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Kacip Fatimah (Labisia Pumila)


Kacip Fatimah (Labisia Pumila)

Kacip Fatimah is traditionally used to maintain a healthy female reproductive system, to help tighten and lubricate, and to enhance sexual function. Kacip Fatimah is rich in phytoestrogen and isoflavones, that may ease menopausal symptoms. Oak Gall is rich in antioxidants and is traditionally used as postpartum care to tighten the reproductive system.

In Malaysia, Labisia pumila is popularly known locally as “Selusuh Fatimah” (literally Fatimah’s childbirth medicine) and “Kacip Fatimah” (Fatimah’s betel scissors).  The Labisia pumila roots were found to contain a benzoquinone derivative and mixture of resorcinol derivatives.  Based on partial characterizations of some isolated compounds, a pelagonidin derivative and long alkenyl chain were suggested to be present.


Traditional Uses:
Kacip Fatimah has been traditionally used by the Malay women for many generations in childbirth in inducing and eases delivery, as a post partum medication to help contract the birth channel, to regain body strength, regulate menstrual cycle and avoid painful or difficult menstration, and to alleviate menopausal symptoms.  The plant is traditionally boiled and the water extraction is taken as a drink.  Other traditional uses include treating dysentery, rheumatism, and gennoehoea.  It is also used as antiflatulence by helping to drive away and prevent the formation of gas.  The plant will also help to firm and tone the abdominal muscles.  Scientific studies have established that the medicinal properties and biological activities of Kacip Fatimah are due to the presence of phyto-estrogen (plant estrogen) that is naturally found in the plant. 

The Labisia pumila is a small herbaceous under shrub that roots from the stem. There are few leaves which point upwards. The root is tough and woody with long primary roots and few secondary roots.  The tip of the leaf is pointed with a base that is tapered or rather broad –rounded. The leaf has a slight odor and taste. The whole leaf is about 5-35cm long and 2-8cm wide finely toothed with numerous veins. It is of a dark green color on adaxial and lighter green on the abaxial.  Flowers on the shrub are very small, generally white or pink, in spike like panicle of small clusters. They range from 6-30 cm long with sepals, petals and stamens. The petals wrap around and enclose the stamens. The fruit are about .5cm in diameter and are either bright red or purple.

Microscopic Characteristics of the Root and Leaf:
Root:
The fairly abundant sclereid, which occur singly are elongated rectangular in outline and have thickened, pitted walls, Lumen maybe present or absent. Starch is sometimes present inside the large lumen. The abundant starch granules are simple and spherical to oval or sometimes rectangular in shape. No bilium or striation is present. The abundant sclereids are found in large fragments.

Leaf
The fragments of the upper epidermis are composed of cells with straight or slightly sinuous walls; stomata are absent.  The cells of the lower epidermis are rather more sinuous in outline, stomata are numerous, paracytic types. Both the upper and lower epidermis show numerous cicatrices where the peltate trichomes were attached: they appear as circular scars around which the epidermal cells occur in a radiating arrangement. The cicatric has an evenly thickened wall.  The fairly abundant trichomes from the leaf epidermis are two types; the peltate and covering trichomes, which are found scattered in the powder.  The covering trichomes are large with numerous thin walled cells radiating form the tip of the central axis. They show considerable variation in size and characteristic feature. The starch granules are not very abundant, they are found scattered but more usually are seen in masses in some of the parenchymatous cells. The granules are simple and spherical.  No bilum is present. The very occasional fibre is thick walled with irregular lumen and few pits.  They very few sclerid are found singly, individual cells are elongated and irregular in outline with moderately thickened walls and numerous pits. The prisms and cluster crystals of calcium oxalate are found scattered as well as associated with the fibre.  They vary in size and are sometimes quite large.

According to Stone (1998), there are three varieties of Kacip Fatimah tin Malaysia that exist. They are Labisia Pumila var., alata L. pumila var pumila and L.pumila var Ianceolata.  Each variety commands a different use and thus, it is important to ensure that the right variety is used in each case. Species identification is made difficult by the lack of difference in the leaves and petioles between var. alata and var. pumila.  Thus, an efficient method of authentification needs to be developed.
Preliminary studies had been conducted previously on Kacip Fatimah using the agro forestry approach involving intercropping of Kacip Fatimah under rubber and rattan (pers. Comm. Khozirah Shaari). However, the planting of Kacip Fatimah as a monoculture crop has yet to be studied but nonetheless, these studies showed that Kacip Fatimah was best propagated by seeds or root cuttings.  The plants thrive best in shady areas and non- waterlogged humus rich soil.

While being used by the indigenous people of Malay the Kacip Fatimah plant were usually boiled and the water soluble extract was taken as drink.  Interest had recently been shown in the herbal preparation to determine its mode of action and potential pharmacological application.  In the mean time commercial preparations as can drinks have been marketed without knowledge of the mode of action potential toxicity and side effects.  Because it is given to women post-partum, the possibility of it being a phyoestrogen was considered highly likely. An earlier in-vitro study using human endometrial adenocarcinoma cells of the Ishikawa Var 1 line showed that extract of the rots of L. pumila var alata exhibited a weak but specific estrogenic effect on the cells, resulting in enhanced secretion of alkaline phosphatase.  Recent studies in the Institute for Medical Research, the water extracts of Kacip Fatimah were able to displace estradiol binding to antibodies raised against estradiol, making it similar to other estrogens such as estrone and estriol.  Binding to estrogen receptors are being investigated.

 If they were phytoestrogens, the extract should also displace estradiol binding to the estrogen receptors.  If they were phytoestrogens, the extract should also displace estradiol binding to the estrogen receptors.  These phyestrogens will then have certain effects on the animals depending on whether they are full estrogen agonists, or antagonists, or partial agonists like clomiphene.  It is also possible that Kacip Fatimah acts as estrogen receptor modulators (SERMS) like Tamosifen or Raloxifene which is active at certain tissues only (4,5).  For example, Reloifene, being active only at the bones and lipids and not the breasts and uterus, commonly target tissues for estrogen action.

On the other hand, a lot more is know about estrogen receptors and how it causes effects at the cellular level. There are two isoforms, alpha(ERa) and beta (ERb) with 97% homology at the DNA binding site and 59% homology at the ligand binding site and more diverse at the or regions of the receptor molecule. Both isomers bind estradiol effectively and combine together or dimerized upon binding to estridol at the DNA binding site called the estrogen response element (ERE). The two isomers differ most at the so called Activation Function 1 and Activation Function 2 (AF1 and AF2) in the N- and C- terminus respectively. When E2 binds to the receptor binding domain, the AF2 is exposed and interacts with cofactors which help transmit the signal to the DNA (5, 6, and 7). Other mechanism of actions also exists in the tissues.  Rather than dimerize, the ER may actually bind to DHA bound protein complexes such as activating protein-1 and causes transrepression.

The gene expressions are controlled by the AP-1 sites.  The SERMS Raloxifene and Tamodifen for example stimulate the AP-1 with Era and ERb, while E2 stimulate the transcription only in presence of ERa. If ERb is present than the AP-1regulated transcription is repressed. (8) The E2 signaling action may also be modified by other signal transducing systems, independent of the ligand itself. Example, epidermal growth factor may cause phosporylation of the serine residues of the ligand itself. Example, epidermal growth factor may cause phosphorylation of the serine residues of the estrogen receptor at the AF-1 region and increase the transcription activity of the E2 ER binding (9).  The action of estrogens may also be modified by enzymes which may convert the active E2 to inactive Estriol or Estone similar to the enzyme 11-╬▓hydroxysteroid dyhydrogenase in the tissues which convert active cortisol to inactive cortisone (10,11).

In theory therefore, the phytoestrogens may have effects at the site of binding at both or one or other of the Estrogen receptor isomers, or act as an AF or as an activating protein or like EGF act by modulating the receptor molecule , or as a peripheral enzyme modulator such as 11 HSD.  Recent studies at the IMR gave some clues to its mode of action.  Given to normal female rats, the serum levels of estradiol E2 were unchanged but the level of free testosterone was significantly higher.  In castrated rats, there were no significant effects on the levels of E2 or testosterone. This preliminary data suggest that Kacip Fatimah does not increase estrogen levels but instead cause increases in free testosterone from the ovaries and it does not work without ovaries.  The increase in free testosterone may cause increase in libido and sexuality in women. This could be the effect that the women taking Kacip Fatimah are looking for!  It also means the herb should not work in menopausal women if the effect is via increased production of testosterone from the ovaries.  On the other hand, if it were to work by peripheral enzymes converting E2 to testosterone, then it is independent of the ovaries but still needs adequate levels of estradiol. In women without pituitaries the herb should not work unless the effect is like Clomiphene and causes increase in secretion of FDH from the pituitary, or by antagonizing the hormone. Inhibin produced by the ovaries at the pituitary level.

Clearly the potential effect of Kacip Fatimah as a SERM and any possible increase risk for breast or uterine cancer has to be considered.  The following pharmacological studies, in-vitro and in-vivo are being proposed to determine the possible mechanism of actions of KF, and the clinical trials (phase I, II, III) would evaluate the physiological effects of Kacip Fatimah in women and support the basic research being carried out in the IMR.

Along with the above claimed uses and science. Other claimed traditional uses of the Kacip Fatimah plant include using it to effectively treat dysentery, rheumatism and gonorrhea. It is also used as anti-flatulence by helping drive away and preventing the formation of gas.  By cleansing and avoiding painful or difficult menstruation it is used as an anti-dysmenorrheal.  This plant will also help to firm and tone the abdominal muscles.  All these properties and biological activity is due to the presence of phytoestrogens that is naturally found in the plant.

ANTIOXIDATIVE PROPERTIES FROM VARIOUS EXTRACTS OF LABISIA PUMILA (KACIP FATIMAH)

E.K. Khairul & I. Zhari
School of Pharmaceutical Sciences, University Science Malaysia, 11800 Minden Pulau Pinang

 A total of 24 extracts of L. Pumila was tested for antioxidant property using zanthine oxidase (XO) inhibitory activity and radical scavenging activity.  Among the tested extracts, four exhibited high XO inhibitory activity which were better than allopurinol(>70%) while others had moderate activity(>50%).  Allopurinol, a known inhibitor of XO, was used as positive control.  Water extract of whole plant was identified as the best extract was shown to be comparable to Quercetin (65%).

FEMALE REPORDUCTIVE TOXICITY STUDY OF AQUEOUS EXSTRACT OF LABISIA PUMILA VAR. ALATA IN RATS

M.F. Wan Ezumi1, S.A. Sulaiman1, M.N. Islam2, A.W.M Suhaim1& S.S.J. Mohsin3
1Department of Pharmacology, School of Medical Sciences, University Science Malaysia,16150 Kubang Kerian, Kelantan Darul Naim, 2Department of Anatomy, School of Medical Sciences, University Science Malaysia, 16150 Kubang Kerian, Kelantan Darul Naim, 3School of Health Sciences, University Science Malaysia, 16150 Kubang Kerian, Kelantan Dural Naim

The reproductive toxicity of the aqueous extract to lobelia pumila var. alata or kacip fatimah was evaluated in female Sprague Dawley rate. This study includes detection of potential adverse effects o the oestrous cycle, reproductive performance, post-natal growth and survival of offspring during lactation.  Thirty-six female rats with consecutive 4 to 5 days oestrous cycle were assigned to 6 groups.  One group of control together with 5 groups receiving 2,20,200,400 and 800mg/kg/day extracts were treated daily by gavaging prior to mating, mating period, gestation and lactation periods of 7 days.  Results obtained revealed that L.pumila extracts did not alter the oestrous cycle in all rats. All the animals proceeded towards successful mating and pregnancies.  All pregnant rats delivered normal. Animals that received extracts gave birth earlier than those in the control group.  However, this observation was not significantly different. There were no test agent-related changes in the number of implantations, litter size and pup weights (males or females) both at birth and at 7 day post natum.  Parameters measured such as pup sex ratio, live birth index, pup viability index and percentage of implantation death were also not significantly different. The slightly earlier delivery dates noted in the treated animals lend support to the traditional practice of using this herb in order to enhance and expedite labor in human.  Further, these findings also indicate that water based extracts of l.pumila do not pose any significant reproductive toxicity in rats.