Antidiabetic Activities of Terminalia Species in Nigeria

1.1 Risk factors

Physical inactivity or sedentary lifestyle, excessive alcohol, overweight, obesity and unhealthy diet intake are modifiable DM risk factors [10]. Family history, hypertension, history of previously impaired glucose tolerance (IGT) or impaired fasting glucose (IFG), advancing age, history of GDM, ethnicity and genetic makeup are some unmodifiable risk factors. However, various researchers have reported that novel risk factors such as short sleep duration [11], noise pollution [12] and environmental toxins [13] contribute to the causal pathways which lead to diabetes. Trade and agricultural production policies are thought to contribute to both individual and societal level risk factors [14].

2.1 Epidemiology

The transition from infectious diseases to non-communicable diseases as leading causes of death is fast becoming a growing epidemiological trend and public health dichotomy in Sub-Saharan African countries [15]. In Africa, there is a 1% estimated prevalence of diabetes in rural areas while in urban areas, the range is from 5–7% [16]. Nigeria accounts for about one-sixth of Africa’s population [1]. The national prevalence of diabetes, which was less than 1% between 1960 and 1990, has risen from 2.2% in 1997 to 5% in 2013 [17]. However, the current prevalence may currently be as high as between 8 and 10% [9], with 4.83% recorded for patients aged 20 and above, accounting for over 3 million people currently living with this condition [18]. This observation makes her the country with the highest number of people living with diabetes and IFG in Africa [19]. Epidemiological statistics show that Nigeria is responsible for one in every five reported sub-Saharan case of diabetes, with a steep increase in the prevalence of this disease from the rural areas to members of the high socio-economic population [9]. Continuous urbanisation, the increasing population and poor economy, will further drive the incidence and burden of diabetes upwards in Nigeria [1, 2, 20]. T2DM appears to be the majority of the DM burden in Nigeria with T1DM accounting for less than 10% of DM cases [21], while tropical DM makes up less than 1% [8]. Lifestyle factors such as sedentary lifestyle, cigarette smoking and generous consumption of alcohol are known risk factors linked to the development of T2DM. Obesity has been reported to be a major contributor to approximately 55% of diagnosed cases of T2DM, with a prevalence of 3.3 to 18% [2]. It has also been associated with several life-threatening diseases such as cardiovascular disease (CVD), several cancer types, as well as reduced quality of life [22, 23]. Diabetes-related morbidity and mortality have been reported to be high in different locations in Nigeria with 105,091 diabetes-related deaths recorded as at 2013 and most patients reported to have been suffering from T2DM [10].

2.2 Management

Given the current DM epidemic and its projected consequences, effective population-based intervention identification has become a priority public health strategy in Sub-Saharan Africa [24]. In Nigeria, insulin, oral glucose-lowering drugs, diet and exercise are used in the management of DM. Complementary and alternative medicine such as concoctions, infusions, tinctures and herbal supplement is also used [1]. Inability to use insulin syringe, the high cost of therapy, few options in the Nigerian market and poor policies on DM management are a few challenges affecting insulin treatment [25]. The medications used in the management of diabetes become less effective over time as most patients do not achieve normal glycaemic control with their use [26], and thus have resulted to possible second-line medications to achieve the normal glycaemic target [27]. Despite the high cost of medication as well as the inability to maintain normal glycaemic control for an extended period, the use of polytherapy to achieve sufficient glucose control is a common feature in Nigeria [28]. Challenges such as needle phobia, hypoglycaemia, drug-associated side effect and cost of medication have made over 46% of diabetic patients opt for complementary and alternative medicine, with Vernonia amygdalinawhich is also known as “bitter leaf” being most utilised [29]. The school of thought that diabetics should abstain from carbohydrate rich meals has led to the intake of monotonous food like unripe plantain, beans and wheat rich diet [1, 30]. This challenge occurs due to the absence of a taste-appealing standardised diet for diabetics as well as their dietary requirements influenced by economic status, religious and cultural beliefs [1].

3.1 Terminaliaspecies in Nigeria

There are about ten species of Terminaliafound in Nigeria, namely; Terminalia altissima(Synonym: superba), Terminalia avicennioides, Terminalia brownii, Terminalia catappa, Terminalia glaucescens, Terminalia ivorensis, Terminalia laxiflora, Terminalia macroptera, Terminalia mollis and Terminalia schimperiana[33, 36, 37]. These species have been reported to be pharmacologically active with antimicrobial, antimycobacterial, wound healing, gastroprotective, antimalarial, antioxidant, antifungal, anthelmintic, antibacterial, antifungal, antiviral, analgesic, radical scavenging, hepatoprotective, anticancer, antimutagenic, antiaging, aldose inhibitory, antiplasmodial, cytotoxic, antipsychotic, sedative, analgesic, anti-inflammatory, trypanocidal, hypolipidaemic, antioxidant, antimycoplasmal and androgenic, properties as shown in Table 1 [34, 35, 38, 39, 40, 41, 42].

Terminaliaspecies in Nigeria, have numerous application in the treatment and management of ailments among the various traditional medicine systems of different ethnic groups. Different parts are utilised by traditional healers to treat cholera, malaria, typhoid, hepatitis, stomach ache, tuberculosis, leprosy, diarrhoea, skin diseases, gastritis, hyperglycaemia, diabetes, gonorrhoea, wounds, epilepsy and catarrh [56, 57, 58]. They are also used as tonic, laxative and chewing sticks [26, 59, 60].

Several reports have highlighted some pharmacological properties of Terminaliaspecies in Nigeria, such as its antimicrobial properties, antibacterial property, anti-inflammatory action, anti-HIV, hypoglycaemic, modulatory properties, analgesic, wound healing, antioxidant and radical scavenging activity, hepatoprotective, anticancer, anti-trypanocidal, antimutagenic and antiaging properties.

Nigeria’s vegetation is made up of forests, savannahs and montane land. All others but the latter are further divided into three parts which have ensured the wide distribution of these species across the country. This variation in the country’s vegetation has not only made these Terminaliaspecies specific to Nigeria and West Africa, but accounts for the difference in their evolutionary relationship, development and pharmacologic activity. Upon assessment of the phylogenetic relationship on www.phylogeny.fr [61], using the available nucleic acid sequence of the Terminaliaspecies that were deposited in National Center for Biotechnology Information (NCBI) GenBank, it was observed that species that were closely related such as T. catappaand T. glaucescensas well as T. superbaand T. avicennioideswere located in the same vegetative region of the country (Figure 1). Irrespective of their evolutionary differences, it was observed that there were conserved regions that were similar in the deposited genetic sequence of the Terminaliaspecies in Nigeria showing over 94% sequence similarity (Figure 2).

3.2 Pharmacologic antidiabetic activities of Nigerian Terminaliaspecies

The pharmacologic antidiabetic activity of Terminaliaspecies have been reported in different climes using various in vitro, in vivoand in silicotechniques in mice, rat, rabbit and humans to elucidate them. Nonetheless, in Nigeria, there is a paucity of data on the antidiabetic mode of action and mechanisms of Terminaliaspp. despite its abundance. However, there are antidiabetic reports of these species from neighbouring countries with similar vegetation.