Proceedings, The 15th Congress of FAVA 27-30 October
FAVA -OIE Joint Symposium on Emerging Diseases Bangkok, Thailand
Photoprotective Effect of Red Ginseng against Ultraviolet Radiation-
induced Chronic Skin Damage in the Hairless Mouse
H.J. Lee1, J.S. Kim2, M.S. Song2, H.S. Seo2, C. Moon2, J.C. Kim2, D.H. Shin2, T.O. Ahn2, S.K. Jo3, S.H. Kim2*
1Korea Institute of Radiological & Medical Science, Seoul 139-240, South Korea
2College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, South Korea
3Advanced Radiation Technology Institute, KAERI, Jeongeup 580-185, South Korea
*Corresponding author
Keywords: Chronic skin damage, Panax ginseng, Photocarcinogenesis, Ultraviolet
Introduciton
evenly to the skin of the back at a rate of 0.2 mg/cm2
Panax ginseng, also known as Korean or Chinese
at least 15 min before UV-irradiation.
ginseng, has been used as a general tonic in
Visual skin evaluation and Histology: Skin
traditional oriental medicine to increase vitality,
wrinkling in mice was assessed as described
health, and longevity, especially in older persons (8).
previously. All mice were euthanized and their
Commercially available ginseng is classified into
dorsal skins were dissected using a rectangular
fresh, white, and red ginseng. White ginseng is made
template (2.5x5 cm) to include the entire treated
by peeling the fresh ginseng roots and drying them
areas. The skin were stapled to cardboard, fixed in
without steaming. To preserve ginseng for an
10% neutral-buffered formalin, embedded in
extended period of time, red ginseng is made by
paraffin, and sectioned at 5 um. These histological
steaming and drying the fresh ginseng, suggesting
changes in mice were assessed as described
chemical transformation by heat (6). In Oriental
previously. The skin with tumors was processed for
medicine, ginseng is extracted with boiling water
microscopic evaluation of tumor. All the analyses
and used for medicinal purposes. Aqueous extracts
were performed using a Graph PAD In Plot
of ginseng are composed of a mixture of glycosides,
computer program (GPIP, Graph Pad Software, Inc.,
ginsenosides, trace minerals and a variety of
USA).
complex carbohydrates as well as proteins, peptides
and amino acids (6). The main pharmacologically
Results and Discussion
active constituents of ginseng are believed to be
At treatment week 12, the mean wrinkle grade of the
ginsenosides, derivatives of the triterpene
RG-treated group was 1.50 (i.p. treatment) or 1.25
dammarane structure (6). The pharmacological
(topical treatment), and that of the vehicle-treated
effects of ginseng have been demonstrated in the
group was 1.88 or 1.85, respectively (Fig. 1). Skin
CNS and in cardiovascular, endocrine, and immune
was taken for histological evaluation at week 22 in
systems. In addition, ginseng and its constituents
the experiment. Irradiated mice showed strikingly
have been ascribed to possess antineoplastic,
better histological scores for epidermal thickening,
antistress, radioprotective, and antioxidant activities
dermal cellularity and cysts than non-irradiated
(5, 7). In this report we described the
mice. The RG (i.p. group) showed reduced damage
photoprotective effect on hairless mice of red
as assessed by a number of parameters (Table 1).
ginseng (RG) against chronic skin damage induced
The tumors were first observed after 14 weeks of
by UV radiation.
UV irradiation and continued to appear throughout
the course of the experiment. The mice treated with
Materials and Methods
RG were substantially protected against the
Irradiation and RG treatment: Seven-week-old
carcinogenic effects of UV radiation. After 22weeks
female SKH-1 hairless mice were used. The UV
of treatment, when the experiment was terminated,
apparatus consisted of four UVB lamps (GL20SE,
88.9% (i.p. with saline vehicle) or 60.0% (topical
Sankyo denki, Japan). The fluence at 40 cm from the
administration with cream base vehicle) of the
dorsal surface of the mice was 0.48-0.50 mJ/cm2/s.
animals in the UV-irradiated groups had developed
Mice were exposed to 90 mJ/cm2 three times per
tumors, while 57.1% (i.p. with RG) or 85.7%
week and the dose was increased by 10% per week
(topical administration with RG cream) of the mice
until the dose reached 175 mJ/cm2. UV treatment
treated with RG were tumor-free. Similarly, tumor
was stopped at 22 weeks. The freeze-dried RG
multiplicity was reduced by 89.3% (i.p. with RG) or
extract powder was kindly provided by the Korea
92.2% (topical administration with RG cream) in the
Ginseng Corporation (Daejon, Korea). For mice
RG treated groups (Table 2). In addition to the
receiving i.p. injection, the RG (25 mg/kg of body
reduction in tumor incidence and multiplicity, there
weight) or vehicle (saline) was given i.p. at 24 hours
was a significant delay in tumor appearance
prior to each UV-irradiation. For mice receiving
(Table 3).
topical treatment with a vehicle (cream base, Kolma
Chronic exposure to UV irradiation leads to
Korea Co., Korea) or RG cream, the RG cream
photoaging, immunosuppression, and ultimately
(0.2% RG in cream base) or vehicle was applied
photocarcinogenesis. Photocarcinogenesis involves
the accumulation of genetic changes, as well as
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27-30 October Proceedings, The 15th Congress of FAVA
Bangkok, Thailand FAVA -OIE Joint Symposium on Emerging Diseases
immune system modulation, and ultimately leads to
References
the development of skin cancers. UVB exposure to
1 Black et al., 1997. J. Photochem. Photobiol. 40:
the skin has been shown to produce excessive
29-47.
generation of ROS, which if not counteracted by the
2 Kim et al., 2003. In Vivo 17: 77-82.
antioxidant defense ability of the living system,
3 Kim et al., 2002. Toxicology 172: 149-156.
creates oxidative stress in the skin (1). This
4 Kitts and Hu, 2000. Pub Health Nut 4: 473-485.
oxidative stress is shown to be responsible for a
5
Lee et al., 2006. Phytother. Res. 20: 392-395.
variety of pathological conditions, including
6
Park, 1996. Kor. J. Ginseng Sci. 20: 389-415.
immunosuppression, inflammation, aging, and skin
7 Shin et al., 2000. Cancer Causes Control 11:
cancer (1). Therefore, prevention/intervention with
565-576.
antioxidant agents is often regarded as a plausible
8 Sonnenborn and Propert, 1991. Br. J. Phytother.
strategy for the management of these oxidative stress
2: 3-14.
conditions.
9 Valli and Giardina, 2002. J. Am. Coll. Cardiol
The strong free radical scavenging effects of P.
39: 1083- 1095.
ginseng have been extensively documented (3, 4, 9).
The effect of P. ginseng has been closely linked to
its antioxidative capability through both the
chelating of transition metal ions and the scavenging
of free radicals responsible for DNA damage (2).
Studies have demonstrated that ginseng root extracts
exhibit both lipid-soluble and water-soluble
antioxidant activity ex vivo, and that this antioxidant
action occurs both directly through free radical
scavenging and indirectly through upregulation of
antioxidant enzymes (9), leading to the prevention of
DNA degradation (4).
Since free radicals play an important role in UV-
induced damage,
the underlying protective
mechanism of ginseng could be linked, either
directly or indirectly, to its antioxidative capability
by the scavenging of free radicals responsible for
DNA damage. In addition, ginseng's photoprotective
potential may
also be related to its
immunomodulating capabilities. The results of the
Fig. 1 Sequential changes of wrinkle grade in the
present study indicate that RG is protective against
skin of UV-irradiated mice and red ginseng (RG)-
chronic damage induced by UV radiation in the
treated mice. The mice were graded using a scale of
hairless mouse. Protection against visible changes
mouse wrinkling. The scale ranges from 0 for the
(wrinkling and tumor formation) and histological
normal skin to 3 for the heavily fixed wrinkling skin.
alterations were demonstrated.
Half-grade increments can be used with this scale
*p<0.01 as compared with corresponding UV+vehicle group.
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Proceedings, The 15th Congress of FAVA 27-30 October
FAVA -OIE Joint Symposium on Emerging Diseases Bangkok, Thailand
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27-30 October Proceedings, The 15th Congress of FAVA
Bangkok, Thailand FAVA -OIE Joint Symposium on Emerging Diseases
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