poster- acute oral tox study of 9 malaysian medicinal herbs on s. dawley rats

ACUTE ORAL TOXICITY STUDY OF NINE MALAYSIAN MEDICINAL HERBS ON SPRAGUE DAWLEY RATS

Teh BP, Naji FH, Siti Nurulsyuhada R, Mohd Afiq FY, Zakiah I, Murizal Z.

Herbal Medicine Research Centre, Institute for Medical Research, Jalan Pahang, 50588 Kuala Lumpur, Malaysia.

Tel. No.: +603-404 11662 Fax No.: +603-404 11657

Contact author: [email protected]

T his study was to investigate in vivo acute toxicity of selected Malaysian medicinal herbs (Polygonum minus (Kesum), Melastoma malabathricum (Senduduk), Garcinia atroviridis (Asam gelugor), Piper betle (Sireh), Elaeis guineensis (Kelapa sawit), Cosmos caudatus (Ulam raja), Tinospora crispa (Patawali), Curcuma xanthorrhiza (Temu lawak), and Gynu-ra procumbens (Sambung nyawa)). These studies were conducted in two phases, sighting and main study, in accordance to Organization for Economic Co-operation and Devel-opment (OECD) Testing Guideline-420. Powdered raw form of each herb’s plant part was mixed with distilled water and administered as a single oral dose to female Sprague

Dawley rats aged between 8-12 weeks. Two doses (300 and 2,000 mg/kg body weight) were administered in the sighting study to two different rats. Since no death and toxic effect was observed in the sighting study, the dose of 2,000 mg/kg body weight was selected for the main study which involved another four rats. The period of clinical observation for both phases was 14 days. Parameters measured during the sighting and main study included general behaviour, body weight, food and water intake of each rat. The animals were then sac-rificed, the organs collected, weighed and examined for any gross abnormality. No abnormality was observed in the animals’ behaviour, body weights, food intake, water intake and organs. No death was observed throughout the study period. All nine medicinal herbs did not cause acute toxicity effects at the highest dose of 2,000 mg/kg BW (LD50 is estimated to be more than 2,000 mg/kg BW).

SUMMARY

Body Weight Food and Water Intake Clinical Observation Gross Organ Examination

As shown in Figure 1, the body weights of animals increased throughout the study period.

Both food and water intake increased throughout the study period, as also shown in Figure 1.

No sudden death or any sign of acute toxic, adverse effects nor abnormality in animal behaviour were found.

Gross examinations on lungs and livers showed slight abnormalities.

RESULTS

DISCUSSIONS & CONCLUSION

1. The increase in food and water intakes were in line with the increase in the body weight, which indicated the normal growth of the animals. These findings suggest that the administration of these medicinal herbs did not affect the growth of the animals.

2. Although gross examinations showed slight abnormalities on few organs, histological examinations revealed no abnormality related to administration of the medicinal herbs.

3. In conclusion, the aqueous mixture of these medicinal herbs administrated orally to female Sprague Dawley rats showed no observable acute toxic effect with LD50 esti-mation of more than 2,000 mg/kg body weight.

4. Based on the intended use and dosing in this study, repeated dose study should be conducted to identify their toxic effects, if any.

1. The Organization for Economic Cooperation and Development (OECD) Guidelines: OECD Guidelines for Testing of Chemicals: Acute Oral Toxicity – Fixed Dose Procedure. (17 December 2001), Part 420.

2. Guidelines of Handling of Laboratory Animals by the Ministry of Health Malaysia (MOH), 2000.

REFERENCES

Figure 1 : Means values are expressed as the %changes (Week 1 and Week 2) of measured parameters of body weight, food intake and water intake of main study’s animals. Positive percentage indicates in-crease of the measured parameters. (n=5 for each herb)

Scientific name: Polygonum minus

Malay name: Kesum

Plant part: Leaves

© NKEA Malaysian Herbal Monograph - GlobinMed

OBJECTIVES

1. To observe any acute toxic effect on the animals resulting from a single exposure to the medicinal herbs.

2. To provide supporting data on safety information of the identified herbs in Malaysian herbal monograph (MHM).

The authors would like to thank Director General of Ministry of Health, Malaysia for his permission to present this study into a poster. This study was supported by NKEA EPP 1 Fund from Ministry of Agriculture & Agro-Based Industry, Malaysia with project number, JPP-IMR 11-045. The authors would like to thank all NKEA MHM committees for their collective efforts in publication of monograph. This poster printing and presentation costs are funded by the Ministry of Health, Malaysia.

ACKNOWLEDGEMENT

MATERIALS & METHODS

Selected medicinal herbs

Each dried herb’s plant part was supplied by Malaysian Agricultural Research and Development Institute (MARDI) in a form of fine powder with respective mesh sizes.

The powdered raw herbs were mixed with distilled water individually, on the day of treatment prior to dosing.

Experiment

Two doses were used in this study, i.e. 300 and 2,000 mg/kg

Used in total of six animals per medicinal herb through oral ga-vage.

Observed for 14 days for the ani-mals’ daily general behaviour, weekly body weight, weekly food intake, and weekly water intake.

These animals were then euthanized to collect any organ which showed abnormality.

Statistical Analysis

The data collected were calculated for its weekly differences.

The mean value (MEAN), standard deviation (STDEV) were calculated for the measured variables using Microsoft Office Excel software.

Animal

Female Sprague Dawley rats aged 8-12 weeks old, nulliparous and non-pregnant.

Purchased from accredited supplier (AAALAC accreditation).

The handling of the animals was according to OECD and MOH guidelines.

The use of laboratory animals were approved by the Institutional Animal Care and Use Committee of Institute for Medical Research (ACUC/KKM/02(2/2012).

Adding distilled water into bottles contained powdered raw herbs.

© Non-Clinical Research Facility , Institute for Medical Research

Individual ventilated cages which used to house the animals during study.


Administered the medicinal herbs via oral route used intubation needle.


Necropysy at the end of study.


Bottles contained mixture of powdered raw herbs with distilled water.


INTRODUCTION

Scientific name: Melastoma malabathricum

Malay name: Senduduk

Plant part: Leaves


Scientific name: Garcinia atroviridis

Malay name: Asam gelugor

Plant part: Fruits


Scientific name: Piper betle

Malay name: Sireh

Plant part: Leaves


Scientific name: Elaeis guineensis

Malay name: Kelapa sawit

Plant part: Leaves

© NKEA Malaysian Herbal Monograph - GlobinMed © NKEA Malaysian Herbal Monograph - GlobinMed

Scientific name: Cosmos caudatus

Malay name: Ulam raja

Plant part: Leaves


Scientific name: Tinospora crispa

Malay name: Patawali

Plant part: Stems


Scientific name: Curcuma xanthorrhiza

Malay name: Temu lawak

Plant part: Rhizome


Scientific name: Gynura procumbens

Malay name: Sambung nyawa

Plant part: Leaves

According to World Health Organization, 80% of population in some African and Asian re-gions (including Malaysia) depend on traditional medicines for treating ailments. The use of medicinal herbs has been widespread among various Malaysian ethnic groups. Nowa-days people are more aware about cost increase and adverse events related to conven-tional drugs which encourages people to use medicinal herbs as an alternative option. Nevertheless, these herbs can also cause adverse reactions if it is in poor quality, or tak-en inappropriately or in conjunction with other medicines. Therefore, an increase of pa-tient awareness about its safety use is essential. The medicinal herbs used in this study cover many traditional claims such as fever, afterbirth treatment, kidney disorders, liver disorders, high blood pressure, high blood glucose, jaundice, wounds and cough. Mono-graph publications will strengthen the potential of these herbs to be turned into high-valued products.

poster- acute oral tox study of 9 malaysian medicinal herbs on s. dawley rats

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