A Review on Medicinal Plants Used in the Management of Headache in Africa

The use of medicinal plants in the management of diverse ailments is entrenched in the culture of indigenous people in African communities. This review provides a critical appraisal of the ethnobotanical uses of medicinal plants for the management of headache in Africa. Research articles published from 2010 (Jan) to 2021 (July) with keywords such as Africa, ethnobotany, headache, medicinal plant and traditional medicine were assessed for eligibility based on sets of pre-defined criteria. A total of 117 plants, representing 56 families, were documented from the 87 eligible studies. Asteraceae (10%), Fabaceae (10%), Lamiaceae (9%) and Mimosaceae (5%) were the most represented plant families. The most popular plant species used in the management of headache were Ocimum gratissimum L. (n = 7), Allium sativum L. (n = 3), Ricinus communis L. (n = 3) and Artemisia afra Jack. ex. Wild (n = 2). The leaves (49%), roots (20%) and bark (12%) were the most common plant parts used. Decoction (40%) and infusion (16%) were the preferred methods of preparation, whereas the oral route (52%) was the most preferred route of administration. The data revealed that medicinal plants continue to play vital roles in the management of headache in African communities. In an attempt to fully explore the benefits from the therapeutic potential of indigenous flora for common ailments, further studies are essential to generate empirical evidence on their efficacies, using appropriate test systems/models. This approach may assist with the ongoing drive towards the integration of African traditional medicine within mainstream healthcare systems.


Introduction
From time immemorial, humans have relied on medicinal plants to fight diseases and provide for diverse health needs. According to the World Health Organisation (WHO), about 80% of the world's population relies on medicinal plants for their primary health care needs [1]. In Africa, many people depend on medicinal plants to fight ailments, including headache. Headache is a common health condition in both children and adults [2]. Primary headache has no fundamental cause, whereas secondary headache is caused by conditions such as brain tumor, neck injury and sinus infection [3]. The pain experienced during headache emanates from a combination of signals in the brain, blood vessels and proximate nerves of an individual. Precise nerves in an individual's blood vessels and the muscles in the head switch on, which send pain signals to the brain [4]. "The common causes of headache are illness (fever, cold and infections), environment noise, stress, pollution, strong smell from perfumes or household chemicals), genetics (children whose parents had migraine headaches history tend to have them in their lifetime)" [5]. Headache accounts for 5% of the worldwide disease burden in terms of disability [6]. The prevalence rate varies across different countries, such as 3% in Ethiopia [7], 52.2% in Turkey [8] and 92.4% in Pakistan [9]. Relative to the low prevalence rate recorded in Ethiopia [7], a higher rate was evident in Turkey and Pakistan, which may be attributed to the presence of heavy industries (major sources of atmospheric pollution). The Ethiopian study was conducted in a rural area (Meskan and Marko) [7] compared to the urban areas (study sites) in Turkey (Mersin) [8] and Pakistan (Karachi) [9].
Generally, the management of headache in orthodox conventional medicine (OCM) involves the use of analgesics, non-steroid anti-inflammatory drugs (NSAIDs), beta-blockers, calcium channel blockers, anticonvulsants and tricyclic antidepressants [10]. As highlighted in Table 1, these drugs are associated with a diverse range of side effects, which continue to stimulate the search for alternative treatment regimens from different sources, especially higher plants. As an indication of the potential of medicinal plants for managing headache, 96 plants were identified as local remedies for headache among three tribes (Zulu, Xhosa and Sotho) in South Africa [11]. Studies have highlighted the potential of medicinal plants in the management of headache in many African countries. A study conducted in Ghana revealed the use of medicinal plants such as Griffonia simplicifolia (DC.) Baill. by the indigenous population in the management of headache [12]. Similarly, Cinnamosma fragrans Baill. was used by the indigenous population in Madagascar for the management of headaches [13]. Given the high reliance on traditional medicine, it is pertinent to identify the common medicinal plants employed to manage headache by the indigenous population across African communities. This will assist with the scientific identification and evaluation of the medicinal plants with the potential to mitigate the effects of headache. Thus, the present review provides an inventory and critical appraisal of medicinal plants used for the management of headache by different tribes in Africa. Table 1. Orthodox conventional medicines used in the management of headache.

Analgesics Analgin Paracetamol
Reduction of the pain impulses via afferent nerves and inhibition of subcortical pain centres [14,15] Reduction of the pain impulses via afferent nerves and inhibition of subcortical pain centres [15].
Non-steroid Anti-inflammatory drugs Aspirin Indomethacin Overpowering the cyclooxygenase activity (COX), subdual of the inflammatory mediators. The reticence of the subcortical pain centres [17].

Beta-blockers
Propranolol Nadolol Metropol Atenolol Beta-blockers help in the reduction of blood flow in the brain by directly acting on the blood vessels in the organ. Significant widening of blood vessels, known as vasodilation, is associated with migraine [20].
Antihypertensive Fatigue, dizziness, poor blood circulation and sexual dysfunction in males [21].

Calcium channel blockers Verapamil
Helps in the inhibition of Ca 2+ ion transport inside the smooth muscles' vessels. This helps in the prevention of the mechanical tightening of the muscle wall of the artery [22].

Anticonvulsants Sodium valproate Topiramate
Helps in the increment of the content of inhibitory transmitter gamma-aminobutyric acid (GABA) in the central nervous system (CNS) [24].

Tricyclic antidepressants Amitriptyline Venlafaxine
Helps in the reduction of noradrenaline, dopamine and serotonin reuptake thereby increasing their accrual in the synaptic cleft [27].

Selection of Published Articles
Google Scholar, Pub-med, the web of science and the Cochrane Library electronic databases were searched to identify potential research articles. Medicinal plants used for the relief of headache in Africa, traditional medicine (TM), TM and headache in Africa and the pathophysiology of headache were a few keywords and phrases used to identify eligible articles.

Selection Criteria
The main inclusion criterion was published research articles related to the use of plants for managing headache, with duration from January 2010-July 2021. The scientific name of the plant had to be provided and the study area had to be located in an African country. The exclusion criteria were published articles not written in the English language. Moreover, review articles (literature or systematic), studies involving the use of OCM in the management of headache, abstract-only accessed published articles, in vivo/in vitro studies, letters, case reports, books, manuals and all those reporting animal/mineral-based TM used in the management of headache were excluded. Generally, four-step selection criteria were employed to identify the published articles included in this study. Firstly, the importance of studies was checked based on the captions of the published articles. Secondly, abstracts of the published articles were assessed to match the inclusion criteria. Thirdly, the full-length text of the identified published articles based on the knowledge acquired in step 2 was obtained and read thoroughly in order for the authors to make an informed decision on whether to include/reject those research articles in this review. Published articles that met the inclusion criteria were retrieved for careful evaluation. In total, 87 published articles were included in this study ( Figure 1). The data were mined to extract information such as botanical names, local names, countries, routes of administration and modes of preparation ( Table 2). The scientific names for the plants were validated using recognised databases including The Plant List (including Global Biodiversity information facility) and Plant ZA [29,30].

Pattern and Distribution of Medicinal Plants Used in the Management of Headache in Africa
The 87 eligible studies included in this study were obtained from 27 African countries ( Table 2). The countries that recorded the highest number of plant species were as follows: South Africa (n = 30), Nigeria (n = 16), Ethiopia (n = 13) and Uganda (n = 12). In total, 117 medicinal plants, representing 56 families, were documented in this review. Irrespective of the geographical location in Africa, the use of medicinal plants in mitigating the effects of headache is of great prevalence ( Table 2). This is in agreement with similar studies conducted in Asia and Europe, which revealed the use of medicinal plants by the general population in the management of headache [31,32].

Overview of Medicinal Plants and Families Used in the Management of Headaches
In this study, most of the identified medicinal plants belonged to Asteraceae (10%), Fabaceae (10%) Lamiaceae (9%) and Mimosaceae (5%) (Figure 2). According to van Wyk [118], African Traditional Medicine in sub-Saharan African is dominated by plant families such as Lamiaceae (142 spp., 37 genera), Asteraceae (314 spp., 112 genera) and Fabaceae (567 spp., 156 genera). This observation is comparable to the dominant plant families (Lamiaceae, Asteraceae, Fabaceae) associated with the identified medicinal plants used for managing headache in Africa. The selection of medicinal plants (for some families) used in the management of diseases in sub-Saharan Africa could be influenced by culture and the availability of a plant species in a geographical location [118]. Significantly, in comparison with studies conducted in different parts of the globe to ascertain the medicinal plants used in the management of headache, most of the identified medicinal plants were members of Lamiaceae and Asteraceae. For instance, in Iran, Lamiaceae and Asteraceae were the most frequently cited plant families used for managing headache [119]. Likewise, in Serbia, the aerial parts of the identified plant species Teucrium montanum L. and Mentha pulegium L. used in the management of headache belonged to the Lamiaceae [120].  Table 2.
Certain plant species associated with the most cited plant families (Lamiaceae, Asteraceae, Fabaceae and Euphorbiaceae) were frequently mentioned in this study. Ocimum gratissimum L. (n = 7), belonging to Lamiaceae, which was frequently mentioned in this study, is known to possess diverse pharmacological activities, such as antioxidant and anti-inflammatory properties [121]. Similarly, Artemisia afra Jack. ex. Wild (n = 2), belonging to the Asteraceae and one of the most cited plant species, possesses analgesic, anti-inflammatory and antidepressant pharmacological activities [122]. Furthermore, Ricinus communis L. (n = 3), which is a member of Euphorbiaceae, is associated with anti-oxidant and anti-inflammatory properties [123].

Commonalities in the Use of Similar Medicinal Plants in the Management of Headache in Africa
The findings of the current review identified some similarities that exist in the use of particular medicinal plants in the management of headache among some African countries. For example, the use of Artemisia afra Jack. ex. Wild was reported in South Africa [35] and Ethiopia [58]. Furthermore, a study conducted in South Africa revealed the analgesic effects of Artemisia afra Jack. ex. Wild, which may attenuate pain associated with headache.
The experimental results confirmed the increase in the reaction time of Wister rats during a hot plate test when the animals were administered with extracts of Artemisia afra Jack. ex. Wild [124]. Similarly, Ocimum gratissimum L., a plant cultivated in both Ghana [125] and Madagascar [13] and used by local inhabitants to manage headache, reduced the pain response of albino rats considerably during a hot plate experimental study [126]. These examples justify the traditional use of the medicinal plants in the treatment and management of headache. However, issues about the safety and efficacy of medicinal plants used by the indigenous population in traditional African communities to mitigate ailments are of great concern to the WHO [127], especially in cases of adverse responses associated with the use of medicinal plants by patients. For example, a medical case report study indicated that the ingestion of Nicotiana glauca Graham, belonging to the same genus as Nicotiana tabacum L., which is used in Cameroon to treat headache [43], caused serious respiratory problems for a 60-year-old healthy patient in Greece [128]. This highlights the need for the standardisation of herbal medicine as it is critical to ensure its safety and efficacy [127].

Plant Parts Used to Manage Headache in Africa
The leaves (49%), root (20%) and bark (12%) were the dominant plant parts used in the management of headache ( Figure 3). This is in agreement with studies conducted in Iran, where the usage of these plant parts (leaves, root and bark) for the management of headache has been documented [45]. The popularity of leaves as the most preferred plant part in the preparation of herbal mixtures by traditional health practitioners (THPs) established in many ethnobotanical studies could be due to the fact that leaves are more accessible. Even though the roots are rich in phytochemicals, their usage for the preparation of herbal mixtures is sometimes restricted because their frequent usage could pose a potential risk to the survival of the plants [46].

Method of Preparation of Medicinal Plants Used in the Management of Headache in Africa
In the included studies, the most common methods of preparation of the medicinal plants were decoction and infusion (Figure 4). Decoction and infusion involve the boiling of different parts of the medicinal plant to extract its bio-active compounds to be administered to patients to mitigate the effects of certain ailments. Decoctions (40%) and infusions (16%) are generally easy to prepare and inexpensive, which is why they are predominantly employed by THPs in the management of diseases [129]. In the Philippines and Pakistan, decoctions and infusions were the preferred methods used for the preparation of medicinal plants [130,131]. Likewise, in similar reviews of ethnobotanical studies about the management of diseases on the African continent, the constituents of herbal mixtures prepared as decoctions and infusions by THPs are rarely mentioned [132,133]. This shortcoming deters the efforts of health departments and policy makers to recommend the use of such herbal mixtures in mainstream healthcare. Thus, the scientific evaluation of herbal mixtures could be instrumental in the development of novel pharmaceuticals for the management of diseases across the continent. To attain such an important goal, collaboration among stakeholders (THPs, researchers and relevant government departments) is needed across the continent. The recognition of the intellectual property of THPs and benefits thereof will be instrumental for collaboration and solving the dilemma of withholding knowledge by THPs.

Route of Administration of Medicinal Plants Used in the Management of Headache in Africa
The route of administration of decoctions, infusions and boiled samples of the medicinal plants was mainly (52%) oral ( Figure 5). These findings corroborate those of previous studies [51,52]. The oral route of administration is mostly preferred because it is an effective, non-invasive and suitable method of administration [53]. In the current study, other routes of administration of the burnt/dried medicinal plants included inhalation/sniffing. Interestingly, the inhalation of burnt and dried roots of Calotropis gigantea was used for the treatment of headache in Gujarat, India [54]. Though not reported in the articles reviewed for this study, inhalation has been shown to be effective as it conveys the drug or active ingredient to the target organ with a reduction in systemic side effects [134]. The topical application of medicinal plants was the third most commonly cited route of administration used in the management of headache ( Figure 5). This is in congruent with studies conducted in other countries. For instance, the topical application of medicinal plants, such as Alpinia galanga Sw. (rhizome) and Baccharis latifolia (Ruiz and Pav.) Pers. (leaves and bark), were used in alleviating the effect of headache in patients in India [135] and Peru [136], respectively.

Conclusions
This review focused on the use of medicinal plants in the treatment and management of headache on the African continent. A total of 117 medicinal plants were documented from the 87 eligible studies included in this study. The most popular plant species used in the management of headache were Ocimum gratissimum, Allium sativum, Ricinus communis and Artemisia afra. The findings from this study revealed, to a certain extent, the holism of traditional health practices across the African continent, given that similar plants, methods of preparation and routes of administration were evident. This interesting observation can assist researchers in the field of TM to design a uniform health protocol(s) to be used by THPs in the management of headache on the continent. This review provided baseline data for scientific considerations in the quest for natural-based drug development for the treatment of headache. Besides, the methodological documentation of medicinal plants which is supported by scientific data is critical for their assimilation into the primary health care system, which many people rely on due to its affordability and perceived safety compared to OCM [137]. However, there is a need to evaluate the efficacy and contraindications of herbal preparations, and to establish an accepted dosage and protocol(s) for THPs across the continent to be administered to patients. This is important because herbal medicines have the possibility of increasing or decreasing the pharmacological action of OCM in older people and people with weaker immune systems [138]. Thus, scientists need to establish the interactions between herbal mixtures and OCM, which may assist in saving lives.  Data Availability Statement: All data used for the review are included in the manuscript.