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Medicinal Plants Used for the Traditional Management of Diabetes in the Eastern Cape, South Africa: Pharmacology and Toxicology

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Medicinal Plants Used for the Traditional Management of Diabetes in the Eastern Cape, South Africa: Pharmacology and Toxicology molecules Review Medicinal Plants Used for the Traditional Management of Diabetes in the Eastern Cape, South Africa: Pharmacology and Toxicology Samuel Odeyemi ID and Graeme Bradley * ID Department of Biochemistry and Microbiology, University of Fort Hare, Alice 5700, South Africa; [email protected] * Correspondence: [email protected]; Tel.: +27-40-602-2173 Academic Editor: Oluwafemi Oguntibeju Received: 24 July 2018; Accepted: 16 August 2018; Published: 25 October 2018 Abstract: The use of medicinal plants for the management of diabetes mellitus is on the rise in the developing countries, including South Africa. There is increasing scientific evidence that supports the claims by the traditional healers. In this review, we compare the families of previously reported anti-diabetic plants in the Eastern Cape by rating the anti-diabetic activity, mode of action and also highlight their therapeutic potentials based on the available evidence on their pharmacology and toxicity. Forty-five plants mentioned in ethnobotanical surveys were subjected to a comprehensive literature search in the available electronic databases such as PubMed, ScienceDirect, Google Scholar and Elsevier, by using “plant name” and “family” as the keywords for the primary searches to determine the plants that have been scientifically investigated for anti-diabetic activity. The search returned 25 families with Asteraceae highly reported, followed by Asphodelaceae and Alliaceae. Most of the plants have been studied for their anti-diabetic potentials in vivo and/or in vitro, with most of the plants having a higher percentage of insulin release and inhibition against carbohydrate digesting enzymes as compared with insulin mimetic and peripheral glucose uptake. Almost all the investigated plants also inhibit oxidative stress as part of their hypoglycemic activity with less toxicity. However, the isolation of their bioactive molecules is still lacking. This review provides a resource to enable thorough assessments of the therapeutic profiles of available medicinal plants used for the management of diabetes in the Eastern Cape, South Africa. Further studies such as the identification of the active ingredients of potent plants still need to be carried out; this may lead to new molecules in drug discovery and development. Keywords: Ethnopharmacology; diabetes; medicinal plants; diabetes mellitus 1. Introduction Diabetes mellitus is a disease associated with high blood sugar levels, a situation where the body is unable to effectively control the metabolism of glucose, the primary source of energy. It is described as a clinical syndrome characterised by inappropriate hyperglycemia caused by a relative or absolute deficiency of insulin or resistance to the action of the hormone at the cellular level [1]. This can be as a result of an auto-immune response where the immune system mistakenly attacks and kills the beta cells of the pancreas, thereby leading to the insufficient availability of insulin to regulate blood glucose levels (type I diabetes), or the cells become insensitive/resistant to the action of insulin (type II diabetes). The deficient or diminished effectiveness of endogenously synthesised insulin increases glucose concentration in the blood and urine. Diabetes mellitus at the advanced stages affects other metabolic pathways of lipids, and manifests as hypercholesterolemia and hyperlipidemia, which are risk factors in atherosclerosis [2–4]. As the Molecules 2018, 23, 2759; doi:10.3390/molecules23112759 www.mdpi.com/journal/molecules Molecules 2018, 23, 2759 2 of 19 disease progresses, vital organs are affected such as the eyes, liver and kidneys, leading to retinopathy, increased gluconeogenesis, ketogenesis, diabetic ketoacidosis, non-ketotic syndrome, polyuria and nephropathy [5–7]. There is also an increase in the concentration of advanced glycation end products (AGEs), leading to the secondary complications of diabetes [7] such as impaired wound healing and foot ulcers, among others [8]. 1.1. Aetiology of Diabetes Mellitus To date, there is no apparent cure for diabetes mellitus type I, and therefore those with type I diabetes need to take insulin for life to control blood glucose levels. Diabetes mellitus type II is associated with the ingestion of high-calorie foods, family history of the disease, obesity, race, genetic disorders, smoking, inactivity, viral infections and drugs or chemicals, and can be managed with drugs and/or changed diet plans. Common symptoms of diabetes mellitus include frequent urination, excessive thirst, intense hunger and fatigue irritability, blurred vision, wounds that do not heal quickly or adequately, sexual dysfunction in men, and gum infections [9]. 1.2. Prevalence In recent times, there has been an increase in the prevalence of diabetes mellitus worldwide. A study in 2017 estimated that about 422–425 million adults were living with the disease and it was projected that this number would rise to 629 million adults (48% increase) affected with the disease by the year 2045 if necessary and adequate actions are not taken [10–12]. The African region has the highest proportion of undiagnosed diabetes, as investments, research, and health systems are slow to respond to this burden [13]. Available information suggests that diabetes is emerging as a significant health problem in Africa, including South Africa [13]. The Eastern Cape Province is estimated to have the highest percentage of poor residents (72.9%), in South Africa, with the majority of residents living in rural communities. The majority of these residents tend to rely on medicinal plants for the treatment of common diseases, including diabetes, because of their availability, affordability, effectiveness, and low side effects [14–16]. This review was therefore undertaken to identify which plants are used by traditional healers within the Eastern Cape province, South Africa, to treat diabetes. It is imperative to continually reassess glycemic control in people with diabetes due to the progressive nature of the disease, which requires constant therapeutic regimen readjustment. Metformin (dimethylbiguanide), the preferred first-line oral blood-glucose-lowering agent to treat type II diabetes, comes from a derivate of French lilac Galega officinalis (also known as goat’s rue), suggesting that medicinal plants could be a rich source of anti-diabetic agents [17]. Several drugs such as biguanides and sulfonylurea which are presently employed in the management of diabetes have side effects such as worsening of heart disease, increased body weight and hypoglycaemia [18,19]. These side effects coupled with the high cost of anti-diabetic drugs has led to the search for plants with anti-diabetic properties and consequently their use in the management of diabetes [19,20]. 1.3. Target Organs in Diabetes Treatment Most conventional and herbal treatments are targeted towards specific organs or metabolic pathways as shown in Figure1. These treatments either activate chemicals that enhance insulin secretion or suppress hepatic glucose output. The potency of the documented medicinal plants used for the treatment of diabetes has been attributed to the presence of their phytochemicals. These phytochemicals are synthesised by plants to protect themselves from internal stresses such as free radicals, and external stresses from insects and pests; this property of plants explains their potential to cure diseases and their benefits in traditional medicine. The phytochemicals of these plants have been reported, and their mechanism of action has been suggested [21,22]. Molecules 2018, 23, 2759 3 of 19 Molecules 2018, 23, x FOR PEER REVIEW 3 of 19 Incretin Incretin (GLP) (GLP) Figure 1. Summary of therapeutic targets for the management of diabetes mellitus. TZD = Figure 1. Summary of therapeutic targets for the management of diabetes mellitus. TZD = Thiazolidinedione. Thiazolidinedione. DPP-IV: Dipeptidyl peptidase IV; GLP: Glucagon-like peptide 1. DPP-IV: Dipeptidyl peptidase IV; GLP: Glucagon-like peptide 1. 1.4. Ethnopharmacological Data 1.4. Ethnopharmacological Data Forty-five plants identified from previous ethnobotanical surveys [15,23–25] for the managementForty-five of plants diabetes identified in Eastern from Cape previous Province, ethnobotanical South Africa, surveys were subjected [15,23–25 to] forelectronic the management searches ofin diabetesall University in Eastern of Fort CapeHare subscribed Province, Southdatabases. Africa, were subjected to electronic searches in all University of Fort Hare subscribed databases. 2. Results and Discussion 2. Results and Discussion Before selecting plants or families of plants to be included, priority was given to investigations carriedBefore out selectingwith samples plants collected or families from of Eastern plants toCape, be included, South Africa. priority Twenty-five was given families to investigations of the 45 carriedplants were out with reported samples in ethnobotanical collected from surveys Eastern (Tab Cape,le 1), South although Africa. some Twenty-five of these plants families have of also the 45been plants scientifically were reported investigated in ethnobotanical elsewhere for surveys their (Tableanti-diabetic1), although properties some to of justify these plantstheir traditional have also beenusage. scientifically Out of the investigated45 plants reviewed elsewhere here, for only their three anti-diabetic have been properties scientifically to justifyevaluated their in traditional vivo, 12 usage.scientifically Out of evaluated
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