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Potential Role of Labisia pumila in the Prevention and Treatment of Chronic Diseases

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Abstract Labisia pumila (Myrsinaceae), also called Kacip Fatimah, is a herbal medicine that has been widely used in South East Asian communities mainly for women’s health. The extensive use of this plant has led to many speculations and studies on its phytoestrogenic properties. This review highlights the studies that involved Labisia pumila, which include phytochemical profiling and its safety. In addition, we also look into its use as an alternative to hormonal therapy in postmenopausal women, and its role in cardiovascular protection and osteoporosis. Further studies are needed to highlight the potential benefits of this plant in promoting advantageous health properties. Keywords: Labisia pumila, postmenopausal, safety profiles, cardiovascular risk factors and phytoestrogen
Journal of Food Research; Vol. 2, No. 4; 2013
ISSN 1927-0887 E-ISSN 1927-0895
Published by Canadian Center of Science and Education
55
Potential Role of Labisia pumila in the Prevention and Treatment of
Chronic Diseases
Nik Hazlina Nik Hussain1 & Azidah Abdul Kadir1
1 School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Malaysia
Correspondence: Nik Hazlina Nik Hussain, Women’s Health Development Unit, School of Medical Sciences,
Health Campus, Universiti Sains Malaysia, Malaysia. E-mail: hazlina2006@yahoo.com
Received: June 5, 2013 Accepted: June 25, 2013 Online Published: June 27, 2013
doi:10.5539/jfr.v2n4p55 URL: http://dx.doi.org/10.5539/jfr.v2n4p55
Abstract
Labisia pumila (Myrsinaceae), also called Kacip Fatimah, is a herbal medicine that has been widely used in
South East Asian communities mainly for women’s health. The extensive use of this plant has led to many
speculations and studies on its phytoestrogenic properties. This review highlights the studies that involved
Labisia pumila, which include phytochemical profiling and its safety. In addition, we also look into its use as an
alternative to hormonal therapy in postmenopausal women, and its role in cardiovascular protection and
osteoporosis. Further studies are needed to highlight the potential benefits of this plant in promoting
advantageous health properties.
Keywords: Labisia pumila, postmenopausal, safety profiles, cardiovascular risk factors and phytoestrogen
1. Introduction
Chronic diseases are diseases of long duration and generally slow in progression. These include diseases such as
heart disease, stroke, cancer, chronic respiratory diseases and diabetes. They are by far the leading causes of
mortality and morbidity in the world. Plants have been one of the sources of medicine to treat various illnesses
since ancient time. Currently in Malaysia, it was estimated that 2,000 species of plants with medicinal and
therapeutic properties have been identified. A study on herbal drug use among multi-ethnic patients in Malaysia
found that about 63% of patients used herbal medicine (Saw et al., 2006). Subsequently, more plants have been
investigated for their phytochemical properties.
In Malaysia, among the famous herbs that have been widely used and studied are Labisia pumila (Kacip
Fatimah), Eurycoma longifolia Jack (Tongkat Ali), Orthosiphon stamineus (Misai Kucing), Quercus infectoria
(Manjakani) and Piper sarmentosum (daun Kaduk) (Nadia et al., 2012). Labisia pumila, a long known herb for
Malay women has received much attention since more than a decade ago. This review will be focusing on the
potential role of Labisia pumila in the management of chronic diseases.
Labisia pumila or popularly known in Malaysia as Kacip Fatimah, is a member of the small genus of slightly
woody plants of the family Myrsinaceae (Burkill, 1935). The locals identify it by the name as Selusuh Fatimah,
Rumput Siti Fatimah, Akar Fatimah, PokokPinggang, and Belangkas Hutan (Burkill, 1935; Rasadah & Zainon,
2003). There are at least four known varieties of Labisia pumila found in Malaysia. However, only three of them
are popularly used by the Malays, which are Labisia pumilavar. pumila, Labisia pumila var. alata and Labisia
pumila var. lanceolata (Stone, 1988). These plants have been utilized by many generations of Malay women.
The plants are usually boiled and the water-soluble extract is taken as a drink. In daily practice, it is used for the
general well-being and vitality of women, maintaining the figure and appearance, aiding in reducing symptoms
related to hormonal imbalance, and increasing libido in women (Burkill, 1935; Prosea, 2003; Wan, 2007; Runi,
2000). Its exclusive use by women has led to the belief that it exhibits (phyto)-estrogenic activity, contains
compounds with similar chemical structures to estrogens (Jamia et al., 2003) and therefore is able to relieve
menopausal symptoms (Bhatena & Velasquez, 2002).
There are numerous scientific researches on L. pumila carried out to identify the bioactive phytochemicals that
contribute to the pharmacological properties. Recently, phyto-chemical studies identified flavonoid, isoflavonoid
and phenolic compounds as bioactive ingredients in leaf extracts of the three varieties of L. Pumila (Chua, 2011;
Karimi et al., 2011; Karimi & Jaafar, 2011). Flavonoids mainly apigenin, kaempferol, rutin and myricetin were
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identified from L. pumila var alata, along with phenolic contents such as gallic acid, pyrogallol and caffeic acid
(Karimi et al., 2011; Karimi & Jaafar, 2011).
A genotoxicity assessment of the herb was carried out using in vivo rodent micronucleus assay where at doses of
up to 2000 mg/kg body weight, L. pumila extract demonstrated no mutagenic potency (Zaizuhana et al., 2006).
Clinical trial on human for 6 months duration also has been done to show that this plant extract is safe in terms
of biochemical and haematological profiles (Hussain et al., 2009). Long term study is needed to assess the
complication of the use of these extract that may happen after longer periods of use.
2. Phytoestrogenic Property of Labisia pumila for Estrogen Replacement Therapy
Women now live more than one third of their life in the menopausal years (Kinlay et al., 1992). The increase in
life expectancy in women will predispose them to suffer from morbidities due to the loss of ovarian function
(Kinlay et al., 1992). Menopause is associated with chronic conditions such as increased cardiovascular risk,
osteoporosis, declined cognitive function and other problems linked with obesity (Kinlay et al., 1992).
Postmenopausal women may also experience vasomotor symptoms such as hot flushes, night sweats, insomnia,
vaginal dryness and urinary symptoms (Kinlay et al., 1992). The current treatment for postmenopausal
symptoms and diseases related to estrogen deficiency is hormone replacement therapy. However, recent studies
have changed this practice due to adverse effects as regards to hormone replacement therapy (HRT) (WHI, 2002).
For this reason, there is tremendous growth in the use of alternative therapies to relieve postmenopausal
symptoms.
In regard to L. pumila, Malaysian women extensively use this plant especially in assisting childbirth and during
postpartum period. This practice has led to the speculation that this plant exhibit (phyto)-estrogenic activity, a
compound that has similar effect with estrogen hormone (Turner et al., 2007). It was also postulated that this
plant have certain effect either they are full estrogen agonists or antagonist or partial agonist. Theoretically, this
plant extracts act by binding to the estrogen receptors and exerting weaker estrogenic effect compared to the
female hormones (IFST, 2001). Researches have shown that Labisia pumila acts as selective estrogen receptor
modulators (SERMs) which is a partial antagonist (Malaysian Herbal Medicine Research Center, 2011). In view
of the initial evidence that it is a phytoestrogen, it is postulated that this plant have a beneficial effect to the
postmenopausal women in terms of its positive effects on the lipids and hormonal profile.
Report had showed that the plant displayed a non-significant response to in vitro estrogen activity (Houghton et
al., 1999). A study by Husniza et al. showed that the water extracts of L. pumila were able to displace estradiol
binding to antibodies raised against estradiol, making it similar to other estrogens such as estrone and estradiol
(Husniza, 2002). In other study, Jamal et al. found that ethanol extract of Labisia pumila exhibited a weak
estrogenic activity in an in vitro assay in Ishikawa cells, but none was observed from the leaf extract. However,
he could not find the same activity in the aqueous extract from the same roots (Jamal al., 2003).
In an animal study done in ovariectomized rats, it showed that this plant extract was able to increase estradiol
level and suppress Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) levels which resemble
the effect of estrogen therapy (Wahab et al., 2011).
The most trustworthy evidence and the best scientific design for herbal efficacy should come from trials on
human and randomized, double blind, placebo controlled trials in order to guarantee the most dependable results.
However, there are still limited trials conducted in human to support the efficacy of the herbal products.
There is a randomized, double blind placebo- controlled study done to assess the effects of water extract of
Labisia pumila var alata on postmenopausal women (Azidah et al., 2012). In the study, there was no significant
difference in terms of menopausal symptoms, cardiovascular profile (blood pressure, body mass index (BMI),
waist circumference, fasting blood sugar and hormonal profile (FSH, LH and estradiol) between the placebo and
active groups on Labisia pumila (Azidah et al., 2012). However, in that study, there was significant reduction of
triglyceride levels in the active group at 6 months of treatment compare to placebo (Azidah et al., 2012). The
study showed that Labisia pumila did not have any effects on the hormonal profile in the postmenopausal
women; however in animal model study it showed that Labisia pumila takes longer time (almost twice) to the
time needed by estrogen to exert its effects on the female hormones. Therefore, a longer study would be
beneficial. Currently, there is still inadequate evidence to show that Labisia pumila has estrogenic activities or
could work as phytoestrogen. Therefore, it is too early to recommend the use of Labisia pumila over
conventional hormone replacement therapy. There was also no evidence to conclude that this plant could reduce
menopausal symptoms.
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3. Cardiovascular Effect of Labisia pumila
Menopause is known to have a link with weight gain and adiposity due to estrogen deficiency, and the theory
behind this is that adipocytes increased in size followed by increased in number (Kinlay et al., 1992). The
increased in adiposity is associated with cardiovascular risks. Since Labisia pumila is thought to behave as
phytoestrogen, the actions of this plant with adiposity have been studied. Animal model of ovariectomized rats
showed that there is an increased in size and vasculature of adipose tissue observed by using transmission
electron microscope (Ayida et al., 2006). Thickening of the adipocyte membrane were also observed in the
ovariectomized rats. However, it was found that in rats given Labisia pumila and estrogen treatment, there are
fragmentation of collagen fibres that hold the adipocytes together. Hence, in this study it showed that there is
possible role for Labisia pumila in modulating postmenopausal adiposity through lipolysis process in adipose
tissue (Ayida et al., 2006).
Aorta stiffness is associated with atherosclerosis and it worsens arterial function. Indirectly, it is one of the
factors associated with cardiovascular risk (Boutouyrie et al., 2002). Thus, aortic stiffness is presented as a
useful measure of cardiovascular health, which has predictive value in cardiovascular morbidity and mortality
(Boutouyrie et al., 2002). In the animal model, it has been showed that the water extract of Labisia pumila has
the capability in maintaining the elastic lamellar architecture of aortae in the ovariectomized rats in a manner
comparable to that of the normal rats (Boutouyrie et al., 2002). This result also indicates that Labisia pumila
extract might be able to modulate postmenopausal cardiovascular risk but probably not through the mechanism
of phytoestrogen (Boutouyrie et al., 2002).
In a separate animal study done by Fazliana et al., it has been shown that both estrogen replacement therapy and
Labisia pumila were able to suppress weight gain in ovariectomized rats by increasing leptin, decreasing resistin
levels and expression of the adipokines in adipose tissues (Fazliana et al., 2009). The study by Fazliana et al.
showed that Labisia pumila appears to show promising results in regulating body weight through the secretion of
leptin and thus might affect insulin sensitivity (Fazliana et al., 2009). The effect of Labisia pumila in polycystic
ovarian syndrome (PCOS) rats induced with dihydrotestosterone was also studied (Manneras et al., 2010) based
on the results by the study done by Fazliana et al. (Fazliana et al., 2009). PCOS is an endocrine and metabolic
disorder that is associated with obesity, insulin resistance and type 2 diabetes. In the study, it showed that PCOS
induced rats treated with Labisia pumila has increased insulin sensitivity without influencing weight gain or
adiposity. There was no difference in body fat or body weight between Labisia pumila treated rats and controls.
After treatment with Labisia pumila, the Polycystic Ovarian Syndrome (PCOS) rats also had decreased levels of
Total Cholesterol and triglyceride levels. However, there were no changes seen in High Density Lipoprotein - C
(HDL-C) and Low Density Lipoprotein- C (LDL-C) levels (Manneras et al., 2010). A study done by Azidah et al
in human trials also showed that there was beneficial effect of Labisia pumilavar alata in reducing triglyceride
level in postmenopausal women (Azidah et al., 2012). The extract was derived from the leaves of the plant and
the marker compound is 3,4, 5-trihydroxybenzoic acid (Azidah et al., 2012). However, the mechanism
underlying the lowering of triglyceride level is unclear. Human trial also showed that there were no significant
changes in terms of body weight, BMI and waist circumference between the group treated with Labisia pumila
and placebo (Azidah et al., 2012).
4. Role of Labisia pumila in Prevention of Osteoporosis
Osteoporosis is defined as a systemic skeletal disease characterized by low bone mass and micro-architectural
deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture
(Consensus Development Conference, 1993). Osteoporosis related fractures have been recognized as a major
health problem, particularly in the elderly. Postmenopausal women are at higher risk to develop osteoporosis due
to the decline in estrogen level during menopause. The decline in estrogen level leads to a decline in bone
formation and an increase in bone resorption activity.
Estrogen Replacement therapy (ERT) is effective for prevention and treatment of postmenopausal osteoporosis
(CPG, 2012). ERT reduces the risk of spine, hip and other osteoporotic fractures by 33-40% (Cauley et al., 2003;
The WHI Initiative Steering Committee, 2004). However, Women’s Health Initiative study found that there are
adverse effects of estrogen replacement therapy (ERT) which increases the risk of breast cancer, stroke and
thromboembolic disease. Due to this effect there are many controversial on the use of ERT.
Based on the possible estrogenic activities of Labisia pumila, it has been considered as an alternative to replace
estrogen for the treatment and prevention of postmenopausal osteoporosis (IFST, 2001; Malaysian Herbal
Medicine Research Center, 2011; Husniza, 2002). Nazrun et al. conducted a study to determine the effects of
Labisia pumila on osteoporosis using ovariectomised rats as the model of postmenopausal osteoporosis (Nazrun
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et al., 2011). Bone biomarkers were measured as indicators of bone formation and resorption, while bone
calcium content was used as an indicator of bone loss in this model (Nazrun et al., 2011). The effects of Labisia
pumila were compared to a group of ovariectomised rats given ERT as the gold standard of treatment (Nazrun et
al., 2011). In the study, it showed that the supplementation Labisia pumila to ovariectomised rats was able to
prevent the changes in bone biochemical markers but failed to prevent the bone calcium loss induced by
ovariectomy (Nazrun et al., 2011).
The effects of Labisia pumila on the bone of ovariectomised rats was measured with histomorphometric
parameters in another animal study (Fathilah et al., 2012a). It showed that supplementation of Labisia pumila to
ovariectomized rats could prevent these osteoporotic changes, as effective as ERT (Fathilah et al., 2012a).
In a different study by Fathilah et al., bone biomechanical strength was assessed to see the effect of Labisia
pumila in ovariectomized rats (Fathilah et al., 2012b). She demonstrated that Labisia pumila supplementation to
the ovariectomized rats improved the femoral strength and may be as effective as ERT in preventing fractures
due to postmenopausal osteoporosis (Fathilah et al., 2012b). Based on previous studies, there are a few
postulated mechanisms of how Labisia pumila worksin prevention and treatment of osteoporosis. It was
postulated that it contains tripertence saponins, which were thought to interact with estrogen receptors (Bharathi
et al., 2011). It was also postulated that this plant works through its antioxidative properties as those exhibits
through beta carotene and flavonoids (Bharathi et al., 2011). Inhibition of cytokine called Tumour Necrosis
factor-α (TNF- α) may be another possible way (Choi et al., 2010). TNF- α is a bone resorbing cytokine that
promotes bone resorption by activating mature osteoclasts or by stimulating proliferation and differentiation of
osteoclasts (Lerner & Ohlin, 1993). Labisia pumila has been shown to markedly inhibit theTNF- α production in
an experimental study (Choi et al., 2010). As a conclusion, Labisia pumila has the potential to prevent
postmenopausal osteoporosis.
5. Future Studies
Recent studies have shown that this plants has anti-oxidant and anti inflammatory properties. The anti-oxidant
property is due to the presence of the phenolic compounds, including phenolic acids and flavonoids (Chua et al.,
2011; Karimi et al., 2011; Karimi & Jaafar, 2011). The phenolic compounds includeflavonoids (quercetin,
myricetin, kaempferol and catechin) and other detected constituents (ascorbic acids, tocopherols, carotene and
carotenoids) (Karimi et al., 2011). Studies have showed that the leaves of the plant from all the varieties showed
higher antioxidant activities compared to the roots and stems. The presence of these anti-oxidant properties could
be used to treat diseases involving oxidative stress such as cancer and certain aspect of cardiovascular disease.
This plant also has been shown to have anti-inflammatory activity. Experimental findings showed that this plant
extract has the ability to markedly inhibit TNF- α production and the expression of cyclooxygenase (COX)-2.
Cox-2 is an enzyme that is responsible for the production of mediators involved in inflammation.
Pharmacological inhibition of COX-2 can provide relief from the symptoms of inflammation and pain thus can
be used in the treatment of chronic disease such as arthritis or asthma. In-vivo study has shown that this plant
extract exhibited bronchodilator activity and inhibition of the inflammatory mediators involved in asthma
(Patrick et al., 2012).
6. Conclusion
Many studies have been done on the Asian plant-based or herbal medicines, and Labisia pumila is one of the
herbal plant that has been extensively studied. The support of efficacy of botanical products can be derived from
animal trials. However, animals may process herbal products differently from humans, thus, results are not
necessarily reliable. It is important that the plant materials of herbal medicines being clinically evaluated in
randomised double blind studies to examine the evidence-based benefits to consumers. Publication on Labisia
pumila from a single well planned human trial had been done and is enough to launch this plant into medical
limelight (Azidah et al., 2012). However, further studies in human are needed to assess the full potential of this
product and not to only depend on animal studies. As for now, there are sizeable evidences to suggest that
Labisia pumila is an alternative to be used as phytoestrogen, prevention and treatment of cardiovascular disease
and also osteoporosis.
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... Pharmacological studies have shown that L. pumila contains flavonoids and phenolic compounds [2], carotenoids, ascorbic acids, alkenyl and benzoquinone which have been reported to possess antioxidant, anti-inflammatory and anti-cancer properties [3]. The antioxidant property is useful to treat disease involving oxidative stress, such as cardiovascular disease [4]. L. pumila exhibited phytoestrogen activity and has benefit in modulating post-menopausal cardiovascular risk [5]. ...
... Endothelium-intact aortic rings were incubated with methylene blue (10 μM) and 1H- [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 μM) for 20 min before precontraction with PE (1 μM), respectively. Cumulative concentrations of WF-LPWE (0.01 μg -3.0 mg/mL) were added into the chamber to determine the concentration-relaxation response curve. ...
... Aortic rings were incubated with methylene blue and there was no significant inhibitory effect on WF-LPWE induced-relaxation had been observed. Since methylene blue is a non-selective inhibitor of NO-sGC pathway of vascular relaxation [10], we explored further by using 1H- [1,2,4]oxadiazolo [4,3-a] quinoxalin-1-one (ODQ), a selective inhibitor of sGC, in order to investigate the NO-independent direct involvement of sGC/cyclic GMP Fig. 2. Effect of WF-LPWE on rat aortic rings pre-incubated with the cGMP inhibitor, methylene blue (A) and the selective cGMP inhibitor, ODQ (B). Comparison between groups was performed by two-way ANOVA followed by Bonferroni's post hoc test. ...
Article
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Introduction Labisia pumila has been reported to possess activities including antioxidant, anti-aging and anti-cancer but there is no report on its vasorelaxant effects. Objective This study aims to fractionate water extract of Labisia pumila, identify the compound(s) involved and elucidate the possible mechanism(s) of its vasorelaxant effects. Methods Water extract of Labisia pumila was subjected to liquid-liquid extraction to obtain ethyl acetate, n-butanol and water fractions. In SHR aortic ring preparations, water fraction (WF-LPWE) was established as the most potent fraction for vasorelaxation. The pharmacological mechanisms of the vasorelaxant effect of WF-LPWE were investigated with and without the presence of various inhibitors. The cumulative dose-response curves of potassium chloride (KCl)-induced contractions were conducted to study the possible mechanisms of WF-LPWE in reducing vasoconstriction. Results WF-LPWE produced dose-dependent vasorelaxant effect in endothelium-denuded aortic ring and showed non-competitive inhibition of dose-response curves of PE-induced contraction, and at its higher concentrations reduced KCl-induced contraction. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) significantly inhibited vasorelaxant effect of WF-LPWE. WF-LPWE significantly reduced the release of intracellular calcium ion (Ca²⁺) from the intracellular stores and suppressed the calcium chloride (CaCal2)-induced contraction. Nω-nitro-L-arginine methyl ester (L-NAME), methylene blue, indomethacin and atropine did not influence the vasorelaxant effects of WF-LPWE. Conclusion WF-LPWE exerts its vasorelaxant effect independently of endothelium and possibly by inhibiting the release of calcium from intracellular calcium stores, receptor-operated calcium channels and formation of inositol 1,4,5- triphosphate. WF-LPWE vasorelaxant effect may also mediated via nitric oxide-independent direct involvement of soluble guanylate cyclase (sGC)/ cyclic guanosine monophosphate (cGMP) pathways.
... Regarding the research location, 27 studies were spread over 2 countries. The studies were from each of the following countries: Twenty-one studies were conducted in Malaysia 1,5,6,7,8,10,11,12,13,15,16,17,18,21,22,23,24,25,26,27,28,and Indonesia 3,4,9,14,19,20. See Figure 1 for details on study settings. ...
... Hussain., et al (2013) reported that a study was conducted on 63 pre and postmenopausal healthy women, the results showed that subjects given fatimah grass experienced an increase in concentration or memory. Indicates that the safety profile is normal and improvements are seen in cardiovascular parameters 17 Phytoestrogenic effects: fatimah grass is believed to have phytoestrogens that function as the main producer of sex hormones in women, especially the hormone estrogen. Phytoestrogens can be either isoflavones, or flavonoids and coumestans. ...
Article
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Introduction: Traditionally, fatimah grass water bath is consumed to help induce labor, but until now there is not enough scientific evidence regarding its safety. Although there are many studies that explain the benefits of Fatimah grass for the female life cycle. For this reason, understanding the benefits of Fatimah grass scientifically for women's life cycles is very important. Methods: The author searches for articles from the databases: PubMed, Scient Direct, MDPI, Google Schoolar, Research Gate, and Semantic Scholar published from January 2007 to May 2021 to find out potential studies that are appropriate and meet the inclusion criteria requirements. From the six electronic databases, 47 articles were identified and reduced to 27 relevant articles. The authors summarize the sample size, study design, research results, conclusions, and recommendations. The keywords used are: 'Fatimah grass' or 'kacip Fatimah' or 'Labisia pumila' or 'Benefits of Labisia Pumila For Women' or 'fatimah grass and its benefits' Results: The authors identified 27 relevant articles that were significantly related to the content of phytochemicals that are beneficial to health, such as the content of flavonoid compounds, saponins, phenolics, phytoestrogenics or natural estrogen benzoquinones, alkenyls.
... Selain diketahui mempunyai potensi dalam rawatan tradisi, L. pumila juga digunakan secara meluas oleh para wanita daripada kalangan etnik Melayu sebagai makanan tambahan (Hussain & Kadir 2013). Menurut Abdullah et al. (2013), kandungan ekstrak daun dan akar L. pumila mempunyai sebatian bioaktif yang tinggi seperti sebatian alkil, saponins, flavonoid, terbitan benzokuinon, isoflavonoid dan asid fenol. ...
Article
Kajian ini melaporkan kesan rawatan bagi dua sediaan krim yang masing-masing mengandungi 1% ekstrak air bagi dua varieti L. pumila iaitu var. alata dan var. pumila terhadap penyembuhan luka melalui uji kaji menggunakan model tikus dan model kulit manusia 3D EpidermFull Thickness (Mat Tek, USA) melalui penentuan penutupan luka dan analisis pengekspresan gen terpilih bagi mekanisme penyembuhan luka tisu kulit (gen TGF-1, IL-6, EGF, CBL dan COL3A1 untuk tikus; gen IL-10, TGFb-1 dan COL3A1 untuk manusia) menggunakan pendekatan tindak balas berantai polimerase kuantitatif (qPCR). Selepas rawatan, kawasan luka pada kulit bahagian atas badan tikus diukur pada hari ke-2, ke-5 dan ke-8, serta disampel untuk analisis pengekspresan gen. Bagi uji kaji in vitro tisu binaan kulit manusia, perubahan terhadap setiap lapisan luka yang dibuat pada binaan tisu kulit tersebut dicerap melalui pemerhatian histologi dan dianalisis bagi profil pengekspresan gen berdasarkan sela hari ke-2, ke-5 dan ke-6. Rawatan krim ekstrak air L. pumilakedua-dua varieti didapati hanya berkesan membantu penutupan luka bagi tikus betina iaitu 79.58% bagi var. alata pada hari ke-5 rawatan dan 75.97 dan 95.04% bagi var. pumila masing-masing pada hari ke-5 dan ke-8 rawatan tetapi tidak berkesan kepada tikus jantan. Namun begitu, dari segi tempoh penutupan luka lengkap, didapati kesemua rawatan menunjukkan luka ditutup lebih cepat berbanding kawalan (17 hari) iaitu di antara 12 sehingga 13 hari. Analisis gen bagi sampel luka tikus menunjukkan peningkatan aras gen hanya melibatkan gen IL-6 untuk tikus jantan yang dirawat dengan L. pumilavar. alata iaitu sebanyak 1722784 salinan mRNA pada hari ke-2 rawatan, gen CBL untuk tikus betina yang dirawat dengan L. pumilavar. alata berjumlah 46137 salinan mRNA pada hari ke-5, dan gen COL3A1 bagi rawatan L. pumilavar. alata untuk kedua-dua kumpulan jantina, iaitu masing-masing 2.44×108 salinan mRNA (betina) dan 3.91×108 salinan mRNA (jantan). Berdasarkan pemerhatian histologi sampel luka model kulit manusia 3D, rawatan kedua-dua varieti L. pumila menunjukkan kesan pengunjuran sel daripada kawasan luka pertumbuhan tetapi analisis gen tidak menunjukkan perubahan yang tidak signifikan terhadap gen kajian. Secara keseluruhannya, hasil kajian ini dapat menunjukkan potensi L. pumiladalam penyembuhan luka tetapi perlu dimantapkan lagi pada masa hadapan melalui strategi uji kaji in vivo dan in vitro yang lebih optimum.
... According to chemical drug regulations, the allowable variation in the release rate is 10% of the reported amount of herbal substance or herbal preparation. 16 In the case of controlled-release herbal medical preparations in which the active components have little or no synergistic response to pharmaceutical activity, in vitro dissolution profiles and in vivo performances are thought to be associated. 17 Physical and chemical qualities, on the other hand, must be considered because they will affect the rate of release of the active component. ...
Article
Full-text available
Herbal supplements often incorporate herb mixtures to prevent clumping and to control the release of medicinal compounds and mask bitter tastes. Medium solution and time affected the release rate of active components. In this study, active compounds from herbal supplements were examined for their release behavior in different media [0.1 M HCl, 30% EtOH, acetate buffer (pH 4.8) and phosphate buffer pH 6.3] at different times upon exposure to different media using a dissolution equipment. An aliquot was collected every 15 minutes for a total of 120 minutes. Analyses of reverse-phase HPLC were used to determine the amount of gallic acid and eurycomanone present in the samples. Reference standards for the study were Kacip Fatimah (KV) and Tongkat Ali (TS). The results demonstrate that the release behaviour of all samples varied, however samples labelled KA and TA displayed the maximum release rate of galic acid and eurycomanone in an acidic medium (0.1 M HCl) at 30 minutes. Meanwhile, the sample labelled as TC had the lowest rate of Eurycomanone emission. The highest gallic acid concentration was found in sample KA and the highest Eurycomanone level was found in sample TA. For both groups ranging from 20 to 60 minutes, the acidic media demonstrated the best results for assessing the release behavior of active components. Data on correlations showed a monotone relationship.
... 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). As secondary metabolites, phenolic compounds have antioxidant properties, quickly absorbed by the digestive system, and offer numerous anti-aging properties. ...
Article
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.
... Furthermore, the growing interests in LP on phytoestrogen effects have shown potential benefits on the women reproductive performance. This phytoestrogen in LP acted as a pair of hydroxyl group and a phenolic ring which function to bind estrogen receptors [8]. Thus, the binding process of phytoestrogen to estrogen receptor may exert the estrogenic and antiestrogenic effects [9]. ...
Article
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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.
... Petri plates and pipette were washed with distilled water and dried. Petri plates were then placed in an oven (Memmert, Germany) at 180 0 C for 2 hr [7]. ...
Article
: Lyophilized from plants extract is a process to prolong the amounts of phytochemicals in a solid form. The bioactive compound in LP, which is Gallic acid should be stable and bioavailable during the downstream processing such as drying process in order to achieve its optimum health benefits. Therefore, this study focuses on the impact of lyophilize methods such as spray drying followed by granulator method in order to determine the stability of bioactive compound in LP during drying and storage. After the powdered produce, it will test on the model of human digestion (dissolution study) either the amounts of phytochemicals still remain stable. Finally, shelf-life quality analysis and the dissolution rate (capsule size 0 and 1) were carried out. The results obtained show the methods employed in this study can be used for analysis of quality content and dissolution tests of LP capsules. For LB in shelf-life quality study, parameters for appearance and TYMC showed no significant difference after 3 months. For pH, the slight decrease in pH level will increase the number of TAMC in powder form. Compared to granule form, the pH level more consistent and the number of TAMC also in a control condition. The dissolution of capsules containing powder and granulated of LP showed a high percentage of bioactive compound released into the dissolution medium, although the bioactive compound content of herbal products (capsule size 1) was found to be half that of capsules size 0. Through observation for both capsules size content of LP, the maximum dissolution was achieved after 100 min.
Poster
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(Introduction) Labisia pumila var. alata has intensively consumed and investigated to reduce menopausal symptoms. It has potential to solve problems related to hormone replacement therapy (HRT) in menopause women. In contrast to the HRT, which is believed to develop cancer, the plant extract also exhibited anticancer effects by inhibiting proliferation of cancer cell lines. Mechanism of the extract in displaying both antiprolirative effects and reducing menopausal syndrome is hypothesised through the binding activity on estrogen receptor and yet to be observed in the study. (Method) Two estrogen receptor (ER)-positive cell lines, human breast adenocarcinoma cell lines (MCF-7) and human normal epithelial breast cell lines (MCF-10A) were treated with several concentrations of Labisia pumila var. alata aqueous extract using methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. The cells were then incubated for 72 hours, either with or without ER-antagonist (ICI 182,780). 17 beta-estradiol (E2) and phosphate buffer saline (PBS) were used as a positive and negative control respectively. (Result) The plant extract significantly increased the proliferation of MCF-10A cell at concentration of 25%, 50%, and 100% of 1μg/mL (p < 0.001). In contrast, it significantly exhibited antiproliferative effect to MCF-7 cell by inhibiting the cell growth at 50% and 100% of 1μg/mL (p < 0.001) with the IC50 value of 94.42. E2 displayed significant proliferation effects on both cell lines. Meanwhile, ER-antagonist blocked both cell proliferation induced by E2 and Labisia pumila var. alata respectively indicating estrogen receptor involved in the mechanism. Interestingly, estrogen receptor binding activity by the plant extract in different cell lines demonstrated divergent effects i.e. inhibited cancer cell growth (MCF7) but increased proliferation of normal cell (MCF10A). Details of the mechanism however required further observation. (Conclusion) Labisia pumila var. alata aqueous extract has potential to replace current treatment for menopausal symptoms. Binding activity of estrogen receptor by the plant extract show selectivity effects, which is crucial in establishing an effective and safe treatment to the menopause women.
Conference Paper
Dissolution behaviour of active ingredients has an important effect on their pharmacological function. In reality, predicting their bioavailability is considered to be one of the most critical quality control tests. In this study dissolution behaviour was carried out using model independent included fit factors which comply with the FDA guidelines. The parameters of test ratio are the fit factors which include difference factor (f1) and similar factor (f2). These parameters were employed to compare in-vitro dissolution behaviour which were tested using different media; 0.1 M HCl, 30% EtOH, acetate buffer (pH 4.8) and phosphate buffer pH 6.8. Three brands of Kacip Fatimah (I,II,III) were compared and brands V is a pure Kacip Fatimah used as a benchmark. The active ingredients namely galic acid in all samples was also quantified using a reverse-phase HPLC. Results obtained indicate that the dissolution efficiency for active ingredients for all brands were not significantly different however, gallic acid in all brands showed the highest solubility in 0.1 M HCl compared to the other three media used. Meanwhile, product I showed the highest amount of galic acid released compared to product II and product III. Using fit factors, only brands 1 and brand V showed similarity in results. Contents of the Gallic acid for brand I and brand V analysed via HPLC were the highest. Both results from in-vitro dissolution and HPLC test could be applied for quality control of gallic acid for Kacip Fatimah as herbal medicinal products available in markets.
Article
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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.
Article
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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.
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This present study was aimed at evaluating the anti-asthmatic effects of crude dichloromethane leaf extract (DELP) (100, 300 and 500 mg/kg), from Labisia pumila (LP). In vivo experiment was done by subcutaneous injection of 0.1ml of 1% histamine, serotonin and bradykinin, dissolved in saline, into the sub-plantar of the experimental rat model to induce edema and 0.2% of histamine and acetylcholine aerosol was used in a transparent glass box using nebulizer. The in vitro anti-histaminergic, anti-cholinergic anti-serotonin and anti-bradykinin studies were examined by using guinea pig ileum (GPI) in an organ bath containing Krebs-Henseleit solution (pH 7.4) gassed with 95% O and 5% CO and maintained at 37°C. Phytochemical 2 2 screening was done using simple biochemical colorimetric test. The result showed a concentration-dependent inhibition of paw edema induced by histamine, serotonin and bradykinin and bronchoconstriction induced by histamine and acetylcholine. The extracts also inhibited the contraction induced by histamine, acetylcholine, serotonin and bradykinin in GPI. Preliminary phytochemical screening revealed the presence of flavonoids, steroids, saponins, alkaloids and tannins. The present study confirmed that the DELP exhibited bronchodilator activity and inhibited actions of the inflammatory mediators involved in asthma.
Article
Context Despite decades of use and considerable research, the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain. Objective To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States. Design, Setting, and Participants A randomized, double-blind, placebo-controlled disease prevention trial (the estrogen-alone component of the Women's Health Initiative [WHI]) conducted in 40 US clinical centers beginning in 1993. Enrolled were 10 739 postmenopausal women, aged 50-79 years, with prior hysterectomy, including 23% of minority race/ethnicity. Intervention Women were randomly assigned to receive either 0.625 mg/d of conjugated equine estrogen (CEE) or placebo. Main Outcome Measures The primary outcome was coronary heart disease (CHD) incidence (nonfatal myocardial infarction or CHD death). Invasive breast cancer incidence was the primary safety outcome. A global index of risks and benefits, including these primary outcomes plus stroke, pulmonary embolism (PE), colorectal cancer, hip fracture, and deaths from other causes, was used for summarizing overall effects. Results In February 2004, after reviewing data through November 30, 2003, the National Institutes of Health (NIH) decided to end the intervention phase of the trial early. Estimated hazard ratios (HRs) (95% confidence intervals [CIs]) for CEE vs placebo for the major clinical outcomes available through February 29, 2004 (average follow-up 6.8 years), were: CHD, 0.91 (0.75-1.12) with 376 cases; breast cancer, 0.77 (0.59-1.01) with 218 cases; stroke, 1.39 (1.10-1.77) with 276 cases; PE, 1.34 (0.87-2.06) with 85 cases; colorectal cancer, 1.08 (0.75-1.55) with 119 cases; and hip fracture, 0.61 (0.41-0.91) with 102 cases. Corresponding results for composite outcomes were: total cardiovascular disease, 1.12 (1.01-1.24); total cancer, 0.93 (0.81-1.07); total fractures, 0.70 (0.63-0.79); total mortality, 1.04 (0.88-1.22), and the global index, 1.01 (0.91-1.12). For the outcomes significantly affected by CEE, there was an absolute excess risk of 12 additional strokes per 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years. The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years. Conclusions The use of CEE increases the risk of stroke, decreases the risk of hip fracture, and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years. A possible reduction in breast cancer risk requires further investigation. The burden of incident disease events was equivalent in the CEE and placebo groups, indicating no overall benefit. Thus, CEE should not be recommended for chronic disease prevention in postmenopausal women.
Article
The major alkaloid of Sida acuta was shown to be cryptolepine which has antimicrobial activity against Proteus vulgaris. Thirty one samples of leaf, stem, root and seed of six Sida species collected from different localities in Sri Lanka were screened for the pharmacologically important alkaloids, cryptolepine, ephedrine, and vasicine. Medicinal applications of S. acuta and S. cordifolia have been related to dieir constituent alkaloids.