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PLANT SPECIES USED IN THE TREATMENT OF DIABETES BY SOUTH AFRICANTRADITIONAL HEALERS: AN INVENTORY

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INTRODUCTION

Diabetes mellitus is recognized as being a syndrome, a collection of disorders that have hyperglycaemia and glucose intolerance as their hallmark, due either to insulin deficiency or to the impaired effectiveness of insulin’s action, or to a combination of these. In order to understand diabetes it is necessary to understand the normal physiological process occurring during and after a meal. Food passes through the digestive system, where nutrients, including proteins, fat and carbohydrates are absorbed into the bloodstream. The presence of sugar, a carbohydrate, signals to the endocrine pancreas to secrete the hormone insulin. Insulin causes the uptake and storage of sugar by almost all tissue types in the body, especially the liver, musculature and fat tissues (Roussel, 1998).
Unfortunately, there is no cure for diabetes yet but by controlling blood sugar levels through a healthy diet, exercise and medication the risk of long-term diabetes complications can be decreased. Long-term complications that can be experienced are: – eyes – cataracts and retinopathy (gradual damaging of the eye) that may lead to blindness – kidneys – kidney disease and kidney failure – nerves – neuropathy (gradual damaging of nerves) – feet – ulcers, infections, gangrene, etc. – cardiovascular system – hardening of arteries, heart disease and stroke (Heart foundation, 2003). The progressive nature of the disease necessitates constant reassessment of glycaemic control in people with diabetes and appropriate adjustment of therapeutic regimens. When glycaemic control is no longer maintained with a single agent, the addition of a second or third drug is usually more effective than switching to another single agent. Medicinal plants which have showed anti-diabetic activity during earlier investigations include Panax species, Phyllanthus species, Acacia arabica, Aloe vera, Aloe barbadensis, Artemisia pallens, Momordica charantia, Alium cepa, Trigonella foenum-graecum etc (Soumyanath, 2006). Very few South-African plants have been scientifically analyzed for their anti-diabetic characteristics. The most recent work was done by Van Huyssteen (2007) and Van de Venter et al. (2008).

CLASSIFICATION OF DIABETES MELLITUS

A major requirement for orderly epidemiologic and clinical research on and for the management of diabetes mellitus is an appropriate classification. Furthermore the process of understanding the etiology of a disease and studying its natural history involves the ability to identify and differentiate between its various forms and place them into a rational etiopathologic framework (Harris and Zimmet, 1997). The contemporary classification of diabetes and other categories of glucose intolerance, based on research on this heterogeneous syndrome, was developed in 1979 by the National Diabetes Data Group.
Two major forms of diabetes are recognized in Western countries; insulin dependent diabetes mellitus (IDDM, type I diabetes) and non-insulin dependant diabetes (NIDDM, type II diabetes). The evidence of this heterogeneity is overwhelming and includes the following: a) there are many distinct disorders, most of which are individually rare, in which glucose intolerance is a feature; b) there are large differences in the prevalence of the major forms of diabetes among various racial or ethnic groups world-wide; c) glucose tolerance presents variable clinical features, for example, the differences between thin ketosis-prone, insulin dependant diabetes and obese, non-ketotic insulin resistant diabetes; d) genetic, immunologic and clinical studies show that in Western countries, the forms of diabetes with their onset primarily in youth or in adulthood are distinct entities; e) the type of non-insulin requiring diabetes in young people, which is inherited in an autosomal dominant fashion is clearly different from the classic acute diabetes of juveniles; and f) in tropical countries, several clinical presentations occur, including fibrocalcific pancreatitis and malnutrition-related diabetes.

Insulin dependant diabetes mellitus (IDDM)

The subclass of diabetes, type I diabetes, is generally characterized by the abrupt onset of severe symptoms, dependence on exogenous insulin to sustain life and proneness to ketosis even in the basal state, all of which is caused by absolute insulin deficiency. IDDM is the most prevalent type of diabetes among children and young adults in developing countries, and was formally termed juvenile diabetes (Harris and Zimmet, 1997). It is a catabolic disorder in which circulating insulin is virtually absent, plasma glucagon is elevated, and the pancreatic B cells fail to respond to all insulinogenic stimuli (Nolte and Karam, 2001).

Non-insulin dependant diabetes mellitus (NIDDM)

Type II diabetes greatly out numbers all other forms of diabetes. Patients with NIDDM are not dependant on exogenous insulin for prevention of ketonuria and are not prone to ketosis. However, they may require insulin for the correction of fasting hyperglycaemia if this cannot be achieved with the use of diet or oral agents, and they may develop ketosis under special circumstances such as severe stress precipitated by infections or trauma (Harris and Zimmet, 1997). The pathogenesis in type II diabetes is that the pancreas produces insulin but the body does not utilize the insulin correctly. This is primarily due to peripheral tissue insulin resistance where insulin-receptors or other intermediates in the insulin signaling pathways within body cells are insensitive to insulin and consequently glucose does not readily enter the tissue leading to hyperglycaemia or elevated blood glucose concentrations (Albright, 1997). Obesity, which generally results in impaired insulin action, is a common risk factor for this type of diabetes, and most patients with type II diabetes are obese (Nolte and Karan, 2001) and will ultimately require multiple anti-diabetic agents to maintain adequate glycaemic control (Gerich, 2001).

Insulin

The beta-cells of the pancreatic islets synthesize insulin from a single chain precursor of 110 amino acids termed preproinsulin. After translocation through the membrane of the rough endoplasmic reticulum, the 24-amino-acid N-terminal signal peptide of preproinsulin is rapidly cleaved off to form proinsulin. Here the molecule folds and the disulfide bonds are formed. On the conversion of human proinsulin to insulin in the Golgi-complex, four basic amino acids and the remaining connector or C peptide are removed by proteolysis. This gives rise to the two-peptide chains (A and B) of the insulin molecule, which contains one intra-subunit and two inter-subunit disulfide bonds. The A chain usually is composed of 21 amino acids and the B chain 30. The two chains of insulin form a highly ordered structure with several helical regions in both the A and B chains (Figure 1.1). Two ions of Zn2+ are coordinated in a proinsulin hexamer and this form of insulin presumably is stored in the granules of the pancreatic ß cells. It is believed that Zn2+ has a functional role in the formation of crystals and that crystallization facilitates the conversion of proinsulin to insulin, as well as the storage of the hormone (Davis and Granner, 1996).

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Table of Contents :

  • DECLARATION
  • SUMMARY
  • CHAPTER DIABETES:LITERATURE REVIEW
    • 1.1. INTRODUCTION
    • 1.2. CLASSIFICATION OF DIABETES MELLITUS
    • 1.2.1 Insulin dependant diabetes mellitus (IDDM)
    • 1.2.2 Non-insulin dependant diabetes mellitus (NIDDM)
    • 1.3.DIABETES MELLITUS IN AFRICA
    • 1.4. RATIONALE
    • 1.5. PATHOPHYSIOLOGY OF DIABETES MELLITUS
    • 1.5.1 Physiological mechanisms and management
      • 1.5.1.1 The endocrine pancreas
      • 1.5.1.2 Diabetes-related islet changes
    • 1.5.2 Insulin
      • 1.5.2.1 Insulin secretion
      • 1.5.2.2 Insulin degradation
      • 1.5.2.3 The insulin receptor
      • 1.5.2.4 Effects of insulin on its targets
      • 1.5.2.5 Action of insulin on glucose transporters (GLUT)
      • 1.5.2.6 Action of insulin on liver
      • 1.5.2.7 Effect of insulin on muscle
      • 1.5.2.8 Effect of insulin on adipose tissue
    • 1.6 Complications of insulin therapy
    • 1.7 Oral antidiabetic agents
    • 1.7.1 Insulin secretagogues: sulfonylureas
    • 1.7.2 Insulin secretagogues: meglitinides
    • 1.7.3 Biguanides
    • 1.7.4 Thiazolidinediones
    • 1.7.5 Alpha-glucosidase inhibitors
    • 1.8 Herbal products currently available in South Africa for the treatment of diabetes
    • 1.9 Hypothesis and objectives of this study
    • 1.10 Scope of this thesis
    • 1.11 Conclusions
    • 1.12 References
  • CHAPTER PLANT SPECIES USED IN THE TREATMENT OF DIABETES BY SOUTH AFRICANTRADITIONAL HEALERS: AN INVENTORY
    • 2.1 Abstract
    • 2.2 Introduction
    • 2.3 Ethnobotany in South Africa
    • 2.4 Plant Material
    • 2.4.1. Elaeodendron transvaalense
      • 2.4.1.1 Description
      • 2.4.1.2 Medicinal uses
      • 2.4.1.3 Phytochemistry / Bioactivity
    • 2.4.2 Euclea undulata
      • 2.4.2.1 Description
      • 2.4.2.2 Medicinal uses
      • 2.4.2.3 Phytochemistry / Bioactivity
    • 2.4.3 Euclea natalensis
      • 2.4.3.1 Description
      • 2.4.3.2 Medicinal uses
      • 2.4.3.3 Phytochemistry/ Bioactivity
    • 2.4.4 Lannea edulis
      • 2.4.4.1 Description
      • 2.4.4.2 Medicinal uses
      • 2.4.4.3 Phytochemistry / Bioactivity
    • 2.4.5 Spirostachys africanus
      • 2.4.5.1 Description
      • 2.4.5.2 Medicinal uses
      • 2.4.5.3 Phytochemistry / Bioactivity
    • 2.4.6 Schkuhria pinnata
      • 2.4.6.1 Description
      • 2.4.6.2 Medicinal uses
    • 2.4.7 Pteronia divaricata
      • 2.4.7.1 Description
      • 2.4.7.2 Medicinal uses
    • 2.4.8 Ziziphus mucronata
      • 2.4.8.1 Description
      • 2.4.8.2 Medicinal uses
      • 2.4.8.3 Phytochemistry / Bioactivity
    • 2.4.9 Aloe ferox
      • 2.4.9.1 Description
      • 2.4.9.2 Medicinal uses
      • 2.4.9.3 Phytochemistry / Bioactivity
    • 2.4.10 Warburgia salutaris
      • 2.4.10.1 Description
      • 2.4.10.2 Medicinal uses
      • 2.4.10.3 Phytochemistry / Bioactivity
    • 2.4.11 Momordica balsamina
      • 2.4.11.1 Description
      • 2.4.11.2 Medicinal uses
      • 2.4.11.3 Phytochemistry / Bioactivity
    • 2.4.12 Kederostis nana
      • 2.4.12.1 Description
      • 2.4.12.2 Medicinal uses
    • 2.4.13 Artemisia afra
      • 2.4.13.1 Description
      • 2.4.13.2 Medicinal uses
      • 2.4.13.3 Phytochemistry / Bioactivity
    • 2.4.14 Catharanthus roseus
      • 2.4.14.1 Description
      • 2.4.14.2 Medicinal uses
      • 2.4.14.3 Phytochemistry / Bioactivity
    • 2.4.15 Cnicus benedictus
      • 2.4.15.1 Description
      • 2.4.15.2 Medicinal uses
      • 2.4.15.3 Phytochemistry / Bioactivity
    • 2.4.16 Psidium guajava
      • 2.4.16.1 Description
      • 2.4.16.2. Medicinal uses
      • 2.4.16.3 Phytochemistry / Bioactivity
    • 2.4.17 Terminaliia sericea
      • 2.4.17.1 Description
      • 2.4.17.2 Medicinal uses
      • 2.4.17.3 Phytochemistry / Bioactivity
    • 2.4.18 Sutherlandia frutescens
      • 2.4.18.1 Description
      • 2.4.18.2 Medicinal uses
      • 2.4.18.3 Phytochemistry / Bioactivity
    • 2.4.19 Bridelia micrantha
      • 2.4.19.1 Description
      • 2.4.19.2 Medicinal uses
      • 2.4.19.3 Phytochemistry / Bioactivity
    • 2.4.20 Sclerocarya birrea
    • 2.4.20.1 Description
    • 2.4.20.2 Medicinal uses
    • 2.4.20.3 Phytochemistry / Bioactivity
    • 2.4.21 Brachylaena discolor
    • 2.4.21.1 Description
    • 2.4.21.2 Medicinal uses
    • 2.4.21.3 Phytochemistry / Bioactivity
    • 2.4.22 Brachylaena elliptica
    • 2.4.22.1 Description
    • 2.4.22.2 Medicinal uses
    • 2.4.22.3 Phytochemistry / Bioactivity
    • 2.4.23 Brachylaena ilicifolia
    • 2.4.23.1 Description
    • 2.4.23.2 Medicinal uses
    • 2.4.23.3 Phytochemistry / Bioactivity
    • 2.4.24 Bulbine latifolia
    • 2.4.24.1 Description
    • 2.4.24.2 Medicinal uses
    • 2.4.24.3 Phytochemistry / Bioactivity
    • 2.4.25 Carpobrotus edulis
    • 2.4.25.1 Description
    • 2.4.25.2 Medicinal uses
    • 2.4.25.3 Phytochemistry / Bioactivity
    • 2.4.26 Chironia baccifera
    • 2.4.26.1 Description
    • 2.4.26.2 Medicinal uses
    • 2.4.26.3 Phytochemistry / Bioactivity
    • 2.4.27 Cissampelos capensis
    • 2.4.27.1 Description
    • 2.4.27.2 Medicinal uses
    • 2.4.27.3 Phytochemistry / Bioactivity
    • 2.4.28 Harpagophytum procumbens
    • 2.4.28.1 Description
    • 2.4.28.2 Medicinal uses
    • 2.4.28.3 Phytochemistry / Bioactivity
    • 2.4.29 Hoodia currorii
      • 2.4.29.1 Description
    • 2.4.29.2 Medicinal uses
    • 2.4.29.3 Phytochemistry / Bioactivity
    • 2.4.30 Nymphaea nouchali
    • 2.4.30.1 Description
    • 2.4.30.2 Medicinal uses
    • 2.4.30.3 Phytochemistry / Bioactivity
    • 2.4.31 Trigonella foenumgraecum
    • 2.4.31.1 Description
    • 2.4.31.2 Medicinal uses
    • 2.4.31.3 Phytochemistry / Bioactivity
    • 2.4.32 Vernonia oligocephala
    • 2.4.32.1 Description
    • 2.4.32.2 Medicinal uses
    • 2.4.32.3 Phytochemistry / Bioactivity
    • 2.5 Conclusion
    • 2.6 Acknowledgement
    • 2.7 References
  • CHAPTER HYPOGLYCAEMIC ACTIVITY OF FOUR PLANT EXTRACTS TRADITIONALLY USED IN SOUTH AFRICA FOR DIABETES
    • 3.1 Abstract
    • 3.2 Introduction
    • 3.3 Material and Methods
    • 3.3.1 Plant material
    • 3.3.2 Preparation of plant extracts
    • 3.3.3 In vitro anti-diabetic and toxicity screening
    • 3.3.4 Routine maintenance of cell cultures
    • 3.3.4.1 Glucose uptake experimental procedures on C2C12 myoblast cells
    • 3.3.4.2 Glucose uptake experimental procedure on Chang liver cells and 3T3-L1 adipose cells
    • 3.3.4.3 Dose response
    • 3.4 Alpha-glucosidase inhibiting activity
    • 3.5 Alpha-amylase inhibiting activity
    • 3.5.1 Enzyme assay
    • 3.5.2 Prussian blue assay
    • 3.6 Results
    • 3.6.1 In vitro
    • 3.6.2 MTT toxicity assay
    • 3.6.3 Alpha-glucosidase and alpha-amalyse assay
    • 3.7 Discussion
    • 3.8 Acknowledgements
    • 3.9 References
  • CHAPTER ISOLATION OF BIOACTIVE COMPOUNDS FROM EUCLEA UNDULATA var MYRTINA ROOTBARK
    • 4.1 Abstract
    • 4.2 Introduction
    • 4.3 Material and methods
    • 4.3.1 Plant material
    • 4.3.2 Extraction of plant material
    • 4..3.3 Fractionation of the crude plant extract
    • 4.4 Determination of hypoglycaemic activity
    • 4.5 Results and discussion
    • 4.5.1 In vitro test results
    • 4.5.2 Alpha glycosidase assay
    • 4.6 Phytochemical examination
    • 4.6.1 Chemical constituents from the root bark of E. undulata
    • 4.6.1.1 -amyrin-3O-ß-(5-hydroxy) ferulic acid (1)
    • 4.6.1.2 Betulin (2)
    • 4.6.1.3 Lupeol (3)
    • 4.6.1.4 Epicatechin (4)
    • 4.7 Conclusions
    • 4.8 References
  • CHAPTER
    • GENERAL DISCUSSION AND CONCLUSION
  • CHAPTER
    • ACKNOWLEDGEMENTS AND PUBLICATIONS
    • 6.1 Congresses attended
    • 6.2 Publications from this thesis
  • CHAPTER
    • REFERENCES
  • CHAPTER
    • APPENDIX

GET THE COMPLETE PROJECT
Isolation and identification of a novel anti-diabetic compound from Euclea undulata Thunb.

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