Download PHYTOESTROGEN IN SKIN AGEING: THE CASE OF LABISIA

Regenerative Research 2(1) 2013 7-13
PHYTOESTROGEN IN SKIN AGEING: THE CASE OF LABISIA PUMILA
Mukrish MH1, Akhir NAM2, Majid FAA2, Yaakob H1, Azila AA1, Sarmidi MR*1
1
Institute of Bioproduct Development (IBD), Universiti Teknologi Malaysia (UTM), 81310 Johor Bahru, Johor, Malaysia
2
Facultyof Chemical Engineering, UTM, 81310 Johor Bahru, Johor, Malaysia
ARTICLE INFO
ABSTRACT
Submitted: 21-02-2013
Accepted: 05-05-2013
*Corresponding Author:
Mohamad Roji Sarmidi PhD
Labisia pumila locally known as Kacip Fatimah is a traditional Malaysian herb
that has a wide range of therapeutic value especially in women‟s health.
Therefore, it is known as the „Queen of Plant‟ in Malaysia. Labisia pumila has
been excessively studied by local researchers and it has been proven scientifically
to have the potential of pre and post-natal treatment which involved much in
hormonal regulation. Phytoestrogen is a plant estrogen that has been identified to
be present in this herb. Phytoestrogen has been identified to have estrogen-like
activity. Phytoestrogen has the ability to enhance the proliferation of cells in the
epidermis, stimulate collagen synthesis and reduce the degradation of collagen by
enzymatic reaction. These characteristics strongly support the huge potential of
Labisia pumila in cosmeceutical applications.
Email:[email protected]
KEYWORDS
Labisia pumila
Phytoestrogen
Skin
Aging
1.0 Introduction
1.1 Labisia pumila – the traditional use
Labisia pumila is under Myrsinaceae family, locally known as
Kacip Fatimah, is one of the herbs that has been widely
applied by decoction in South East Asian communities for a
variety of illnesses. It is an indigenous medicinal herb of
Malaysia and sometimes also referred locally as Akar
Fatimah, Selusoh Fatimah, Tadah Matahari, Rumput Siti
Fatimah, Bunga Belangkas Hutan and Pokok Pinggang [1].
There are three types of Labisia pumila, i.e. Labisia pumila
var. alata (LPva), Labisia pumila var. pumila (LPvp) and
Labisia pumila var. lanceolata (LPvl) [2]. Each variety
commands a different use and traditionally, local healers tend
to use Labisia pumila var. alata and Labisia pumila var.
pumila [3]. This herb‟s extract is prepared by boiling the
roots, leaves or the whole plant with water and the extract is
taken orally [4][5]. The decoction of the roots is also given to
pregnant women between one or two months before delivery,
as this is believed to induce and expedite labour [1]. It has
been also widely used with a long history by women in
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Malaysia to treat post-partum illnesses, to assist contraction of
the birth channel [1], shrink the uterus, improve menstrual
cycle, and weight loss [2]. It was also reported that Labisia
pumila can be used for delaying fertility and to regain body
strength; while some other folkloric uses include treatment of
flatulence, dysentery, dysmenorrhoea, gonorrhoea and
“sickness in the bones”[1].Therefore Labisia pumila is known
as the “queen of plants” of all Malaysian herbs [6].
1.2Phytoestrogen – towards skin perfection
With such a massive research concentrated on identifying the
presence of phytoestrogen in Labisia pumila, it is possible for
this herb to have a potential towards skin perfection.
Nowadays, women especially are obsessing with good skin
care and a promising effect in skin care products. They are
now more careful in the selection of beauty products and they
are more attracted with the nature-based products compared
with chemical-based-products. At present, traditional methods
for skin care has been recognized by many around the world.
Researchers are now actively looking for the advantages
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available to the ingredients used in making herbal-based
cosmetics.
Isoflavons and coumenstan are two categories in
phytoestrogen. Isoflavons are the one that has been
thoroughly studied which displays similarity to those in
mammal estrogen molecules. Isoflavons can be found in soy
beans, lentils and red clover. Genistein and daidecin are the
most important isoflavones as their structures are similar to
17β-estradiol. This explains the estrogen effects of genistein
and daidecin which involve the interaction of these substances
with estrogen receptor [7].
In Asia, the nutrition contents in food intake with its large
phytoestrogen content are thought to be the reason why Asian
women rarely suffer from climacteric symptoms. The use of
isoflavons which is significantly superior to the synthetic
estrogen could be useful in skin beautification. When
phytoestrogens are topically applied, they behave like
estrogens which enhance proliferation of the epidermis,
supporting collagen synthesis and reducing enzymatic
collagen degradation [8].
The application of phytoestrogen in skin beautification has
been used recently as the cosmetic ingredient in one of the
skin care products known as Novadiol®. A controlled open
European multicenter study examined the effect of a
cosmeceutical preparation including isoflavone (Novadiol®)
on 234 women: maximum age of 65 years, at least 3 years
since menopause, no HRT or other substances affecting the
skin aging process[8][9]. From this study, skin dryness and
roughness were significantly improved at the treated areas as
compared to untreated skin areas. Facial wrinkles were
significantly reduced by 22% and skin looseness was
significantly reduced by 24% [8].
with the increased of uterine weight in ovariectomized and
dihydrotestosterone-induced polycystic ovarian syndrome
rats, post-treatment with Labisia pumila [14]. Labisia pumila
also initiate lipolysis in adipose tissue which is a similar effect
as reported for estrogen [15].
Phytoestrogen is also known to be responsible in abortion and
contraception. It is believed that estrogen plays an important
role in causing uterine contraction during later stages of
pregnancy and labour [1]. This herb would be able to relieve
menopausal symptoms [16]. Treatment with this herb
maintained the elastic lamellae architecture of the
ovariectomized rat aorta as compared to normal rats. The
comparison of both Labisia pumila extract and estrogen
replacement therapy showed Labisia pumila extracts could
thicken aortic wall as compared to estrogen treatment. The
benefit of having a more elastic aorta is to allow the smooth
flow of blood from the heart without putting unnecessary
stress on other organs [16]. These results are consistent with
previous research which phytoestrogen intake was also
reported to be involved with low aortic stiffness [17] thus it
would be possible to apply the same concept to Labisia
pumila, based on the estrogenic activity of the extract.
Few phytochemicals have been identified in Labisia pumila
[18] such as anthocyanins, phenolic acids, and flavanoids
[19]. These components are believed to be responsible for the
wide spectrum of pharmacological activities attributed to the
herb. It was reported that antioxidant activity from aqueous
extract of this herb provides significant protection to human
fibroblast, from cell damage caused by UV irradiation [20],
most likely to the presents of these components. The roots and
leaves of Labisia pumila were found containing two novel
benzoquinod compounds 1,2 as major components [18].
1.3 Labisia pumila - the presence of phytoestrogen
A preliminary screening of total phenolic content (TPC) was
done by Chua et al [21]. The study shows that MeOH extract
of this herb contained the highest amount of phenolic
phytochemicals, as compared to 60% MeOH extract.
Flavonoids constituted a large portion of the phytochemicals
in the 60% MeOH leaf extract. The 40% MeOH fraction was
found to have the highest DPPH scavenging activity. Nine
flavonols, two flavanols and nine phenolic acids were
detected in this fraction using UPLC–ESI-MS/MS coupled
with powerful software for data processing and interpretation
[21].
The specific usage towards women‟s health has led to the fact
that this herb has high phytoestrogenic activity, or
phytoestrogen, a compound with almost similar chemical
structure to women‟s hormone, estrogen [1]. In theory, the
phytoestrogen acts as an anti-estrogen agent by limiting
estrogen receptors and impose a much weaker effect of
estrogen compared with the actual hormone [12][13].
Furthermore, exhibition of estrogenic activity has been shown
It is believed that extracts of Labisia pumila have
antioxidative properties comparable to Silymarin, an extract
of the well-known European milk thistle plant Silybum
marianum [22]. A study done by Norhaiza, Maziah and
Hakiman [18] showed that varieties, L. pumila var. alata and
L. pumila var. Pumila have high antioxidant activity. There is
a positive correlation between antioxidant capacities and
individual antioxidative compounds in the following order β-
The effect of phytoestrogen was actively observed in soy. In
fact, the benefits of soy in skin health have been focused on
the isoflavones towards skin aging. Isoflavons from soy has
been reported to support skin health which may not be related
to the antioxidant properties but through other mechanism.
Sudel et al [10] demonstrated that in vitro treatment of human
fibroblast with purified genistein increased collagen synthesis
[11].
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carotene > flavonoid > vitamin C > total anthocyanins >
phenolics [18].
Karimi et al [23] used L. Pumila to determine the
phytochemical compound and antimicrobial activities of
methanolic extract of this plant. In this study, three varieties
were used L. pumila alata, L. pumila pumila, L. pumila
lanceolata. The result shows that this herb has high content of
flavanoid especially in pumila variety while gallic acid and
caffeic acid present in all varieties. L. pumila alata has the
highest gallic acid content as compared to other varieties and
as compared to gallic acid found in fresh Mauritian black tea
leaves[24]. Pumila variety has higher content of kaempherol
value as compared to the famous ginkobiloba [25]and the leaf
of pumila variety also has higher content of quercetin as
compared to onion and garlic[26], and high content of saponin
[23].
The identification of these components such as β-carotene and
flavanoid which is the highest antioxidative compounds
present in this herb has led Choi et al[ 20]to see the potential
of this herb in skin protection. The study demonstrated the
efficacy of Labisia pumila extract for specifically protecting
skin against photo-aging with 50% of free radical scavenging
activity (FSC50) to be equal to that produced by 156 µM
ascorbic acid, inhibition of TNF-α production and the
expression of COX-2. Collagen restoration was also back to
normal after treatment with this herb. On the other hand,
Labisia pumila extract has down regulated in a dosedependent manner to enhanced MMP-1expression upon UVB
irradiation. Normal keratinocytes were treated with this herb
extract attenuated UVB-induced MMP-9 expression. From
these results, it clearly indicates that Labisia pumila has a
great potential to be used as an anti photo-aging cosmetic
ingredients [20].
1.4 The post-menopausal skin and estrogen
Aging is a continuous process from birth to the end of life.
Menopause is one major phase in women‟s life which has
been a big concern especially in skin modification. The
decrease in estrogen production is the hallmark of menopause
which may be followed by gradual changes in menstrual
cycle, accompanied by changes in gonadotrophine hormone
with the increase of follicle stimulating hormone (FSH)[27].
The number of ovarian premature follicles is fixed at birth and
gradually decreases each time follicles mature and release
oocytes for reproduction. At certain stage, the follicular
number has decreased substantially and responds poorly to
FSH and LH, resulting in cycle irregularity and erratic
ovulation. Hormone fluctuations are common at this stage,
and there will be gradual decrease in progesterone and
estrogen. This stage, which is called pre-menopause stage,
will last from 3 to 10 years before menopause. Women will
have irregular menstrual cycles as the first sign of preRegenerative Research Vol2 Issue1 June 2013
menopause along with increasing levels of FSH. Estrogen
production continues to decrease due to the decreased number
of follicles and leads to non-ovulatory cycles. At the onset of
menopause, when ovulation ceased entirely, LH starts
increasing again [27].
Ovarian steroidogenesis during menopause is restricted to
androgen production. It is established that menopausal theca
cells are responsive to LH and produce androstenedione and
testosterone. Most of the circulating androgens come from the
adrenal gland. During menopause, estrone is exclusively
produced at remote sites (mainly adipose tissue) by the
conversion of androstenedione. The rate of this conversion
correlates to body size (amount of adipose tissue )[28].
The skin is a target of many hormones, especially estrogens.
Estrogen and other hormone receptors have been detected,
inter alia, in keratinocytes, fibroblast, sebaceous glands, hair
follicles, endocrine glands, and blood vessel [29]. This is one
of the main reasons of postmenopausal women having aged
skin – they are lacked of estrogens hormone. In clinical terms,
many females experience a sudden onset of skin aging
symptoms several months after menopause. Several studies
showed that the lack of estrogens in the system is associated
with aging effects, especially for women who experience
menopause.
The first sign of menopause which women experience is
increasing skin dryness followed by a loss of skin firmness
and elasticity that lead to wrinkles. Every year, skin collagen
content in adults will decrease 1% gradually [30] and this
process is more obvious to women than men. Approximately,
nearly 30% of skin collagen will be lost in the first five years
after menopause, with an average decline of 2.1% per
postmenopausal year over a period of 20 years. However,
with estrogens, this trend will be reversed and due to several
pathways, the skin collagens increase [31] and enhance the
synthesis of hyaluronic acid and promote water retention [32]
hence correcting skin function and structure. Animal studies
indicate that estrogen induce several changes in the
connective tissue of the dermis, including increment of
mucopolysachharide incorporation, hydroxyl-prolyn turnover
and alterations in the extracellular matrix [33]. Other studies
has yet to be done for suitable candidate in combating aging
skin towards these women and several hormone-based
products have been tested to be positive in reducing aging
effect.
1.5 Hormone replacement therapy and skin aging
Hormone Replacement Therapy (HRT) plays a huge role in
such circumstances as to counter the effect of further
deleterious skin changes. Estrogen and androgen receptors
have been identified to contribute positively towards dermal
9
fibroblast and epidermal keratinocytes [34]. In a study to
identify specific estrogen-sensitive structures, normal human
skin was investigated for the binding of the ER D5 antibody
which is associated with p29, a 29kD protein found in
cytoplasm of normal estrogen-sensitive cells[35].Strong and
specific staining was seen in the epidermis, with a gradient
showing the most intense staining in the granular layer.
Similar positive staining was seen in the hair follicles and
sebaceous glands. Variable staining was seen in the endocrine
glands and vessels. These findings demonstrate the receptor
p29 to be present in these structures, and hence suggest that
estrogens may exert a specific effect on these tissues.
Estrogen could increase the rate of collagen production also
influencing the degree of polymerization of GAG‟s
(glycosaminoglycans). Estrogens increase dermal hydroscopic
qualities [36], probably through enhanced synthesis of dermal
hyaluronic acid [37]. Collagenous fibrils were found to be less
fragmented in the dermis in women treated with estrogens.
The decline in skin collagen content after the menopause
occurs at a much more rapid rate in the initial postmenopausal
years than in the later ones. Some 30% of skin collagen is lost
in the first 5 years after the menopause with an average
decline of 2.1% per postmenopausal year over a period of 20
years [38]. The increase in skin collagen content after 6
months of sex hormone therapy depends on the collagen
content at the start of treatment [38]. In women with a low
skin collagen content, estrogens are initially of therapeutic
and later of prophylactic value while in those with mild loss
of collagen content in the early menopausal years estrogens
are of prophylactic value only. Thus a deficiency in skin
collagen can be corrected but not over corrected [39].
Following the menopause, skin collagen content and skin
thickness are increased in women on estrogen replacement
therapy compared to age matched women on no treatment
[40][41]. Prospective studies have shown that skin thickness,
skin collagen and bone mass increase in postmenopausal
women who start estrogen replacement. Beneficial changes
can be obtained using both topical [42] as well as oestradiol
implants. Topical oestradiol gel has also been shown to
increase skin collagen content as measured by skin
hydroxyproline. Skin blister fluids were assayed and an
increase of both Procollagen C-End Terminal Pro Peptide
(PICP) and Procollagen N-End Terminal Pro Peptide (PINP)
characterized with the gel. Pro Collagen C-End Terminal
polypeptide protein and Pro Collagen N-End Terminal
polypeptide are released by enzymatic cleavage when the pro
collagen molecule is released extracellularly. This is therefore
a posttranslational event and the presence of free PICP and
PINP serves to indicate collagen production. The „I‟ in PICP
and PINP refer to Type I Collagen.
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A study done by Patriarca et al. [43] evaluates the additional
benefits of topical estrogen on the dermal collagen of the
facial skin in postmenopausal women using oral hormone
therapy. Estrogen receptors have been detected in skin, and
recent studies suggest that estrogens exert their effect in skin
through the same molecular pathways used in other nonreproductive tissues. Although systemic menopausal hormone
therapy (MHT) has been used for many years, recent trials
have reported a significant increased risk of breast cancer and
other pathologies with this treatment. This has led to
reconsider the risks and benefits of MHT [44]. For this reason,
high doses of systemic MHT cannot be recommended to treat
skin aging. Therefore, the topical estrogen treatment may be
an alternative for ameliorating the skin, specially the collagen
amount. Patriarca et al. showed that the addition of estrogen
gel may be useful for increasing the dermal collagen.
Patriarca et al. also suggests that topical estrogen could act on
the skin without increasing its systemic level by the fact that
topical estrogen may increase the collagen amount and
prevent the cutaneous aging [45]. From this study, the
systemic estrogen alone did not seem to have a positive effect
in skin collagen. Otherwise, some studies showed that the
decrease in skin collagen in women of postmenopausal age
may not be an exclusive age-related phenomenon, but could
be related to hypoestrogenism [41][43][46][47].
1.6 Labisia pumila – as a hormonal therapy towards skin
aging
Based on the evidence shown in this paper, it is possible for
this herb to be a hormonal therapy towards skin aging
especially amongst premenopausal and post-menopausal
women who are exposed directly towards skin aging.
According to previous studies, this herb contains various
kinds of phenolic compounds which demonstrated high
antioxidant activity. There are very few researches conducted
using this herb towards skin perfection and it was proved that
this herb could protect skin cells from photo-aging caused by
UVB irradiation. However, the important components of the
plant such as phytoestrogen, also need to be taken into
accountdue to the usage of this herb towards women‟s health.
It is possible that this herb has the same benefits as soy, which
is rich in phytoestrogen. Soy has so much benefit towards
women‟s health and studies of this plant is already massively
done by researchers. Phytoestrogen has been known by
manyto have the ability to mimic the estrogen functionality
and could bind estrogen receptors and had higher affinity for
estrogen receptor β (ERβ) than ERα. Estrogen can be replaced
by phytoestrogen especially in hormone replacement therapy
that has been widely used for treatment in postmenopausal
women. Hormone replacement therapy is a way of
menopausal women to treat skin aging.
10
2.0 Discussion and Conclusion
Labisia pumila is a Malaysian traditional herb that has been a
centre of popularity among all herbs in Malaysia after
Euricoma longifolia. Although studies are more into Labisia
pumila var. alata and Labisia pumila var. pumila, it is
believed that other varieties of Labisia species have also
possess a therapeutic value as those two. It is known amongst
the traditional practitioners as queen of herbs and all the
scientific knowledge from this herb is now being actively dug
out by local researchers. It is interesting that this herb could
be a possible candidate in replacing estrogenic drugs. Due to
high phytoestrogen content in this herb, the potential to make
it one of the key ingredients in the production of cosmetic
products is very good, especially for women who suffer from
premenopausal aging. As estrogen is one of the key factors in
revitalizing women‟s health, this herb is also useful in
replacing synthetic drugs used in HRT. Estrogen is a type of
hormone that is responsible for restoration of skin structure
which is proof to be lacking in menopausal women. The
mechanism of actions of the phytochemicals present in
Labisia pumila might be similar to those demonstrated by
estrogen. This herb also shows a great potential and might be
equivalent to soy itself. Soy is one of the great sources of
phytoestrogen and has been used widely in cosmeceutical
products. As Labisia pumila is rich in antioxidant compound
and shows phytoestrogenic properties, it can lead up to any
research area especially in skin restoration therapy.
Acknowledgement
This review article was produced with the support from
Universiti Teknologi Malaysia (UTM) Research University‟s
fund Q.J130000.7125.01H23 and facilities provided by
Institute of Bioproduct Development (IBD), UTM.
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