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Bouchra Meddah et al. World Journal of Pharmaceutical Research 

Article Received on 

05 November 2012, 

CYTOTOXIC ACTIVITY, ACUTE AND SUB-ACUTE TOXICITY OF 

METHANOLIC ROOT EXTRACT OF CORRIGIOLA TELEPHIIFOLIA 

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POURR 

L. Doudach 1, 2 *, B. Meddah 1 , L. Rouas 3 , Mya Faouzi 1 , L. Benbacer 4 , M.Bouabdellah 5 , 

Z. Alhamany 3 , L.Chabraoui 5 , A. Elomri 2 , and Y. Cherrah 1 

1 Laboratory of Pharmacology and Toxicology, Faculty of Medicine and Pharmacy, 

Mohammed V Souissi University, Pharmacokinetic Research Team, Rabat, Morocco 

2 Laboratory of Pharmacognosy, CNRS, UMR 6014, C.O.B.R.A, Faculty of Medicine and 

Pharmacy, University of Rouen, Rouen, France 

3 Department of Anatomy and Cytology. Pediatric hospital of Rabat. CHU Ibn Sina. FMPR. 

UM5 Souissi. Rabat 

4 Biology Unit and Medical Research CNESTEN, PB 1382 RP, 10001 Rabat, Morocco 

Revised on 29 November2012, 

Accepted on 09 December 2012 

*Correspondence for 

Author: 

* Pr. Bouchra Meddah, 

laboratory of Pharmacology 

and Toxicology, Faculty of 

Medicine and Pharmacy, 

Mohammed V Souissi 

University, Rabat, Morocco 

World Journal of Pharmaceutical research 

Volume 2, Issue 1, 1-15. Research Article ISSN 2277 – 7105 

5 Central Laboratory of Biochemistry, Ibn Sina Hospital Rabat, Morocco. 

ABSTRACT 

Corrigiola telephiifolia Pourr. (Caryophyllaceae) is an herbal plant 

commonly used in Moroccan traditional medicine for treatment of 

many disorders. In the present study, we investigated cytotoxic 

activity by an in vitro assay system of growth inhibition against a 

human cancer cell line, namely cervix adenocarcinoma (HeLa) and 

breast adenocarcinoma cells (MCF-7), the results demonstrated that 

cyclohexane extract show a moderate cytotoxic activity against HeLa 

cell lines . The acute and sub-acute toxicity of the crude methanolic 

extract of C. telephiifolia root parts was evaluated. For acute toxicity, 

a single oral administration was performed at a dose of 2000 mg/kg 

body weight (six females, six males mice). The study of sub-acute 

toxicity was evaluated by daily oral (five females, five males mice) 

with the extract at doses of 10, 50, 100 and 500 mg/kg/day for forty 

five days. No mortality or signs of toxicity were observed in the acute study.Mice were 

analyzed for final body and organ weights, necropsy, blood chemical and histopathological 

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parameters. In the forty five days study in mice the extract at 10 and 50 mg/kg/day showed no 

toxicity, mortality, macroscopic or microscopic change of internal organs or tissues in either 

sexe in comparison with the control group. The bodyweight of both sexes decreased at the 

dose of 100, 500 mg/kg/day and clinical blood chemistry revealed slightly changes.The 

extracts of Corrigiola telephiifolia showed a cytotoxic activity without mortality in 

laboratory animals .They are good candidates for further investigations in the fields of new 

anticancer drugs discovery. 

Keywords: Corrigiola telephiifolia, acute toxicity, sub-acute toxicity, cytotoxic activity. 

INTRODUCTION 

The use of medicinal plants has always been part of human culture [1] . Today, medicinal 

plants play a great role in human health services worldwide. Diverse medicinal species in 

Morocco has constituted the main source of products used in folk medicine and have been 

described in older Moroccan pharmacopoeia [2,3,4] . Herbal sources from medicinal plants are 

presumed to be safe without any complications or toxicity however it is necessary to focus on 

all aspects of medicinal plant research: from cultivation, ethno-pharmacology, utilization, 

isolation andidentification of active constituents to efficacy evaluation, pharmacology, safety, 

standardization, formulation and clinical evaluation, this scientific studies are presumed to 

prove that natural products from remedies can be safe without any health effect, further 

investigations are vitally needed and the same applies for Corrigiola telephiifolia Pourr. It is 

a perennial species [5] woody distributed throughout the north of Africa. The root releases an 

aromatic fume and used for medicinal and cosmetic purposes, it is the most effective part 

traditionally described to treat flu, dermatological diseases, inflammation, ulcer, cough, and 

jaundice; it is also used as an anasthenic and a diuretic [6] , root decoction is reported be used 

to treat the cancer in Morocco [7] . Some studies have reported that the extract of Corrigiola 

telephiifolia have been investigated for a toxicological study [8] , this study completed other 

investigations by the identification of possible target organs involved in the plant toxicity. 

The present study was carried out to evaluate the cytotoxic activity, acute and sub-acute 

toxicity of the root parts of C. telephiifolia Pourr. in mice. 

MATERIALS AND METHODS 

Plant material: Corrigiola telephiifolia Pourr. (Family-Caryophyllaceae) was collected 

based on ethnopharmacological information and traditional uses, in May 2009, 4km south of 

Ben Slimane (Morocco) with the agreement from the authorities and respecting the United 

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Nations Convention of Biodiversity. The plant was identified by a botanist from the Scientific 

Institute. (Pr. M. Fennane). A voucher specimen (N° 77766) was deposited in the Herbarium 

of Scientific Institute, University Mohammed V–Rabat–Morocco. 

Extraction procedure: The dried roots (970g) of C. telephiifolia were extracted successively 

with cyclohexane, dichloromethane and methanol by maceration at room temperature (22°C) 

over period of 24h the extraction process was repeated again for a three time, the extracts 

were then filtered through Whatman paper and the solvents were vacuum-distilled in a rotary 

evaporator (Rotavap: Buchi). The remaining extracts were finally dried in the oven at 30°C 

for 2h to ensure the removal of any residual solvent. Final extracts were a yellow powder in 

percentage dry weight 0.11, 0.18 and 7.32% of cyclohexane, dichloromethane and methanol 

extract respectively; the extracts was kept in deep freeze at -20°C until use. Phytochemical 

screening of C. telephiifolia root parts was subjected to the tests tube to identify the major 

groups of secondary metabolites [9] . 

Cytotoxic activity 

Cell lines and culture medium: Cervical cancer cell lines (HeLa) and breast 

adenocarcinoma cells (MCF-7) obtained from the American Type Culture Collection (ATCC) 

were used in this study. Cells were grown at 37°C in humidified 5% CO2 and 100% relative 

humidity atmosphere in Dulbecco’s Modified Eagle Media (DMEM) (1% glutamine, 100 

U/ml Penicillin-Streptomycin mixtures and 10% fetal bovine serum). 

Cytotoxicity assay: Cytotoxicity of sample on tumor cells was measured by microculture 

tetrazolium (MTT) assay [10] . For the assays, 96-well microplates were seeded with 100 µl 

medium containing 10, 000 cells in suspension. After 24 h incubation and attachment, the 

cells were treated with 6 fourfold dilution of crude extracts. Exactly from the stock solution 

(40 mg/ml), each extract sample was applied in a series of 6 dilutions (final concentrations 

ranging from 31.25 to 1000 µg/ml) with a final DMSO concentration of 0.1% and was tested 

in quadruplicate. After 48 h incubation, cell viability was determined by adding (Sigma) 

tetrazolium salt as cytotoxicity indicator and by reading absorbance at 590 nm with a 

scanning multiwell spectrophotometer (Spectra Count, Packard, Ont., Canada). Tetrazolium 

salts are cleaved to formazan dye by cellular enzymes (only in the viable cells). The level of 

absorbance directly correlates to the metabolically active cells. Vinblastine was used as a 

positive control. Cells were observed before and after treatment by the plants extracts for 24 

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and 48h using optic microscopy for any change in their morphology and to exanimate the 

cellular process and the characteristics of the cells. 

Toxicological studies 

Animals: Animals were obtained from the animal experimental center of Mohammed V- 

Souissi University, Medicine and Pharmacy Faculty – Rabat. They were housed three per 

plastic cage for acute, five mice per cage for sub-acute toxicity, and under a controlled room 

conditions: temperature (22 ± 1°C), humidity of about 60–80%, photo-periodicity of 12 h 

day/12 h night and air changes. Mice were treated according to directives of the Official 

Journal of the European Community about the care and of the use of the animals of 

laboratory. All animals had free access to tap water and at ad-libitum feeding; the general 

behavior of mice was observed continuously for 1h after treatment, intermittently for 6h and 

over period of 24h [11] and all signs of toxicity and deaths and their latencies were recorded. 

Acute toxicity: Acute toxicity study for the extracts is conducted according to the method of 

Organization of Economic Co-operation and Development, as per 423 guidelines (OECD) 

[12,13] . Following the fasting period, body weight of the mice were determined and the dose 

was calculated in reference to the body weight, C. telephiifolia extracts were dissolved in 

distilled water and given by orally way in a single dose (2 000 mg / kg) of body weight. The 

control group received only the water. Observations were made and recorded systemically 

continuously observed for 6h and at 24h to detect any eventual symptoms of toxicity: changes 

in physical appearance, skin, pain, stress, abdominal contraction or mortality and observed 

for 14 days after administration of the substances. Care and treatment of the mice were in 

compliance with the guidelines of the guide for the care and use of laboratory animals 

(commission on life science, National Research Council 1996). 

Sub-acute toxicity: We used 50 albino Swiss mice aged 10-12 weeks and weighing 22-30 g, 

divided into five groups of mice (ten mice per dose, five males and five females) at single 

doses of 0 (control, filtered water), 10, 50, 100 and 500 mg/kg bodyweight. The dose 200 mg 

(methanolic extract) is equivalent to double the dose used by traditional healers and from the 

acute toxicity study 2000 mg (the oral LD50 obtained higher than 2000mg/kg). The amount 

of food and water consumed was measured daily from the quantity of food and water 

supplied and the amount remaining after 24h for 45 days of the study period. The animals 

were weighed and observed daily for clinical symptoms include hemorrhage, diarrhea, 

convulsions, sedation, stimulation, colic and death. After 45 days of the treatment, blood was 

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collected into dried tubes the biochemical analyses of serum samples was performed using an 

automatic chemistry analyzer (Architect 8000, Abbott). Biochemical parameters measured 

were alanine aminotransferase (ALT), aspartate amino transferase (AST), blood urea g/l and 

creatinine. A macroscopic examination of vital organs was carried out soon after sacrifice, 

vital organs such as heart, kidneys, liver, lung and spleen were isolated, weighed and 

examined for any lesions preserved in10% phosphate buffered formalin solution and 

dissected out for histopathological examination, this organs have been fixed for 12 hours and 

then embedded in paraffin using conventional methods [14] cut into 5 micrometer tick sections 

and stained using hematoxylin eosin dye. The sections are then observed under microscope 

for degeneration, necrotic changes and evidence of damage if any. 

Statistical analysis: Results were expressed as the mean ± standard error of mean (SEM). 

Statistical analysis of data was carried out using one-wayanalysis of variance (ANOVA) 

followed by student’s t-test. Differencesin mean were considered to be significant when P < 

0.05. 

RESULTS AND DISCUSSION 

Cytotoxic effect: The traditional medicine all over the world is nowadays revalued by an 

extensive activity of research on different plant species and their therapeutic principles. Plant 

kingdom is a potential source of chemical constituents with antitumor and cytotoxic activities 

owing to their enormous propensity, which synthesize a variety of structurally diverse 

bioactive compounds [15,16] . The rich and diverse plant sources of Morocco are likely to 

provide effective anticancer agents. Using the ethnomedical data approach, C. telephiifolia is 

used in the Moroccan traditional medicine for various diseases, including cancer, was 

collected and evaluated for its cytotoxic effect. Uncontrolled proliferation is a universal 

property of tumour cells. Investigation of the cellular growth control mechanisms has 

contributed to the understanding of carcinogenesis and identification of compounds with 

specific antitumoral activities. Thus, cytotoxicity screening models provide important 

preliminary data to help select plant extracts with potential antitumoral properties for future 

studies [17] . The cytotoxic activity was evaluated on two human cancer cell lines, HeLa and 

MCF7. The cytotoxic effect of methanolic, dichloromethane and Cyclohexane extracts on 

cancer cells was determined using the MTTassay. The MTT assays data are presented 

respectively in figures 1. The cyclohexane extract of Corrigiola telephiifolia root displayed 

moderate cytotoxicity (IC50 = 200 µg/ml) against HeLa cell line, whereas the 

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dichloromethane and methanol extracts showed significantly lower IC50 values (more than 

400 ug/ml). All the extracts tested are inactive against breast cancer cells, (IC50 350 to 400 

ug/ul). To be a good drug candidate, the IC50 value of such agent should be sufficiently low 

to avoid any possible unspecific effects. According to the US NCI plant screening program, a 

crude extract is generally considered to have in vitro cytotoxic activity if the IC50 value is 

less than 30 µg/ml [18,19] . Since the IC50 concentrations of C. telephiifolia extract in tree 

cancerous cell lines were more than 200 µg/ml, we believe that they are not very potent as 

anticancer therapeutic agent. Moreover, In terms of toxicity to the Chang cervical cell, 

cyclohexane extract was more toxic than methanolic and dichloromethane extracts since the 

IC50 cyclohexane extract is around 200 µg/ml while the value of IC50 dichloromethane and 

methanolic extracts were more than 200 µg/ml. The root cyclohexane of Corrigiola 

telephiifolia could be a source of anticancer therapeutic agent against HeLa cell line. Well 

that little remarkable, the cytotoxic effect of cyclohexane extract on the cervical line is 

notable compared to that observed in cell lines of colon and breast. Thus, we are tempted in 

perspective, to test the cyclohexane extract on other cell lines of the cervix, to examine the 

specific effect on cancer of the cervix. It is useful and necessary to carry out other 

investigations to better assess the cytotoxic effect of the cyclohexane extract of C. 

telephiifolia. 

Acute toxicity: The oral administration of a single dose (2000 mg/kg bodyweight) of C. 

telephiifolia root extracts (cyclohexane, dichloromethane and methanol) to mice did not cause 

death within the fourteen five days of the study. The evolution of the weight varied in the 

mice weighed daily. Based on the symptoms observations animals under positive control 

group treated orally with the C. telephiifolia, Mice were perturbed during the first 30 minutes 

in 80% of mice. These effects are disparate in 1h after the treatment. Generally At a dose of 

2000mg/kg, the extracts of the plants don’t lead to mortality by orally way. Under the system 

of global harmonization of Chemicals (GHS), this product is classified Category 5, which the 

higher LD50 is 2000mg/kg.Toxicological research and testing helps to live safely and to 

derive benefit from natural and synthetic substances In this study no changes attributable to 

treatment were found in body weight and any macroscopic changes that could point to the 

cause of the death observed up to the maximum dose of 2000mg/kg body weight of the 

extract administered orally which the single high dose is recommended by OECD guidelines 

423 for testing acute toxicity, this result suggested that extracts of Corrigiola telephiifolia 

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don’t cause any acute toxicity and the high safety margin through oral route justified it 

therapeutic use by the traditional healers. 

Sub-acute toxicity 

Bodyweight, Mortality, and Clinical Signs: The results of in vivo toxicity show that the 

treated groups at the administered doses of 10, 50 mg/kg/day appear normal, presented a 

significant weight gain in both sexes of the mice. Weight loss was significant (p < 0.05) in 

the 100 mg extract/kg group and in 500 extract/kg group in the 2nd and 3rd weeks of the 

study, the reduction in body weight gain is a simple and sensitive index of toxicity after 

exposure to toxic substances [20,21] . There was 3 mortality recorded in the group treated by the 

extract at dose 500 and 100 mg/kg. The result of the effect of the extract on the bodyweight 

and internal organs weight is presented in Table 2 and 3. There was no significant difference 

in the water and food intake in the treatment group at dose 10 and 50 mg/kg/day when 

compared to the control. Results showed that treatment with the extract at doses 100 and 500 

mg/kg/day induced loss of appetite it then become normal and this may due to the stress of 

receiving the oral administration of the extract and some significant changes are observed 

skin effects, breathing, impairment in food intake and water consumption, abdominal 

contraction, salivation and hair loss. Body weight is known to be one of the most sensitive 

indicators of adverse effects may be due to the plant toxicity, especially to the presence of 

some toxic principles in the extract such as saponins (table 1). It is a known fact that oral 

administration of saponins containing compounds could cause bloat, thereby reducing 

appetite in animals [22] . 

Biochemical analysis: The data in Table 4 showed an elevation of readings for the various 

biochemical parameters for most of the mice groups. The values for biochemistry analysis for 

each data represent the value of n=10 for each group except for the group treated by the 

extract at dose 500 (n=8) and 100 mg/kg (n=9). Significant reductions were recorded in the 

serum creatinine concentration in directly suggested no kidney damage specifically by renal 

filtration mechanism; Reduction in creatinine level is observed in cases of muscle wasting as 

seen in malnutrition 

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[23] .The highly significant (P < 0.01) reduction in creatinine 

concentration in all the extract-treated groups indicates that the extract does not exert 

deleterious effect on the renal function and that the decrease in body weight of mice at 100 

and 500 mg extract/kg body weight might be due to muscle wasting possibly due to toxic 

effect of the extract. The extract produced a highly significant (p < 0.01) increase in the levels 

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of alkaline phosphatase at all dose levels but there was no significant change in the levels of 

the urea in all the treated groups. The liver and heart release ALP and an elevation in it 

plasma concentrations are indicators of hepatic and cardiac damage and toxic activity in the 

tissues [24,25] . The aminotransferases (formerly transaminases) are the most frequently utilized 

and specific indicators of hepatocellular necrosis, the alanine amino transferase (ALT) is 

primarily localized to the liver and the aspartate aminotransferase (AST) is present in a wide 

variety of tissues like the heart, skeletal muscle, kidney, brain and liver [26,27] . The increase in 

ALP level is observed in bone disorders involving osteoblastic activity. However, an 

elevation in ALP activity is the first clue to intra hepatic and extra hepatic cholestasis (biliary 

obstruction) [28,29] . A typical myocardial infarction gives an AST/ALT ratio greater than 1 

while an AST/ALT ratio less than 1 is a result of release of ALT from the affected liver [30] , 

AST /ALT of more than 2 indicates alcoholic hepatitis or cirrhosis [30] .These results indicated 

that the methanolic extract of C. telephiifolia when taken for long periods of time might cause 

a liver damage. 

Histopathology: Figures 2-5 showed the histological studies of some vital organs of the 

animals treated with root extract of C. telephiifolia. Histopathology results showed that 

Corrigiola telephiifolia methanolic extract at 500mg/kg caused a significant damage in liver 

as revealed by severe inflammatory granuloma subcapsular rounded shape with necrotic 

debris in the center and clarified hepatocytes (hepatocytes signs of suffering). However, there 

are no significant morphological changes detected in kidney and heart. Sub-acute toxicity of 

medicinal plants help in the identification of possible target organs involved and the toxic 

symptoms. The use of herbal preparations may lead to hypersensitivity reactions; sensitivity 

to the toxic effects of plants differs with regard to the species [31,32,33] . Many widely used 

medicinal plants have been implicated in the occurrence of liver lesions and tumors, lung and 

kidney diseases [34] . Observations of liver and lung section tissues of control and animals in 

group treated by extract at 500 mg/kg body weight shows possible toxics effects of the 

methanolic extract of the plant. The severity was mostly noticed for the younger animals in 

the liver. Lung showed no pathological changes; however Persistent inflammation may lead 

to parenchymal necrosis and fibrosis. The liver is the main target for the toxicity of several 

compounds among which many medicines, although drugs can cause hepatotoxicity through 

different ways [35] , mitochondrial dysfunction is one major mechanisms underlying 

hepatotoxicity, many drug compounds can be metabolized and involve conjugation with 

endogenous compounds via transferase enzymes and many chemicals damage mitochondria, 

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an intracellular organelle that produce energy. Its dysfunction releases excessive amount of 

oxidants which, in turn, injure hepatic cells [36] . In the development of necrosis the damage 

first appears at cytoplasmatic level; next, it spreads to the rest of the cell involving 

mitochondria and the nucleus, and finally results in swelling and loss of plasma membrane 

integrity leading to lysis [37] . 

Table 1: Phytochemical screening of C. telephiifolia root parts 

Chemical groups C. telephiifolia root 

Flavonoids (-) 

Tannins and polyphenols (-) 

Saponins (+) 

Anthocyanin (-) 

Steroids / triterpenes (+ 

Alkaloids (-) 

(+) : présence (-) : absence 

Table 2: Changes in the bodyweight of mice after daily oral treatment with Corrigiola 

telephiifolia Methanolic extract. 

Males Control 10 50 100 500 mg/kg 

J1 18.81 ± 2.24 20.58 ± 1.36 20.78 ± 1.55 23.42 ± 1.03 22.47 ± 1.74 

J5 19.27 ± 1.81 21.66 ±1.52 20.95 ±1.06 23.20 ±1.17 22.08 ±1.12 

J10 19.76 ± 1.06 22.43 ±1.91 21.71 ±1.21 23.12 ±1.43 21.93 ±1.52 

J15 20.44 ± 1.34 22.5 ±1.69 22.58 ±1.67 22.95 ±1.56 21.59 ±1.07 

J20 21.09 ± 2.13 23.53 ±1.89 23.09 ±1.54 22.56 ±1.75 21.43 ±1.43 

J25 22.61 ± 1.64 23.67 ± 2.12 23.53 ± 1.15 22.32 ± 1.12 * 21.08 ± 1.22 * 

J30 23.12 ± 2.75 23.86 ± 1.13 23.70 ± 1.11 22.26 ± 1.54 * 20,89 ± 1.68 * 

J35 23.53 ± 3.05 24.01 ± 1.45 24.12 ± 1.80 22.01 ± 1.09 * 20.72 ± 2,15 * 

J40 23.88 ± 1.59 24.27 ± 2.29 24.29 ± 1.14 21.77 ± 2.08 * 20.57 ± 1.18 * 

J45 24.14 ± 1.12 24.73 ±2.65 24.63 ±2.09 21.53 ±1.16 * 20.31 ±1.05 * 

Values are expressed as mean ± S.D. of 10 mice in each group 

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Femelles Control 10 50 100 500 mg/kg 

J1 21.94 ± 1.23 25.02 ±1.06 21.94 ±1.45 24.53 ±1.08 25.82 ±1.12 

J5 22.14 ±1.56 25.26 ±1.12 22.07 ±1.09 23.67 ±1.33 25.56 ±1.54 

J10 22.38 ±1.50 25.41 ±1.21 22.13 ±1.22 23.52 ±1.07 25.44 ±1.87 

J15 22.75 ±1.22 26.23 ±1.49 22.29 ±1.53 22.76 ±1.05 24.75 ±1.91 

J20 23.32 ±1.09 26.43 ±1.57 23.34 ±1.67 22.50 ±1.43 * 24.56 ±1.23 

J25 23.77 ± 1,13 26.79 ± 1,12 23.77 ± 2.09 22.37 ± 1.12 * 24.12 ± 1,13 

J30 23.96 ± 1.37 26.81 ± 1.45 23.98 ± 2.13 21.75 ± 1.56 * 23.95 ± 1.53 * 

J35 24.23 ± 1.08 27.18 ± 1.67 24.29 ± 1.42 21.23 ± 1.67 * 23.66 ± 1.45 * 

J40 24.58 ± 1.17 27.33 ± 1.22 24.59 ± 1.26 21.10 ± 1.29 * 23.47 ± 1.10 * 

J45 24.79±1.05 27.49 ±1.35 24.86 ±1.55 21.03 ±1.5 * 23.13 ±1.15 * 

Dose mg/kg 

bwt 

Liver 

Heart 

Lung 

Kidney 

The different superscript letters indicate statistically significant differences (P


Cell viability % 

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150,00 

100,00 

50,00 

0,00 

Hella cell line (n=4) 

1000 500 250 125 62,5 31,25 

Concentration (µg/ml) 

CyHex ext 

Dich ext 

MeOH ext 

Fig. 1: Percentage cell viability curve of C. telephiifolia (CT) extracts again HeLa cell 

lines. 

Cell viability was plotted via the concentration. 

All samples were run in quadruplicate (n=4). 

Percentage viability = absorbance of test wells/absorbance of control wells) × 100) plotted 

against the concentration of extract. 

Fig. 2: Liver sections were stained with hematoxylin and eosin (H&E-stained 40×) 

showing the effects of Corrigiola telephiifolia Pourr. extract on sub-acute toxicity study. 

C0: Negative control, L1and L2(x10): C. telephiifolia 500 mg/kg body weight. Arrow shows 

inflammatory granuloma sub capsular rounded shape with necrotic debris in the center and 

clarified hepatocytes (hepatocytes signs of suffering). 

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Fig.3: The cross section of renal tissue of the control group (CI, x4) and the group 

treated with 500mg/kg body weight (K2x 40 and K3, x10) of the extract. No renal 

abnormality was observed, an artery with inflammatory cells around an arteriole normal and 

tubes not necrotic. 

Fig. 4: Photomicrograph of the lung for control (C2) and of testis treated with 100mg/kg 

(L1x4) and 500mg/kg (L2 x10) of the extract. Arrow shows inflammation and congestion in 

the vascular parenchyma and pulmonary lymph node with normal appearance 

Fig. 5: The histology of the cross section of the cardiac muscle of the control group C3 

and H2 of the animals treated with 50mg/kg body weight. No abnormality was observed 

(x100). 

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CONCLUSION 

The toxicity study of C. telephiifolia in mice indicated that the methanol extract at the doses 

used ethnomedicinally do not produce significant changes of biochemical parameters or 

histopathology of internal organs. The highest dose of extract also induces sub acute severe 

hepatotoxicity in mice liver. This was evidenced mainly by histopathological study on all 

particular organs and has been supported by biochemistry findings this study provides 

valuable data on the toxicity profile of Corrigiola telephiifolia that should be essential for 

future study. 

ACKNOWLEDGEMENTS 

The authors wish to thank all the individuals and institutions who made this survey possible. 

REFERENCES 

1. Shrestha PM, Dhillion SS., Nepal. J. Ethnopharmacol. 2003, 86: 81-96. 

2. Bellakhdar J. Médecine traditionnelle et toxicologie ouest- sahariennes. Contribution à 

l’étude de la pharmacopée marocaine. Editions techniques nord-africaines, Rabat, 1978, 

358 

3. Bellakhdar J, Honda G, Miki W. Herb drugs and herbalists in the Maghreb. Institute for the 

study of Languages and Cultures of Asia and Africa, Tokyo. 1982, 339. 

4. Boulos L. Medicinal Plants of North Africa. Algonac, Michigan. (1983) 

5. MM. De Lamarck et Decandolle. Flore française, ou descriptions succinctes de toutes les 

plantes qui croissent naturellement en France. 3 éme édition, Tome quatrième (seconde 

partie) p : 401-402 

6. C. Al Faız, I. Thami Alami, and N. Saıdi, “Domestication of some MAP species,” in 

Biological Diversity, Cultural and Economic Value of Medicinal, Herbal and Aromatic 

Plants in Morocco. Annual report, Ed.2006- 2007, 15–22 

7. Kabbaj FZ., Meddah B., Cherrah y., Faouzi mya., Phytopharmacology 2012, 2(2) 243-256 

8. H. Lakmichi, H. Lakmichi, FZ. Bakhtaoui, CA. Gadhi, A. Ezoubeiri, Y. El Jahiri, A. 

ElMansouri, I. Zrara and K. Loutfi. Evidence-Based Complementary and Alternative 

Medicine, 2011, 10.1155 

9. I. Ciulei. Methodology for analysis of vegetable drugs. Bucharest: Ministry of Chemical 

Industry, Bucharest, 1982; 67 

10. Mosmann T. J Immunol Methods 1983, 65, 55-63. 

11. Twaij HA, Kery A, Al-Khazraji NK. J Ethnopharmacol. 1983, 9(2-3):299-314. 

www.wjpr.net 

13


12. Organization for Economic Co-operation and Development (OECD), Guidance Notes for 

Analysis and Evaluation of Chronic Toxicity and Carcinogenicity Studies, Series on 

Testing and Assessment, no. 35 and Series on Pesticides, no. 14, OECD Environment, 

Health and Safety Publications, 2002. 

13. Donald J, Ecobichon J. CRC Press, New York. 1997, 43– 49 

14. Galighor, A.E., Kozloff, E.N., (1976): Essentials of practical microtechnique 2 nd edn, Lea 

and Febiger, NewYork. 

15. Kim JB, Koo HN, Joeng HJ. J. Pharmacol. Sci., 2005, 97: 138-45. 

16. Indap MA, Radhika S, Motiwale L, Rao KV. J Exp Biol. 2006; 44(3):216-20. 

17. Cardellina JH, Fuller RW, Gamble WR, Westergaard C, Boswell J, Munro MHG, 

Currens M, Boyd MP. In: Bohlin, L., Bruhn, J.G. (Eds), Bioassay Methods in Natural 

Product Research and Development. Kluwer Academic Publishers, Dordrecht. 1999, 25- 

36. 

18. Boik J 2001. Natural compounds in cancer therapy: Oregon Medical Press 

19. Suffness M, Pezzuto J.M. Assays related to cancer drug discovery. In: Hostettmann, K. 

(Ed). Methods in Plant Biochemistry: Assays for Bioactivity, Academic Press, London, 

1990, (6). 71-133. 

20. Raza M, Al-Shabanath OA, El-Hadiyah TM, Al-Majed AA. Effect of prolonged 

vigabatrin treatment on hematological and biochemical parameters in plasma, liver and 

kidney of Swiss albino mice, Scientia Pharmaceutica 2002. 70: 135-145. 

21. Teo S, Strlig D, Thomas S, Hoberman A, Kiorpes A, Khetani V. Toxicol. 2002. 79: 183- 

196. 

22. Trease GE and Evans WC. Pharmacogonasy, 14 th Edition, Brown Publication 1989 

23. Pincus MR. Interpreting Laboratory Results: Reference Values and Decision Making. In: 

Henry JB Ed. Clinical Diagnosis and Management by laboratory Methods. 19 Th ed. 

Philadelphia: WB Saunders. 1996, 162-193 

24. Mythilypriya R, Shanthi P and Sachdanandam P. J Health Sc. 2007 53(4): 351-358. 

25. Wasan K. M., Najafi. S., Wong J and Kwong M. J Pharm Sci (www.ualberta.ca/~csps). 

2001, 4(3): 228-234. 

26. Rosen HR, Keefe EB. Evaluation of abnormal liver enzymes, use of liver tests and the 

serology of viral hepatitis: Liver disease, diagnosis and management. 1 st ed. New York; 

Churchill livingstone publishers, 2000; 24-357 

www.wjpr.net 

14


27. Friedman SF, Martin P, Munoz JS. Laboratory evaluation of the patient with liver 

disease. Hepatology, a textbook of liver disease. Philedelphia; Saunders publication, 

2003; 1: 661-709. 

28. Moss DW. Clin. Biochem. 1987, 20: 225-230 

29. Young LY, Holland EG. Applied therapeutics: the Clinical use of Drugs. 6 th ed, W.A. 

Applied Therapeutics, Inc. 1995, 14-20. 

30. Sacher RA, Mepherson RA. Widmann’s. Clinical interpretation of laboratory test, 

U.S.A., Pennsylvania. 1991. 3rd edition pp. 416-443 

31. Hardin, J., W. Jay and M. Arena. Human Poisoning from Native and Cultivated Plants. 

2nd ed. Duke University Press, Durham, N.C., 1974, 233. 

32. Nielson, D.B., N.R. Rimbey and L.F. James.. Economic Considerations of Poisonous 

Plantson Livestock, In: The Ecology and Economic Impact of Poisonous Plants on 

Livestock Production (eds. James et al.), Westview Press, Boulder, USA, 1988,5-16 

33. Kaiser Permanente-Northwest. 2003. Common Poisonous Plants and Non-poisonous 

Plants. Available at: http://www.universityofcalifornia.edu/health/ 

34. E. Ernst, “Harmless herbs. American Journal of Medicine, 1998. 2 (104), 170–178 

35. Lee W.M. N. Engl. J. Med. 2003. 349 474–485. 

36. Jaeschke H, Gores GJ, Cederbaum AI, Hinson JA, Pessayre D, Lemasters JJ. Toxicol. 

Sci. 2002, 65 (2): 166–76. 

37. Ignazio Grattagliano MD, Piero Portincasa MD PhD, Vincenzo O Palmieri MD PhD, 

Giuseppe Palasciano MD PhD. Annals of Hepatology 2002; 1(4): 162-168 

www.wjpr.net 

15

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