Effect of Bridelia ferruginea (Euphorbiaceae) Leaf Extract on ...

Research Article 

Ezzeldi & Nahhas 

Tropical Journal <strong>of</strong> Pharmaceutical Research October 2012; 11 (5): 759-765 

© Pharmacotherapy Group, 

Faculty <strong>of</strong> Pharmacy, University <strong>of</strong> Benin, 

Benin City, 300001 Nigeria. 

All rights reserved. 

Available online at http://www.tjpr.org 

http://dx.doi.org/10.4314/tjpr.v11i5.9 

<strong>Effect</strong> <strong>of</strong> <strong>Bridelia</strong> <strong>ferruginea</strong> (<strong>Euphorbiaceae</strong>) <strong>Leaf</strong> 

<strong>Extract</strong> on Sucrose-induced Glucose Intolerance in 

Rats 

Dieudonne Njamen 1 , Benedicta N Nkeh-Chungag 2 , Emmanuel Tsala 3 , 

Zacharias T Fomum 3 , Jean Claude Mbanya 4 and George F Ngufor 5 

1 Department <strong>of</strong> Animal Biology and Physiology, Faculty <strong>of</strong> Science, University <strong>of</strong> Yaounde1, PO Box 812, Yaoundé, 

Cameroon, 2 Department <strong>of</strong> Zoology, Faculty <strong>of</strong> Science, Engineering and Technology, Walter Sisulu University, 

Mthatha, 5117, South Africa, 3 Department <strong>of</strong> Organic Chemistry, Faculty <strong>of</strong> Science, University <strong>of</strong> Yaoundé 1, PO 

Box 812 Yaoundé, 4 Department <strong>of</strong> Internal Medicine, Faculty <strong>of</strong> Medicine and Biomedical Sciences, University <strong>of</strong> 

Yaounde1, 5 Department <strong>of</strong> Health, Yaoundé, Cameroon. 

Abstract 

Purpose: To evaluate the hypoglycaemic effect <strong>of</strong> the methanol extract <strong>of</strong> <strong>Bridelia</strong> <strong>ferruginea</strong> leaves 

(MEBF) on sucrose-induced glucose intolerance in rats. 

Methods: Male Wistar rats, aged 6 - 7 weeks and weighing 140 - 160 g, were used. The animals were 

fed standard rat chow supplemented with 35%, 50% or 65% sucrose for 8 weeks while control animals 

were fed standard rat chow. The hypoglycaemic effect <strong>of</strong> MEBF and the reference drugs (tolbutamide, 

and metformin) in the animals were evaluated following a single dose <strong>of</strong> these drugs and 6-day 

treatment. Plasma lipid pr<strong>of</strong>iles were also determined. 

Results: Fasting glucose concentrations ranged from 45 to 70 mg/dl, and the increase was significant in 

the sucrose diet groups from week 1. After 2 weeks on these diets, oral glucose tolerance test showed 

that sucrose feeding significantly impaired glucose homeostasis 1 and 2 hours after a glucose challenge 

(76.7 2.0 versus 86.4 8.5 and 66.7 1.4 versus 75.5 3.0, respectively). Fasting blood sugar 

levels were significantly (p < 0.05) reduced in sucrose-induced, glucose-intolerant rats after a single 

dose <strong>of</strong> MEBF. The extract also significantly reduced blood glucose (from 167 ± 23 mg/dL to 126 ± 5 

mg/dL), serum total cholesterol (from 161 ± 20 mg/dL to 93 ± 10 mg/dL) and triglyceride levels (281 ± 25 

mg/dL to 228 ± 5 mg/dL) in glucose intolerant rats after 6 days <strong>of</strong> treatment. 

Conclusion: The methanol leaf extract <strong>of</strong> <strong>Bridelia</strong> <strong>ferruginea</strong> exhibited hypoglycaemic effect in glucoseintolerant 

rats. 

Keywords: Sucrose-induced, Glucose intolerance, <strong>Bridelia</strong> <strong>ferruginea</strong>, Hypoglycaemia, Metformin, 

Tolbutamide. 

Received: 10 March 2012 Revised accepted: 12 September 2012 

*Corresponding author: Email: bnkehchungag@wsu.ac.za; Tel/Fax: (+27) 47 502 1989 

Trop J Pharm Res, October 2012;11 (5): 759

INTRODUCTION 

Diabetes mellitus is one <strong>of</strong> the most common 

endocrine and metabolic disorders affecting 

over 170 million people worldwide [1,2]. 

Insulin resistance is a key phenomenon in the 

pathogenesis <strong>of</strong> type 2 diabetes and is 

usually associated with the obesity, dyslipidaemia 

and hypertension. Insulin resistance, 

characterised by hyper-insulinemia, hypertriglyceridemia 

and hypertension, has been 

reported in primary normoglycaemic and 

normotensive, genetically non-susceptible 

Sprague-Dawley rats fed high sucrose or 

fructose diets [3,4]. Increased fructose 

consumption, on the other hand, has been 

associated with obesity epidemic as well as 

metabolic syndrome [5,6]. Fructose-rich and 

high fat diets, commonly consumed in 

emerging urban areas, has been associated 

with increased prevalence <strong>of</strong> 

overweight/obesity and diabetes in these 

communities [7]. 

Among the many challenges faced by 

developing countries in the face <strong>of</strong> rapid 

urbanization is the need for medications to 

address emerging diseases such as diabetes 

mellitus. To address this need, indigineous 

knowledge is <strong>of</strong>ten referred to, including the 

use <strong>of</strong> extracts from medicinal plants. Several 

plant extracts are reported to have 

hypoglycaemic effect including <strong>Bridelia</strong> 

<strong>ferruginea</strong> (<strong>Euphorbiaceae</strong>) [8] - a woody 

shrub which grows in the Savannah or rain 

forests <strong>of</strong> Africa. Traditionally, B. <strong>ferruginea</strong> 

bark extract is used as a milk coagulant, 

mouth wash, purgative and vermifuge. It is 

also used for the treatment <strong>of</strong> diabetes, 

arthritis and boils. <strong>Extract</strong>s <strong>of</strong> the plant have 

been shown to have molluscidal effect [9], 

antibacterial activity [10], anti-inflammatory 

property [11] and hypoglycaemic effect [12]. 

Several compounds with cytotoxic and 

cytostatic activity on tumor cell lines, such as 

β-peltatin-5-O-β-D-glucopyranoside, deoxypodophyllotoxin 

and 5’demethoxy-β-peltatin- 

5-O-β-D-glucopyranoside, have been isolated 

from B. <strong>ferruginea</strong> [13]; so also is the 

biflavanol gallocatechim-[4-O-7]-epigalloca- 

Njamen et al 

techim [14]. Although this plant extract has 

been shown to have hypoglycaemic effect, its 

effect has not been studied in sucroseinduced 

glucose intolerance. The objective <strong>of</strong> 

the present study was, therefore, to induce 

glucose intolerance in normal Wistar rats 

using sucrose loading and to investigate the 

hypoglycaemic effect <strong>of</strong> the methanol leaf 

extract <strong>of</strong> <strong>Bridelia</strong> <strong>ferruginea</strong> in the rats. 

EXPERIMENTAL 

Plant material 

<strong>Bridelia</strong> <strong>ferruginea</strong> was collected in May 2000 

in Yaoundé – Cameroon. It was identified and 

authenticated by Mr Nana, a taxonomist at 

the Cameroon National Herbarium in 

Yaoundé where a voucher specimen 

(32266/HNC) was deposited. Air-dried and 

powdered leaves (1 kg) were extracted with 

methanol at room temperature for 72 h 

followed by evaporation <strong>of</strong> the solvent under 

reduced pressure using a Büchi Rota-vapor 

(Bioblock, Illkirch-France). A greenish crude 

extract (80 g) was obtained, from which test 

solutions <strong>of</strong> the required concentrations were 

prepared in Tween 80/ethanol/water (1:1:10) 

for subsequent evaluation. 

Drugs 

Tolbutamide and metformin, used in these 

experiments were obtained from Norvo 

Nordisk. 

Experimental animals 

Six to seven week-old male Wistar rats, 

weighing 140 – 160 g, were used in these 

experiments. Housing <strong>of</strong> animals and all in 

vivo experiments were carried out following 

the guidelines <strong>of</strong> the Institutional Ethics 

Committee <strong>of</strong> the Cameroon Ministry <strong>of</strong> 

Scientific Research and Technology 

Innovation, which has adopted the guidelines 

established by the European Union on 

Animal Care (CEE Council 86/609EEC, 

EMBO, 2005) [15]. 


Induction <strong>of</strong> glucose intolerance 

At the start <strong>of</strong> the experiment, baseline 

fasting blood glucose level was determined 

for all animals after a 12-h fast. A 

spectrophotometer, Hemocue R B-Glucose 

Analyser (Angelholm, Sweden), was used to 

measure blood glucose levels in whole 

capillary blood obtained by puncturing the tail 

vein. Animals with normal blood glucose 

levels were then randomly allocated to each 

<strong>of</strong> four experimental groups (5 rats/group). 

The control group was fed regular laboratory 

rat chow (standard diet) consisting <strong>of</strong> 58.1 % 

wheat flour, 5.8 % corn flour, 7.0 % ground 

palm nut extract, 11.6 % ground cotton nuts, 

5.8 % powdered bone and 11.7 % ground 

smoked fish. The other three groups were 

placed on experimental diets, consisting <strong>of</strong> 

the standard diet enriched with 35, 50 or 65 

% (w/w) sucrose, respectively (hereafter 

referred to as sucrose diets). Blood glucose 

levels were determined for all animals weekly 

during the 8-week diet period. 

Glucose tolerance test 

After 2 weeks on assigned diets, fasting 

blood glucose levels were determined in 

control and 50 % sucrose-fed animals. These 

animals were then orally challenged with 3 g 

glucose/kg and fasting blood glucose levels 

determined 30 min, 1 and 2 h after glucose 

administration. 

Assessment <strong>of</strong> hypoglycaemic effect <strong>of</strong> 

single dose <strong>of</strong> drugs 

Whole capillary blood glucose levels were 

determined using a blood glucose 

spectrophotometer, after an overnight fast. 

Glucose concentration was measured at time 

0 h, i.e., just before administration <strong>of</strong> the 

drugs and then at 30 min intervals for 24 h 

after drug administration to the groups which 

received either tolbutamide (50 mg/kg) or 50 

mg/kg <strong>of</strong> (MEBF). For the group which 

received metformin (38 mg/kg), blood 

glucose level was measured after 2, 4, 6, 12, 

Njamen et al 

18 and 24 h post-treatment. Animals which 

received insulin (4 U) were tested before 

insulin administration and also 2 h after 

insulin administration. 

Hypoglycemic and lipid-lowering effects 

<strong>of</strong> MEBF 

The animals which showed glucose 

intolerance after the 8-week dietary period 

were used for this experiment. Ten <strong>of</strong> these 

rats were maintained on 50 % sucrose 

enriched diet and allocated to one <strong>of</strong> the two 

groups - 5 to the control group which 

received no treatment and 5 to the group 

treated daily for 6 days with MEFB (50 

mg/kg). Serum glucose concentration, 

triglycerides and total cholesterol were 

determined before treatment and after 6 days 

<strong>of</strong> treatment after a 12 h fast. Briefly, serum 

total cholesterol, HDL cholesterol and 

triglycerides levels were measured in animals 

enzymatically using Cobas Mira S analyzer 

with kits purchased from Biolabo (France). 

LDL-choloesterol was calculated from 

concentrations <strong>of</strong> total cholesterol, HDL 

cholesterol and triglycerides according to 

Friedewald [16]. 

Measurement <strong>of</strong> insulin secretion 

Pancreatic islet cells from NMRI mice 

(Charles River, Sulzfeld, Germany) were 

used for these experiments. Mice were 

sacrificed by inhalation <strong>of</strong> excess CO2 and 

batches <strong>of</strong> 5 pancreatic islets isolated 

microscopically and incubated for 60 min at 

37 °C with 3 or 15 mM glucose. The 

incubation medium (pH 7.4) contained (in 

mMol/l): 122 NaCl, 4.8 KCl, 2.5 CaCl2, 1.1 

MgCl2, 10 (4-(2-Hydroxyethyl)piperazine-1ethanesulfonic 

acid (HEPES), as well as 0.5 

% bovine serum albumin. The plant extract 

was added at different concentrations in the 

presence <strong>of</strong> 3 or 15 mM glucose. The amount 

<strong>of</strong> insulin secreted was determined by 

radioimmunoassay using rat insulin (Crystal 

Chem. Inc., USA) as standard. 


Statistical analysis 

GraphPad Instat was used to carry out oneway 

analysis <strong>of</strong> variance (ANOVA) followed 

by Tukey-Kramer Multiple Comparisons Test. 

For data on insulin secretion, multiple 

comparisons were made by ANOVA followed 

by Student-Newman-Keuls test. The results 

are expressed as mean ± standard error. A pvalue 

<strong>of</strong> < 0.05 was considered significant. 

RESULTS 

<strong>Effect</strong> <strong>of</strong> diet on glucose tolerance 

Baseline fasting blood glucose levels in 

normoglycemic rats were between 45 - 52 

mg/dL. Sucrose diets induced significant 

increases in the mean blood glucose 

concentration. Animals fed 35% and 50% 

sucrose showed significant (p

Njamen et al 

Table 3: Hypoglycaemic effect <strong>of</strong> porcine insulin (4 U/rat, s.c.) in 50 % sucrose-fed and control rats after 12 

h <strong>of</strong> fasting 

Time Control Sucrose fed rats 

(h) 

Blood glucose 

(mg/dL) 

Reduction in blood 

glucose (%) 

Blood glucose 

(mg/dL) 

Reduction in blood 

glucose (%) 

0 46.7 1.4 - 73.3 4.0* - 

2 16.7 0.3* 64.5 35.0 0.1* 52.3 

*p < 0.05, n = 5 

fed standard diet (Fig 2a). Total serum 

cholesterol level was significantly higher (p < 

0.05) in sucrose-fed rats than in control rats, 

while serum triglyceride levels were 280.7 

23.1 and 169 17.1 mg/dL (p < 0.05) in 50 % 

sucrose-fed and control rats, respectively. 

The 50 % sucrose diet significantly (p < 0.05) 

increased blood glucose, serum triglyceride 

and total cholesterol levels 

Fig 1: Hypoglycaemic effect <strong>of</strong> MEBF, tolbutamide 

and metformin in 50% sucrose-fed rats after an 

overnight fast; * p < 0.05 compared to control, n = 

5. 

<strong>Effect</strong> <strong>of</strong> 6-day treatment with MEBF on 

blood glucose and lipid levels 

After 6 days <strong>of</strong> oral MEBF treatment (50 

mg/kg/day), fasting blood glucose levels in 50 

% sucrose-fed rats decreased significantly (p 

< 0.05) to levels similar to those observed in 

control animals (126.4 ± 2.9 versus 167.7 

mg/dL ± 13 for control). Sucrose-fed rats 

treated with MEBF significantly (p < 0.05) 

reduced serum triglyceride and total 

cholesterol relative to control values. 

Although both triglyceride and total 

cholesterol levels were significantly reduced 

by MEBF, post-treatment levels were not 

different from pre-treatment levels in control 

animals (Fig 2b). 

(a) 

(b) 

Fig 2: (a) <strong>Effect</strong> <strong>of</strong> sucrose-enriched diet on blood 

glucose, triglyceride and total cholesterol levels <strong>of</strong> 

rats after 8 weeks on 50 % sucrose diet; (b) <strong>Effect</strong> <strong>of</strong> 

6-day MEBF treatment on fasting blood glucose 

level, serum triglyceride and serum total cholesterol 

levels in 50 % sucrose-fed animals, compared to 

control animals; *p < 0.05, **p < 0.01, n= 5. 


<strong>Effect</strong> <strong>of</strong> MEBF extract on insulin 

secretion 

MEBF, at all dose levels tested, did not 

induce any significant effect (p < 0.05) on 

insulin secretion. 

DISCUSSION 

The results presented demonstrate that rats 

fed sucrose-rich diets for 8 weeks developed 

higher fasting blood glucose concentrations. 

After 2 weeks <strong>of</strong> ingesting sucrose-enriched 

diet, the rats showed intolerance to glucose 

as indicated by the oral glucose tolerance 

test. Blood glucose levels were significantly 

higher from the 5 th week <strong>of</strong> sucrose enriched 

diet, indicating that the impairment <strong>of</strong> glucose 

homeostasis is dependent on the duration <strong>of</strong> 

exposure to large amounts <strong>of</strong> sucrose. 

When sucrose is consumed, it is broken 

down to glucose and fructose. Absorbed 

fructose is converted to lipogenic precursors 

leading to increase in plasma triglyceride 

levels [17,18]. Our results show that at the 

end <strong>of</strong> the 8-week diet period, total 

cholesterol and triglyceride levels were 

significantly higher in sucrose-fed rats, 

compared to control. High fructose diets are 

associated with increased serum triglyceride 

[19] and total cholesterol [18] levels. Longterm 

effects <strong>of</strong> fructose administration include 

significant lipotoxicity and hepatic insulin 

resistance which may eventually lead to a 

more generalized insulin resistance [20,21]; 

this was reflected by the significantly higher 

blood glucose levels in sucrose-fed animals. 

Unlike glucose, fructose does not induce the 

release <strong>of</strong> insulin or leptin, both <strong>of</strong> which are 

necessary for glucose handling [19]. 

Importantly, Wei et al [22] reported that 

fructose administration may cause oxidative 

stress leading to the release <strong>of</strong> reactive 

oxygen species which, in turn, may be 

associated with impaired insulin signalling. 

This observation is in agreement with our 

findings which show that sucrose-fed rats had 

higher blood glucose levels when challenged 

Njamen et al 

with oral glucose, indicating impairment in 

glucose handling mechanisms. The 

administration <strong>of</strong> insulin to sucrose-fed rats 

induced a smaller glucose lowering effect 

compared to control, suggesting that the 

sucrose-fed rats had developed impaired 

response to insulin action. Consistent with 

this observation, metformin, which acts by 

increasing insulin-mediated glucose uptake 

by cells [23], failed to show significant 

hypoglycaemic activity in sucrose-fed animals 

until 18 h post-metformin administration. 

MEBF extract exhibited significant 

hypoglycaemic activity in sucrose-fed, 

glucose-intolerant rats compared to control 

rats, indicating that this extract may contain 

metabolites with anti-diabetic properties. 

Cholesterol as well as triglyceride levels were 

also decreased in these rats compared to 

untreated animals. These two observations 

suggest that B. <strong>ferruginea</strong> leaf extract lowers 

blood glucose concentration by improving 

insulin sensitivity and not by stimulating 

insulin secretion. 

CONCLUSION 

The leaf extract <strong>of</strong> <strong>Bridelia</strong> <strong>ferruginea</strong> 

exhibited hypoglycaemic effects in sucroseinduced 

glucose intolerant rats as well as 

improved lipid pr<strong>of</strong>iles. However, further 

studies are required to ascertain if these 

findings can be translated to applications. 

ACKNOWLEDGEMENT 

This work was supported by the IFS/OPCW 

(grant no. F/3336-1 to Dr Njamen) and the 

Walter Sisulu Institutional Research Fund. 

We wish to thank Mr Nana Victor (National 

Herbarium, Yaoundé - Cameroon) for his 

assistance with ethnobotanical survey and 

collection <strong>of</strong> the plant material. 

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