrane was measured using
permeability, which was a parameter
widely used to describe the absorption of
a drug. Absorption of a molecular via
intestinal epithelial cells was a complex
process that may involve mutiple pathways
(figure 1) [7]. The stages of process
greatly affected the absorption of drugs
including passive diffusion, absorption,
and excretion. Poor membrane permeability
was one of the significant factors
decreasing the absorption of saponin in
the digestive system. Although the addition
of sugar chains increases the solubility, it
reduces the permeability of saponin due
to considerable changes of hydrogen bonds,

polarized surface area, and the flexibility
of the molecular [7].


JOURNAL OF MILITARY PHARMACO-MEDICINE N07-2016

Figure 1: The absorption and metabolisms of saponins in intestine and liver [7].
ENHANCING BIOAVAIBILITY OF
SAPONIN BY USING PHYTOSOMAL
FORM
Phytosome complex is a combination
of the active compounds or standardized
herbal extracts and phospholipids at
molecular level phytosome form has many
advantages such as rapid absorption of
the active ingredients, enhancing bioavailability,
increasing efficacy, reducing dose, improving
the stability of the substance [4].
The research has been conducted to
improve the absorption of the Rg1 and
Rb1 ginsenosides from Panax notoginseng
(PNS) [2]. Figures 2 and 3, respectively
show the mean plasma concentration versus
time profiles of ginsenoside Rg1 and Rb1

obtained with PNS aqueous solution,
PNS-phospholipid complex, and the
complex dissolved in Labrafac cc/Capmul
MCM (3:1). It was apparent that the markedly
higher plasma levels of ginsenoside Rg1

and Rb1 were obtained when administered
as dissolved complex in Labrafac cc/Capmul
MCM (3:1), compared with those obtained
as an aqueous solution [2]. The peak
plasma levels of ginsenoside Rg1 and
Rb1 administered as PNS phospholipid
complex were even lower than that given
as aqueous solution. Both the PNSphospholipid complex and the oil solution
of the complex appeared to be absorbed
at a slower rate and much longer residence
time, so as to achieve higher extent of
absorption [2].

Figure 2: Concentration of Rg1 in plasma after oral PNS administration (at dose of
600 mg/kg body weight in rats): PNS
, PNS-phospholipid complex
,
PNS-phospholipid complex in glyceride medium chain
[2].
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JOURNAL OF MILITARY PHARMACO-MEDICINE N07-2016

Figure 3: Concentration of Pb1 in plasma after oral PNS administration (at dose of 600
mg/kg body weight in rats): PNS
; PNS-phospholipid complex
, PNSphospholipid complex in glyceride medium chain
[2].
The study prepared glycyrrhizic acidphospholipid complex (GL-PLC) as to

improve the oral bioavailability of
glycyrrhizic acid (GL), enhance the drug
efficacy and reduce the side effects (GL is
a aglycon of glycyrrhizin). The results of
pharmacokinetic study displayed that the
plasma concentration of glycyrrhetic acid,
the metabolite of GL in vivo, increased
after oral administration of GL-PLC. The
Cmax of GL-PLC was 2.14 times higher
than that of free glycyrrhizic acid, while
the AUC of GL-PLC was 1.74 times
higher than that of free GL. The results
proved that GL-PLC improved the
lipophilic property of GL, increased
the bioavailability and anti-inflammatory
activity [3].
CONCLUSION
Saponins have significant biological
effects. Poor bioavailability of saponins is
affected by a number of factors including
solubility, stability, and permeability. Some
studies have shown that phytosome
84

technology is a modern pharmaceutical
technology to enhance the bioavailability
of saponins in vivo. Because of remarkable
effects of phytosomal form, researchers at
Vietnam Military Medical University have
studied phytosome formulation from

standardized
saponin
extract
of
Gynostemma pentaphyllum. to prepare
several products to serve soldiers and
public healthcare.
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