Diabetes mellitus (DM) is a group of complex and chronic metabolic disorders with diverse multiple etiologies. It is characterized by high blood glucose (hyperglycemia) resulting from malfunction in insulin secretion and/or insulin action, both leading to impair metabolism of carbohydrates, lipids and proteins (ADA, 2015). The alterations in the utilization of complex biomolecules by the most affected tissues (liver, muscle and adipose tissue) due to hyperglycemia initiate a sequence of oxidative processes that cause dysfunction and failure of other organs in the body.
Long-term complications may affect the organs such as kidneys, eyes, nerves, heart and blood vessels, and in absence of effective treatment result into death (ADA, 2015; Surampud et al. 2009; Maritim et al. 2003).
At present, different approaches are used to control diabetes using modern synthetic anti-diabetic drugs, insulin injection and life style modification. The synthetic anti-diabetic drugs include sulphonylureas, glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors and biguanide.
However, these synthetic drugs have characteristic profiles of serious side effects, which include hypoglycemia, weight gain, gastrointestinal discomfort and nausea, liver and heart failure, and diarrhea (Hung et al. 2012; Michael et al. 2005). This is in addition to being rather costly and not affordable by the majority of people in developing countries especially for African populations. These limitations coupled with an exponential increase in the prevalence of diabetes motivate researchers to scientifically validate the folkloric use of a number of medicinal plants and/or their isolated bioactive compounds as possible alternative therapies for diabetes. The prime target for such research is to pave the way for the development of newer plant-derived anti-diabetic compounds that could be used to ameliorate the diabetes associated complications. This can subsequently be standardized and be used as drug for the treatment of the DM.
Furthermore, in many continents such as Africa, herbs and natural products form an integral component of the health care delivery system (Cragg and Newman, 2013). This has been further supported by the World Health Organization (WHO) report that 80% of the population in Africa depends almost entirely on traditional medicines, herbal medicines in particular, for their primary health care needs (WHO, 2001). This is attributed to the proven effectiveness of the plant-based therapies as well as the availability of these medicinal plants. Because, the African continent accounts for about 25% of the total number of higher plants in the world where more than 5400 medicinal plants were reported to have over 16300 medicinal uses (van Wyk et al. 2008). Fortunately, some plant products either in the form of crude extracts, fractions or isolated compounds have been screened or investigated for possible anti-diabetic remedy in Africa (Mohammed et al. 2014). However, the number of plants
and/or isolated bioactive compounds with potential anti-diabetic actions is very limited and many of their anti-diabetic effects have not yet been scientifically validated.
1.1 Literature Review
1.2 Diabetes Mellitus
Diabetes mellitus (DM) is a disorder that causes elevation of blood glucose, otherwise known as hyperglycemia (fasting blood glucose level: ≥126 mg/dL or 7.0 mmol/L; or postprandial hyperglycemia:
≥200 mg/dL or 11.1 mmol/L) due to either decrease in insulin secretion and/or insulin sensitivity of target tissues (Panini, 2013; ADA, 2015).
1.2.1 Types of diabetes mellitus
Originally, diabetes has been classified into two major classes: (1) type 1 or insulin dependent diabetes mellitus (IDDM) and (2) type 2 or non-insulin dependent diabetes mellitus (NIDDM) (WHO, 1980). However, rapidly changing pathogenesis of diabetes has been taken into account for the new classification of DM. The recent classification by the American Diabetes Association (ADA), diabetes is categorized into four types: type 1 diabetes, type 2 diabetes, gestational diabetes and the secondary form of diabetes which encompasses all types of diabetes due to other causes, for instance, monogenic diabetes syndromes, diseases of the exocrine pancreas and drug- or chemical-associated diabetes (ADA, 2015).
1.2.2 Type 1 diabetes mellitus
This form of diabetes is due to autoimmune-mediated destruction of the pancreatic β-cells as a result of production of humoral auto antibodies (ADA, 2015; Canivell and Gomis, 2014). Although the cause of type 1 diabetes (T1D) remains elusive, it is strongly linked to interplay between genetic predisposition and environmental factors that possibly triggers an autoimmune destruction of the pancreatic β-cells leading to absolute insulin deficiency (Patterson et al. 2014). The environmental factors include infectious agents such as viruses (coxsackie B virus, rubella virus) and food toxins. The destruction of pancreatic β-cells is gradual and variable, being rapid in infants and children and slower in adults (Joslin and Kahn, 2005). The mechanism involves on selective destruction of pancreatic β-cells in T1D is poorly understood due to the dissimilarities of pancreatic lesions (Ozougwu et al. 2013). The proposed mechanism involves the infiltration of lymphocytes (innate immune cells) or insulitis due to co-interaction of genetic and environmental factors. The infiltration of innate immune cells produces cytokines such as glutamic acid decarboxylase antibodies (GAD-65), islet cell antibodies (ICA512A/ICA) and insulin antibodies (IAA), which promote pancreatic β-cell apoptosis and increase
infiltration of islet reactive T cells that ultimately attack and destroys pancreatic β-cells (Szablewski, 2014).
Similarly, other form of T1D categorized as ʺidiopathic diabetesʺ which includes all forms of T1D with no known etiology and is mostly found among individuals from Asian or African regions.
Individuals with this type of diabetes demonstrate no evidence of autoimmunity and exhibit insulinopenia and are prone to ketoacidosis (ADA, 2015; Canivell and Gomis, 2014). Apart from above, a brief summary of the pathogenesis of T1D is presented in Figure 1.1.
Figure 1.1: Pathogenesis of type 1 diabetes (copied without permission from Atkinson and Eisenbarth, 2001). FPIP, first phase of insulin response; GADA, glutamic acid decarboxylase antibodies; ICA512A/ICA, islet cell antibodies; IAA, insulin antibodies.
1.2.3 Type 2 diabetes mellitus
Type 2 diabetes (T2D) is a heterogeneous disorder characterized by insulin resistance and partially dysfunctional pancreatic β-cells which cannot properly secrete insulin in response to hyperglycemia (Hui et al. 2007). It is the most prevalent type of diabetes, accounting for more than 90%
of all reported diabetes cases in the world (IDF, 2014). The insulin deficiency is relative rather than absolute and usually no insulin treatment (unless special cases) is required for T2D (ADA, 2015). The pathogenesis of insulin resistance in T2D is complex and involves genetic (defect on insulin and its receptor genes etc.) and environmental (obesity, sedentary life, age and physical inactivity) factors (Tuomilehto et al. 2001). Furthermore, inadequate insulin secretion by pancreatic β-cell in type 2 diabetic individuals disrupts the regulation of hepatic gluconeogesis, muscles glucose uptake and lipolysis in adipose tissues (Gastaldelli, 2011). The consequence is postprandial hyperglycemia which results in to T2D. The summary of the pathogenesis for T2D is presented in Figure 1.2.
Figure 1.2: Pathogenesis of type 2 diabetes (copied without permission from Caballero, 2005).
1.2.4 Gestational diabetes mellitus
Gestational diabetes mellitus (GDM) have been defined as heterogeneous group of disorders associated with any glucose intolerance diagnosed usually in the third trimester of the pregnancy (Ashwal and Hod, 2015) when in many cases disorder may improve or disappear after the delivery of baby. Similarly, it has been reported that about 3% to 65% of women with a history of GDM are at high risk of developing T2D in the later part their lives (Lee et al. 2008). In genetic predisposed women (during pregnancy), the alterations in glucose metabolism may lead to mix insulin resistance and impaired insulin secretion (Whitelaw and Gayle, 2010). This condition usually exaggerates as the pregnancy period increases which ultimately result in to hyperglycemia. The pathogenesis of GDM is summarized in Figure 1.3.
Figure 1.3: Pathogenesis of gestational diabetes mellitus (GDM) (prepaid based on Whitelaw and Gayle (2010) report).