35 J I M D C   2 0 1 7  35 

Op e n  Ac c e ss  
F u l l  L e n g t h  A r t i c l e  

Comparison of Anti-Diabetic Activity of Berberis lycium 
Royle Stem bark (Barberry) and Pioglitazone in Type 2 

Diabetes Induced Mice Model 
 

Hina Aslam1, Akbar Waheed2, Muhammed Nauman Shad3, Khalid Niaz4    

1Assistant Professor Pharmacology, Islamabad Medical & Dental College 
2Professor & Head of Pharmacology Department, Islamic International Medical College IIMC-T 

3Associate Professor Pharmacology, Islam Dental College, Sialkot 
4.Assistant Professor Pharmacology, Islamabad Medical & Dental College 

A B S T R A C T  

Objective: To compare the anti-diabetic activity of aqueous extract of stem bark of Berberis lycium Royle and 

Pioglitazone –a thiazolidinedione in a type 2 diabetes mellitus induced male mice model. 

Material and Methods: This Randomized control trial was carried out in the animal house of National Institute of Health 

(NIH), Islamabad for 10 weeks. Fifty albino Balb/C male mice were divided randomly into groups I-V (10 in each group). 

Group I served as normal control group. In rest of the forty mice from group II-V, type 2 diabetes mellitus was induced by 

administration of high fat diet (HFD) for two weeks followed by low dose (40 mg/kg) intra-peritoneal Streptozotocin (STZ) 

injections for four consecutive days. Group II served as the disease control group, group III received the aqueous extract 

of stem bark of Berberis lycium Royle in dose of 50 mg/kg body wt. while group IV received the aqueous extract of stem 

bark of Berberis lycium Royle in dose of 100 mg/kg body wt. Group V was administered Pioglitazone in a dose of 

30mg/kg body wt. The herb extract and the drug was given orally once a day for six consecutive weeks. Samples were 

taken at the end of ten weeks.  

Results: The blood samples estimated for fasting blood glucose (FBG) & glycosylated hemoglobin (HbA1c %) levels 

showed that the aqueous extract of stem bark of Berberis lycium Royle in a high dose (100 mg/kg body wt.) maximally 

lowered the FBG and HbA1c% levels followed by its low dose (50 mg/kg body wt.) Pioglitazone also reduced the FBG 

and HbA1c% to normal limits but its extent was less than the aqueous extract of stem bark of Berberis lycium Royle. 

Conclusion: The aqueous extract of stem bark of Berberis lycium Royle lowers the FBG and HbA1c levels in a type 2 

diabetes induced male mice in a dose dependent manner.  

Key words: Berberis lycium Royle, Diabetes Mellitus type 2, Pioglitazone, Streptozotocin,. 

Author`s Contribution 
1Conceived the topic of research and 
designed the study,2Literature review and 
manuscript writing,3Data Analysis and 
Discussion 

Address of Correspondence 
Dr. Hina Aslam 
doc.hina.aslam1@gmail.com   

Article info. 
Received: Jan 6, 2017 
Accepted: Mar 22, 2017 
 

Cite this article: Aslam H, Waheed A, Shad MN, Niaz K. Comparison of Anti-Diabetic Activity of 
Berberis lycium Royle Stem bark (Barberry) and Pioglitazone in Type 2 Diabetes Induced Mice 
Model. JIMDC. 2017; 6(1):35-39. 

 

Funding Source: Nil 
Conflict of Interest: Nil 

I n t r o d u c t i o n  
 

Around the world, Diabetes affects 2-3% of the total 

population. So, Diabetes Mellitus is now a clinical 

syndrome.1 It is characterized by long standing 

hyperglycemia along with the disturbances of 

carbohydrate, fat and protein metabolism due to a defect 

in either insulin secretion, action or both.2 Everyday new 

O R I G I N A L  A R T I C L E  

mailto:doc.hina.aslam1@gmail.com


                           36 J I M D C   2 0 1 7  36 

researches are taking place to discover more efficacious 

drugs. Thus modern medicine has been famous for its 

efficient role but the side effects have always been a 

grim.3 So the trends have gradually started shifting 

towards the use of natural products.4 Berberis lycium 

Royle (family Berberidaceae) is a famous medicinal herb.5 

It is known as Barberry in English.6 Berberis lycium Royle 

is found in Pakistan, Indian Occupied Kashmir, Bhutan, 

Japan, China, Nepal, United Kingdom, Ireland, Turkey 

and parts of Asia, South America, Southern Argentina, 

Chile and Europe.1,2  In Pakistan, it is abundantly found in 

Margalla Hills.7  It is also distributed in northern areas 

such as Gilgit, Baltistan, Ghizer, Astor, Diamer and Swat, 

Khyber Pakhtunkhwa.8  

Berberis lycium Royle as an anti-diabetic agent has been 

investigated. Studies have been conducted on its different 

parts like the root, stem, leaves, fruit and root bark, both 

in crude and extracted forms. Its stem bark has not been 

investigated yet, despite the fact that the stem bark is 

readily available in local market.  Berberine-the active 

ingredient with the anti-diabetic potential, is present in 

highest concentrations in roots followed by stem bark.9,10 

So far the anti-diabetic activity of Berberis lycium Royle 

has been compared with the current anti-diabetic agents 

like Insulin, Gliclazide, Glibenclamide.10,11 In the present 

study, aqueous extract of stem bark of the herb was 

selected and its anti-diabtic property was compared to 

another oral anti-diabetic drug; Pioglitazone.  

    M a t e r i a l  a n d  M e t h o d s  

A randomized controlled study of ten weeks’ duration was 

carried in the animal house of National Institute of Health 

(NIH), Islamabad. A total of fifty healthy male albino 

Balb/C mice, weighing 28-38g and aged between 6-8 

weeks, having fasting blood glucose (FBG) levels not 

more than 110 mg/dl and HbA1c <6.0 were included in 

study. All mice were acclimatized for one week and then 

they were randomly divided in five groups (group I-V), 

each group containing 10 mice in total. Group I (n=10) 

served as the normal control group. In rest of forty mice 

(group II-V), type 2 diabetes mellitus was induced by 

administration of high fat diet (HFD) for two weeks 

followed by low dose intra-peritoneal injection of freshly 

prepared Streptozotocin (STZ), once daily for four 

consecutive days.12,13 A persistent FBG level >250mg/dl 

was selected as the cut off point for the confirmation of 

Diabetes.14 Group II was the diabetes control group to 

which no drug or herb was given. Group III received 50 

mg/kg body wt. (low dose) of aqueous extract of stem 

bark of Berberis lycium Royle while the group IV received 

100 mg/kg body wt. (high dose) of aqueous extract of 

stem bark of Berberis lycium Royle. The group V received 

the drug; pioglitazone in a dose of 30mg/kg body wt. The 

herb and the drug were given orally once daily for six 

consecutive weeks. Mice were housed under the 

controlled conditions of room temperature 20+2o C, 

relative humidity 50%-70% and 12-h light-dark cycle. 

They were provided free access to water ad libitum. All 

mice were handled in accordance to the NIH guidelines. 

The stem bark of Berberis lycium Royle was collected 

from village Prang, Charsadda. It was identified by a 

botanist at Botany department, Peshawar University. It 

was then washed thoroughly with water and shade dried. 

It was grounded into a fine powder with an electrical 

grinder and taken into a non-metallic jar. The bark powder 

was soaked in distilled water for 72 hours with periodic 

stirring. It was then filtered using Whatmann filter paper 

no.1. The filtrate was evaporated at 55 0C in a rotary 

evaporator at the research laboratory of Riphah Institute 

of Pharmaceutical Sciences (RIPS), Islamabad. The 

extract was obtained as a dark brown semi-solid sticky 

paste. It was stored in air tight glass bottles, protected 

from light and kept in refrigerator at 2-8 oC to be used 

throughout the experiment. The yield of aqueous extract 

of stem bark of Berberis lycium Royle with respect to the 

original dry plant material was about 25%.15 

Blood samples were taken at the end of week 4 for the 

confirmation of diabetes mellitus and at the end of week 

10 for final sampling. The 6-hr fasting blood samples were 

preferred as blood glucose levels vary widely together 

with food intake during a typical day.16-18 Fasting blood 

glucose (FBG) levels were measured using glucose 

oxidase/ GOD POD method1 while glycosylated 

hemoglobin (HbA1C%) of the mice were determined by 

cation exchange resin method.19,20  

Descriptive statistics were applied using one way ANOVA 

test on SPSS 20. The level of significance was pre-

defined as <0.05 (p<0.05).  

 



                           37 J I M D C   2 0 1 7  37 

R e s u l t s  

The final blood sampling at the end of week 10 i.e. 

termination of study, showed the following results: 

Significant difference was observed between group II & III 

at the end of week 10, regarding the mean FBG levels 

(457.3+19.6 vs. 87.2+1.8) p<0.05 and mean HbA1c% 

(9.8+0.5 vs. 4.7+0.1) p<0.05 as shown in figure I & II. It 

was thus reported that the low dose (50mg/kg body wt.) of 

aqueous extract of stem bark of Berberis lycium Royle 

significantly decreased the mean FBG and HbA1c levels 

in diabetic mice as compared to disease control group.  

Significant difference was observed between group II & IV 

at the end of week 10 in their mean FBG levels by Kit 

method (457.3+19.6 vs 77.4+2.0) p<0.05 and mean 

HbA1C% of group IV (9.8+0.5 vs 4.4+0.1) p<0.05 as 

shown in figure I & II. Thus, it is observed that the high 

dose (100mg/kg body wt.) of aqueous extract of stem 

bark of Berberis lycium Royle significantly decreased the 

mean FBG and HbA1c levels in diabetic mice as 

compared to disease control group.  

Significant reduction in the mean FBG 

(457.3+19.6vs.96.1+2.4) p<0.05 and HbA1c% levels 

(9.8+0.5vs.5.1+0.1) p<0.05 was observed in group V at 

the end of week 10 in comparison with group II (diabetes 

mellitus control group) as shown in figure I & II.  

0

100

200

300

400

500

Grou
p 1

Grou
p 2

Grou
p 3

Grou
p 4

Grou
p 5

FBG by Kit 77.2 457.3 87.2 77.4 96.1

A
x

is
 T

it
l 

Le
v

e
l 

o
f 

F
B

G
 

m
g

/d
L

 

Figure I: Effect of herb extract and drug on FBG(mg/dl) 

levels of group I-V (n=50) 

 

Maximum reduction was observed in high dose group, 

followed by low dose group and then pioglitazone group. 

Statistically difference was insignificant (p>0.05) among 

the group III, IV, V in their FBG and HbA1c levels.  

0

2

4

6

8

10

Grou
p I

Grou
p II

Grou
p III

Grou
p IV

Grou
p V

HbA1c% 4.8 9.8 4.7 4.4 5.1

H
b

Figure 2: Effect of herb extract and herb on HbA1c levels 

(%) of group I-V (n=50) 

D i s c u s s i o n  

Naturopathy is the current trend now.21 In this study, the 

hypoglycemic activity of stem bark of Berberis lycium 

Royle was observed and compared with pioglitazone. The 

results indicated that the aqueous extract of stem bark of 

Berberis lycium Royle has a significant hypoglycemic 

effect (p<0.05), in a dose-dependent manner. FBG levels 

were lowest in the group receiving aqueous extract of 

Berberis lycium Royle stem bark at a dose of 100mg/kg 

body wt. (p=0.00) The levels were even lower than those 

of the normal control. However, statistically insignificant 

difference (p>0.05) was observed among the group III, IV, 

V in their FBG and HbA1c levels. These results correlate 

with the study carried by Gulfraz and Mahmood which 

reported hypoglycemic activity of methanolic extract of 

root of Berberis lycium Royle.10 These results also 

correlate with the study done by Maqsood Ahmed which 

showed the glucose lowering ability of powdered root bark 

of Berberis lycium Royle and its extracts.11 The other 

parameter of the study was the glycosylated hemoglobin 

(HbA1c) levels. The aqueous extract of Berberis lycium 

Royle stem bark also decreased the level of glycosylated 

hemoglobin (HbA1c%) in a dose dependent manner. High 

dose (100mg/kg body wt.) produced marked reduction in 

HbA1c level followed by the low dose (50mg/kg body wt.) 

(p<0.05) These results again are in accordance with the 

work of Gulfraz and Mahmood on the extract of Berberis 

lycium Royle root.10 Pioglitazone also reduced the FBG 

and HbA1C% upto the normal levels but to a lesser extent 

then the herb stem extract. 



                           38 J I M D C   2 0 1 7  38 

The glucose lowering effect of aqueous extract of stem 

bark of Berberis lycium Royle is probably due to presence 

of an alkaloid- berberine in stem.22 A study by Yin J and 

co-workers in 2002 demonstrated the blood glucose 

lowering activity of berberine was similar to that of 

metformin.23 Another study showed that berberine 

decreases blood glucose levels by increasing glucose 

transport by enhancement of GLUTs.24 Berberine has 

also found to stimulate the activity of AMPK (AMP 

mediated protein kinase) by mitochondrial inhibition and 

thus enhancing the GLUT-4 and GLUT-1 translocations 

resulting in insulin independent mechanism of glucose 

consumption.25 

Further studies are required to investigate the 

pharmacokinetic properties and drug interactions of the 

aqueous extract of stem bark of Berberis lycium Royle so 

that the desired effects produced by the herbal extract 

can be promptly achieved.  

C o n c l u s i o n  

The aqueous extract of stem bark of Berberis lycium 

Royle significantly lowered the fasting blood glucose and 

HbA1c levels in diabetes mellitus type 2 induced male 

mice model in a dose dependent manner. The glucose 

lowering effects of the aqueous extract of stem bark of 

Berberis lycium Royle in type 2 diabetes mellitus induced 

male mice were comparable with the glucose lowering 

effects of Pioglitazone. Although the extent of the glucose 

lowering effects of extract was greater than Pioglitazone.  

Acknowledgments: We are deeply grateful to Dr. 

Hussain-incharge animal house NIH, and Dr. Tahira- 

RIPS for their support and help in this project. 

Study Limitations: Due to financial constraints, study 

could not be extended upto or beyond 12 weeks to further 

validate the HbA1c% levels 

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https://dx.doi.org/10.3389%2Ffphar.2017.00074