Despite
Medicinal plants, either as an extract, pure compound or as a derivative, offer unlimited opportunities for the discovery of new drugs. Most of the natural products used in folk remedy have solid scientific evidence with regard to their biological activities. However, there is little information or evidence available concerning the possible toxicity that medicinal plants may cause to the consumers [
Recent studies also reported the standardization of
Samples of
Male and female Sprague Dawley (SD) rats were used for the acute and subchronic toxicology studies. The rats were obtained from the Animal Research and Service Centre (ARASC), Universiti Sains Malaysia. The animals were acclimatized to laboratory conditions for 7 days prior to the experiments. The rats were maintained at a room temperature of 22–24°C, with a 12 h light/dark cycle. During acclimatization, the animals were housed in polycarbonate cages with a standard pellet diet and tap water
An acute toxicity test was performed according to the Organization of Economic Co-operation and Development (OECD) guideline 420 for testing of chemicals [
The subchronic toxicity test was performed following the protocol described by the OECD guideline 408 for testing chemicals [
After sacrificing the rats, parts of the liver, kidney, lung, heart, and spleen tissues were collected for histological studies. The tissues were washed in normal saline and fixed immediately in 10% formalin for a period of at least 24 h, dehydrated with alcohol, embedded in paraffin, cut into 4-5
All values are expressed as mean ± SEM. Comparisons between groups were performed using one way analysis of variance (ANOVA) followed by Tukey’s multiple comparison tests using SPSS statistical software. A
To standardize the fingerprint, ten batches of
GC/MS chromatogram of
Methanolic extract of
Relative organ weights of rats receiving single dose of
Organs | Treatment | |
---|---|---|
Control |
| |
Male | ||
Heart |
|
|
Liver |
|
|
Spleen |
|
|
Kidneys |
|
|
Lungs |
|
|
Female | ||
Heart |
|
|
Liver |
|
|
Spleen |
|
|
Kidneys |
|
|
Lungs |
|
|
Values are expressed as mean ± SEM (
Relative organ weight was calculated as (organ weight/body weight)
Effect of
Unit | Treatment | ||
---|---|---|---|
Control |
| ||
Male | |||
Haemoglobin | g/L |
|
|
Total red blood cells | 1012/L |
|
|
Packed cells volume | L/L |
|
|
Mean corpuscular volume | fL |
|
|
Mean corpuscular Hb | pg |
|
|
Mean corpuscular Hb conc | g/L |
|
|
Red blood cells distribution width | % |
|
|
Total white blood cells | 109/L |
|
|
Neutrophils | % |
|
|
Lymphocytes | % |
|
|
Monocytes | % |
|
|
Platelet count | 109/L |
|
|
Female | |||
Haemoglobin | g/L |
|
|
Total red blood cells | 1012/L |
|
|
Packed cells volume | L/L |
|
|
Mean corpuscular volume | fL |
|
|
Mean corpuscular Hb | pg |
|
|
Mean corpuscular Hb conc | g/L |
|
|
Red blood cells distribution width | % |
|
|
Total white blood cells | 109/L |
|
|
Neutrophils | % |
|
|
Lymphocytes | % |
|
|
Monocytes | % |
|
|
Platelet count | 109/L |
|
|
Values are expressed as mean ± SEM (
Effect of
Unit | Treatment | ||
---|---|---|---|
Control |
| ||
Male | |||
Sodium | mmol/L |
|
|
Potassium | mmol/L |
|
|
Chloride | mmol/L |
|
|
Urea | mmol/L |
|
|
Creatinine |
|
|
|
Uric acid | mmol/L |
|
|
Total protein | g/L |
|
|
Albumin | g/L |
|
|
Globulin | g/L |
|
|
Albumin/globulin ratio |
|
|
|
Alkaline phosphatase | U/L |
|
|
AST | U/L |
|
|
ALT | U/L |
|
|
Female | |||
Sodium | mmol/L |
|
|
Potassium | mmol/L |
|
|
Chloride | mmol/L |
|
|
Urea | mmol/L |
|
|
Creatinine |
|
|
|
Uric acid | mmol/L |
|
|
Total protein | g/L |
|
|
Albumin | g/L |
|
|
Globulin | g/L |
|
|
Albumin/globulin ratio |
|
|
|
Alkaline phosphatase | U/L |
|
|
AST | U/L |
|
|
ALT | U/L |
|
|
Values are expressed as mean ± SEM (
Mean body weight of rats receiving
Daily oral administration of
Mean body weight of male rats receiving
Mean body weight of female rats receiving
Effects of the 5000 mg/kg of
Relative organ weights of 90-day treated rats are shown in Table
Relative organ weights of rats treated with
Organs | Control |
|
|||
---|---|---|---|---|---|
50 mg/kg | 250 mg/kg | 1000 mg/kga | 1000 mg/kgb | ||
Male | |||||
Heart |
|
|
|
|
|
Liver |
|
|
|
|
|
Spleen |
|
|
|
|
|
Kidneys |
|
|
|
|
|
Lungs |
|
|
|
|
|
Female | |||||
Heart |
|
|
|
|
|
Liver |
|
|
|
|
|
Spleen |
|
|
|
|
|
Kidneys |
|
|
|
|
|
Lungs |
|
|
|
|
|
Values are expressed as mean ± SEM (
Relative organ weight was calculated as (organ weight/body weight)
aA group was treated with methanol extract of
bA satellite group was treated with the methanol extract of
The effects of subchronic administration of
Effect of
Unit | Control |
|
||||
---|---|---|---|---|---|---|
50 mg/kg | 250 mg/kg | 1000 mg/kga | 1000 mg/kgb | |||
Male | ||||||
Haemoglobin | g/L |
|
|
|
|
|
Total red blood cells | 1012/L |
|
|
|
|
|
Packed cell volume | L/L |
|
|
|
|
|
Mean corpuscular volume | fL |
|
|
|
|
|
Mean corpuscular Hb | pg |
|
|
|
|
|
Mean corpuscular Hb conc | g/L |
|
|
|
|
|
Red blood cells Distribution width | % |
|
|
|
|
|
Total white blood cells | 109/L |
|
|
|
|
|
Neutrophils | % |
|
|
|
|
|
Lymphocytes | % |
|
|
|
|
|
Monocytes | % |
|
|
|
|
|
Platelet count | 109/L |
|
|
|
|
|
Female | ||||||
Haemoglobin | g/L |
|
|
|
|
|
Total red blood cells | 1012/L |
|
|
|
|
|
Packed cell volume | L/L |
|
|
|
|
|
Mean corpuscular volume | fL |
|
|
|
|
|
Mean corpuscular Hb | pg |
|
|
|
|
|
Mean corpuscular Hb conc | g/L |
|
|
|
|
|
Red blood cell distribution width | % |
|
|
|
|
|
Total white blood cells | 109/L |
|
|
|
|
|
Neutrophils | % |
|
|
|
|
|
Lymphocytes | % |
|
|
|
|
|
Monocytes | % |
|
|
|
|
|
Platelet count | 109/L |
|
|
|
|
|
Values are expressed as mean ± SEM (
aA group was treated with methanol extract of
bA satellite group was treated with the methanol extract of
Effect of
Unit | Control |
|
||||
---|---|---|---|---|---|---|
50 mg/kg | 250 mg/kg | 1000 mg/kga | 1000 mg/kgb | |||
Male | ||||||
Sodium | mmol/L |
|
|
|
|
|
Potassium | mmol/L |
|
|
|
|
|
Chloride | mmol/L |
|
|
|
|
|
Urea | mmol/L |
|
|
|
|
|
Creatinine |
|
|
|
|
|
|
Uric acid | mmol/L |
|
|
|
|
|
Total protein | g/L |
|
|
|
|
|
Albumin | g/L |
|
|
|
|
|
Globulin | g/L |
|
|
|
|
|
Albumin/globulin ratio |
|
|
|
|
|
|
Alkaline phosphatase | U/L |
|
|
|
|
|
AST | U/L |
|
|
|
|
|
ALT | U/L |
|
|
|
|
|
Female | ||||||
Sodium | mmol/L |
|
|
|
|
|
Potassium | mmol/L |
|
|
|
|
|
Chloride | mmol/L |
|
|
|
|
|
Urea | mmol/L |
|
|
|
|
|
Creatinine |
|
|
|
|
|
|
Uric acid | mmol/L |
|
|
|
|
|
Total protein | g/L |
|
|
|
|
|
Albumin | g/L |
|
|
|
|
|
Globulin | g/L |
|
|
|
|
|
Albumin/globulin ratio |
|
|
|
|
|
|
Alkaline phosphatase | U/L |
|
|
|
|
|
AST | U/L |
|
|
|
|
|
ALT | U/L |
|
|
|
|
|
Values are expressed as mean ± SEM (
aA group was treated with methanol extract of
bA satellite group was treated with the methanol extract of
Macroscopic examination of the vital organs of treated animals revealed no abnormalities in the colour or texture when compared with the organs of the control group. The light microscopy examinations of the transverse section of
Effects of the 1000 mg/kg of
For centuries, natural products, such as medicinal plants have been the basis for the treatment of various ailments [
During the evaluation of the toxic characteristics of medicinal plants, the determination of LD50 is usually an initial step to be conducted. Data from the acute toxicity study may (a) serve as the basis for classification and labelling; (b) provide initial information on the mode of toxic action of a substance; (c) help arrive at a dose of a new compound; (d) help in dose determination in animal studies; and (e) help determine LD50 values that provide many indices of potential types of drug activity [
Subchronic studies assess the undesirable effects of continuous or repeated exposure of plant extracts or compounds over a portion of the average life span of experimental animals, such as rodents. Specifically, they provide information on target organ toxicity and are designed to identify noobservable adverse effect level [
Administration of extracts of
The body weight changes serve as a sensitive indication of the general health status of animals [
Similarly, no significant changes in the weights of the heart, liver, spleen, kidneys, or lungs were observed, suggesting that administration of
The serum haematology and clinical biochemistry analyses were done to evaluate the possible alterations in hepatic and renal functions influenced by the extracts. Liver and kidney function analysis is very important in the toxicity evaluation of drugs and plant extracts as they are both necessary for the survival of an organism [
Evaluation of haematological parameters can be used to determine the extent of the deleterious effect of
The macroscopic examinations of the organs of rats treated with various doses of
In light of these findings, we may conclude that
The authors of this paper have no conflict of interests.
Kwan Yuet Ping is supported by the MyPhD fellowship from the Ministry of Higher Education of the Malaysian Government. This work was partly supported by UM-MoHE HIR Grant (no. UM-MoHE HIR H-18001-C0020) from the University of Malaya, Malaysia.