Review ArticleABSTRACT
Among the most prevalent diseases caused by protozoan parasites, malaria is caused by parasites of the genus Plasmodium and transmitted to humans by infected female anopheles’ mosquito. Plants are considered to be the richest resource of active molecules in traditional systems of medicine and modern medicines. The use of plants and plant products both in medicines and as medicine could be traced as far back as the beginning of human civilization. In human history medicinal plants, a source of remedies, are widely used as alternative therapeutic tools for the prevention or treatment of many diseases. The genus Aloe is one of the top medicinal plants that have obtained its popularity from time to time. Aloe plants are used from immemorial time to nowadays. Combinations of active molecules extracted from Aloe species have been indicated to confer a variety of biological effects with different mechanisms of action. The chemical compositions that have been identified in Aloe plants include simple and complex polysaccharides, minerals, vitamins, enzymes, hydrocarbons, fatty acids, indoles, pyrimidines, aldehydes, and ketones, dicarboxylic acids, phenolic compounds, phytosterols, and alkaloids with potential biological and toxicological activities. Among these compounds several investigations revealed antimalarial activities. Generally, Anthraquinoes, anthrones, chromones and others are active compounds against malaria. Considering that natural molecules have acted as natural templates in the development of antimalarial agents, it is encouraged to investigate further analyses into Aloe constituents and their values against malaria. It should be followed with phytochemical and pharmacological analyses in order to give scientific ground to medicinal knowledge and future potential utilization. Therefore, further studies are needed to determine which compound act as a strong antimalarial agent or synergistic effects of the compounds are used for antimalarial activities. In addition, it is recommended to test other parts of Aloe plants like flowers, leaf gel, leaf skin, etc. against malaria.
Keywords: Antimalarial; Aloe; Compounds; Anthraquinoes; Anthrones; Chromones
Introduction
Among the most prevalent diseases caused by protozoan parasites, malaria is caused by parasites of the genus Plasmodium and transmitted to humans by infected female anopheles’ mosquito [1]. Plasmodium falciparum, Plasmodium malaria, Plasmodium knowlesi Plasmodium ovale, and Plasmodium vivax are the five parasite species that cause malaria in humans. Among these species, P. falciparum causes the most severe form of malaria and hence higher mortality rates [2]. The estimated number of malaria deaths stood at 627, 000 of the estimated 241 million cases of malaria in 2020 worldwide [3]. To control malaria, many popular practices exist to avoid the nuisance of mosquito bites such as fumigation, burning green leaves on the hut’s threshold, mosquito coils, insecticide sprays, and repellents. Smoke is a common method of repelling biting mosquitoes that is used throughout the world from ancient times to current [4]. To treat infectious diseases such as malaria, herbal medicine plays a great role. Due to the vast metabolic diversity of plants, natural products may be an alternative treatment opportunity of cheap and easy to treat malaria infection. For instance, artemisinin and quinine are antimalarial drugs that were isolated from plants. As a result, it can be generalized that plants have potential as sources of active chemical components used for antimalarial drugs [5].
Plants are considered to be the richest resource of active molecules in traditional systems of medicine and modern medicines. The use of plants and plant products both in medicines and as medicine could be traced as far back as the beginning of human civilization [6]. In human history medicinal plants, a source of remedies, are widely used as alternative therapeutic tools for the prevention or treatment of many diseases [7]. The genus Aloe is one of the top medicinal plants that have obtained its popularity from time to time. Aloe plants are used from immemorial time to nowadays. Therefore, they become a popular household remedy exhibiting a range of beneficial health-promoting properties. Aloe in one form or another is a common domestic medicine and is the basis of most pharmaceutical preparations [8]. For instance, investigations have led to increased importance of the mostly known Aloe species, A. vera due to its dependable medicinal properties, and it has been used in the preparation of pharmaceutical products [9].
Chemical Compositions of Aloe
Figure 1: Structures of some antimalarial compounds.
Combinations of active molecules extracted from Aloe species have been indicated to confer a variety of biological effects with different mechanisms of action [10]. The chemical compositions that have been identified in Aloe plants include simple and complex polysaccharides, minerals, vitamins, enzymes, hydrocarbons, fatty acids, indoles, pyrimidines, aldehydes, and ketones, dicarboxylic acids, phenolic compounds, phytosterols, and alkaloids with potential biological and toxicological activities [11]. Various components present in Aloe species have been found effective against many diseases, including malaria. In every application of Aloe species, preparing extracts of Aloe parts is mandatory. The leaves of Aloe plants are the most commonly used are heterogeneous and can be divided into three major parts. These are,
1. The majorly consists of structural components of the leaf part, the outer green epidermis.
2. The part that vascular bundles are placed where the bitter latex or sap is obtained, the outer pulp region below the epidermis; and
3. The inner leaf pulp, which consists of Aloe gel and containing parenchyma cells [12,13]. Although leaves are the most used part of the plant, recently some studies have reported the bioactive roots [14] and flowers [15] of the plant. Aloe species have become of great interest to researchers who have tried to identify the compounds responsible for these beneficial effects. Several constituents from various classes such as alkaloids, anthrones, chromones, flavonoids, glycoproteins, naphthalene’s, and pyrones have been isolated from the genus Aloe [16]. Aloin, aloesin, aloenin, aloeresin, aloe-emodin, apigenin, acemannan, and chrysophanol are some examples of such bioactive compounds Table 1 and Figure 1 [17-25].
Table 1: The bioactive compounds in the genus Aloe.
The Antimalarial Aloe Compounds
Anthraquinones
Above all the genus Aloe is rich in anthraquinones which play a crucial role in medicinal applications. Many investigators showed the antimalarial activities of anthraquinones of Aloe species. In the literature, the leaves and roots of different Aloe species were tested and showed variable antimalarial activities. One of the most known anthraquinones, aloe-emodin emodin which was isolated from leaf latex of Aloe, A. macrocarpa Todaro showed potential antimalarial activity against malaria when compared with chloroquine [26]. In addition to this the chrysophanol, aloesaponarin I, and aloesaponarin II are anthraquinones that were isolated from the root of A. pulcherrima showed ant plasmodial activity against both chloroquine-resistant and -sensitive malaria parasites, P. falciparum [27].
Anthrones
The most studied Aloe constituents against malaria were anthrones. Anthrones are large classes of the genus Aloe and they are biologically active. Table 2 shows the specific anthrones of Aloe species against malaria along with parts of the plant [28-30].
Table 2: Antimalarial anthrones of Aloe species.
Chromones
Chromones also showed potential antimalarial compounds isolated from the Aloe species. In the literature, the compound, (E)-2-(1-hydroxy-2-methylpropyl)-8-(6’-O-cinnamoyl)-β-Dglucopyranosyl- 7-methoxy-5-methylchromone (HCGMM) has been reported as is a potential antimalarial compound from A. debrana Chrstian. When compared to the mice in the negative control group HCGMM showed significant suppression (p<0.05) against P. berghei at dose levels of 25, 50, and 100 mg/kg/day [31].
Other Compounds
The potential of Aloe species means the molecules in them have wide applications in combating malaria. From A.otallensis, naphthalene derivative identified as 2,8-O,O-di(β-D-glucopyranosyl)- 1,2,8-trihydroxy-3-methylnaphtalene (plicataloside) evaluated for its in vivo antimalarial activity using a 4- day Plasmodium berghei suppressive test method. The plicataloside (100 mg/kg) inhibited parasite growth by 40.7%. It was proposed that plicataloside may minimize oxidative stress thereby contributing to the antimalarial activity of the plant [32]. The literature shows that some flavonoid derivatives, xanthones, stilbenes, coumarins, lignans, tannins, quinones, terpenoids, steroids, and alkaloids possess antimalarial activity [33]. Among these, natural, semi-synthetic, and synthetic quinones are effective antimalarials [34]. Several investigations showed that many naturally occurring compounds possess antimalarial activity when tested in different malarial diseases [31].
Conclusion and Future Aspects
Based on the indigenous antimalarial effects of Aloe plants, the scientific studies, in vitro and in vivo reports confirmed that the leaves and roots of Aloe plants possessed genuine antimalarial activities which could be attributed to the presence of the active chemical constituents. More, the activity of the active constituents along with their relative margin of safety merit the use of these compounds as leads to the development of safer, cost-effective, and more potent alternative drugs for the treatment of malaria. Considering that natural molecules have acted as natural templates in the development of antimalarial agents, it is encouraged to investigate further analyses into Aloe constituents and their values against malaria. It should be followed with phytochemical and pharmacological analyses in order to give scientific ground to medicinal knowledge and future potential utilization. Therefore, further studies are needed to determine which compound act as a strong antimalarial agent or synergistic effects of the compounds are used for antimalarial activities. In addition, it is recommended to test other parts of Aloe plants like flowers, leaf gel, leaf skin, etc. against malaria. Further analysis is important to identify the result; if malaria drugs like chloroquine are incorporated into Aloe extracts/ isolated compounds. Although most studies are directed towards the curative effect of the test substances, in-depth pharmacokinetic and pharmacodynamic studies are needed to elucidate their mechanism of action.
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