A review for selecting medicinal plants commonly used for malaria in Uganda

The menace of current cases of parasite resistance to antimalarial drugs, nonavailability and accessibility, and the high costs of pharmaceutical products contribute to the high rate of medicinal plants consumption in the treatment of malaria in Uganda. Different ethnobotanical surveys on medicinal plants with antimalarial properties have been conducted across different geographical regions in Uganda in order to identify and select the most commonly used antimalarial plants as candidates in the proposed national herbal pharmacopoeia. The available literature on the medicinal plants used against malaria in the western, central, eastern and northern geographical regions in Uganda was selected from reputable journals using various citation databases as guides. The commonly used antimalarial plants in the regions were searched using relevant journals on previously established ethno-botanical survey. They were then ranked in order of percentage frequency of appearance in the literature from surveys across the country. Fifteen medicinal plants were selected in this way from several antimalarial plants cited. Vernonia amygdalina and Azadirachta indica appeared most (100%), followed by Carica papaya, Mangifera indica and Hoslundia opposita with 80% appearance each across the 4 regions.The medicinal plants from this review were therefore ranked as the most used for treatment of malaria in Uganda and therefore, could be recommended for herbal pharmacopoeial standards development.


INTRODUCTION
Malaria remains one of the major health challenges in developing countries despite the efforts of different organizations including the World Health Organization (WHO), West African Health Organization (WAHO), Centers for Disease Control and Prevention (CDC), the African Union's Scientific, Technical and Research Commission (AU/STRC) among others to control and eradicate it (WHO, 2018).
It was reported that 219 million cases of malaria occurred worldwide in 2017 and 92% of these cases *Corresponding author. E-mail: cajayi2013@yahoo.com. Tel: +256705608441.
Author(s) agree that this article remain permanently open access under the terms of the Creative Commons Attribution License 4.0 International License were from African region with 435,000 mortalities. This malaria endemic region was followed by the South-East Asia Region with 5% and the Eastern Mediterranean Region with 2% (WHO, 2017(WHO, , 2018. The Uganda Malaria Reduction Strategic Plan (UMRSP) reported malaria cases of 1 out of 3 out-patient visits to health facilities and 50% of the in-patient pediatric mortalities are associated with malaria disease yearly (MoH, 2016). The setback to malaria fight has been attributed to nonavailability of effective vaccine, resistance to pyrethroidtreated mosquito nets, high costs of antimalarial drugs and the recent widespread chloroquine-resistant Plasmodium falciparum (WHO, 2018).
In malaria chemotherapy, medicinal plants have always played a leading role in drug discovery and such drugs are used in natural form or synthesized or act as structural models for semi-synthetic antimalarial drugs. Quinine was first time isolated from Cinchona bark against malaria in the early 18 th century and became a skeleton from which chloroquine (resochin), mefloquine and other similar antimalarial drugs were later synthesized (Achan et al., 2011).
The most successful battle against the sudden appearance of chloroquine-resistant P. falciparum led to the isolation of artemisinin from the Chinese Artemisia annua. Its synthetic chemical derivatives (e.g. artemether, dihydoartemisinin and artesunate) are now combined with existing antimalarial drugs to artemisinin-based combination therapy (ACT) such as artemartemetherlumefantrine, artesunate-amodiaquine, etc. which are referred to as ACT (Chen, 2014). Currently, ACTs remain the recommended choice of drugs for malaria despite recent reports on the P. falciparum resistance in Greater Mekong subregion (GMS) including Cambodia, Lao People's Democratic Republic, Vietnam, Thailand and Myanmar (WHO, 2018), etc.
Historically (from Cinchona to Artemisia), the plant kingdom remains the source for antimalarial drug discovery. Similar history has shown many current therapeutic drugs (e.g. digoxin, reserpine, morphine, etc.), at conventional health care levels for the management of other diseases from medicinal plants. According to the World Health Organization, 60% of the world's population depends on traditional medicine and 80% of the people in developing countries depend entirely on traditional medicine practices due to their accessibility, folklore and affordability for their primary health care needs (Chikezie and Ojiako, 2015).
The high acceptability of medicinal plants therefore requires the needs for their national standards which guarantee the consistence, definite identification, reproducible safety, efficacy and qualities as a valuable scientific reference for drug authorities, manufacturers, general public and researchers (WHO, 2011). These plants are normally selected based on their frequent used across the country. This review exercise aimed at compiling the most used medicinal plants for malaria in Uganda with a view to developing their national standards which will subsequently be used to develop their herbal monographs.

Literature data collection for the selection of antimalarial medicinal plants
The plants were searched through different search engines including Google Scholar, Institute for Scientific Information, PubMed, Scopus, Hinari, Scientific Information Database, etc., using antimalarial plants, antiplasmodial, malaria endemic, ethnopharmacology and Uganda regions as the keywords.
In this progression, different ethno-botanical survey articles on antimalarial plants in a particular region were first compiled and then ranked based on their frequency of occurrence in literature within the same region. Thereafter, their physical occurrences in the literature from other geographical regions of Uganda were considered. The antimalarial plants, found occurring in at least 2 out of the 4 regions (Central, Eastern, Northern and Western Uganda) and those mentioned in PROMETRA records (Association for the Promotion of Traditional Medicine), Uganda, East Africa, were selected. The following formula was applied to the plant collected prior to their ranking: Where, x is the total number of appearances ascribed to each antimalarial plant across the regions, while N (5) is the total number of regions together with PROMETRA antimalarial plants.
A comprehensive literature search was thereafter carried out to review the extent of previous studies on each of the selected plants.

RESULTS AND DISCUSSION
Fifteen medicinal plants belonging to 12 families were found to be commonly used for the control of malaria in Uganda among which 4 species (Bidens pilosa L.,  (Tugume et al., 2016).
The results of interview on about 28 traditional birth attendants (TBAs) by Stangeland et al. (2011) in the Nyakayoko sub-County of Mbarara District on medicinal plants commonly-used for malaria, have revealed 56 plant species from 23 families. The leaf part was found to be most widely used but the plants in this sub-County were either used individually or in combination (Table 1) Table 1 with some of their active ingredents, being reported. Also, reports on the safety of some of these plants have been reported with some showing degenerative effects such as nephro-/hepato-toxicity, vacuolar degeneration, necrosis, etc. (Adebayo et al., 2009;Elufioye et al., 2009;Passoni et al., 2013). This review exercise is necessary to select the plants that are commonly used as antimalarial across the country in order to develop their national standards by taking into consideration their botany, safety, efficacy and chemistry.

Conclusion
Through the literature search, fifteen medicinal plants were selected as the most commonly used in Uganda for the treatment of malaria out of many medicinal plants reported in ethnobotanical surveys across the regions and these plants could be standardized for pharmacopoeial inclusion.

CONFLICT OF INTERESTS
The authors have not declared any conflict of interests.