ARTICLE
Auteur(s) : Sang-Cheol Kim1, Jung-Il
Kang1, Min-Kyoung Kim1, Jae-Hee
Hyun1, Hye-Jin Boo1, Doek-Bae
Park1, Young-Jae Lee2, Eun-Sook
Yoo1, Young Ho Kim3, Young Heui
Kim4, Hee-Kyoung
Kang1
1Department of Medicine, School
of Medicine, Jeju National University, 66 Jejudaehakno,
Jeju 690-756, Korea
2Department of Veterinary Medicine, College
of Veterinary medicine, Jeju National University,
66 Jejudaehakno, Jeju 690-756, Korea
3College of Pharmacy, Chungnam National University,
Daejeon 305-764, Korea
4R&D Center, Bioland Ltd., Songjeong, Byongchon,
Cheonan-si, Chungnam, 330-863, Korea
accepté le 16 Août 2009
The hair follicle is a small and dynamic organ which
periodically synthesizes the biological fibers termed as hair [1].
The cyclic change of the hair follicle, which occurs over the
entire lifetime of a mammal, involves a growth phase (anagen), an
involution phase (catagen) and a resting phase (telogen) [2].
Recently, there has been an increasing number of people
suffering from hair loss or thinning [3, 4]. Androgenetic alopecia
(AGA), which is the most common type of alopecia, is a common
problem in men over the age of 40. However, the underlying causes
of baldness are poorly understood [3, 5]. Many materials have been
used to cure alopecia. However, only two drugs so far have been
approved for hair loss treatment by the Food and Drug
Administration (FDA, USA); i.e., finasteride and minoxidil [3, 6].
Finasteride is a type II 5α-reductase inhibitor. It was initially
used for curing prostatic hypertrophy [7] but later found to
stimulate hair growth [8-10]. Nevertheless, its use is limited
because of potential side effects, especially in women [11].
Minoxidil was originally synthesized as a potassium channel opener
and was further developed as an anti-hypertensive. Moreover, it was
also found to stimulate the growth of hair follicle cells in vitro
[12] and to have hair cycle converting activity in vivo [13].
Recently, Han et al. [14] reported that minoxidil has
proliferative and anti-apoptotic effects on dermal papilla cells.
The dermal papilla cells consist of a cluster of specialized
fibroblasts that play important roles in the regulation of the hair
follicle through the secretion of diffusible proteins. Such
proteins include insulin-like growth factor-1(IGF-1) [15],
hepatocyte growth factor/scatter factor (HGF/SF) [16] and
fibroblast growth factor-7 (FGF-7) [17]. In addition, other growth
factors are also found to be involved in hair growth regulation.
For example, vascular endothelial growth factor (VEGF) [18] and
keratinocyte growth factor (KGF) [19] have a stimulatory effect on
hair follicle growth, while transforming growth factor-β (TGF-β)
[20], fibroblast growth factor-5 (FGF-5) [21], epidermal growth
factor (EGF) [22], interleukin-1α (IL-1α) [23], and
interleukin-1β(IL-1β) [24] are known to negatively regulate hair
growth.
To develop new therapies to enhance hair growth, we screened the
extracts of plants that have traditionally been used in oriental
medicine and discovered that Crinum asiaticum has the best
promoting effect. Crinum asiaticum var. japonicum (Amaryllidaceae)
is only distributed in Korea and Japan. In Korea, the plant has
been used as a rheumatic remedy, an anti-pyretic, an anti-ulcer
treatment, and for the alleviation of local pain and fever.
Regarding phytochemical studies on this plant, the isolation of
phenanthridine alkaloids, sterols, flavonoids and triterpene
alcohols have been previously reported [25, 26]. Alkaloids isolated
from the bulbs of Amaryllidaceae plants have shown various
pharmacological and microbiological effects, such as antiviral
[27], antimalarial [28], cytotoxic [28-30], and antineoplastic
activities [31], as well as effects on diseases of the nervous
system [32]. In a report by the same authors, C. asiaticum was also
reported to have an anti-inflammatory effect by inhibition of iNOS
and release of PGE2, IL-6, and IL-8, which are known as the
cytokines associated with inflammation [33]. In addition, crinamine
from C. asiaticum has been reported to inhibit HIF-1 activity [34].
Alkaloids with the galanthamine-type skeleton, isolated from the
Amaryllidaceae family, are potent acetylcholinesterase (AChE)
inhibitors [35] and have been used to treat the symptoms of
Alzheimer’s disease [36]. It has been reported that lycorine has
antitumor activity [29]. However, the promotion effect of C.
asiaticum on hair growth has not yet been reported.
Therefore, the present study was carried out to investigate the
promotion effect of the extract of C. asiaticum, as well as
norgalanthamine and lycorine (isolated alkaloids from C.
asiaticum), on the growth of hair.
Materials and methods
Materials
The 95% EtOH extract of Crinum asiaticum and lycorine were kindly
provided by R&D center, Bioland Ltd (Chungnam, Korea).
Norgalathamine was generously gifted by Dr Young Ho Kim (Chungnam
National University, Chungnam, Korea). Their chemical structures
are shown in figure
1, and were freshly dissolved in dimethyl sulfoxide (DMSO)
(Sigma, Mo, USA) for subsequent treatment.
Animals
Male Wistar rats (3 weeks of age) were supplied from Orient Bio
(Seongnam, Gyeonggi, Korea). 6-week-old female C57BL/6 mice were
purchased from Dae-Han Biolink (Eumsung, Chungbuk, Korea) and
provided with a standard laboratory diet and water ad libitum. All
animals were cared for by using protocols (20070002) approved by
the Institutional Animal Care and Use Committee (IACUC) of the Jeju
National University.
Cell Culture
Rat vibrissa immortalized dermal papilla cell line [37] was donated
by the Skin Research Institute, Amore Pacific Corporation R&D
Center, South Korea. The dermal papilla cells were cultured in DMEM
(Hyclone Inc, UT, USA) supplemented with 10% fetal bovine serum
(Gibco BRL, NY, USA) and penicillin/streptomycin (100 unit/mL
and 100 μg/mL, respectively) at 37 °C in a humidified atmosphere
under 5% CO2.
Isolation and culture of rat vibrissa follicles
Isolation of rat vibrissa follicles was performed as described
previously [38]. Briefly, rat vibrissa follicles were harvested
from male Wistar rats that were 23 days old. To accomplish this,
the rats were sacrificed under diethyl ether. Next, both the left
and right mystacial pads were removed from the rats and placed in a
1:1 (vol/vol) solution of Earle’s balanced salts solution (EBSS,
Sigma, MO, USA) and phosphate buffered saline (PBS, Sigma, MO, USA)
that contained 100 unit/mL of penicillin and 100 μg/mL of
streptomycin. Anagen vibrissa follicles were then carefully
dissected under a stereomicroscope (Olympus, Tokyo, Japan) from
posterior parts of the mystacial pads with considerable care being
taken to remove the surrounding connective tissue without damaging
the vibrissa follicle. Using this method we were able to routinely
isolate more than 40 follicles from each animal. The isolated
follicles were then placed in separate wells in 24-well plates that
contained 500 μL of Williams medium E (Gibco Inc, NY, USA)
supplemented with 2 mM L-glutamine (Gibco Inc, NY, USA), 10 μg/mL
insulin (Sigma, MO, USA), 50 nM hydrocortisone (Sigma, MO,
USA), 100 unit/mL penicillin and 100 μg/mL streptomycin
at 37 °C and cultivated in an atmosphere comprised of 5%
CO2 and 95% air. The isolated follicles were then
treated with vehicle (DMSO diluted 1:1000 in Williams medium E) as
a control, C. asiaticum extract (0.01 ~ 100 μg/mL),
lycorine (0.001 ~ 0.1 μM) and norgalathamine
(0.001 ~ 0.1 μM). Minoxidil sulfate (MS) (Sigma, MO, USA)
was used as a positive control in the culture systems [39]. The
culture medium was changed every 3 days and photographs of the
cultured rat vibrissa follicles were taken using a stereomicroscope
for 3 weeks. The length of the hair follicles was measured using a
DP controller (Olympus, Tokyo, Japan).
Hair growth activity in vivo
Anagen was induced by depilation on the back skin of C57BL/6 mice
that were in the telogen phase of the cycle, as described
previously [40]. Briefly, 6 week old female C57BL/6 mice were
allowed to adapt to their new environment for one week. The anagen
was then induced in the back skin of the seven week old female
C57BL/6 mice by shaving, which led to synchronized development of
anagen hair follicles. From the following day (day 1),
0.2 mL of a 1 mg/mL solution of C. asiaticum extract in
50% ethanol was topically applied every day for 31 days. 5%
Minoxidil (MINOXYLTM; Hyundai Pharm. Co. Ltd., Cheonan,
Chungnam, Korea) was used as a positive control. The back skin of
the mice was then observed and photographed at 1, 10, 17 and 31
days after shaving.
MTT Assay
The proliferation of dermal papilla cells was evaluated by
measuring the metabolic activity using a
3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT)
assay [41]. Briefly, dermal papilla at 1.0 × 104
cells/mL were seeded into 96-well plate, cultured 24 h in
serum-free DMEM, and then treated with vehicle (DMSO diluted 1:1000
in serum-free DMEM) as a control, C. asiaticum extract (0.01 ~
10 μg/mL), lycorin (0.001 ~ 0.1 μM) and
norgalathamine (0.001 ~ 0.1 μM) for 4 days. After
incubation, 0.1 mg (50 μL of a 2 mg/mL solution) of
MTT (Sigma, MO, USA) was added to each well, and the cells were
then incubated at 37 °C for 4 h. Next, the plates were
centrifuged at 1000 rpm for 5 min at room temperature and
the media was then carefully aspirated. 200 μL of dimethyl
sulfoxide was then added to each well to dissolve the formazan
crystals and the absorbance of the plates at 540 nm was then
read immediately on a microplate reader (BioTek Instrument, Inc.,
VT, USA). All experiments were performed three times and the mean
absorbance values were calculated. The results are expressed as the
percentage reduction in the absorbance caused by treatment with the
extract or the active component compared to that of the untreated
controls.
Immunohistochemistry
For immunohistochemistry, vibrissa follicles were collected from
each group on days 0 and 7 of treatment. The vibrissa follicles
were fixed in 4% paraformaldehyde (Sigma-Aldrich, MO, USA), and the
tissues were then dehydrated and embedded in paraffin.
Immunohistochemistry was then performed according to the
manufacturer’s instructions (Santa Cruz Biotechnology, CA, USA).
The following primary antibodies were used at the indicated
concentrations: PCNA (1:200; Santa Cruz Biotechnology, CA, USA). In
addition, the relevant goat secondary antibodies (1:200; Santa Cruz
Biotechnology, CA, USA) were used for detection of the primary
antibodies.
Statistical analyses
The hair growth data are expressed as the mean of the follicle
lengths ± the standard errors (SE) of at least three independent
experiments performed in triplicate. The Student’s t-test was used
to determine the statistical significance (P-value < 0.05) of
the differences between the values for the various experimental and
control groups.
Results
The effects of C. asiaticum extract on rat vibrissa
follicle elongation
To determine if C. asiaticum induced hair growth, we first examined
the activity of C. asiaticum extract using an organ culture of the
rat vibrissa follicle. When rat vibrissa follicles were treated
with various concentrations of C. asiaticum extract for 3 weeks,
the hair-fiber length of the vibrissa follicles was significantly
increased in a dose-dependent manner with respect to the control
(figure 2). In
particular, in the vibrissa follicle that was treated with
10 μg/mL of C. asiaticum extract for 21 days, the vibrissa
follicles were 177.3 ± 30.7% longer (P < 0.05) than those in the
control group. These results indicate that C. asiaticum extract is
capable of promoting hair growth.
The effects of C. asiaticum extract on anagen
induction in C57BL/6 mice
To investigate whether anagen induction was promoted by C.
asiaticum, we used C57BL/6 mice. C57BL/6 mouse dorsal hair is known
to have a time-synchronized hair growth cycle [40]. Shaved skin of
telogen mice is pink and darkens along with anagen initiation.
After being shaved, the skin color of the mice was observed to be
pink. As shown in figure
3, C. asiaticum extract and minoxidil almost exhibited gray
skin at 10 days post-hair growth induction, and their hair shafts
were visible at 14 days (data not shown). The control groups
remained pink until day 10 and exhibited gray skin by day 12 (data
not shown). The hair shafts of the control groups were first
visible on days 15 (data not shown) to 17. On the 31st day, the
back skin was in the anagen phase in all the mice. Overall, these
results indicate that C. asiaticum extract induced early
telogen-to-anagen conversion of hair follicles in the C57BL/6 mice.
The effects of C. asiaticum extract on cell
proliferation of hair follicles
To evaluate the effect of C. asiaticum on cell proliferation of
hair follicles, proliferation of dermal papilla cells and the
expression of PCNA were examined.
Immortalized rat vibrissa dermal papilla cells were treated with
various concentrations of C. asiaticum extract, and the mitogenic
effect on the dermal papilla cells was examined. C. asiaticum
extract promoted the proliferation of dermal papilla cells at a
concentration of 0.1 μg/mL compared with the vehicle-treated
control. However, 0.01, 1 and 10 μg/mL of C. asiaticum extract
did not affect the proliferation of dermal papilla cells (figure 4). These
results suggest that the hair growth promoting effect of C.
asiaticum extract may be mediated through a mitogenic effect on
dermal papilla cells. The isolated rat vibrissa follicles were
treated with C. asiaticum extract and then examined for activation
of PCNA (figure
5). In the anagen vibrissa follicles (0 day), the
expression of PCNA was positively stained in the bulb region,
whereas the 7-day cultured vibrissa follicles, which were expected
to be in the anagen-catagen transition phase, were negatively
stained. The vibrissa follicles treated with 10 μg/mL C.
asiaticum extract for 7 days were positively stained in the bulb
regions. In addition, the bulb regions of the vibrissa follicles
that were treated with 1 μM minoxidil sulfate for 7 days were
positive for PCNA. These results indicate that the cells in the
bulb regions of follicles treated with C. asiaticum extract or
minoxidil sulfate were induced to grow (figure 5).
The effects of isolated compounds from C. asiaticum
on the promotion of hair-growth
We next examined which compounds are responsible for the hair
growth promoting activity of C. asiaticum. As shown in figure 6A, when rat
vibrissa follicles were treated with lycorine (the main component
of C. asiaticum) at 0.001, 0.01 and 0.1 μM for 21 days, a hair
growth effect was not shown. On the other hand, norgalanthamine,
another component of C. asiaticum, significantly increased hair
growth promoting activity by 110.3 ± 14.4% at a dose of
0.001 μM, 128.7 ± 13.8% at a dose of 0.01 μM and 139.2 ±
10.3% at a dose of 0.1 μM compared, with the control group. As
shown in figure
6B, when immortalized rat vibrissa dermal papilla cells
were incubated with 0.01 μM norgalanthamine for 4 days, the
immortalized rat vibrissa dermal papilla cells were 114.0 ± 4.3%
longer (P < 0.05) than those in the control group. However,
lycorine did not affect the proliferation of dermal papilla cells.
Therefore, norgalathamine is very likely responsible for the hair
growth promoting activity of C. asiaticum.
Discussion
In this study, the hair growth promoting effects of C. asiaticum in
vitro and in vivo were investigated. To the best of our knowledge,
this study is the first to demonstrate that C. asiaticum and
norgalanthamine, a main principal of C. asiaticum, have the
potential to promote hair growth via the proliferation of dermal
papilla.
The difficulties in developing effective therapies for hair
growth lie in the fact that a single proper evaluation method has
not yet been established. In 1990, Philpott et al.
demonstrated that a human hair follicle could be cultured
organo-typically in vitro [42]. Using a similar experimental
technique, culture of the hair follicle from many other species,
such as rat, sheep and horse, has also been successfully
established [43, 44]. Many investigators have adopted hair follicle
culture models to evaluate the effects of several compounds [45,
46]. Moreover, vibrissa follicles from rats are much larger than
pelage follicles and can be successfully cultured in vitro [39]. In
particular, the hair growth cycles of the rat vibrissa follicles
have been reported to be synchronized according to their age [47]
and large posterior vibrissae of 21 d rats have been shown to be
always in anagen and show no sign of catagen [38]. The isolated rat
vibrissa follicles could be maintained in vitro up to 23 days and
then the follicles may enter into catagen phase [38]. Recently, an
in vitro culture system for murine vibrissae to reinitiate anagen
was developed [48]. In this study we isolated large posterior
vibrissa follicles from 23 d old rats and maintained them for
up to 21 d in vitro.
In the continuing search for hair-growth promoting compounds
from natural sources, we have examined more than 5 kinds of natural
products for growth promoting effects with rat vibrissa in vitro
culture system. We found that the extract of Schisandra nigra [49]
and C. asiaticum extract increased hair-fiber length in cultured
rat vibrissa follicles, whereas Schisandra chinensis, Cudrania
tricuspidata and Eclipta prostrate extract did not show hair
growth-promoting activity (data not shown). Specifically,
10 μg/mL of C. asiaticum extract was found to induce a greater
increase in hair-fiber length than minoxidil sulfate, a positive
control. The use of organ culture methods to evaluate hair follicle
growth is thought to be correlated with in vivo systems because the
extent of hair growth can be observed as the sum of the function of
each cell [42]. The hair growth promoting in vitro effect of C.
asiaticum extract was also observed in vivo using C57BL/6 mice. The
topical application of 5% minoxidil (MINOXYLTM) promoted
hair growth faster than C. asiaticum. This suggests at least the
following possibilities: 1) The active component of C. asiaticum
extract was absorbed into skin much less than minoxidil; 2) After
being absorbed into the skin, the active component of C. asiaticum
extract was metabolized to inactive metabolites faster than the
minoxidil; 3) Another unexpected factor was involved in the in vivo
activity.
The mesenchyme-derived dermal papilla cells play a pivotal role
in hair growth regulation. The morphology of dermal papilla cells
can be altered through the hair growth cycle, being maximal in
volume in the growing phase (anagen) and least in the resting phase
(telogen). Evidence has shown that the size of dermal papilla cells
is well correlated with hair growth, and the cell number of dermal
papilla cells is increased in the growing phase of hair cycle [50,
51]. Therefore, to investigate the effect of C. asiaticum on cell
growth in the hair follicles, we examined whether C. asiaticum
influenced the proliferation of dermal papilla cells. As shown in
figure 4, C.
asiaticum extract was found to increase the growth of dermal
papilla cells. We further tested the expression of PCNA as an index
of cell proliferation [52]. As shown in figure 5,
immunohistochemical analysis revealed that C. asiaticum extract was
found to increase the expression of PCNA in the bulb region of the
7-day cultured follicles. Taken together, the results of this study
indicated that hair growth induced by C. asiaticum may be mediated
through mitogenic effects that occur in the dermal papilla
region.
C. asiaticum have been reported to contain various
phenanthridine alkaloids, flavonoids and sterols [25, 26]. We have
recently isolated crinamine, lycorine and norgalanthamine from C.
asiaticum var. japonicum [33, 34]. Crinamine was reported to have
strong cytotoxic activity and an HIF-1 inhibitory effect [34].
Lycorine also showed cytotoxic and anti-inflammatory activities
[29, 33]. Galanthamine-type skeleton has been reported to have
acetylcholinesterase (AChE) inhibition [35]. Therefore, we examined
which compounds are responsible for the hair growth promoting
activity of C. asiaticum. As shown in figure 6, lycorine, the
main component of C. asiaticum, did not show hair growth, thereby
indicating that it has cytotoxic activity. On the other hand,
norgalanthamine, another component of C. asiaticum, showed activity
that increased hair-fiber lengths of vibrissa follicles and
proliferation of dermal papilla cells. Therefore, among the
compounds tested, norgalanthamine is very likely responsible for
the hair growth promoting activity of C. asiaticum.
Overall, the results of this study demonstrated that C.
asiaticum is capable of promoting hair growth in vitro and in vivo
via the proliferation of dermal papilla cells. In further studies,
the mechanisms by which C. asiaticum and norgalanthamine promote
hair-growth as well as other hair-growth promoting compounds should
be elucidated.
Acknowledgements
This research was supported by the second stage of BK21 (Brain
Korea 21) Project and SMBA. Conflict of interest: none.
References
1 Stenn KS, Paus R. Controls of hair follicle cycling.
Physiol Rev 2001; 81: 449-94.
2 Paus R, Müller-Röver S, Van Der Veen C,
et al. A comprehensive guide for the recognition and
classification of distinct stages of hair follicle morphogenesis. J
Invest Dermatol 1999; 113: 523-32.
3 Kaufman KD, Olsen EA, Whiting D, et al.
Finasteride in the treatment of men with androgenetic alopecia.
Finasteride Male Pattern Hair Loss Study Group. J Am Acad Dermatol
1998; 39: 578-89.
4 Kerscher M, Williams S, Dubertret L. Cosmetic
dermatology and skin care. Eur J Dermatol 2007; 17: 180-2.
5 Van Neste D. Placebo pills, lotions or potions and the
natural progression of patterned hair loss in males: another step
away from “trichoquackery”? Eur J Dermatol 2008; 18: 373-5.
6 Burton JL, Marshall A. Hypertrichosis due to
minoxidil. Br J Dermatol 1979; 101: 593-5.
7 Gromley GJ. Finasteride: a clinical review. Biomed
Pharmacother 1995; 49: 319-24.
8 McClellan KJ, Markham A. Finasteride: a review of
its use male pattern hair loss. Drugs 1999; 57: 111-26.
9 Kaufman KD, Rotonda J, Shah AK, Meehan AG.
Long-term treatment with finasteride 1 mg decreases the likelihood
of developing further visible hair loss in men with androgenetic
alopecia (male pattern hair loss). Eur J Dermatol 2008; 18:
400-6.
10 Kaufman KD, Girman CJ, Round EM,
Johnson-Levonas AO, Shah AK, Rotonda J. Progression
of hair loss in men with androgenetic alopecia (male pattern hair
loss): long-term (5-year) controlled observational data in
placebo-treated patients. Eur J Dermatol 2008; 18: 407-11.
11 Price VH. Treatment of hair loss. N Engl J Med 1999;
341: 964-73.
12 Tanigaki-Obana N, Ito M. Effects of cepharanthine
and minoxidil on proliferation, differentiation and keratinozation
of cultured cells from the murine hair apparatus. Arch Dermatol Res
1992; 284: 290-6.
13 Uno H, Cappas A, Schlagel C. Cyclic dynamics
of hair follicles and the effect of minoxidil on the bald scalps of
stumptailed macaques. Am J Dermatopathol 1985; 7: 283-97.
14 Han JH, Kwon OS, Chung JH, Cho KH,
Eun HC, Kim KH. Effect of minoxodil on proliferation and
apoptosis in dermal papilla cells of human hair follicle. J
Dermatol Sci 2004; 34: 91-8.
15 Itami S, Kurata S, Takayasu S. Androgen
induction of follicular epithelial cell growth is mediated via
insulin-like growth factor-1 from dermal papilla cells. Biochem
Biophys Res Commun 1995; 212: 988-94.
16 Jindo T, Tsuboi R, Imai R, Takamori K,
Rubin JS, Ogawa H. The effect of hepatocyte growth
factor/scatter factor on human hair follicle growth. J Dermatol Sci
1995; 10: 229-32.
17 Rosenquist TA, Martin GR. Fibroblast growth factor
signalling in the hair growth cycle: expression of the fibroblast
growth factor receptor and ligand genes in the murine hair
follicle. Dev Dyn 1996; 205: 379-86.
18 Ozeki M, Tabata Y. Promoted growth of murine hair
follicle through controlled release of vascular endothelial growth
factor. Biomaterials 2002; 23: 2367-73.
19 Werner S, Smola H, Liao x et al. The function of KGF in
morphogenesis of epithelium and reepithelialization of wounds.
Science 1994; 266: 819-22
20 Seiberg M, Marthinuss J, Stenn KS. Changes in
expression of apoptosis-associated genes in skin mark early
catagen. J Invest Dermatol 1995; 104: 78-82.
21 Ota Y, Saitoh Y, Suzuki S, Ozawa K,
Kawano M, Imamura T. Fibroblast growth factor 5 inhibits
hair growth by blocking dermal papilla cell activation. Biochem
Biophys Res Commun 2002; 290: 169-76.
22 Hansen LA, Alexander N, Hogan ME, et al.
Genetically null mice reveal a central role for epidermal growth
factor in the differentiation of the hair follicle and normal hair
development. Am J Pathol 1997; 150: 1959-75.
23 Harmon CS, Nevins TD. IL-1α inhibits human hair
follicle growth and hair fiber production in whole-organ cultures.
Lymphokine Cytokine Res 1993; 12: 197-203.
24 Xiong Y, Harmon CS. Interleukin-1 β is
differentially expressed by human dermal papilla cells in response
to PKC activation and is a potent inhibitor of human hair follicle
growth in organ culture. J Interferon Cytokine Res 1997; 17:
151-7.
25 Kobayashi S, Ishikawa H, Kihara M,
Shing T, Uyeo S. Isolation of N-Demethylgalanthamine from
the Bulbs of Crinum asiaticum L. var. japonicum Baker
(Amaryllidaceae). Chem Pharm Bull 1976; 24: 2553-5.
26 Takagi S, Yamaki M. On the constituents of the
bulbs of Crinum asiaticum var. japonicum BAK. On the neutral
constituents. Yakugaku Zasshi 1977; 97: 1155-7.
27 Gabrielsen B, Monath TP, Huggins JW,
et al. Antiviral (RNA) activity of selected Amaryllidaceae
isoquinoline constituents and synthesis of related substances. J
Nat Prod 1992; 55: 1569-81.
28 Likhitwitayawuid K, Angerhofer CK, Chai H,
Pezzuto JM, Cordell GA. Cytotoxic and antimalarial
alkaloids from the bulbs of Crinum amabile. J Nat Prod 1993; 56:
1331-8.
29 Min BS, Gao JJ, Nakamura N, Kim YH,
Hattori M. Cytotoxic Alkaloids and a Flavan from the Bulbs of
Crinum asiaticum var. japonicum. Chem Pharm Bull 2001; 49:
1217-9.
30 Abdel-Halim OB, Morikawa T, Ando S,
Matsuda H, Yoshikawa M. New Crinine-Type Alkaloids with
Inhibitory Effect on Induction of Inducible Nitric Oxide Synthase
from Crinum yemense. J Nat Prod 2004; 67: 1119-24.
31 Pettit GR, Cragg GM, Singh SB, Duke JA,
Doubek D. Antineoplastic agents. 162. Zephyranthes candida. J
Nat Prod 1990; 53: 176-8.
32 Houghton PJ, Agbedahunsi JM, Adegbulugbe A.
Choline esterase inhibitory properties of alkaloids from two
Nigerian Crinum species. Phytochemistry 2004; 65: 2893-6.
33 Kim YH, Kim KH, Han CS, et al.
Anti-inflammatory activity of Crinum asiaticum Linne var.japonicum
extract and its application as a cosmeceutical ingredient. J Cosmet
Sci 2008; 59: 419-30.
34 Kim YH, Park EJ, Park MH, Badarch U,
Woldemichael GM, Beutler JA. Crinamine from Crinum
asiaticum var.japonicum inhibits hypoxia inducible factor-1
activity but not activity of hypoxia inducible factor2. Biol Pharm
Bull 2006; 29: 2140-2.
35 López S, Bastida J, Viladomat F,
Codina C. Acetylcholinesterase activity of some Amaryllidaceae
alkaloids and Narcissus extracts. Life Sci 2002; 71: 2521-9.
36 Maelicke A, Samochocki M, Jostock R,
et al. Allosteric sensitization of nicotinic receptors by
galanthamine, a new treatment strategy for Alzheimer’s Disease.
Biological Psychiatry 2001; 49: 279-88.
37 Filsell W, Little JC, Stones AJ,
Granger SP, Bayley SA. Transfection of rat dermal papilla
cells with a gene encoding a temperature-sensitive polyomavirus
large T antigen generates cell lines a differentiated phenotype. J
Cell Sci 1994; 107: 1761-72.
38 Philpott MP, Kealey T. Cyclical changes in rat
vibrissa follicles maintained in vitro. J Invest Dermatol 2000;
115: 1152-5.
39 Buhl AE, Waldon DJ, Baker CA, Johnson GA.
Minoxidil sulfate is the active metabolite that stimulates hair
follcles. J Invest Dermatol 1990; 95: 553-7.
40 Müller-Röver S, Handjiski B, van der Veen C,
et al. A comprehensive guide for the accurate classification
of murine hair follicles in distinct hair cycle stages. J Invest
Dermatol 2001; 117: 3-15.
41 Carmichael J, DeGraff WG, Gazdar AF,
Minna JD, Mitchell JB. Evaluation of a tetrazolium-based
semiautomated colorimetric assay: assessment of chemosensitivity
testing. Cancer Res 1987; 47: 936-42.
42 Philpott MP, Green MR, Kealy T. Human hair
growth in vitro. J Cell Sci 1990; 97: 463-71.
43 Philpott MP, Green MR, Kealy T. Rat hair
follicle growth in vitro. Br J Dermatol 1992; 127: 600-7.
44 Williams D, Siock P, Stenn KS. 13-cis-retinoic
acid affects sheath-shaft interaction of equine hair follicles in
vitro. J Invest Dermatol 1996; 106: 356-61.
45 Buhl AE, Waldon DJ, Conrad SJ, et al.
potassium channel conductance: a mechanism affecting hair growth
both in vitro and in vivo. J Invest Dermatol 1992; 98: 315-9.
46 Taylor M, Ashcroft AT, Messenger AG.
Cyclosporin A prolongs human hair growth in vitro. J Invest
Dermatol 1993; 100: 237-9.
47 Ibrahim L, Wright EA. The growth of rats and mice
vibrissae under normal and some abnormal conditions. J Embryol Exp
Morphol 1975; 33: 831-44.
48 Lee J, Wu W, Kopan R. Murine vibrissae
cultured in serum-free medium reinitiate anagen. J Invest Dermatol
2008; 128: 482-5.
49 Kang JI, Kim SC, Hyun JH, et al.
Promotion effect of Schisandra nigra on the growth of hair. Eur J
Dermatol 2009; 19: 119-25.
50 Jahoda CAB, Horne KA, Oliver RF. Induction of
hair growth by implantation of cultured the dermal papilla cells.
Nature 1984; 311: 560-2.
51 Elliott K, Stephenson TJ, Messenger AG.
Differences in hair follicle dermal papilla volume are due to
extracellular matrix volume and cell number: implications for the
control of hair follicle size and androgen responses. J Invest
dermatol 1999; 113: 873-7.
52 Hall PA, Levison DA, Woods AL, et al.
Proliferating cell nuclear antigen (PCNA) immunolocalization in
paraffin sections: an index of cell proliferation with evidence of
deregulated expression in some neoplasms. J Pathol 1990; 162:
285-94.
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