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The Side Effects of Kacip Fatimah Extract

Introduction

Kacip Fatimah (Labisia pumila) has been widely used by the traditional practitioners as the remedial for involution of birth channel, delay fertility and to regain body strength. Kacip Fatimah is also used to reduce excessive gas in the body, treat flatulence, dysentery, dysmenorrheal, gonorrhea and “sickness in the bones” (Burkill, 1935). Apart from those, the extract from the plant is also used as a drink to gain energy and medicinal usage. Unfortunately the scientific data to support the claims are still scarce. There is no available international publications regarding this plant is effect in human reproduction.

Although Kacip Fatimah is generally assumed as safe and sound for human consumption, this study is carried out to determine the side effects of petroleum-ether extract of Labisia pumila var. alata on liver and kidney of white rats by histological examination.
Abstract In Malaysia, most traditional practitioner would recommend Kacip fatimah (Labisia pumila) for the treatment of flatulent, dysentery and post-partum herbs.

Although some herbs contain hazardous compound that might be harmful to the host system, Kacip Fatimah is known to be safe for human consumption. This study was conducted to determine the side effects of petroleum-ether extract of Labisia pumila var. alata on liver and kidney of white rats. Thirty-six female Albino Winstar rats were equally divided into four groups.
Group A was set as the control untreated group, while Group B, C and D were subjected to subcutaneous injection of the extract at 0.1 mg/ml, 0.05 mg/ml and 0.025 mg/ml respectively. Three animals from each group were euthanized at days 1, 3 and 7 post-treatment. Samples of liver and kidney were collected and fixed in 10% buffered formalin overnight before being processed for histology. Liver impairment was indicated by the development of hydrophic degeneration in sinusoid area as early as day 1 post treatment.

The lesion progress more severe on day 3 and 7. Inflammatory of the renal tubules were also observed during the development of lesion in the liver. Glomerulonephritis and nephrosis of the kidney were observed until day 7. This abnormality in the liver and kidney tissue suggested the presence of toxin compound from Kacip Fatimah.
Correspondence: Mohd Effendy Abd Wahid, Kolej Universiti Sains dan Teknologi Malaysia, 21030 Kuala Terengganu, Terengganu D. I. Malaysia Material and methods Labisia pumila var. alata (Kacip Fatimah) samples were freshly collected from Setiu Reserve Forest in Terengganu. The roots of were separated and dried before grinding into fine powder. The powder were then soaked into the petroleum-ether for three consecutive days at room temperature for extraction. The process was repeated twice before the whole extract containing the solvent was collected, filtered and evaporated to dryness under reduces pressure in a rotary evaporator at 40oC. Concentrated extracts of the roots were place in glass container for future use.

Thirty-six female Albino Winstar rats were equally divided into four groups; Group A was used as untreated group,
while Group B was treated with 100% (0.1 mg/ml) of Labisia pumila petether extract dilute inside 1ml solvent. Group C and D were treated with 50% (0.05 mg/ml) and 25% (0.025 mg/ml) of Labisia pumila pet-ether extract dilution inside 1 mL solvent. Rats in Group B, C and D were given subcutaneous injection by using 23-gauge needle and euthanized at days 1, 3 and 7 post-partum. Liver and kidney samples were collected and fixed in 10% buffered formalin for histology preparation. Histopathological changes were examined by using research compound microscope with computerized Image Analyzer Software (Leica DM LB2-Image analyser) to determine the lesions in those organs. Results Liver Histology examination of the liver and kidney of rats in Group A showed no abnormal changes from day 1 until day 7. On contrary, abnormalities were observed in Group B, C and D. Hydropic degeneration of the liver progress severely from day 1 to day 3 and continuously progress until the last day of experiment that is on day 7. Other abnormalities observed in the liver were hyaline degeneration, fatty changes and necrosis of the hepatocytes. Kidney No significant changes were observed in the kidney of rats in Group A at day 1, 3 and 7. However, rats in Group B, C and D showed mild to moderate hemorrhage lesions in their kidneys. Inflammation was observed in the cells tubule and progressed to more severe condition at day 7.

The lesions were more severe when red blood cells were observed outside the blood vessels almost every part of the kidney tubule. Results showed that the extract of Kacip Fatimah contains one or more active compound that may injure and caused irritation to the liver and kidney tissues. This irritant toxic compounds produce cellular damage either morphologically or biochemically (Donovan, 1985).
The development of lesions in the liver and kidneys of rats suggested that Kacip Fatimah could be poisonous and hazardous if it is consumed in large quantity in a short period of interval. As the second largest organ and gland in the body, liver is recognized as the most important organ for excretion of drugs or other metabolites. It performs many functions, such as transferring and accumulating metabolites, aiding food digestion, controlling the production, storage of glucose and producing blood-clotting factors. The most vital function of the liver is to neutralize and elim inates toxic substances from the body (Runnells et al., 1995). Some of the available chemotherapy drugs are toxic and have the potential to cause liver damage. Liver will remove toxins and chemicals from the blood stream and changes them into products that can be readily removed through the bile or urine through the kidney. If toxins accumulate in the body faster than the liver can process them, then liver damage will result.

The development of the lesions in the liver highly suggested that Kacip Fatimah extract contains toxin material that is harmful to the liver filtering system. Early evidence of liver damage is usually manifested by the fatty change which is indicated by the form of cytoplasmic vacuoles in the liver cells. The vacuoles will displace the nucleus to one side. When the metabolic disruption is becoming more severe, hydropic degeneration will be noticed and cells will become swollen. Unless the restoration of the normal functions is in pla ce, the liver function will be impaired.


Eventually, the affected cells will undergo necrosis or die. Kidney is the second target in the body after the liver. The main functions of the kidney are the excretion of the by-products of the metabolism, foreign substances such as body pigments (Runnells et al., 1965) and maintaining homeostasis. Exposure to circulating toxins will lead to pathological changes and disruption of glomerular functions.
Subsequently, the renal tubular functions will also be affected. The results showed varying degree of irritation to the glomerulus and tubular structures, indicating harmful metabolic activity.Phytotoxins are also potential to cause glomerulonephritis and nephrosis.

This study highly suggested the presence of toxin compound in Kacip Fatimah extract which will cause lesions in liver and kidney in the model animal.
Observation showed that petroleum-ether extract of Kacip Fatimah can caused lesion in the endothelium and tissue of kidney and liver. The most severe lesion occurred in Group B which was treated with high dose (100%) 0.1 mg/ml. Group C had moderate lesion whereas Group D showed mild lesion. Future study needs to carry out to eliminate the presence of harmful compound in Kacip Fatimah for the safety and soundness of the herb. Labisia pumila (Myrsinaceae), popularly known as "Kacip Fatimah", has been used by many generation of the Malay women to induce and facilitate childbirth as well as a post-partum medicine (Burkill, 1935). Three varieties of L. pumila had been identified and found in Malaysia, they are var. alata, var. pumila and var. lanceolata (Stone, 1988). It is imperative to differentiate the three varieties in terms of their physical and chemical characteristics as well as biological activity, in order to determine the proper plant material for use, hence producing quality herbal medicines with proven safety and efficacy.

The current high rate of demand and methods of harvesting medicinal plants, particularly from the wild, for the herbal market has lowered natural population sizes for many species. Even for wild American ginseng (Panax quinquefolius), regardless of its historical abundance, in some locations it has been reduced to populations of a few dozen individuals (Van der Voort, 1998). This has made research on the propagation of medicinal plants more urgent than ever.There is, presently, a great local market demand for Kacip fatimah especially as afterbirth tonics, however, a paucity exists in technical information on plant identification, propagation techniques, agronomy and sivicultural aspects (Jaganath & Ng, 2000).According to Stone (1988), there exists three varieties of Kf in Malaysia, namely, Labisia pumila var. alata, L. pumila var. pumila and L. pumila var. lanceolata. 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 need to be developed.

Preliminary studies had been conducted previously on Kf using the agroforestry approach involving intercropping of Kf under rubber and rattan (pers. Comm. Khozirah Shaari). However, the planting of Kf as a monoculture crop has yet to be studied but nonetheless, these studies showed that Kf was best propagated by seeds or root cuttings. The plants thrive best in shady areas and non-waterlogged, humus rich soil.Kacip Fatimah (KF) has also been used by the indigenous people of the Malay archipelago for menstrual irregularities and post partum .

The plants are usually boiled and water soluble extract taken as a drink. Interest has 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 phytoestrogen was considered highly likely. An earlier in-vitro study using human endometrial adenocarcinoma cells of the Ishikawa-Var I line showed that the ethanolic extract of the roots of L. pumila var. alata exhibited a weak but specific estrogenic effect on the cells, resulting in enhanced secretion of alkaline phosphatase.

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