Approximately half of the world's population suffers from malaria, a fatal infectious illness that is brought on by five Plasmodium species. Malaria accounts for 77% of pediatric malaria fatalities [1, 2]. Compared to 245 million cases in 2020, there will be 247 million cases in 2021 [3]. The majority of those impacted are the world's poorest, who often turn to traditional remedies due to their accessibility and low cost. The goal of the ethnobotanical study was to document medicinal plants used in malaria prevention and treatment, as well as the preparation and administration techniques, and to gain insight into the diagnosis and understanding of malaria among traditional healers [4, 5].
Bacteria and viruses use phosphoinositide metabolism to ensure efficient replication and survival. Phosphatidylinositol 4-kinase (PI4K) plays a crucial role in virus replication, which is linked to malaria. PI4K-related inhibitors have been found to inhibit virus replication, treat cancer, treat malaria, and reduce organ transplant rejection [6, 7]. MMV390048, a compound used for full chemoprotection in monkeys, has been identified as a molecular target of the Plasmodium parasite PI4K. This compound blocks all life cycle stages of the malaria parasite in a monkey model, which recommends further development and potential contribution to malaria control and eradication [8].
Plasmodium falciparum, the primary malaria parasite, is resistant to standard antimalarial drugs, evading treatment with artemisinin. This resistance necessitates the development of new therapeutics to combat malaria [9]. Quinine and chloroquine poisoning, characterized by severe cardiovascular toxicity, occurs because of the drug’s ability to interfere with the normal electrical conduction of the heart, leading to abnormal heart rhythms. In severe cases, immediate medical intervention is required to stabilize the patient and prevent further complications [10]. Artemisinins have toxic effects on erythropoiesis in both animal and human studies [11]. A report showed that 70–80% of rural communities rely on medicinal plants for primary treatment and traditional and contemporary medicine, with impoverished individuals in developing nations relying on these plants because of their unique nutritional profile [12].
Barleria, a genus of over 300 species in the Acanthaceae family, is known for its diverse taxonomy, cytogenetics, phytochemistry, and pharmacological potential [13]. Barleria buxifolia is an attractive shrub with sharp spines and white to pink blooms. Its leaves contain anthelmintic qualities, and it is historically used to cure inflammation, bronchitis, and cough [14]. Barleriaquinone, a root derivative of B. buxifolia, was isolated, and its structure was found to be 1-hydroxy-7-methylanthraquinone by decomposition and spectroscopy [15]. Three novel anthraquinones were isolated from B. buxifolia roots, and spectrum analysis was used to determine their structures as l-hydroxy-7-carbomethoxy anthraquinone, l-hydroxy-Z-carbomethoxy-7-methylanthraquinone, and I-hydroxy-5-carbomethoxy-7-methylanthraquinone. These newly isolated anthraquinones may show promising potential therapeutic efficacy in various biological activities [16]. A total of 4 Acanthaceae family plants were reported for antimalarial activity, i.e., Andrographis paniculata, Justicia adhatoda, Justicia flava, and Acanthus polystachyus [17–20]. Nonetheless, as far as we are aware, no research on the antimalarial properties of this plant material has been published.
B. buxifolia roots are useful for the treatment of stomach ache, tonic and febrifuge [21], reduce inflammation and cough [22]. Roots and leaves have traditionally been used for cough, bronchitis, and inflammation [23]. A recent study explored the use of the leaf of B. buxifolia extract for ultrasonication-enhanced green synthesis of silver nanoparticles, which have the highest antioxidant, antibacterial, and anti-biofilm activity [24]. B. buxifolia fraction was isolated using ethyl acetate solvent for antifeedant, larvicidal, and ovicidal activity [25]. GC-MS study of the aerial portions of B. buxifolia methanolic extract, a notable ethnomedicinal plant used to cure a variety of diseases [26]. Stem bark, its prophylactic and curative effects on calcium oxalate-induced nephrolithiasis, antimicrobial activity, and the cytotoxic action of two anthraquinones, barleriaquinone-I and barleriaquinone-II, extracted from B. buxifolia [27–28]. To the best of our knowledge, this is the first antimalarial study from the root extract of B. buxifolia.
A member of the naphthoquinone medication family, atavaquone is used to treat acute, uncomplicated malaria caused by Plasmodium falciparum that is resistant to chloroquine in conjunction with proguanil [29]. Recent advancements in promising antimalarial candidates in clinical and preclinical phases, ranging from quinine to the latest marketed drugs [30]. This study has shown that antimalarial compounds were isolated from the root of B. buxifolia against PI4KIIIβ using in silico molecular docking and dynamic simulation. Metabolite profile analysis using LC-MS/HRMS. Therefore, the primary goals of this work are as follows: to extract and use LC-MS/HRMS to analyze phytochemicals found in B. buxifolia root extract (a); and to utilize in silico methods to assess anti-malarial capabilities and find potential lead compounds against the PI4KIIIβ target (b). This study found that it effectively treated the PI4KIIIβ target through in silico analysis, confirming previous claims that 1-[2-(benzhydryloxy)ethyl]-4-(3-phenylpropyl)piperazine derivatives were effective in treating trypanothione reductase inhibitors [31]. This study reports for the first time that this compound is effective against the PI4KIIIβ malarial target. Furthermore, this compound’s binding energy is higher than that of standard artemisinin, as shown by in silico molecular docking and dynamic simulation.