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Review on Labisia pumila (Kacip Fatimah): Bioactive phytochemicals and skin collagen synthesis promoting herb


Abstract and Figures

Labisia pumila is a traditional herb widely used as post-partum medication for centuries. Recently, extensive researches have been carried out on the phytochemical identification, biological and toxicological studies for the herb. Phytochemicals found in the herbal extract showed high antioxidant properties, which were essential for various pharmacological activities. The significant findings are anti-estrogenic deficiency and -immunodeficiency diseases. Another finding that has considerable impact on natural product research is the contribution of L. pumila in promoting skin collagen synthesis. The performance of the herb as anti-aging agent due to natural aging process and accelerated by UV radiation was reviewed critically.
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Review on Labisia pumila (Kacip Fatimah): Bioactive
phytochemicals and skin collagen synthesis promoting herb
Lee Suan Chua , Sze Yean Lee, Norhanisah Abdullah, Mohamad Roji Sarmidi
Metabolites Proling Laboratory, Institute of Bioproduct Development, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor, Malaysia
article info abstract
Available online 10 April 2012 Labisia pumila is a traditional herb widely used as post-partum medication forcenturies. Recently,
extensive researches have been carried out on the phytochemical identification, biological and
toxicological studies for the herb. Phytochemicals found in the herbal extract showed high
antioxidant properties, which were essential for various pharmacological activities. The sig-
nificant findings are anti-estrogenic deficiency and -immunodeficiency diseases. Another finding
that has considerable impact on natural product research is the contribution of L. pumila in
promotingskin collagen synthesis.The performance of the herbas anti-aging agent dueto natural
aging process and accelerated by UV radiation was reviewed critically.
© 2012 Elsevier B.V. All rights reserved.
Labisia pumila
Collagen synthesis
1. Introduction to Labisia pumila .............................................. 1321
2. Phytochemicals and pharmacological properties of L. pumila ................................ 1323
2.1. Phenolic compounds and antioxidant activities .................................. 1323
2.2. Saponin and antimicrobial activity ........................................ 1324
2.3. Phytoestrogen and anti-estrogenic deciency diseases ............................... 1325
3. Toxicological studies on L. pumila ............................................ 1327
4. Rationale of L. pumila as collagen synthesis promoting herb ................................ 1328
4.1. Common active ingredients for skin care ..................................... 1329
4.2. Relationship between photoaging and skin collagen ................................ 1329
4.3. L. pumila as collagen synthesis promoter ..................................... 1330
4.4. Photoaging mechanism by UV radiation ...................................... 1331
5. Future perspectives of L. pumila ............................................. 1332
6. Conclusion ....................................................... 1332
References ......................................................... 1332
1. Introduction to Labisia pumila
Labisia pumila, locally known as Kacip Fatimah, is the
queen of the herbs in Malaysia. It is a genus of small woody
and leafy plants of the Myrsinaceae family that can widely
Fitoterapia 83 (2012) 13221335
The manuscript is a contribution for the special issue on the 70th birthday
of Prof. Dr. Atta-ur-Rahman.
Corresponding author. Tel.: + 60 197214378; fax: + 60 75569706.
E-mail address: (L.S. Chua).
0367-326X/$ see front matter © 2012 Elsevier B.V. All rights reserved.
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be found in the tropical forest of South East Asian countries.
Fig. 1 is the photo of the mature plant taken from the
garden of Institute of Bioproduct Development, Universiti
Teknologi Malaysia. To the natives, this plant is also known
as Selusuh Fatimah, Rumput Siti Fatimah, Akar Fatimah,
Kachit Fatimah, Kachip Patimah, Pokok Pinggang, Rumput
Palis, Tadah Matahari, Mata Pelandok Rimba, Bunga Belangkas
Hutan and many more.
According to Sunarno [1], there are eight varieties of
L. pumila distributed in Malaysia. Of the varieties, L. pumila
var. pumila, var. alata and var. lanceolata are widely found
and studied so far. These varieties can be differentiated from
each other by their petiole and leaf characteristics. L. pumila var.
alata has a winged petiole and red veins, while var. pumila has a
marginate petiole and ovate leaf blade shape, and var. lanceolata
has a long and non-winged petiole. The var. alata is widely
used in traditional medicine preparation because it is the most
commonly encountered variety in Malaysia [2].
L. pumila is traditionally used by generations of Malay
women by decoction. It is believed that the decoction drink
can induce and facilitate childbirth, as well as being a post
partum medication to help contract the birth channel, to tone
the abdominal muscles and to regain body strength [3,4].
Till now, it is taken by local people to maintain a healthy
female reproductive system, to treat menstrual irregularities,
as well as to enhance sexual function. Although L. pumila is
commonly used by female, male from several ethnic groups
in Sarawak, Malaysia consumed it to maintain and increase
stamina [5]. Other traditional uses of the plant include treat-
ment for dysentery, rheumatism, gonorrhea and excessive
gas elimination from the body [3,6]. It was also reported that
plants from the same genus (Myrsinaceae) are being used to
treat respiratory tract infections and menstrual disorders [3].
Owing to the high demand and relatively slow growth rate
of the plant, several researchers have studied new propagation
techniques to grow the plant in larger scale and in shorter time.
In vitro seed germination and shoot proliferation investigated
by Hartinie and Jualang [7] were able to grow a large number
of seedlings in a relatively short time (5 weeks). The presence of
6-benzylaminopurine (BAP), sucrose and cytokinin in Murashige
and Skoogs (MS) media are the key elements affecting the
growth rate. However, the in vitro plantlets were faced
with the difficulty in growing under the external harsh
conditions, especially by microbial infection. Jaafar et al. [8]
reported that this herb was very sensitive to the microclimate
conditions, namely sunlight, temperature and relative humid-
ity. The growing profile of the herb was monitored under both
greenhouse and open field conditions. In open field, most
plants were expected to receive more sunlight than they
needed for photosynthesis. Hence, the high amount of sunlight
triggered the production of NADPH and ATP higher than
required. Consequently, the accumulation of redox energy
decreased the plastoquinone pool and inhibited the water
splitting complex, which led to the inactivation of Photosys-
tem, PSII. This phenomenon is known as photoinhibition.
Plants grown in greenhouse encountered less photoinhibition
than plants in open field condition. It was found that L. pumila
var. alata and var. pumila have better acclimatization than var.
lanceolata under both growing conditions [9].Asanother
alternative, Rozihawati et al. [10] reported the significantly
satisfying result in cultivating the herb in sand, sawdust and
mixture of sand and sawdust media, with and without the
supply of hormone treatment by using the cut leaf, petiole or
stem from the plant.
The aim of this article is to provide a comprehensive
review on L. pumila, which covers from the herbal traditional
usage, phytochemicals that have been identified till to date,
and their pharmacological applications. The discussion has also
extended to the topical application, which has been proven
for its effectiveness practically and in cell based assays. How-
ever, the availability of the scientific information regarding
this herb is very limited and not in proper documentation for
reference. Therefore, this review is likely to provide a platform
for those who are interested to further study the herb, either
Fig. 1. Photo of Labisia pumila var. alata.
1323L.S. Chua et al. / Fitoterapia 83 (2012) 13221335
for phytochemical profiling, for pharmacological investigation
or for anti-aging purpose. This platform is crucial as a guideline
since many positive results have been reported on the herb,
which might be beneficial for a new drug discovery in the near
2. Phytochemicals and pharmacological properties
of L. pumila
Recently, the exploitation of the herbal plant for com-
mercial demand is gradually increasing. Its popularity can be
seen from the availability of commercial products derived
from the herbs, either in the form of capsules or canned
drinks in the market, especially in Malaysia and Indonesia.
The increasing trend is most probably due to the awareness
of public to use natural product as foods, nutraceuticals or
functional foods to maintain body health and treat illness.
The preference of natural product derived products is getting
to be significant because of the negative side effects caused
by chemically synthetic drugs. Therefore, numerous scientific
researches on L. pumila are carrying out, especially for the
identification of bioactive phytochemicals that contribute to
the pharmacological properties. Table 1 lists the identified
phytochemicals and reported biological activities for the herb
till to date. The chemical structures of the phytochemicals are
presented in Fig. 2.
2.1. Phenolic compounds and antioxidant activities
To our knowledge, a few phytochemicals have been iden-
tified from the extract of L. pumila. Most of them are phenolic
compounds, including phenolic acids and flavonoids as reported
by Chua et al. [11],Karimietal.[12,13] and Norhaiza et al.
[14]. These phenolic compounds include flavonoids (quercetin,
myricetin, kaempferol and catechin) and other detected constit-
uents (ascorbic acids, tocopherols, β-carotene and carotenoids)
have been proven spectrophotometrically for high antioxidant
properties by measuring their free radical scavenging, ferric
reducing antioxidant power (FRAP) and β-carotene bleaching
activities. Different parts of the plant had been used for the
antioxidant assays by Karimi et al. [13]. They found that the
leaves of the plant from all the varieties showed higher anti-
oxidant activities compared to the roots and stems. It is note-
worthy that the antioxidant properties of flavonoids have been
reported to be higher than vitamin C and E [15].
The presence of the phenolic compounds might also con-
tribute to the anticarcinogenic activity of L. pumila [16].The
exhibition of the anticarcinogenic property might be due to the
role of phenolic compounds participating in the antioxidant
mechanisms such as radical scavenging, reducing or bleaching
mechanisms. Although Pihie et al. [17] did not report the active
compound responsible for the anticarcinogenic activities, they
found that the ethanolic extract of L. pumila at the dosage of
100 mg/kg body weight of mice could have almost equipotent
Table 1
The identified phytochemicals and reported biological activities of L. pumila extracts.
Author/year Chemical classication Phytochemical identied Biological activities
Chua et al. [11] Favonols Quercetin, myricetin and kaempferol Antioxidant (free radical
scavenging activity)Favonols Catechin and epigallocatechin
Phenolic acids (benzoic acid
and cinnamic acid)
Salicylic acid, syringic acid, vanillic acid,
protocatechin acid, gallic acid, coumaric acid,
caffeic acid, chlorogenic acid
Karimi et al. [12] Phenolics Gallic acid, caffeic acid and pyrogallol Antibacterial (Gram positive
and Gram negative bacteria)
and antifungal
(Fusarium sp., Candida sp. and
Mucor sp.)
Flavonoids Kaempferol, myricetin, naringin,
quercetin and rutin
Karimi et al. [13] Phenolics Gallic acid, pyrogallol and caffeic acid Antioxidant (free radical
scavenging and ferric reducing
antioxidant potential activities)
Flavonoids Apigenin, kaempferol, myricetin, naringin,
quercetin and rutin
Isoflavonoids Daidzein and genistein
Hydrocarbons See [13]
Norhaiza et al. [14] Phenolics Ascorbic acid and β-carotene Antioxidant (free radical
scavenging, ferric reducing
antioxidant potential and
β-carotene bleaching activities)
Flavonoids Anthocyanins
Avula et al. [18] Saponins (triterpene) Ardisiacrispin A, ardisicrenoside B,
ardisimamilloside H, 3-O-α-L-rhamnopyranosyl-
(12)-β-D-glucopyranosyl-(1 4)-α-
L-arabinopynanosyl cyclamiretin A
Alkenated phenolics Irisresorcinol, belamcandol B and
demethylbelamcandaquinone B
Ali and Khan [19] Dialkenated benzoquinone-phenol
Demethylbelamcandaquinone B Antibacterial and antifungal
Dialkenated dibenzofuran Fatimahol
Dexyloprimulanin 13,28-epoxy-oleanane glycoside
Jamia et al. [90] Alkenyl resorcinols (Z)-5-(pentadec-4enyl)-resorcinol, (Z)-5-
(pentadec-8-enyl)-resorcinol and (Z)-5-
Houghton et al., 1999 [110] Benzoquinoid na na
na: not available.
1324 L.S. Chua et al. / Fitoterapia 83 (2012) 13221335
effects in terms of reducing both tumor incidence and tumor
burden with curcumin (10 mg/kg body weight of mice). Be-
sides showing intact basement membrane in the histopatho-
logical examination, the 7,12-dimethylbenz(α)anthracene and
croton oil induced mice treated with the ethanolic extract also
suppressed the progression of benign tumors to malignant stage.
2.2. Saponin and antimicrobial activity
Besides the antioxidant properties, the other pharmaco-
logical activities such as hemolytic and anti-microbial have
been reported due to the saponin content exhibited in the
various parts of the plant extracts, namely the leaves, stems
and roots. A newly published article by Avula et al. [18]
reported four triterpene saponins detected from the plant.
The work of Ali and Khan [19] also reported dexyloprimulanin
(13,28-epoxyoleanane glycoside) from the methanolic ex-
tract. Somehow, the total saponin content was found to be
in the highest concentration in the leaves of all varieties of
L. pumila, compared to the roots and stems [12]. The crude
methanolic extracts of the plant exhibited antibacterial
activities against both Gram positive and Gram negative
pathogens. However, the antibacterial activities were rela-
tively low compared to kanamycin, which was used as
control. While, the antifungal activity contributed by the
methanolic extracts was moderate to appreciable compared
to streptomycin. As a comparison, most saponins were
detected from the widely used medicinal herb, ginseng. It is
also interesting to note that ginseng contains a series of
tetracyclic triterpenoid saponins, which make up the active
ingredients [20]. Ginseng saponins have been shown to
exhibit a wide range of biological properties which include
Fig. 2. Chemical structures of phytochemicals indentified from L. pumila extracts.
1325L.S. Chua et al. / Fitoterapia 83 (2012) 13221335
aphrodisiac and adaptogenic activities, and which have been
reviewed by Nocerino et al. [21].
2.3. Phytoestrogen and anti-estrogenic deciency diseases
Based on the traditional practice, L. pumila is used as
woman post partum medicine. It is believed that the plant
contains phytoestrogen, which acts as the primary female
sexual hormone, namely estrogen. Phytoestrogens are essen-
tial to protect body against hormonal dependent cancers
such as breast, uterine and prostate. Theoretically, it acts as
anti-estrogenic agents by blocking the estrogen receptors and
exerting weaker estrogenic effect compared to hormones. It was
likely to be estrogen receptor modulators by displacing 17β-
estradiol binding to antibodies raised against estradiol, making
it similar to other estrogens such as esterone and estradiol
(estrogen-like compounds) [22]. Moreover, the aqueous extract
has been found to produce a doseresponse effect on the
reproductive hormones of female rats, notably on the estradiol
and free testosterone levels. In vitro study conducted by Jamal
et al. [2] on human endometrial adenocarcinoma cells of the
Ishikawa-var 1 line showed that the ethanolic extract of the
roots of L. pumila var. alata exhibited significant oestrogenic
effect on the cells, resulting in an enhanced secretion of alkaline
Estrogen deficiency is a very common health phenomenon
in post-menopausal women. This phenomenon would cause
weight gain and increase adiposity by hypertropic growth
(adipose tissue increase in size) and consequently by hyper-
plastic growth (adipocytes increase in number). It is a natural
response of the body because adipose tissue is not only used
for energy storage, it is also an important endocrine organ for
sex steroid metabolism [23]. The increase of adipocyte mem-
brane in thickness was observed in ovariectomized rats by
using transmission electron microscopy [24]. It was found that
the administrated L. pumila extract (17.5 mg/kg/day) to the
ovariectomized rats for 3 months could break the membrane
of adipocytes. The breakage of adipose membrane had been
shown by the fragmentation of collagen fibers that hold the
adipocytes together. Hence, this plant might pose a potential
role in modulating post-menopausal adiposity through the
initiation of lipolysis process in adipocytes.
The increase in adipocity is always associated with car-
diovascular risks, including aortic stiffness. Aorta stiffens
naturally with age and worsens the arterial function, which
will associate with cardiovascular risks, particularly after
menopause. Statistical data showed that more than 30% of the
female population in Malaysia who are at risk for coronary
artery disease was accounted for post-menopausal women
[25]. As a result, the same group of researchers studied the
effect of L. pumila extract on the elasticity of aortae in the
ovariectomized rats in the following year. Water extract of
L. pumila has subsequently been reported for its capability
in maintaining the elastic lamellae architecture of the
Fig. 2 (continued).
1326 L.S. Chua et al. / Fitoterapia 83 (2012) 13221335
ovariectomized rat aortae in a manner comparable to that of
the normal rats [26]. Furthermore, the positive responses
from the use of phytochemicals in pharmacology studies are
quite encouraging recently. For instance, soy isoflavones were
found to be used for the improvement of endothelial-
dependent vascular reactivity [27] and arterial elasticity [28],
obesity and lipid metabolism [29], as well as aortic stiffness in
post-menopausal women [30]. Results indicated that L. pumila
extract might be able to modulate postmenopausal cardiovas-
cular risks, although no inverse relationship between phytoes-
trogen intake and cardiovascular disease risk had been reported
in Western women [31].
The estrogenic properties of L. pumila var. alata have been
proven in uterotropic effects and body weight regulation
[32]. The polycystic ovary syndrome (PCOS) rats treated with
L. pumila extracts appeared to have no significant effect on
body weight and composition, but have better lipid profiles
such as reduced levels of total cholesterols and triglycerides
[33]. The increase of plasma resistin levels in PCOS rats
treated with L. pumila extracts was in contradiction with
the results reported in the ovariectomized rats treated with
estrogen and the plant extracts [32,34]. The divergent results
could be explained by the difference in resistin expression
at different adipose depots and cell types [35]. This can be
proven by the difference in the circulating level of leptin and
leptin mRNA expression in mesenteric adipose tissue.
The previously reported reduction in resistin might in-
crease insulin sensitivity without affecting body weight [32].
The explanation was based on the observation of high cir-
culating level of adiponectin after plant extract treatment in
the PCOS rat model. However, adiponectin mRNA expression
levels in mesenteric adipose tissue were not significantly
affected by the plant treatment. Adiponectin is an adipocyte-
derived plasma protein and its concentration is closely asso-
ciated with metabolic abnormalities such as insulin sensitiv-
ity and obesity [36].
The phytoestrogenic effects have extended the herbal
usage to the treatment of post-menopausal osteoporosis.
L. pumila has the potential to be used as an alternative agent
for estrogen replacement therapy (ERT). ERT is usually used
for post-menopausal osteoporosis treatment nowadays, but
most of the therapies cause several side effects in the later
Fig. 2 (continued).
1327L.S. Chua et al. / Fitoterapia 83 (2012) 13221335
days. The most common side effects include breast cancer,
uterine cancer and thromboembolic problems. Ahmad et al.
[37] reported that the administration of L. pumila extracts
(17.5 mg/kg) was able to increase osteocalcin and lower
the C-terminal telopeptide of type 1 collagen levels in the
ovariectomized rats, as are the results shown in ERT groups.
However, the ovariectomized rats treated with L. pumila extract
have lower bone calcium level than in ERT groups. Therefore,
L. pumila could prevent the changes in bone biochemical
markers, but could not prevent the loss of bone calcium induced
by ovariectomy.
Another beneficial phytoestrogenic potential of the plant
is its capability against uropathogenic Escherichia coli infection
by inducing programmed cell death and reducing bacterial
invasion of the uroepithelium [38]. However, the plant extract
did not exhibit any direct inhibitory activity against uropatho-
gens such as E. coli, proteus mirabilis, Pseudomonas aeruginosa,
Staphylococcus saprophyticus and Candida albicans.Itisagreat
therapeutic activity found from the plant because the preva-
lence and risk of recurrent urinary tract infection are the
highest among women, especially after menopause.
The rejuvenating effect of L. pumila had also been proven
to have the immunomodulatory potential in T helper1 up-
regulating activity [39]. This kind of therapeutic activity is useful
for the treatment of immunodeficiency diseases. The ethyl
acetate fraction from the ethanolic extract showed significant
expression of pro-inflammatory cytokines such as tumor necro-
sis factor alpha (TNF-α), interleukin-6 (IL-6) and interleukin-12
(IL-12). IL-12 is an important regulatory cytokine secreted by
stimulated helper T cells (CD4+) to initiate and regulate
cellular immune responses. It also stimulates the synthesis of
interferon-gamma (IFN-γ) by T cells.
Similar to Eurycoma longifolia (the king of herbs), a bio-
active peptide (4.3 kDa) was also detected in L. pumila water
extract [40,41]. This peptide has been proven as an aphrodi-
siac marker for the treatment of male infertility and sexual
dysfunction by increasing testosterone synthesis.
3. Toxicological studies on L. pumila
Apart from the pharmacological effects, there is still very
little information on the safety and efficacy of L. pumila for
human consumption and medical application. Investigators
from the Institute for Medical Research, Malaysia have tested
the cytogenetic toxicology of L. pumila extract in bone marrow
cells obtained from SpragueDawley rats using micronucleus
assay [42]. Micronucleus frequencies have been considered to
be a reliable index for detecting chromosome breakages and
Fig. 2 (continued).
1328 L.S. Chua et al. / Fitoterapia 83 (2012) 13221335
loss in vivo, recommended by international regulatory
agencies for product safety assessment [43]. There was no
significant increase in micronucleated polychromatic eryth-
rocytes (MNPCEs) at administrated dose level (100, 700 and
2000 mg/kg of body weight rat) and harvest time (24, 48 and
72 h). Somehow, the study did not report on the doseeffect
relationship. The dose dependent effect is of high concern to
users because it is closely related to the safety issue for long
term consumption of L. pumila.
The teratogenic and reproductive toxicities of the herb
have been evaluated by investigators from the Universiti
Sains Malaysia on pregnant SpragueDawley rats from days 6
to 16 of pregnancy and which were sacrificed on day 21 [44].
The study has been conducted to investigate the possibility of
offspring being born with structural and functional abnor-
malities as a result of the herbal extract consumption. The
embryonic development was studied in order to establish the
herbal safety profile, since L. pumila extract is usually given to
pregnant women, starting from one or two months before
childbirth till after delivery to regain body strength of
mothers. Results indicated that aqueous extracts of L. pumila
var. alata up to 1000 mg/kg/day did not show significant
teratogenic effects, including gravid uterine weight, number
of corpora lutea, number of implantation sites, percentage of
fetal resorptions, and number of life fetuses, fetal weight and
fetal sex ratio. In contrast, the maternal body weight was
slightly higher in animals receiving low dose of the herbal
extract (2 mg/kg/day) as compared to all groups of animals.
However, the body weight gain in the low dose extract
treated rats was not statistically significant.
In the following year, the toxicity level of L. pumila was
also tested on the estrous cycle, reproductive performance,
post-natal growth and offspring survival of rats [3]. Again,
water extract of L. pumila var. alata has been proven not
to pose any significant reproductive toxicity in pregnancy,
delivery and early pup growth in rats. The mean duration
of pregnancy was 21 days in animals, which received the
herbal extract at a dose of 20800 mg/kg/day. The herb was
reported to be non-toxic because none of the rats exhibited
significant amounts of fetal resorption. However, petroleum
ether extract of the plant has been reported to cause sinu-
soidal degeneration of liver [45]. The degeneration was due
to the inflammation of the renal tubules during days 17
post-partum in female Wistar rats. Somehow, the investiga-
tors did not mention the phytochemical that was causing the
inflammation from the petroleum ether extract.
Subsequently, a 28-day sub-acute toxicity of the aqueous
extract to Wistar rats was carried out by researchers from
India [46]. This method is widely accepted for health hazard
assessment, particularly on herbal supplement. No treatment
related mortality of animals was reported at the dosages of
50, 250, 500 and 1000 mg/kg body weight. At higher doses
(>50 mg/kg), there were some pathological effects in the
histological profiles of liver, lung and kidney in the treated
rats, but not in a dose response related manner. The macro-
scopic examination of vital organs such as brain, heart, spleen,
stomach, small intestine and ovary/testes did not show any
pathology after the herbal treatment. The analysis results of
urine, hematology and serum withdrawn from the treated rats
were comparable to the results obtained from the control
4. Rationale of L. pumila as collagen synthesis
promoting herb
Indeed, natural products have long been exploited in
medical and skin care since the beginning of civilization. For
instance, the Egyptian queen, Cleopatra used to bathe in sour
milk containing lactic acid for skin exfoliation. Athletes in
ancient Greece used to bathe in olive oil to modulate body
temperature and scattered fine sand on their skin to make it
more resistant to the sun rays. For the Romans, they used
scented oil to clean and lather the skin for beauty purpose.
European women often bathe in wine to obtain smooth and
silky skin. Since the Qin Dynasty (221 to 205 BC), Angelica
dahurica (Bai Zhi) has been used in Chinese medicines in
whitening facial creams.
Nowadays, the number of natural products that has been
used for the development of skin care products is in the
increasing trend. Mostly, these natural products have been
proven to exhibit significant antioxidant [47], emollient [48]
and UVB protection [49] properties, which are crucial for skin
care product formulation. The properties are most probably
due to the presence of particular phytochemicals in the natural
products as active compounds. Moreover, natural ingredients
are easier to be absorbed by the superficial layers of the skin
and lower skin allergy problems.
In most circumstances, the production of ROS in excessive
amounts is triggered by external stimuli such as exploration
of UVB light. The production of ROS in dermal fibroblast
would accelerate the damage to the cellular components
such as lipid membranes, mitochondria and DNA. Under such
a stress condition, cytokine, namely transforming growth
factor-β(TGF-β) that promotes collagen production would
be affected and then contribute to the formation of wrinkles
[50]. The anti-stress property of L. pumila aqueous extract has
been tested on animals under different stressful experimen-
tal conditions [51]. Although none of the stressful conditions
in the study was due to the UVB light exploration, gallic acid
from the plant extract might be the main marker contribut-
ing to the anti-stress property. The animal models treated
with the plant extract would reverse the stress reactions
behaviorally, biochemically and immunologically to restore
homeostasis. In fact, plant based anti-stress drugs such as
dibazol (2-benzylbenzimidazol) have been reported earlier
by Lazarev [52]. These anti-stress drugs are likely to induce
the non-specifically increased resistance in stressful animals
as well as emotional stress in humans.
In addition to the phytochemicals, vitamins such as A, C and
E are the commonly used chemical compounds in skin care
product formulation. The preference of vitamins as additive
in the product formulation is likely to enhance the value of
the product, especially modulating the effects of UV-induced
ROS damage [53]. Owing to the high demand and costly
vitamin extraction from plants, most of the cosmetic products
use chemically synthesized vitamins. However, plant based
cosmetic products are still preferable because of the negative
side effects of chemical derivatives, which might cause skin
irritation, inflammation and allergy. Hence, natural skin care
products continue to gain favor in modern era till to date. To a
further extent, not only natural resources, but also people start
focusing on the amount of active ingredients present in the
natural resources.
1329L.S. Chua et al. / Fitoterapia 83 (2012) 13221335
4.1. Common active ingredients for skin care
Retinols and carotenoids are the two main forms of vitamin
A found in nature. Though vitamin A cannot be found as an
individual compound in plants, many plants with yellow
pigments contains β-carotene [54], which serves as a potent
precursor of vitamin A [55]. It was reported that 10% or less of
retinaldehyde formed from β-carotene cleavage would then be
oxidized to retinoic acid (tretinoin) [56]. Tretinoin is the first
retinoid developed for acne and photo-aging treatment.
Retinoic acid has been proven for its capability to remove
wrinkles and revitalize the photo-damaged cells via restorative
mechanism. It is widely used to limit the progression of
damage by stimulating the proliferation of fibroblasts and to
enhance the production of collagen in the dermis [57].The
stimulated skin cellsfor collagensynthesis could partly reverse
the skin aging process. Type I collagen formation was found to
be 56% less in the papillary dermis of photo-damaged skin than
in the skin protected from the sun [57]. The tretinoin treatment
for photo-damaged skin has increased the formation of 80%
type I collagen [57]. Retinoic acid is also believed to have the
ability to induce the keratinocyte proliferation, resulting in
smoother skin-surface structure. Apart from that, retinoic acid
inhibits the UV-induced pigmentation and blocks the UV
induction of the matrix metalloproteinases. Therefore, retinoic
or retinol is widely used as key ingredient in cosmetic product
formulation. However, special care must be taken because it
might cause irritation and promote skin sensitivity to sunlight.
The skin thinning effect of tretinoin might increase the risk of
sunburn, redness, scaling and itching. Because of the side effect,
retinoic acid is usually available as prescription products. The
instability of retinoic acid, especially in the presence of oxygen
also requires special delivery system in product formulation.
Vitamin C is commonly known as ascorbic acids. This
compound is an important regulator for collagen biosynthesis
(collagenase-digestible protein) and as one of the cofactors in
proline and lysine hydroxylations. The hydroxylation pro-
duces collagen with higher thermal stability, which is the
essential characteristic required for photo-damaged skin [58].
The stimulation of ascorbic acid on cell proliferation and
collagen expression in dermal fibroblast appeared to be age
independent [59]. The relationship was inversely related to
age in the absence of ascorbic acid. The cell proliferation and
collagen expression were reflected by the coordinate increases in
steady-state proα1(I) and proα1(II) collagen mRNAs, suggesting
a pretranslational mechanism. Several researchers reported that
the gene expression of collagen was increased when fibroblasts
were stimulated by ascorbic acid in vitro [60,61]. It has been
shown to upregulate types I and II collagen syntheses in human
dermal fibroblasts [59].
Vitamin E is a mixture of organic compounds including
α-,β-, γ-, δ-tocopherols and α-,β-, γ-, δ-tocotrienols [62].It
has been used for more than 50 years in experimental and
clinical dermatologies [63]. It is one of the essential lipophilic
nutrients found in a variety of natural sources such as nuts,
vegetable oils and green leafy vegetables. Recently, it is
gaining increasing attention in the skin care industry because
of the antioxidant properties [63,64],as well as photo-
protective and skin barrier stabilizing properties [63]. Nev-
ertheless, there is still a lack of controlled clinical studies on
the dosage of vitamin E application either topically or orally.
It has the potential to slow down the collagen breakdown
rate by protecting membranes against lipid peroxidation
and to maintain the integrity of membranes [63]. In vitro
experiments with skin fibroblasts showed that α-tocopherol
was able to diminish the age dependent collagenase gene
(MMP-1) transcription via protein kinase C (PKC) activity
inhibition [65]. In vivo murine experiments showed that the
topical application of vitamin E (5% tocopherol) before UVB-
exposure was found to be 75% of wrinkle reduction from skin
surface and considerabe reduction in skin tumor formation.
This suggests that vitamin E could be a skin aging protective
agent against the damaging effects of UV irradiation [65,66].
According to the antioxidant network theory, the combina-
tion of co-antioxidants such as vitamin C may help to enhance
the antioxidant effects as well as the stability of vitamin E
Apart from vitamins, Co-enzyme Q
present in foods and taken as a dietary supplement, which may
serve as an antioxidant to protect cellular membranes and
plasma lipoproteins from free radical induced damage. CoQ
is a lipid soluble and endogenous hydroxybenzoquinone com-
pound containing 10 isoprenoid units in the side chain [67],
which is well known as en essential electron carrier in the
mitochondrial respiratory chain [67,68]. The three main func-
tions of CoQ
in quenching ROS includes transfer of reducing
equivalents in the electron transport chain, generation of
superoxide anion radical, O
and quenching of free radicals.
Besides animal sources, it is widely isolated from plants such as
tobacco [69] and rapeseed oil [67] for halal market. The other
well known compound in cosmetics industry is alpha-hydroxyl
acids (AHA). AHA based cosmetic products are often claimed
for their efficiency in reducing wrinkles or the signs of aging.
The only drawback is AHA requires low pH condition to be
active. Too acidic cosmetic products might have higher pos-
sibility to cause skin irritation or even inflammation.
4.2. Relationship between photoaging and skin collagen
It is interesting to note that aging can be slowed down, or
even stopped for a while and sometimes it can be reversed
[70]. By definition, aging is a time-dependent series of
cumulative, progressive, intrinsic, and deleterious functional
and structural changes that usually begin to manifest at
reproductive maturity and eventually culminate in death
[71]. In fact, aging is a natural biological process, which can
be classified into intrinsic and extrinsic aging. The former is
due to the chronological genetic changes in the body where
cell renewal process is slowing down [72]. The endocrine
system of an organism will be gradually altered and degraded
reflecting endogenous aging. Human body has to cope with
endogenous generation of reactive oxygen species (ROS),
which are continuously produced during physiological cellular
metabolism. The latter is caused by environmental factors such
as climate, pollution, emotional stress and sickness [73].Ofthe
environmental factors, the ultraviolet irradiation is the main
factor contributing to premature skin aging due to photoaging
or what is known as the exogenous aging factor. Excessive
exposure to ultraviolet irradiation is of high concern to those
staying in the tropic region.
One of the most well known methods to delay or slow
down the process of skin aging is by enhancing the condition
1330 L.S. Chua et al. / Fitoterapia 83 (2012) 13221335
of collagen in the skin layer. Collagen is a type of protein
that is formed ubiquitously in multi-cellular animals as the
primary component for intracellular gum. It is the major
structural component of extracellular matrix in skin, covering
more than 50% [59,74]. It is produced by fibroblasts in the
dermis layer of the skin. The other extracellular matrices in
the dermis are elastin, proteoglycans and fibronectin. Type I
and type III collagens comprise 8590% and 811% of the total
collagen synthesized, respectively. Both types of collagen are
closely associated in a well organized fibrillar structure [75,76].
The fibril-forming collagen is likely to be one of the most
studied types of collagen with about 90% of the total collagen
The flexional stability and tensile strength of collagen
contribute to the integrity of tissues. The connective tissues
such as collagen fibrils are mainly to provide skin resilience
and flexibility to prevent tissues from overstretching or
tearing. Collagen also work together with elastin to provide
flexibility, structure and firmness to body tissues, bones,
tendons, cartilage, lung tissue and skin. As the body aged,
these connective tissues will slowly deteriorate, resulting in
loss of collagen and less firmness to body tissues. Thus, anti-
aging effort is focused on the reduction of collagen degrada-
tion and the increase of collagen synthesis.
The deteriorating conditions of the earth ecosystems due
to excessive development and pollutions are believed to
accelerate the aging process. The aging process becomes
obvious and noticed, once the symptom physically appears.
Since skin is the largest and outermost organ in the human
body, the aged skin is easy to be detected in the transforma-
tion of skin conditions. Approximately, the skin starts to age
at about 25 years old [73]. The transformation will affect
the three layers of the skin, namely epidermis, dermis and
hypodermis by changing the skin's biochemical profile. Bio-
chemical studies have revealed that the levels of types I and
III collagen precursors and crosslinks are reduced, whereas
elastin levels are increased in the photo-aged skin [77,78].
The mitochondrial activity is affected and the skin suffers
from progressive morphologic and physiologic decrements.
The skin surface will become coarse and irregular providing
the evidence that aging process has been taking place. The
other significant symptoms for skin aging include skin dryness,
dark spots and wrinkles on the skin surface.
The deleterious effects of photoaging caused by solar
radiation on type I and III collagens showed that there is a
transient decrease in type I procollagen mRNA (3070%), but
there is no effect on type III procollagen mRNA at the steady
state levels [79]. However, the matrix metalloproteinases such
as interstitial collagens (MMP-1) and stromelysin (MMP-3)
as degrading enzymes were increased 2 to 5 folds after solar
radiation in a dose-dependent manner. An age dependent
decrease in gene expression coding for type I and III collagens
has also been reported [80,81]. The collagen IV content in the
basement membrane showed a progressive decline in relation
to age [82]. It was suggested that the decline of collagen IV
might be due to the reduction of the protein content resulting
from degrading process, and also due to the decrease in
collagen synthesis. The shift in the relative proportions of
collagen types are both tissue and age-dependent [83].
Collagen fibrils in photo-aged skin are disorganized and
abnormal elastin-containing materials are accumulated [84].
The alterations either in number or structure of dermal con-
nective tissues are thought to be responsible for wrinkle
formation. The collagen bundles start to disperse and granulate
in aged skin, compared to dense and compact collagen bundles
in young skin. The degradation of collagen due to the irreversible
cross-linkage in aged skin is likely to reduce the collagenase
activity and to slow down the synthesis of new collagen, which
will affect the firm and youthful appearance of skin.
4.3. L. pumila as collagen synthesis promoter
Since skin appearance directly relates to the health condition
and image of an individual, people start taking precaution to
reduce the aging rate, or even to stop the aging process using
various approaches. The common approaches include taking
supplements, therapies or combination of both methods. A large
amount of money has been spent regardless the price, purposely
to make them look younger and more beautiful.
Following the demand and concern from the public, recently
researchers have found another alternative from plant derived
ingredients for skin care. Previous study on L. pumila extract
clearly showed the potential of this herbal extract to be used as
a photo protective agent against extrinsic aging [85]. The results
explained the capability of this herbal extract to stimulate
growth of human skin fibroblast cells in vitro after exposure
to ultraviolet (UV) radiation. Apart from that, L. pumila could
also up-regulate the synthesis of collagen in human dermal
fibroblast cells, which is responsible for the integrity, and
mechanical strength of the human skin [85]. The herbal extract
also has the ability to protect the human skin from the ROS
attacks generated by critical UVB exposure. This is mainly due
to the presence of bioflavonoids and phenolic acids in the
plant extract [11]. Of the polyphenols, quercetin is one of
the flavonoids detected from the herb. Chondrogianni et al.
[86] reported that quercetin and its derivative, namely querce-
tin caprylate were likely to be proteasome activator having
cytoprotective property against oxidative stress. These com-
pounds possessed rejuvenating effect on the cell proliferation
and morphology, as well as oxidation related diseases including
aging. The rejuvenating effect was also reported on tyrosinase
reduction, which would provide the whitening effect on skin
The presence of these highly antioxidative phytochemi-
cals is likely to promote L. pumila extract as great potential
ingredient for cosmeceutical formulation. Plant antioxidants
are believed to play an essential role in delaying the aging
process and disease protection against ROS. Aging is defined
as a natural process that is closely related to the oxidative
stress, which leads to the imbalance between free radicals
and antioxidant defense in skin [85]. Researchers from the
Dongguk University, Korea and Universiti Teknologi Malaysia,
Malaysia have reported the capability of L. pumila extract
in restoring skin pro-collagen that has been destroyed by
ultraviolet irradiation in vitro using human dermal fibroblast
and immortalize human keratinocytes. In addition to that,
L. pumila extract was likely to reduce the secretion of pro-
inflammatory cytokines, which are usually associated with
various skin diseases and the progression of photo-damaged
skin. The photo-protective effects and dermatological bene-
fits of L. pumila have surpassed the purpose of cosmetic to
further extend into an area of cosmeceuticals. Consequently,
1331L.S. Chua et al. / Fitoterapia 83 (2012) 13221335
a research team from the Institute of Bioproduct Develop-
ment (formerly known as Chemical Engineering Pilot Plant),
Universiti Teknologi Malaysia in Johor Bahru has formulated
a series of cosmeceutical products from L. pumila, including
moisturizer and anti-aging serum. Based on the end user
feedbacks, the effect of the cosmeceutical products is very
promising and encouraging (personal communication). Kim
et al. [87] reported that phenolic acids were also easily
absorbed in human systems and subsequently offered a serial
of anti-aging benefits. Of the benefits, the cell structure
becomes stronger, with higher decay resistance and prevents
the growth of abnormal cells. Meta-analysis conducted by
Köpcke and Krutmann [88] revealed that β-carotene supple-
ment could protect human skin from sunburn effect effi-
ciently. β-carotene might provide nutritional protection against
skin damage from sunlight.
Nevertheless, a well established extraction process must be
developed, so that only the phenolic compounds are extracted
from the plant. This is because the plant has been reported to
contain alkyl and alkenyl resorcinol, which might cause skin
irritation, inflammation and blistering [89]. The alkenyl resor-
cinol derivatives detected in L. pumila were (z)-5-(pentadec-4-
enyl)-resorcinol, (z)-5-(pentadec-8-enyl)-resorcinol and (z)-
5-(pentadec-10-enyl)-resorcinol [90].
The type and quantity of flavonoids used in the product
formulation must be well characterized, because Stipcevic et al.
[91] reported different results exhibited by different flavonoids
at the particular concentration on the synthesis of collagen in
human dermal fibroblasts. At the concentration of 80 μg/ml,
flavonoids such as quercetin-3,3,4,5,7-pentahydroxyflavone,
3-methyl quercetin, and 7-hydroxyflavone decreased the total
protein concentration significantly, which might be due to the
cytotoxicity effect. However, naringenin exhibited no effect
on the total collagen and total protein concentrations at that
4.4. Photoaging mechanism by UV radiation
Biosynthesis of collagens is a complex process. Since type I
collagen predominates in human dermis, most studies are
focused on type I collagen synthesis by monitoring the for-
mation of procollagen I within dermal fibroblasts [57].Itbegins
with the transcription of genes within the nucleus and ends
with the conglomeration of collagen heterotrimers into large
fibrils. The transcriptional activities are initiated in the nucleus,
generating different types of mRNA according to its function
thereafter. For example, a short form of type IX collagen mRNA
is generated in the cornea and vitreous body [92], while a
longer form of type II collagen mRNA can be found in chondro-
progenitor cells [93]. This pro-alpha chain will then be
translated to rough endoplasmic reticulum and attached to
the site for further protein synthesis. The soluble pro-collagen is
a larger precursor protein that possesses a central triple helical
domain and non-collagenous pro-peptide domain at both their
N- and C-terminal ends. This pro-collagen molecule will
undergo multiple post-translational modification steps, which
take place in the Golgi compartment of endoplasmic reticulum.
The first modification is hydroxylation of proline and lysine to
produce hydroxyproline and hydroxylysine. These reactions are
catalyzed by hydroxylase enzymes, with ascorbate (vitamin C)
and ferrous ion as the cofactors. Without the hydroxyproline, the
collagen molecules will not be able to form a proper helical
structure, causing it to lose its thermal stability and be easily
destroyed. This is portrayed in a poor wound healing of the
skin [94]. On the other hand, the hydroxylysine is responsible to
form stable inter-molecular cross linking of collagen molecules
in fibrils. It reacts with the carbohydrates to form glycosidic
hydroxylysines with the addition of galactose and glucose. This
glycosylation step is catalyzed byenzymessuchasgalactosyland
glucosyl transferases in the presence of trace mineral manganese
). The glycosylation enzymesarefoundtobeveryactive
at a young age and to slow down as they aged [95].Thepro-
collagen peptides will then be secreted to the extracellular
space through specialized structures known as microtubules.
After the pro-collagen is secreted, it will then be converted into
collagen by a specific enzymic cleavage of terminal propeptides
by the pro-collagen metalloproteinases [96]. The portions of the
digested end pieces are assumed to re-enter the cell via a feed-
back mechanism and regulate the quantity of collagen synthesis.
In the extracellular space, these triple helical collagen molecules
will begin to form fibrils and then fibers. This is a crosslinking
process within the molecule (intramolecules) and between
the molecules (inter-molecules). The biosynthesis pathway of
collagen in human cells is outlined in Fig. 3.
Over the years, substantial progress has been made in
elucidating the underlying molecular mechanisms in photo-
Fig. 3. The biosynthesis of collagens: (1) transcription of gene in nucleus; (2) attachment to site of actual protein synthesis; (3) post-translational modification;
(4) pro-collagen registration and hydroxylation; (5) cleavage of N- and C-terminal pro sequences; (6) covalent cross-linking of collagen fibers; and (7) extension
peptides feedback mechanism.
1332 L.S. Chua et al. / Fitoterapia 83 (2012) 13221335
aging. Numerous studies have been carried out to investigate
the effects of aging on the chemical constitution and phys-
ical transformation of human skin. Over exposure of skin
to UV radiation (UV) might result in skin modification in-
cluding erythema, tanning, immune-modulation and possi-
bly cancerogenesis [97]. These clinical responses are dose
dependent and the modifications are not necessarily linked to
each other by direct causeeffect relationship. The modifica-
tion might be contributed by the consequence of pleitropic
behavior of UV radiation [98100]. However, the clear mech-
anism of photoaging caused by UV radiation in collagen
synthesis is not yet known. It is only clear that both UVB
(290320 nm) and UVA (320400 nm) radiations contribute
to photoaging, as well as the induction of metalloproteinases
(MMPs) in the pathogenesis. The failure in the recovery of the
damaged collagen resulted from MMP induction that has
contributed to photoaging. Skin collagen content was found
to decrease with age [101], approximately at a rate of 1% a
year through adult life [102]. UVA is 10100 times more
abundant in sunlight than UVB, depending on the season and
time of the day. UVA radiation could penetrate far deeper
into the skin, and hence it exerts direct effect on both the
epidermal and the dermal compartments. UVA radiation could
trigger thegeneration of ROS, particularly singlet oxygenwhich
can subsequently exert several effects such as lipid peroxida-
tion, activation of transcription factors, and generation of DNA
strand breaks [103]. Although UVA photons areless biologically
active than UVB photons, the pathogenesis of UVA irradiated
photoaging is comparable to UVB [104].Incontrast,UVBwas
found to act preferentially at the epidermis by causing the
damage to keratinocytes and melanocytes, followed by the
production of proteolytic enzymes at the dermis layer. UVB
radiation not only induces the production of MMP, but also the
generation of ROS [104107], which have a direct interaction
with DNA and cause DNA damage. The UV induced alterations
at the dermis layer appeared to be largely responsible for the
phenotype of photo-aged skin. The topical pre-treatment with
tretinoin was found to inhibit the induction and activity of
MMPs in the UVB-irradiated skin from the activation of AP-1.In
chronically photo-damaged skin, collagen synthesis is down
regulated as compared to sun protected skin [108]. However,
recent study has reported that fibroblasts in severely photo-
damaged skin have less interaction with intact collagen, and
thus are exposed to less mechanical tension, which might lead
to decreased collagen synthesis [109].
5. Future perspectives of L. pumila
Based on the review of this article, L. pumila is likely to have
many beneficial effects in various fields of applications, par-
ticularly in the medical and cosmeceutical applications. Each
application might be due to the presence of specific functional
group of phytoconstituents in the plant. Therefore, it is of great
importance to know about the application before preparing the
plant extract. This is because the choice of solvents and the
operating conditions of extraction will directly affect the type of
active compounds to be extracted from the plant. Furthermore,
the preparation of the plant extract with known biological
activity could avoid undesirable side effects from the other
group of phytochemicals.
Even though L. pumila is widely used as traditional medicine
in the Malay community, its significant beneficial effects are
attractive enough to draw the attention of researchers from
other regions such as America [18,19],Sweden[33,38],Australia
ganda[38], India [39,46] and Korea [85]. It is foreseen
that the usage of L. pumila would be increasingly accepted with
the support of scientific data. In the near future, the acceptability
of the plant extract in pharmacological and cosmeceutical
applications would be in the increasing trend.
Due to the great demand for herbal products from global
consumers, scientific studies have been extensively carried
out worldwide. Most of the studies are focusing on biological
activities of plant extracts, toxicology based on dosage and
active compound identification. The demand is not only focused
on quantity basis, but also on the herbal quality basis. The herbal
quality is very much dependent on the content of bioactive
marker, besides nutritional composition.
With the advancement of herbal processing technology
as well as analytical equipments nowadays, the standardization
of L. pumila and products derived from the plant extract is
possible to be implemented even in a larger scale. Standardiza-
tion is very important for herbal processing industries because it
ensures the consistency in the quality of herbal products. It is
believed that herbal products with known quality, in terms of
phytochemical profile and biological property will increase the
value of the particular herbal product significantly. Previously,
the herbal quality consistency is a major issue, mainly because
of the great variation in plant physical and chemical properties.
The variation is solely dependent on the botanical, seasonal and
processing factors.
6. Conclusion
This article reviews the current studies and future
prospect of L. pumila, especially in cosmeceutical application.
Many phytochemicals have been identified to date and most
of them have been reported to exhibit beneficial properties
such as antioxidant, antimicrobial and anti-estrogenic dis-
eases, which are in line with the traditional uses of the herb as
post-partum medication, to maintain the female reproductive
system, as well as to enhance sexual function. The herbal
extracts have also been proven for its efficiency in dealing
with growth promotion in human skin fibroblasts and
keratinocytes. The promoting effects can be seen from the
significant contribution of the herbal extracts in collagen
synthesis and reducing matrix metalloproteinase production,
supported by the outstanding antioxidative activity com-
pared to synthetic vitamins. Therefore, L. pumila extracts have
high potential to be the key ingredient in cosmeceutical
industries in order to maintain skin physiology and integrity.
The efficacy of the plant extracts in cosmeceuticals is believed
to be comparable with the existing active ingredients found in
cosmetic products nowadays.
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... The Labisia pumila (LP) is a traditional plant that is commonly known as Kacip Fatimah, Selusuh Fatimah, and Pokok Ringgang by the indigenous people. It is believes to facilitate during a childbirth, treating their postchildbirth and menstrual irregularities [1]. LP is plant grown in low cluster, and it has rarely branching stems with a hairy root. ...
... However, LP has received wide attention on its phytoestrogenic effect on women. [1] show that anthocyanin in LP is high compared to other phytoconstituents. More studies are needed to prove on the phytoestrogenic properties of each phytoconstituent in LP, perhaps on the specific phytoconstituent of LP such as anthocyanin which promotes benefits on cardiovascular diseases. ...
... The chronic exposure of skin towards the sun will cause the skin to age even faster which is known as photoaging. This is due to the ultraviolet (UVB) irradiation that promotes premature aging characteristics such as wrinkles, roughness, laxity, and pigmentation [1]. Interestingly, the aging process can slow down or even be reversed which is a time-dependent series [64]. ...
Full-text available
The Labisia pumila (LP) is a traditional plant that is locally known as Kacip Fatimah, Selusuh Fatimah, or Pokok Ringgang by the Malaysian indigenous people. It is believed to facilitate their childbirth, treating their postchild birth and menstrual irregularities. The water extract of LP has shown to contain bioactive compounds such as flavonoids, ascorbic acid, β-carotene, anthocyanin, and phenolic acid, which contribute extensive antioxidant, anti-inflammatory, antimicrobial, and antifungal. The LP ethanolic extract exhibits significant estrogenic effects on human endomentrial adenocarcinoma cell in estrogen-free basal medium and promoting an increase in secretion of alkaline phosphate. Water based has been used for many generations, and studies had reported that it could displace in binding the antibodies and increase the estradiol production making it similar to esterone and estradiol hormone. LP extract poses a potential and beneficial aspect in medical and cosmeceutical applications. This is mainly due to its phytoestrogen properties of the LP. However, there is a specific functionality in the application of LP extract, due to specific functional group in phytoconstituent of LP. Apart from that, the extraction solvent is important in preparing the LP extract as it poses some significant and mild side effects towards consuming the LP extracts. The current situation of women reproductive disease such as postmenopausal syndrome and polycystic ovary syndrome is increasing. Thus, it is important to find ways in alternative treatment for women reproductive disease that is less costly and low side effects. In conclusion, these studies proven that LP has the potential to be an alternative way in treating female reproductive related diseases such as in postmenopausal and polysystic ovarian syndrome women.
... Labisia pumila (Blume) Mez is a member of the Myrscinaceae family, and it is known by several vernacular names, such as Selusuh Fatimah, Tadah Matahari, Mata Pelanduk Rimba, and others [1]. It is primarily found in Southeast Asia's lowlands and forests with hills [2], and Ibrahim and Jaafar [3] described it as a shade-loving plant that thrives in thinned jungle with 70% to 90% shade. This plant is well known as a medicinal plant, with a long history of use in traditional medicine, especially for postpartum medicine for pregnant women [4][5][6]. ...
... L. pumila has been sought after since the discovery of its medicinal properties, and there is a strong demand for its raw materials on the market [4]. However, because of its slow growth rate, the source of this herb in its natural habitat is diminishing [2]. As a result, plant tissue culture techniques are used to promote large-scale production in order to maximize supply and ensure that this plant does not become extinct. ...
... Callus initiation is the first step in cell growth and the development of secondary metabolites [15]. There have been a few studies on enhancing essential oils, antioxidant activity, and secondary metabolite production [16,17], particularly polyphenolics via callus culture [2,6,18], but none have been conducted on L. pumila. ...
Full-text available
This study aims to investigate whether the in vitro-cultured L. pumila var. alata has higher antioxidant activity than its wild plant. An 8-week-old L. pumila var. alata nodal segment and leaf explants were cultured onto Murashige and Skoog (MS) medium supplemented with various cytokinins (zeatin, kinetin, and 6-benzylaminopurine (BAP)) for shoot multiplication and auxins (2,4-dichlorophenoxyacetic acid (2,4-D) and picloram) for callus induction, respectively. The results showed that 2 mg/L zeatin produced the optimal results for shoot and leaf development, and 0.5 mg/L 2,4-D produced the highest callus induction results (60%). After this, 0.5 mg/L 2,4-D was combined with 0.25 mg/L cytokinins and supplemented to the MS medium. The optimal results for callus induction (100%) with yellowish to greenish and compact texture were obtained using 0.5 mg/L 2,4-D combined with 0.25 mg/L zeatin. Leaves obtained from in vitro plantlets and wild plants as well as callus were extracted and analyzed for their antioxidant activities (DPPH and FRAP methods) and polyphenolic properties (total flavonoid and total phenolic content). When compared with leaf extracts of in vitro plantlets and wild plants of L. pumila var. alata, the callus extract displayed significantly higher antioxidant activities and total phenolic and flavonoid content. Hence, callus culture potentially can be adapted for antioxidant and polyphenolic production to satisfy pharmaceutical and nutraceutical needs while conserving wild L. pumila var. alata.
... The 3T3F442A fibroblasts and L6 myoblast cells were trypsinized and seeded into a 96-well plate with the respective seeding densities of 2 × 10 5 and 2.5 × 10 5 cells/well. [15] Following a 24-h incubation period, all cells had been treated with varied H. sabdariffa Linn fruit methanolic extract and fractions (7.81-1000 μg/mL) concentrations, and then, were incubated for another 72 h. After that, phosphate buffer saline (5 mg/mL) was used to dissolve MTT, which was later filtered with a 0.22 μm Sartorius syringe filter (Sartorius Stedim Malaysia Sdn Bhd, KL, Malaysia) for sterilization purpose. ...
... The next step was to add 1 NHCl-isopropanol buffer (225 μL) into all the emptied wells to solubilize the purple crystals. [15] Finally, the rate of absorbance had been read at 560 nm by using a PromegaGloMax microplate reader (Promega, Wisconsin, USA). [16] Examination of glucose uptake activity in 3T3F442A adipocytes displayed by Hibiscus sabdariffa Linn extracts and fractions ...
Full-text available
Objective: As such, this study reports the effects of Hibiscus sabdariffa Linn fruit methanolic extract and fractions (ethyl acetate, n‑hexane, and butanol) on glucose uptake stimulation, as well asregulation of glucose transporter‑4 (GLUT4) in L6 myotubes and 3T3F442Aadipocytes cells. Materials and Methods: The stimulating effects of methanolic extract and fractions of H. sabdariffa Linn fruit on glucose uptake in 3T3F442A adipocytes through in vitro assay assessment are reported. The GLUT4 translocation of L6 myotubes membrane was also investigated. Results: The outcomes of this study revealed that methanolic extract and fractions were unable to induce glucose uptake in 3T3F442A adipocytes. In addition, the methanolic extract and fractions were incapable of enhancing both the distribution and the regulation of GLUT4 in L6 myotubes, in relation to the control. Conclusion: The systematic empirical works performed in this study conclude that the H. sabdariffa Linn derivatives are unsuitable potentials for the progression of new anti‑diabetic drugs.
... M. pumilum has been the subject of numerous researches to discover the bioactive phytochemicals that contribute to its wide range of pharmacological effects such as antioxidant activity, anti-carcinogenic, antibacterial, anti-viral, anti-stress, and anti-inflammatory activities (Chua et al., 2012;Pan et al., 2012;Rahmi et al., 2020;Tan et al., 2019). It is composed of numerous phytochemicals present in various parts of the plant, namely: phenolic compounds such as pyrogallol, gallic acid/methyl gallate, and caffeic acid; flavonoid compounds such as apigenin, quercetin, myricetin, kaempferol, catechin, epigallocatechin, naringin, and rutin; β-carotene; ascorbic acids (Chua et al., 2011;Nik Hussain and Kadir, 2013); resorcinol derivatives (Jamal et al., 2011;Muhamad et al., 2019); fatty acids; saponins; alkenyl compounds; and benzoquinone derivatives (Al-Mekhlafi et al., 2012;Avula et al., 2011). ...
... To our knowledge, no comprehensive technique using computational target fishing has been employed to discover Marantodes pumilum therapeutic potential. 1) were selected in this study as the efficacy of these compounds are well established (Chua et al., 2012;Giaze et al., 2019;Pan et al., 2012). ...
Ethnopharmacological relevance Marantodes pumilum (MP) herbs, locally known as Kacip Fatimah, are widely used traditionally to improve women's health. The herb is frequently used for gynecological issues such as menstrual problems, facilitating and quickening delivery, post-partum medication, treats flatulence and dysentery, and. MP extracts are thought to aid in the firming and toning of abdominal muscles, tighten breasts and vaginal muscles, and anti-dysmenorrhea. It also was used for the treatment of gonorrhea and hemorrhoids. As MP product has been produced commercially recently, more in-depth studies should be conducted. The presence of numerous active compounds in MP might provide a synergistic effect and potentially offer other health benefits than those already identified and known. Aim of the study This study aimed to use a computational target fishing approach to predict the possible therapeutic effect of Marantodes pumilum and evaluated their effectivity. Materials and methods This study involves a computational approach to identify the potential targets by using target fishing. Several databases were used: PubChem database to obtain the chemical structure of interested compounds; Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) server and the SWISSADME web tool to identify and select the compounds having drug-likeness properties; PharmMapper was used to identify top ten target protein of the selected compounds and Online Mendelian Inheritance in Man (OMIM) was used to predict human genetic problems; the gene id of top-10 proteins was obtained from UniProtKB to be analyzed by using GeneMANIA server to check the genes’ function and their co-expression; Gene Pathway established by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) of the selected targets were analyzed by using EnrichR server and confirmed by using DAVID (The Database for Annotation, Visualization and Integrated Discovery) version 6.8 and STRING database. All the interaction data was analyzed by Cytoscape version 3.7.2 software. The protein structure of most putative proteins was obtained from the RCSB protein data bank. Thedocking analysis was conducted using PyRx biological software v0.8 and illustrated by BIOVIA Discovery Studio Visualizer version 20.1.0. As a preliminary evaluation, a cell viability assay using Sulforhodamine B was conducted to evaluate the potential of the predicted therapeutic effect. Results It was found that four studied compounds are highly correlated with three proteins: EFGR, CDK2, and ESR1. These proteins are highly associated with cancer pathways, especially breast cancer and prostate cancer. Qualitatively, cell proliferation assay conducted shown that the extract has IC50 of 88.69 μg/ml against MCF-7 and 66.51 μg/ml against MDA-MB-231. Conclusions Natural herbs are one of the most common forms of complementary and alternative medicine, and they play an important role in disease treatment. The results of this study show that in addition to being used traditionally to maintain women's health, the use of Marantodes pumilum indirectly has the potential to protect against the development of cancer cells, especially breast cancer. Therefore, further research is necessary to confirm the potential of this plant to be used in the development of anti-cancer drugs, especially for breast cancer.
... lanceolata (Scheff.) Mez. are widely distributed in Malaysia rain forest and have attracted the researcher's interest thus far (Sunarno, 2005;Chua et al., 2012). The three varieties can be distinguished by their petioles and leaf characteristics. ...
Full-text available
Botanical drug products consist of complex phytochemical constituents that vary based on various factors that substantially produce different pharmacological activities and possible side effects. Marantodes pumilum (Blume) Kuntze (Primulaceae) is one of the most popular Malay traditional botanical drugs and widely recognized for its medicinal use. Many studies have been conducted focusing on the identification of bioactive substances, pharmacological and toxicological activities in its specific varieties but less comprehensive study on M. pumilum authentication. Lack of quality control (QC) measurement assessment may cause different quality issues on M. pumilum containing products like adulteration by pharmaceutical substances, substitution, contamination, misidentification with toxic plant species, which may be detrimental to consumers’ health and safety. This systematic literature review aims to provide an overview of the current scenario on the quality control of botanical drug products as determined by pharmacopoeia requirements specifically for M. pumilum authentication or identification. A systematic search for peer-reviewed publications to document literature search for M. pumilum authentication was performed using four electronic databases: Web of Science, PubMed, Scopus and ScienceDirect for related studies from January 2010 to December 2021. The research studies published in English and related articles for identification or authentication of M. pumilum were the main inclusion criteria in this review. A total 122 articles were identified, whereby 33 articles met the inclusion criteria. Macroscopy, microscopy, chemical fingerprinting techniques using chromatography, spectroscopy and hyphenated techniques, and genetic-based fingerprinting using DNA barcoding method have been used to identify M. pumilum and to distinguish between different varieties and plant parts. The study concluded that a combination of approaches is necessary for authenticating botanical drug substances and products containing M. pumilum to assure the quality, safety, and efficacy of marketed botanical drug products, particularly those with therapeutic claims.
... These herbs have been commonly used for centuries as traditional medicines for reproductive health, promoting energy and enhancing mental alertness (14)(15)(16)(17)(18). The effectiveness of L. pumila is attributed to the flavonoid and phenolic contents; as well phytoestrogenic properties (19), L. pumila has been used traditionally to ease childbirth, postpartum rejuvenation (20) and relieve from menopausal symptoms (21). E. longifolia, known as Malaysian ginseng, contains a variety of metabolites including eurycomanone and a 4.3 kDa peptide, which influence testosterone production. ...
... The decoction and infusion of these plants and fungi mixture were traditionally consumed by Jakun women for post-partum recovery and boosting energy. The above-mentioned plants have shown high quantity of bioactive compounds with promising antioxidants acitivities (Chua et al., 2012;Dej-adisai et al., 2015;Lar, 2014). ...
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Aging is a naturally biological process with adverse effects. The continuous accumulation of reactive oxygen species (ROS) trigger cellular and tissue damage by activating several aging enzymes. The antioxidant properties of traditional medicinal plants used by Jakun aborigine's community are a promising approach to alleviate aging process and prevent Alzheimer. The aim of the current investigation was to optimize a novel anti-aging formulation from traditional plants (Cnestis palala stem, Urceola micrantha stem, Marantodes pumilum stem and Microporus xanthopus fruiting bodies) using simplex centroid mixture design (SCMD). After selecting the optimal formulations based on desirability function of antioxidant activity (DPPH_, ABTS _+ and FRAP), they were further examined against the activity of aging-related-enzymes (collagenase, tyrosinase, acetyl-and butyrylcholinesterase). The single extracts of C. palala, U. micrantha and the binary mixture of C. palala and U. micrantha were the optimal formulations with high antioxidant activities. Single extract of U. micrantha showed the highest inhibition towards matrix metalloproteinase-1 (49.44 ± 4.11 %), while C. palala water extract showed highest inhibitions towards tyrosinase (14.06 ± 0.31%), acetylcholinesterase (32.92 ± 2.13%) and butyrylcholinesterase (34.89 ± 2.8 4%) enzymes. The single extracts of C. palala and U. micrantha displayed better activity as compared to the binary mixture formulation. In conclusion, these findings could be a baseline for further exploration of novel anti-aging agents from natural resources. Ó 2021 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (
PurposeDiabetes accelerates peripheral, distal symmetric polyneuropathy, small fiber predominant neuropathy, radiculoplexopathy, and autonomic neuropathy. This study investigated the neuroprotective effects of gallic acid and myricetin-rich Labisia pumila extract in a diabetic neuropathy rat model and evaluated the neuropathy correlationship with serum inflammatory biomarkers.Methods Thirty male rats were divided into 5 groups (n = 6), namely: healthy control; non-treated diabetic control; and diabetic-rats treated with 200 mg/kg metformin; Labisia pumila ethanol extract (LP) at 150 mg/kg or 300 mg/kg doses. Diabetes was induced by 60 mg streptozotocin /kg intraperitoneal injection. Rats were orally treated daily for ten weeks. Their fasting blood glucose (FBG), neurological functions (hot plate and tail immersion; thermal hyperalgesia; cold allodynia; motor walking function), biomarkers for inflammation and oxidative stress, the neuro-histopathological changes, and brain somatic index were measured.ResultsThe extract significantly prevented abnormal increases in FBG and decreases in body weight gain. It attenuated behavioral dysfunctions (hot plate and tail immersion; thermal hyperalgesia; cold allodynia; motor walking function), systemic inflammation (serum TNF-α, prostaglandin-E2) oxidative tension (malondialdehyde), histological brain and sciatic nerve injuries in the diabetic-rats, better than Metformin.ConclusionLP mitigated neural dysfunction better than metformin partly by amending diabetic systemic inflammation, oxidative tension, and diabetic abnormalities. The nerve injuries were strongly correlated to serum prostaglandin-E2, TNF-α levels, and walking functions. The motor function was correlated to sensory neuronal functions, inflammation, and oxidation. The sensory neuronal functions were more affected by TNF-α than prostaglandin-E2 or oxidation. Diabetic brain and sciatic nerve deteriorations were influenced by serum TNF-α, PGE2, and MDA levels.
Ethnopharmacological relevance Marantodes pumilum (Blume) Kuntze has been claimed to be beneficial in protecting the bone against loss in post-menopausal women. In view of increased incidence of diabetes mellitus (DM) in post-menopausal period, M. pumilum ability to overcome the detrimental effect of estrogen-deficiency and DM on the bones were identified. Aim of the study To identify the mechanisms underlying protective effect of MPLA on the bone in estrogen-deficient, diabetic condition. Methods Adult female, estrogen-deficient, diabetic rats (225±10 g) were divided into untreated group and treated with M. pumilum leaf aqueous extract (MPLA) (50 mg/kg/day and 100 mg/kg/day) and estrogen for 28 days (n=6 per group). Fasting blood glucose (FBG) levels were weekly monitored and at the end of treatment, rats were sacrificed and femur bones were harvested. Bone collagen distribution was observed by Masson’s trichome staining. Levels of bone osteoblastogenesis, apoptosis and proliferative markers were evaluated by Realtime PCR, Western blotting, immunofluorescence and immunohistochemistry. Results MPLA treatment was able to ameliorate the increased in FBG levels in estrogen deficient, diabetic rats. In these rats, decreased bone collagen content, expression level of osteoblastogenesis markers (Wnt3a, β-catenin, Frizzled, Dvl and LRP-5) and proliferative markers (PCNA and c-Myc) and increased expression of anti-osteoblastogenesis marker (Gsk-3β) and apoptosis markers (Caspase-3, Caspase-9 and Bax) but not Bcl-2 were ameliorated. Effects of 100 mg/kg/day MPLA were greater than estrogen. Conclusion MPLA was able to protect against bone loss, thus making it a promising agent for the treatment of osteoporosis in women with estrogen deficient, diabetic condition.
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Labisia pumila is a precious herb in Southeast Asia that is traditionally used as a health supplement and has been extensively commercialized due to its claimed therapeutic properties in boosting a healthy female reproductive system. Indigenous people used these plants by boiling the leaves; however, in recent years it has been marketed as powdered or capsuled products. Accordingly, accuracy in determination of the authenticity of these modern herbal products has faced great challenges. Lack of authenticity is a public health risk because incorrectly used herbal species can cause adverse effects. Hence, any measures that may aid product authentication would be beneficial. Given the widespread use of Labisia herbal products, the current study focuses on authenticity testing via an integral approach of DNA barcoding and qualitative analysis using HPLC. This study successfully generated DNA reference barcodes (ITS2 and rbcL) for L.pumila var. alata and pumila. The DNA barcode that was generated was then used to identify species of Labisia pumila in herbal medicinal products, while HPLC was utilized to determine their quality. The findings through the synergistic approach (DNA barcode and HPLC) implemented in this study indicate the importance of both methods in providing the strong evidence required for the identification of true species and to examine the authenticity of such herbal medicinal products.
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Labisia pumila or locally known as Kacip Fatimah, is one of the most popular medicinal herb in Malaysia. Anticarcinogenic activity of this medicinal herb however, has not been reported until today. In this paper, the in vivo anticarcinogenic activity of L. pumila ethanol extract on two-stage mouse skin carcinogenesis model is reported. In the present study, we investigated whether L. pumila ethanol extract have an effect on tumor growth in vivo. Therefore, varying doses (25, 50 and 100 mg/kg bwt) of L. pumila ethanol extract were tested on 7, 12-dimethylbenz(a)anthracene (DMBA)/croton oil-induced mouse skin carcinogenesis. At the end of the experiment of 20 weeks, animals in carcinogen control group developed a mean number of 5.70 ± 1.3 skin tumors per tumor-bearing mouse and on the 16th week prompted a tumor incidence of 100%. Animals that have been treated with 25, 50 and 100 mg/kg bwt of L. pumila extract topically for 30 min developed a mean number of 3.60 ± 1.1, 3.20 ± 0.8 and 2.40 ± 0.7 skin tumors per tumor-bearing mouse with tumor incidence of 90, 60 and 50%, respectively. The tumor volume per tumor-bearing mice of carcinogen control animals was 121.03 ± 3.46 mm3, which was significantly (p<0.05) reduced to 92.27 ± 2.68, 69.24 ± 3.93 and 54.24 ± 4.38 mm3 for the animals treated with 25, 50 and 100 mg/kg bwt of L. pumila extract, respectively. In terms of tumor incidence and tumor burden, the highest dose (100 mg/kg bwt) of L. pumila ethanol extract was almost equipotent with curcumin (10 mg/kg bwt). The extract of L. pumila not only decreased the tumor incidence, tumor burden and tumor volume in DMBA/croton oil-induced mice but also delayed the skin tumor growth as compared to carcinogen control group. Further histopathological examination revealed that tumors from animals that have been treated with L. pumila showed intact basement membrane as compared to the tumors from the untreated animals. This finding suggested that L. pumila extract was able to suppress the progression of benign tumors to malignant stage in DMBA/croton oil-induced mice. Further studies should be carried out in order to identify the active compound responsible for the anticarcinogenic activities and the mechanism of action of L. pumila at the molecular level.
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Introduction:Labisia pumila var alata or as known among Malay women as Kacip Fatimah (KF), has long being recognized for its medicinal value. Recently, researches have demonstrated its estrogenic activity. Ovariectomy (surgical menopause) is known to cause weight gain and increase adiposity due to estrogen deficiency. Objective: This study was aimed to investigate the effect of Labisia pumila consumption and Estrogen Replacement Therapy (ERT) on the morphology of adipose tissue following ovariectomy. Methodology: 6 months old female (Sprague Dawley) rats were ovariectomized (bilaterally) under anesthesia using the ventral approach and randomly divided into OVXC (ovariectomized control), KF and ERT. KF and ERT received daily oral treatment of water extract of Labisia pumila (17.5 mg/kg/day), and ERT (64.5 µg/kg/day) respectively for a period of three months. A group of 9 normal rats was left intact and used as normal control (NOR). Rats were sacrificed by cervical dislocation and tissue samples from abdominal fat were collected and fixed immediately either in 4% paraformaldehyde for electron microscopy or in 10% formalin for light microscopy. Results: Light microscopy revealed hypertrophic growth (increase in the size of adipocytes) as well as increasing vasculature of adipose tissue in the OVX rats compared to the normal rats. Transmission electron microscopy (TEM) revealed thickening of the adipocyte membrane of the OVXC rats. KF and ERT-treatment were demonstrated to cause adipocytes membranes' breakage as shown by the fragmentation of the collagen bands. Conclusion: Results implied a possible role for Labisia pumila var alata in modulating postmenopausal adiposity through the initiation of the lipolysis process in adipose tissue.
Kacip Fatimah also known as Labisia pumila (Myrsinaceae), is a traditional herbal medicine with a long history in the Malay community. It has been used by many generations of Malay women to induce and facilitate childbirth as well as a post-partum medicine. We tested the genotoxic potential of Kacip Fatimah in bone marrow cells obtained from Sprague-Dawley rats using micronuclei formation as the toxicological endpoints. Five groups of five male rats each were administered orally for two consecutive days with doses of 100, 700 and 2000 mg/kg body weight of Kacip Fatimah extract dissolved in distilled water. Micronucleus preparation was obtained from bone marrow cells of the animals following standard protocols. No statistically significant increase in micronucleated polychromatic erythrocytes (MNPCEs) was observed at any dose level and sacrifice/harvest time point (24, 48 and 72h). However, a significant decrease in polychromatic erythrocytes/normochromatic erythrocytes (PCE:NCE) ratio was observed from the highest dose level (2000 mg/kg of body weight) at 48h harvest time point. In this study, we investigated the effect of Kacip Fatimah on mammalian bone marrow cells using micronuclei formation to assess the genotoxicity of the herb.
The molecular events underlying skin aging have been carefully studied. Signaling pathways induced by UV light lead to sequential events culminating in an increase in collagen degradation and a decrease in collagen formation. This article reviews the mechanisms underlying these pathways and discusses how various therapeutic modalities intervene at specific sites in the pathways.