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Plant Profiler
Ginseng (Panax ginseng)
Note: This review is focused on Panax ginseng species. Avoid confusing with Eleutherococcus
senticosus, which is also known as Siberian ginseng. In Russia, Siberian ginseng was promoted
as a cheaper alternative to ginseng as it was believed to have identical benefits. However, it is
void of the ginsenosides contained in Panax spp. Other species may be referred to as ginseng as
well, but they are from either a different family or genus; examples include Eleutherococcus
senticosus (Siberian ginseng), Pseudostellaria heterophylla (prince ginseng), Angelica sinensis
(female ginseng, or dong quai), Withania somnifera (Indian ginseng or ashwagandha), Pfaffia
paniculata (Brazilian ginseng), Lepidium meyenii (Peruvian ginseng or maca), Gynostemma
pentaphyllum (southern ginseng or jiaogulan). Siberian ginseng is not covered in this review.
Mechanism of Action
Pharmacology:
symptoms caused by excessive apoptotic cell death in the skin through the Fas/FasL
pathway.168
Shengmai injection has also shown anti-tumor effects in mice.169 The inhibition
mechanism might be related to IL-2 receptor levels.170
The role of cancer-preventative effects of ginseng have been discussed in various
reviews.171,162
Antiemetic effects: The results of an in vitro study indicate that ginseng
saponins, especially the panaxatriol saponin fraction, have substantial inhibitory
effects on the recombinant serotonin type 3A receptor, suggesting that some specific
ginsenosides might have an antagonistic action against serotonin type 3A receptor
related to nausea and vomiting.12 These antiemetic results are supported by an
animal study using Korean red ginseng total extract.28
Anti-inflammatory effects: Panax ginseng may reduce muscle injury and
inflammation following exercise in humans, as demonstrated by reduced levels of
creatine kinase, beta-glucuronidase, and glucose-6-phosphate dehydrogenase
(G6PDH) following oral Panax ginseng administration.172 In a clinical trial of patients
with obstructive jaundice, postoperative Salvia miltiorrhiza and shengmai decreased
the postoperative levels of plasma LPs, ET, TNF-alpha, IL-6 and IL-8, and inhibited
inflammatory mediator and improved blood dynamics.42 Administration of shenmai
injection also significantly reduced the expression of TNF-alpha mRNA in peritoneal
macrophages.173
Antimicrobial effects: In an animal study, mice treated with ginseng before a
bacterial challenge of Staphylococcus aureus were protected from sepsis, possibly
due to early suppression of acute inflammatory responses and later enhancement of
macrophage activity.174 Juzen-taiho-to, a Japanese traditional medicine containing
ginseng radix, enhanced the anti-Candida activity of macrophages in Candida
albicans infected mice.175 Belogortseva et al. found polysaccharide fractions from the
root of Panax ginseng to inhibit Helicobacter pylori hemagglutination.176 Patients
treated with ginseng exhibited a significant improvement in clearance of
Pseudomonas aeruginosa from the lungs (p<0.04), lower lung abscess incidence
(p<0.01), and lower mast cell numbers in the lung foci (p<0.005).34
Antioxidant effects: Panax ginseng and Panax quinquefolius have antioxidant
activity.177,19 This is thought to be due to ginsenoside content178 and saponins, which
can decrease oxidation of low density lipoprotein in vitro122, 179. In addition, Panax
ginseng extracts have antioxidant activity in vitro in brain tissue180, and its properties
may be enhanced by using a heat treatment on the ginseng36. Benzoic acid
derivatives, salicylic acid, and vanillic acid also showed antioxidant activity in
assays.181 Not surprisingly, shenmai (Panax ginseng, Schizandra fruit, Ophiopogon)
has also shown antioxidant activity in vitro, in rats, and in heart attack patients.46, 182
Lee et al. found a reduction of oxidative deoxyribonucleic acid (DNA) damage and
protein oxidation in smokers who were supplemented with ginseng183, the
compounds that mediate such effects remains unclear.
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capacity, possibly due to American ginseng's ability to reduce cellular and muscle
damage.18
Fertility effects: Panax notoginseng extracts enhanced sperm motility in vitro
after one and two hours of incubation.243 Ginsenosides enhanced nitric-oxide release
from nitrergic nerves in tissue samples of rabbit corpus cavernosum244,2 and caused
relaxation of the smooth muscle245. Choi et al. found that long-term administration of
Korean red ginseng enhanced erectile capacity by endothelium-derived relaxing
factor.246 Use of Panax ginseng C.A. Meyer extract showed an increase in
spermatozoa number/mL and progressive oscillating motility, an increase in plasma
total and free testosterone, dihydrotestosterone (DHT), follicle stimulating hormone
(FSH), and luteinizing hormone (LH) levels, but a decrease in mean prolactin
(PRL).108 In another clinical trial, Panax ginseng decreased in the percentage of
diskinetic forms of spermatozoids.107
Helicobacter pylori inhibitory effect: Acidic polysaccharides from Panax
ginseng may inhibit Helicobacter pylori adhesion to human gastric epithelial cells.41
Hemological effects: Saponins from Panax ginseng, including ginsenosides Rb1,
Rb2, and Rg1, inhibited the hyperosmotic hemolysis of erythrocytes in an in vitro
study.247 In an in vitro trial using bone marrow from patients with aplastic anemia, the
total saponins of Panax ginseng increased bone marrow cultures possibly by
prompting proliferation of normal progenitor cells.248 In a clinical study, shenmai
injection (Panax ginseng, Schizandra fruit, Ophiopogon) decreased the concentration
of tumor necrosis factor (TNF)-alpha in blood serum and the apoptosis rate of bone
marrow CD34. cell249
Hepatoprotective effects: The metabolite of oral ginsenosides, 20-O-beta-D-
glucopyranosyl-20(S)-protopanaxadiol, protected mouse liver cells from cytotoxicity
induced by tert-butyl hydroperoxide and significantly inhibited the increment of
alanine amino transferase (ALT) and aspartate transaminase (AST) induced by tert-
butyl hydroperoxide in mice.250 The metabolite also stabilized cell membranes.
Hormonal effects: The estrogenic effects of ginseng are not well defined, due to
conflicting studies. Some in vitro studies indicate an estrogenic effect in human
breast cancer cells, possibly by binding and activating the estrogen
receptor.64,251,109,10,67,252 Other in vitro studies do not show this effect.66 This
discrepancy may be due to the type of ginseng extract used, as King et al. showed
that a methanol extract did have estrogenic properties in vitro in breast cancer cells,
but a water extract did not.8 The traditional Japanese herbal medicine unkei-to, which
contains Panax ginseng and other herbs, stimulated the secretions of 17ß-estradiol
and progesterone from highly luteinized granulosa cells obtained from in vitro
fertilization patients; the stimulated effect on estradiol secretion occurred with
0.3mcg/mL, while a significant effect on progesterone secretion was obtained at
10mcg/mL.50
Ginseng has been postulated to stimulate adrenocorticotropic hormone and thereby
increase plasma cortisol levels.123 In rats fed with ginseng for 60 days, a significant
increase of blood testosterone levels was found, combined with a significantly
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(Panax notoginseng) have also been reviewed.292 The potential for interactions with
anti-cancer agents of herbal products, including ginseng, has been reviewed.293
Pharmacodynamics/Kinetics:
The ginsenosides found in ginseng appear to be poorly absorbed, either after both
oral and intravenous administration in rats.294,295,296 For example, the bioavailability
of Rb1 and Rg1 after oral administration is 0.71% and 3.29%, respectively.294 Other
unsubstantiated sources have reported that the bioavailability of beta-sitoserol, a
steroid sapogenin, and ginsenoside Rg1 after oral administration to rats was 50-60%.
However, intranasal administration may increase absorption.297,298 High elimination in
the stomach, large intestine, and liver may contribute to the low bioavailability of
these ginsenosides, but low membrane permeability is probably a greater limiting
factor294,295, especially as ginsenosides may be passively absorbed by simple
diffusion294 or dependent on active transport299. The low absorption rate by the
intestinal wall could be enhanced by carbomer and borneol.296 Once absorbed, the
distribution of ginsenosides could be described by a two-compartment model.300
Although several recent studies have examined the ginsenosides themselves, some
researchers have focused on the intestinal metabolites of these compounds, which
may have the active processes that medical researchers are interested in, such as
antitumor effects. A couple of these metabolites are 20- O-(beta-D-
glucopyranosyl)-20(S)-protopanaxadiol, known as compound K or IH-901, and 20(S)-
protopanaxatriol, known as M4.301,302,303,304 The metabolism of ginsenoside Rb1 to
compound K was shown in a rat study by Akao et al., when rats deprived of
Eubacterium sp. and orally administered Rb1 had neither compound K nor any other
metabolite in their plasma, intestinal tract, or feces; Rb1 was only found in fecal
contents and not in the plasma.304
Compound K seems to be efficiently removed from blood by the liver301 and showed
little excretion in the urine302. Compound K may also be passively absorbed from the
digestive tract.302 The ginsenoside Rg1 may have a plasma protein binding of 24%
and tissue protein binding of 48% in the liver although confirmation is needed.
In a study of rats administered with the metabolite M4, M4 was absorbed from the
small intestine, was esterified with fatty acids, then accumulated in tissues, including
the lungs and liver.303
The metabolism and excretion of the constituents of ginseng has not been
extensively studied. It appears that ginsenosides are excreted in the urine only in
trace amounts. One study has focused on the pharmacokinetics of shenmai injection
(Panax ginseng, Schizandra fruit, Ophiopogon) by tracking the plasma concentrations
of the ginsenosides Rg1 and Re after shenmai injection into human volunteers.305
The results indicate that the distribution and elimination of Rg1 and Re were rapid
after intravenous infusion, and the pharmacokinetic characteristics indicate a two-
compartment model.
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