UNIVERSITI PUTRA MALAYSIA THE HYPOGLYCAEMIC ACTIVITY...

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UNIVERSITI PUTRA MALAYSIA THE HYPOGLYCAEMIC ACTIVITY OF MENGKUDU (MORINDA CITRIFOLIA) CHEE BENG JIN FSAS 2001 49

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UNIVERSITI PUTRA MALAYSIA

THE HYPOGLYCAEMIC ACTIVITY OF MENGKUDU (MORINDA CITRIFOLIA)

CHEE BENG JIN

FSAS 2001 49

THE HYPOGLYCAEMIC ACTIVITY OF MENGKUDU (MORINDA CITRIFOLIA)

By CHEE BENGJIN

Thesis Submitted to the School of Graduate Studies, Universiti Putra Malaysia, in Fulfilment of the Requirements for the Degree of Master of Science

November 2001

A Work, Dedicated to ...

My parents, brother and my beloved family members,

Relatives and friend s,

Brothers and sisters in Christ,

Diabetes research.

Worship the LORD your God, and his blessings will be on your food and water. I will take away sickness from among you.

Cbee Beng Jin Biology Department, Universiti Putra Malaysia, 43400 Serdang.

Exodus 23:25

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Abstract of thesis presented to the Senate of Universiti Putra Malaysia in fulfilment of the requirement for the degree of Master of Science

THE HYPOGLYCAEMIC ACTIVITY OF MENGKUDU (MORINDA CITRIFOLIA)

By

CHEE BENG JIN

November 2001

Chairman: Associate Professor Hamdan Noor, Ph.D.

Faculty: Science and Environmental Studies

Diabetes mellitus has existed for at least 2000 years and has been treated with

materials derived from plants in many cultures of the world. The mengkudu

(Morinda cUrl/olia) are known for countless medicinal values and the ripe fruits

were being used traditionally in Malaysia for the treatment for diabetes mellitus. This

study was carried out to verify the hypoglycaemic property and its possible effect on

insulin secretion. Freeze-dried aqueous extracts of various doses of3mglkg, 30mglkg

and 300mglkg were administered to normal rats in an acute effect study and the

doses of 3mglkg, 3Omglkg, 300mglkg, 60Omglkg, 900mglkg and 1200mglkg were

administered to streptozotocin induced type 2 diabetic rats in a chronic effect study

in an Oral Glucose Tolerance Test (OGTI). Results from the choric effect study

showed that the 300mglkg dose treated rats had an apparent hypoglycaemic effect as

evident from the blood glucose level measured as the area under the OGTT curve

(AUe: 4370.70 ± 99.13 mgo/omin) after 6 weeks of oral administration.

Hypoglycaemic activity was also observed in the 600mglkg dose after 5 weeks of

oral administration (AUe: 4486.70 ± 35.60 mgo/omin), the 900mglkg dose after 4

weeks of oral administration (AUe: 4340.40 ± 72.90 mg%min) and the 1200mglkg

dose after 4 weeks of oral administration (AUe: 4554.00 ± 49.80 mg%min). All the

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Ave values were significantly lower compared to control. The aqueous extracts

were also able' to impede the rate of glucose increase and enhance the glucose

clearance. However, the results from the insulin assay did not show any significant

change in the insulin release profile as compared to control. As a conclusion, the

aqueous extract of mengkudu (Morlnda eim/olia) fruit preparations in the doses of

30Omglkg, 6OOmg/kg, 90Omg/kg and 1200mglkg might contain plant compounds

that have substantial hypoglycemic property only in the chronic effect study but did

not affect the insulin secretion in the type 2 diabetic rats. Future studies should be

carried out in order to further discover its mechanisms of action, isolation and

identification of the hypoglycaemic components particularly with regard to the

healing of diabetes by means of plant resources.

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Abstrak tesis yang dikemukakan kepada Senat Universiti Putra Malaysia sebagai memenulu keperluan untuk ijazah Master Sains

AKTIVITI HIPOGLISEMIK BUAH MENGKUDU (MORINDA CITRIFOLIA)

Oleh

CHEE BENG JIN

November 2001

Pengerusi: Profesor Madya Hamdan Noor, Ph.D.

Fakulti: Sains dan Pengajian Alam Sekitar

Penyakit diabetes mellitus telah dikesan semenjak 2000 tahun dahulu dan eara

rawatannya dengan menggunakan tumbuhan telah dikenalpasti di pelbagai

kebudayaan di merata dunia. Mengkudu (Morinda citrifolia) amat terkenal dengan

pelbagai nilai perubatan dan telah digunakan seeara tradisional untuk merawat

diabetes mellitus di Malaysia. Objektif eksperimen ini ialah untuk membuktikan

kesan bipoglisemik dan kesannya terhadap perembesan hormon insulin. Ekstrak buah

berakua yang telah disejukbekukan telah diberikan kepada tikus normal (3mglkg,

30mglkg dan 30Omglkg) untuk kajian kesan akut dan tikus diabetik jenis 2 (3mglkg,

30mglkg, 300mglkg, 60Omglkg, 9OOmg/kg dan 1200mg/kg) untuk kajian kesan

kronik di dalam Ujian Toleransi Glukosa. Keputusan kajian kesan kronik

menunjukkan bahawa tikus kajian yang diberikan dos 300mg/kg mempunyai aras

glukosa darah yang lebih rendah berdasarkan nilai keluasan dibawah graf (AUC:

4370.70 ± 99.13 mg%min) setelah rawatan oral selama 5 minggu. Kesan

bipoglisemik juga diperhatikan untuk dos 600mglkg selepas rawatan 5 minggu

(AUe: 4486.70 ± 35.60 mgo/omin), dos 900mg/kg selepas rawatan 4 minggu (AUC:

4340.40 ± 72.90 mg'l/omin) dan dos 1200mg/kg juga selepas 4 minggu rawatan

(AUe: 4554.00 ± 49.80 mgolomin). Kesemua nilai keluasan di bawah graf (AUC)

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adalah lebih rendah berbanding dengan kumpulan kawalan .. Ekstrak berakua tersebut

juga berupaya untuk merendahkan kadar peningkatan glukosa darah dan

mempercepatkan kadar penghapusan glukosa d.arah. Walau bagairnanapun,

keputusan ujian am insulin menunjukkan bahawa ekstrak tersebut tidak

mempengaruhi corak perembesan harmon insulin. Sebagai kesimpulan ekstrak

berakua buah menglrudu (Monnda citrifolia) berdos 300mglkg, 60Omglkg,

900mglkg dan 1200mglkg berupaya untuk merendahkan aras glukosa darah tikus

diabetik jenis 2 di dalam kajian kronik sahaja dan tidak mempengarnhi perembesan

hormon insulin. Berdasarkan kepada keputusan iDL kajian lanjutan masih perlu

dilakukan untuk mengkaji mekanisme tindakannya, pengasmgan dan

pengenalpastian komponen-komponen bipoglisemik di da1am eksttak tersebut

seiringan dengan kajian 1D1tuk rawatan diabetes mellitus dengan menggunakan

sumber tumbuhan tempatan.

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ACKNOWLEDGEMENTS

My sincere praises and thanksgiving to God Almighty for His tmfailing love and

grace in guiding me to complete my Master of Science project successfully.

I am very grateful to my supervisors. Associate Professor Dr. Hamdan Noor,

Associate Professor Dr. Umi Kalsom Yusuf and EnCk Zolkepli Othman.

Remembering you for your patience and assistance throughout my work.

My warmest gratitude to EnCk Haji Nordin Kassim for guiding and passing on your

experiences and advices on animal physiology experiments.

Last but not least, thanking my beloved family members, friends, Animal Physiology

T earn, all the academic and non-academic staff in the Biology Department.

The prayers, time, effort, energy and finances sacrificed throughout the years are

indeed a memorable event in my life. May God bless each one of you abundantly.

Amen.

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I certify that an Examination Committee met on 5th November 2001 to conduct the fmal examination of Mr. Chee Beng Jin on his Master of Science thesis entitled "The Hypoglycaemic Activity of Mengkudu (Morinda citri/olia)" in accordance with Universiti Pertanian Malaysia (Higher Degree) Act 1980 and Universiti Pertanian Malaysia (Higher Degree) Regulations 1981. The Committee recommends that the candidates be awarded the relevant degree. Members of the Examination Committee are as follows:

ABDUL SALAM ABDULLAH, Ph.D. Professor, Faculty of Veterinary Medicine, Universiti Putra Malaysia. (Chairman)

HAMDAN NOOR, Ph.D. Associate Professor, Faculty of Science and Environmental Studies, Universiti Putra Malaysia. (Member)

UMI KALSOM YUSUF, Ph.D. Associate Professor, Faculty of Science and Environmental Studies, Universiti Putra Malaysia. (Member)

ZOLKEPLI OTHMAN, Faculty of Science and Environmental Studies, Universiti Putra Malaysia. (Member)

SHAMSHER MOHAMAD RAMADILI, Ph.D. Professor/Deputy Dean School of Graduate Studies Universiti Putra Malaysia

Date: 1 3 MAY 2002

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The thesis submitted to the Senate of Universiti Putra Malaysia has been accepted as fulfilment of the requirement for the degree of Master Science.

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AINI IDERIS, Ph.D. ProfessorlDean School of Graduate Studies Universiti Putra Malaysia

Date: t 3 JffM 2m?

DECLARATION

I hereby declare that the thesis is based on my original work except for quotations and citations which have been duly acknowledged. I also declare that it has not been previously or concurrently submitted for any other degree at UPM or other institutions

a:k=. Chee Beng Jin

Date: 13th May 2002

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TABLE OF CONTENTS

Page DEDICATION ABSTRACT 3

5 7 8 10 11 l3 16 20

ABSTRAK ACKNOWLEDGEMENTS APPROVAL SHEETS DECLARATION FORMS TABLE OF CONTENTS LIST OF TABLES LIST OF FIGURES LIST OF ABBREVIATIONS

CHAPTER

1 INTRODUCTION 21

2 LITERATURE REVIEW

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2.1 The Regulation of Blood Glucose Level 25 2.2 Diabetes Mellitus

2.2.1 Type 1 Diabetes Mellitus 28 2.2.2 Type 2 Diabetes Mellitus 30

2.2.3 Glibenclamide 31 2.3 Modem Treatment for Diabetes Mellitus and Side Effects 32 2.4 Plants with Hypoglycaemic Property 37 2.5 Hypoglycaemic Mechanism. of Plant Extract

2.5.1 Stimulation of Insulin Secretion 44 2.5.2 Reduction of Hepatic Glucose Output 47 2.5.3 Fiber in Blood Glucose Regulation 49 2.5.4 Insulin-1ike Compounds or Chemica1s 56 2.5.5 Other Proposed Mechanisms 58

2.6 Morinda cim/olia: A Plant of Many Uses 59 2.6.1 Traditional Use of M citrifolia 60 2.6.2 Scientific Research onM citri/olia 63 2.6.3 The Morinda citrifolia Plant as a Traditional

Cure for Diabetes 67

METHODOLOGY. 3.1 Type 2 Diabetic Rat Model 3.2 Plant Extract Preparation 3.3 Experimental Design. 3.4 Oral Glucose Tolerance Test (OOTT). 3.5 Blood Glucose Assay 3.6 Blood Insulin Assay

3.6.1 Insulin Hormone Level Test 3.7 Statistical Analysis

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68 68 68 69 69 70 70 71

4 RESULTS 4. 1 Hypoglycaemic Studies

4. 1 . 1 Acute Effect Study (3mglkg, 3Omglkg, 300mglkg) 72 4. 1 .2 Chronic Effect Study

4. 1.2. 1 Aqueous Fruit Extract (3mlY'kg, 30mg1kg, 30Omglkg) 78

4. 1 .2.2 Aqueous Fruit Extract (6OOmglkg, 900mglkg, 120Omglkg) 94

4.1.3 Area Under Curves (AUCs) for Glucose Level (mgo/omin) 4. 1 .3. 1 Aqueous Fruit Extract (3mglkg, 3Omglkg,

30Omg/kg) 107 4.1 .3.2 Aqueous Fruit Extract (60Omglkg, 9OOmglkg,

1200mWkg) 113 4.2 Insulin Studies

4.2.1 Blood Insulin Level in Chronic Effect Study 4.2 .1 . 1 Aqueous Fruit Extract (3mg/kg, 3Omglkg,

300mglkg) 120 4.2. 1 .2 Aqueous Fruit Extract (60Omglkg, 9OOmg/kg,

1200mglkg) 127 4.2.2 Area Under Curves (AUCs) for Insulin Level (pg/mbnin)

4.2.2.1 Aqueous Fruit Extract (3mWlcg, 30mg1kg, 30Omg/kg) 135

4.2.2.2 Aqueous Fruit Extract (600mg/kg, 900mglkg, 120Omglkg) 138

4.3 Rate of Glucose Increase and Decrease 4.3. 1 Aqueous Fruit Extract (3mg/kg, 3Omg/kg, 300mg/kg) 141 4.3.2 Aqueous Fruit Extract (6OOmglkg, 900mglkg, 1200mglkg) 143

5 DISCUSSION 5.1 Experimental Animal and Blood Sampling 145 5.2 Type 2 Diabetic Model 1 46 5.3 Hypoglycaemic Property of the Aqueous Extracts 147 5.4 Effect of the Aqueous Extract on Insulin 153 5.5 Possible Hypoglycaemic Effect of Morindo citrifolia

Aqueous Extract 155

6 CONCLUSION 157

REFERENCES 1 60 APPENDICES 174 BIODATA OF THE AUTHOR 220

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LIST OF TABLES

Table Page

1 The blood glucose level for different treatments (3mg1kg, 30mglkg and 30Omglkg) at different time intervals in the acute effect study 74

2 Area under glucose tolerance curves for different treatments (3mglkg. 30mg1kg and 300mg/kg) in the acute effect study 75

3 Rate of glucose increase for saline, glibenclamide, 3mglkg, 30mglkg and 300mglkg dose. 76

4 Rate of glucose decrease for saline, glibenclamide, 3mglkg, 30mglkg and 300mglkg dose. 77

5 Blood glucose levels for different treatments (3mglkg, 30mglkg and 300m.g/kg) at Trial I 80

6 Blood glucose levels for different treatments (3mglkg, 30mglkg and 300mglkg) at Trial 2 81

7 Blood glucose levels for different treatments (3mglkg, 30mglkg and 300mglkg) at Trial 3 82

8 Blood glucose levels for different treatments (3mglkg, 30mgikg and 300m.g/kg) at Week I 83

9 Blood glucose levels for different treatments (3mglkg, 30mglkg and 300mglkg) at Week 2 84

10 . Blood glucose levels for different treatments (3mg/kg, 3Omg/kg and 30Omglkg) at Week 3 85

11 Blood glucose levels for different treatments (3mglkg, 30mWkg and 300mg/kg) at Week 4 86

12 Blood glucose levels for different treatments (3mglkg, 30mglkg and 300mglkg) at Week 5 87

13 Blood glucose levels for different treatments (3mglkg, 30mWkg and 300mglkg) at Week 6 89

14 Blood glucose levels for different treatments (3mglkg. 30mglkg and 300mg/kg) at Week 7 90

15 Blood glucose levels for different treatments (3mg/kg, 3Omw'kg and 300mglkg) at Week 8 91

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16 Blood glucose levels for different treatments (3mglkg, 3�glkg and 30Omg/kg) at Week 9 92

17 Blood glucose levels for different treatments (3mglkg, 30mglkg and 30Omg/kg) at Week 10 93

18 Blood glucose levels for different treatments (60Omglkg, 900mglkg and 1200 mglkg) at Trial 1 95

19 Blood glucose levels for different treatments (60Omglkg, 900mglkg and 1200 mglkg) at Trial 2 96

20 Blood glucose levels for different treatments (6OOmglkg, 900mglkg and 1200 mglkg) at Trial 3 97

21 Blood glucose levels for different treatments (60Omglkg, 9OOmg/kg and 1200 mg/kg) at Week 1 98

22 Blood glucose levels for different treatments (60Omg/kg, 900mglkg and 1200 mglkg) at Week 2 99

23 Blood glucose levels for different treatments (600mglkg, 900mglkg and 1200 mglkg) at Week 3 100

24 Blood glucose levels for different treatments (60Omglkg, 9OOmg/kg and 1200 mg/kg) at Week 4 102

25 Blood glucose levels for different treatments (60Omglkg, 9OOmg/kg and 1200 mg/kg) at Week 5 103

26 Blood glucose levels for different treatments (6OOmg;lkg, 900mglkg and 1200 mglkg) at Week 6 104

27 Blood glucose levels for different treatments (60Omglkg, 900mglkg and 1200 mglkg) at Week 7 105

28 Blood glucose levels for different treatments (600mg/kg, 900mglkg and 1200 mglkg) at Week 8 106

29 Area under glucose tolerance curves for different treatments (3mglkg, 30mglkg and 30Omg/kg) at different weeks 109

30 Area under glucose tolerance curves for different treatments (60Omglkg, 9OOmg/kg and 1200 mglkg) at different weeks 115

31 Blood insulin levels for different treatments (3mg;1kg, 30mglkg and 300mg/kg) at Week 5 122

32 Blood insulin levels for diffeIent treatments (3mglkg, 30mglkg and 30Omglkg) at Week 6 123

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33 BI90d insulin levels for different treatments (3mglkg, 30mglkg and 30Omglkg) at Week 7 124

34 Blood insulin levels for diffelent treatments (3mglkg, 30mglkg and 30Omglkg) at Week 8 125

35 Blood insulin levels for different treatments (3mglkg, 30mglkg and 30Omglkg) at Week 9 126

36 Blood insulin levels for different treatments (600mglkg, 900mglkg and 1200 mglkg) at Week 3 129

37 Blood insulin leve1s for different treatments (600mglkg, 900mglkg and 1200 mglkg) at Week 4 130

38 Blood insulin levels for different treatments (600mglkg, 900mg/kg and 1200 mglkg) at Week 5 131

39 Blood insulin levels for different treatments (6OOmg/kg, 9OOmg/kg and 1200 mglkg) at Week 6 132

40 Blood insulin levels for different treatments (6OOmglkg, 900mglkg and 1200 mglkg) at Week 7 133

4 1 Area under insulin curves for different treatments (3m.g1kg, 30mglkg and 300mg/kg) at different weeks 135

42 Area under insulin curves for different treatments (6OOmg/kg, 9OOmg/kg and 1200 mglkg) at different weeks 138

43 Rate of glucose increase for saline, glibenclamide and 300m.glkg dose 141

44 Rate of glucose decrease for saline, glibenclamide and 300mglkg dose 142

45 Rate of glucose increase for saline, glibenclamide, 600mglkg, 900mglkg and 1 200mglkg dose 143

46 Rate of glucose decrease for saline, glibenclamide, 6OOmglkg, 900mglkg and 1200mglkg dose 144

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LIST OF FIGURES

Figure Page

1 Blood glucose tolerance curves for different treatmmts (3mglkg, 30mglkg and 300mglkg) in acute effect study 74

2 Blood glucose tolerance curves for different treatments at Trial 1 (3mglkg, 30mglkg and 300mglkg) 80

3 Blood glucose tolerance curves for different treatments at Trial 2 (3mglkg, 30mglkg and 300mglkg) 81

4 Blood glucose tolerance curves for different treatments at Trial 3 (3mglkg, 30mglkg and 300mg/kg) 82

5 Blood glucose tolerance curves for different treatments at Week 1 (3mglkg, 30mglkg and 30Omglkg) 83

6 Blood glucose tolerance curves for different treatments at Week 2 (3mglkg, 3Omg/kg and 30Omglkg) 84

7 Blood glucose tolerance curves for different treatments at Week 3 (3mglkg, 3Omg/kg and 300mglkg) 85

8 Blood glucose tolerance curves for different treatments at Week 4 (3mglkg, 3Omg/kg and 30Omglkg) 86

9 Blood glucose tolerance curves for different treatments at Week S (3mglkg, 30mglkg and 30Omglkg) 87

10 Blood glucose tolerance curves for different treatments at Week 6 (3mglkg, 3Omg/kg and 30Omglkg) 89

1 1 Blood glucose tolerance curves for different treatments at Week 7 (3mglkg, 30mglkg and 30Omglkg) 90

12 Blood glucose tolerance curves for different treatments at Week 8 (3mglkg, 30mglkg and 300mg1kg) 91

13 Blood glucose tolerance curves for different treatments at Week 9 (3mglkg, 30mglkg and 30Omglkg) 92

14 Blood glucose tolerance curves for different treatments at Week 10 (3mglkg, 30mglkg and 30Omglkg) 93

15 Blood glucose tolerance curves for different treatments at Trial 1 (600mglkg, 900mglkg and l200mglkg) 95

16 Blood glucose tolerance curves for different treatments at Tria12 (600mglkg, 900mglkg and 1200mglkg) 96

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17 Blood glucose tolerance curves for different treatments at Trial 3 (6OOmglkg, 900mglkg and 1200mglkg) 97

18 Blood glucose tolerance curves for different treatments at Week 1 (6OOmglkg, 900mglkg and 1200mglkg) 98

19 Blood gluoose tolerance curves for d.iffaent treatments at Week 2 (600mglkg, 900mgIkg and 1200mglkg) 99

20 Blood glucose tolerance curves for different treatments at Week 3 (6OOmglkg, 900mglkg and 1200mglkg) 100

21 Blood glucose tolerance curves for different treatments at Week 4 (6OOmglkg, 900mglkg and 1200mg1kg) 102

22 Blood glucose tolerance curves for different treatments at Week 5 (6OOmglkg, 900mgIkg and 1200mglkg) 103

23 Blood glucose tolerance curves for different treatments at Week 6 (6OOmglkg, 900mglkg and 1200mglkg) 104

24 Blood glucose tolerance curves for·different treatments at Week 7 (6OOm.glkg, 900mglkg and 1200mglkg) 105

25 Blood glucose tolerance curves for different treatments at Week 8 (6OOmglkg, 900mglkg and 1200mglkg) 106

26 Area under glucose tolerance curves for saline at different weeks 110

27 Area under glucose tolerance curves for g1ibenclamide at different weeks 110

28 Area under glucose tolerance curves for 3mglkg aqueous extract at different weeks 110

29 Area under glucose tolerance curves for 30mglkg aqueous extract at different weeks 111

30 Area under glucose tolerance curves for 300mg/kg aqueous extract at different weeks 111

31 Areas under glucose tolerance curves for different treatments (3mglkg, 30mglkg and 300mglkg) at Week 6 112

32 Areas under glucose tolerance curves for different treatments (3mg/kg, 30mg1kg and 300m.gIkg) at Week 7 112

33 Areas under glucose tolerance curves for different treatments (3mg1kg, 30mg1kg and 300mglkg) at Week 8 112

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Area under glucose tolerance curves for saline at different weeks

Area under glucose tolerance curves for glibenclamidc at different weeks

Area under glucose tolerance curves for 600mgIkg at different weeks

Area under glucose tolerance curves for 900mglkg at different weeks

Area under glucose tolerance curves for 120Omg/kg at different weeks

AIeas under glucose tolerance curves for different treatments (600mglkg, 900mglkg and 1200mglkg) at Week 4

AIeas under glucose tolerance curves for different treatments (6OOmglkg, 900mglkg and 1200mglkg) at Week 5

AIeas under glucose tolerance curves for different treatments (6OOm.gIkg, 900mglkg and 1200mglkg) at Week 6

Blood insulin curves for different treatments at week 5 (3mg/kg, 30mglkg and 300mglkg)

Blood insulin curves for different treatments at week 6 (3mglkg, 30mglkg and 300mglkg)

Blood insulin curves for different treatments at week 7 (3mglkg, 30mglkg and 3�g)

Blood insulin curves for different treatments at week 8 (3mglkg, 30mglkg and 300mglkg)

Blood insulin curves for different treatments at week 9 (3mglkg, 30mglkg and 300mglkg)

Blood insulin curves for different treatments at week 3 (6OOmglkg, 900mglkg and 1200mglkg)

Blood insulin curves for diffenD treatments at week 4 (6OOmg/kg, 900mglkg and 120Omglkg)

Blood insulin curves for different treatments at week 5 (6OOmglkg, 900mglkg and 1200mglkg)

Blood insulin curves for different treatments at week 6 (6OOmglkg, 900mglkg and 1200mglkg)

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5 1 Blood insulin curves for different treatments at week 7 (�glkg. 900mglkg and 120Omglkg) 134

52 Areas under insulin curves for saline at different weeks 136

53 Areas under insulin curves for glibenclamide at different weeks 136

S4 Areas under insulin curves for 3mglkg aqueous extract at different weeks 1 36

5S Areas under insutin curves for 30mglkg aqueous extract at different weeks 137

56 Areas under insutin curves for 300mglkg aqueous extract at different weeks 137

57 Areas under insulin curves for saline at different weeks 1 39

58 Areas under insulin curves for glibenclamide at different weeks 139

59 Areas under insulin curves for 600mglkg aqueous extract at different weeks 139

60 Areas \Ulder insulin curves for 900mg/kg aqueous extract at different weeks 140

61 Areas under insulin curves for 1200mg/kg aqueous extract at different weeks 140

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LIST OF ABBREVlA TIONS

mgolo milligram per 100 milliter

00 Optical Density

n number of replicates or individuals

b.w. body weight

[G] Blood glucose concentration

[I] Blood insulin concentration

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CHAPTERl

INTRODUCTION

Diabetes mellitus is currently a major global issue in public health. The

occurrence and prevalence of this disease are alanningly escalating in developing and

newly industrialized countries (King, 1993). The prevalence of diabetes worldwide was

estimated to be 4% (135 million people) in 1995 and to increase to 5.4% (estimated 300

million people) by the year 2025 (King et aI., 1998.)

The World Health Organization (WHO) bas recognized 2 major clinical forms of

diabetes mellitus, namely Insulin-Dependant Diabetes Mellitus (lDDM) or Type 1

Diabetes Mellitus and Non-Insulin-Dependent Diabetes Mellitus (NIDDM) or Type 2

Diabetes Mellitus. About 9C)OA, of all cases of diabetes in developed and developing

countries are NIDDM, primarily found in adult of more than 30 years old (WHO Study

Group, 1994).

Asia faces the greatest threat of an epidemic of NIDDM. In 1994, over 43

million people in Southern, Southeast and East Asia were estimated to have NIDDM.

WHO has recognized that Asia as having a potential increase with 2.5 to 3 times more

common diabetes than the situation today. Hence by the year 201 0, Asia is estimated to

have 138 million diabetic patients (Amos et aI., 1997).

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In Malaysia, diabetes is a growing concern among the population especially the

government and health practitioners. Throughout the six years Healthy lifestyle

Campaign by the Ministry of Hea.lth, which started in 1991, diabetes mellitus became

the theme for the year 1995. Tn 1986, the prevalence of the disease in Peninsular

Malaysia as reported in the First National Health and Morbidity Survey was 6.3% and in

1995, the Cardiovascular Unit in the Department of Public Health, Ministry of Health

...

reported that the prevalence to at 7.7010. The prevalence seemed to be on the rise.

Recognizing diabetes as a growing public health problem in Malaysia, a scope on

diabetes was introduced in the Second National Health and Morbidity Survey (NHMS2).

It was carried out to provide a comparative picture of the epidemiology of diabetes

mellitus in the population of Malaysia within the last ten years since 1986. In 1997, the

survey reported that the national prevalence was found to be 8.3% in the population of

age 30 years and above. (Ministry of Health, 1999)

The highest occurrence of identified diabetics by ethnicity was amongst Indians

(11.5%) and they were considerably higher than other ethnic groups. The prevalence

amid Chinese was 6.3% and Malays was 5.2% whilst other Bmniputera had significantly

lower prevalence 2.7%. The prevalence of known diabetics by gender showed that males

reported to have higher prevalence (5.9%) compared to females (5.8%)(Ministry of

Health, 1999).

Undiagnosed diabetes was defined as whole blood capillary glucose level of

equal or more that 11.1 mmoll1 among those who did not report themselves as known

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diabetics. From the survey, the national prevalence of undiagnosed diabetics was 2.5%.

By ethriicity, Indians had the highest prevalence of undiagnosed diabetics, which was

3.4% and by gender� females recorded higher prevalence (2.6%) than males

(2.5%)(Ministry of Health, 1999).

In Malaysia, a number of reported death cases from the Ministry of Health

(1999) were related to heart disease, stroke or chronic renal failure, some of which might

be associated to diabetes. It is projected that the number of diabetics will be rising from

418,000 cases in 1994 to 810,000 cases and 1,201,000 estimated cases in year 2000 and

2010 respectively (Ministry of Health, 1999)

The Ministry of Health in Malaysia has reported that in 1994, about 4.3% of

diabetic patients seek treatment in private and government hospitals and about 0.9%

seeks treatment in traditional medicine practitioner (Ministry of Health, 1995). Even

today, the practice of various traditional medicinal systems are still flourishing in

different countries and among different ethnic groups and nearly 80% of the rural

population still depend on plant based medicines (Sasson, 1996). About 80% of the rural

population in many tropical developing countries still depends on traditional

practitioners for their health care, which means that the community has to rely on

medicinal plants for treatment (Farnsworth, 1983).

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The traditional method of treating diabetes is yet to be explored; Malaysia is

richly endowed with diverse flora with good potential to be developed into various

useful natural products (Soepadmo, 1993). Our country is known to have a large amount

of plant species and a number of them have been traditionally used to treat many disease

and ailments. Similar to other diseases, diabetes mellitus has been treated traditionally

by oral consumption of plant extracts based on folk and traditional cures since ancient

times (Ajgoankar, 1979).

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