Exploring the antimalarial potential of whole Cymbopogon citratus plant therapy
Graphical abstract
Introduction
Malaria is a devastating infectious disease that is concentrated in low-income Sub-Saharan African countries where it mainly affects marginalised communities (Omumbo et al., 2013). The high cost of and poor access to antimalarial drugs and the development of drug resistance has increased the problems associated with malaria (Chukwuocha and Dozie, 2011, Onwujekwe and Uzochukwu, 2005). Plants play a noteworthy role in therapeutics and have been the principal source of drugs for many centuries (Phillipson and Wright, 1991b, Zirihi et al., 2005). In malaria-endemic areas, accessible malaria treatments are primarily based on the use of traditional herbal remedies. In fact, most antimalarial drugs, such as quinine, atovaquone, chloroquine (CLQ) and primaquine, are either obtained directly from plants or developed using the chemical structures of plant-derived compounds as templates (Gomez Castellanos et al., 2009, Willcox and Bodeker, 2004). Artemisinin is another antimalarial drug isolated from Artemisia annua, a plant that has been traditionally used for the treatment of malaria in China for over 1000 years. Artemisinin represents a new class of highly effective antimalarial drugs that have positively influenced malaria therapy (de Ridder et al., 2008, Hsu, 2006, Phillipson and Wright, 1991a). However the high demand of artemisinin and the high cost of its chemical synthesis make this drug unaffordable for most individuals in malaria-endemic areas (Barbacka and Baer-Dubowska, 2011, Ro et al., 2006). Emerging resistance to artemisinin, particularly in association with its use in combined therapies, has been reported in Asia and is of major concern (Amaratunga et al., 2014, Fairhurst, 2015). Interestingly, treatment with the whole plant has been shown to overcome parasite resistance and to be even more resilient to the evolution of this resistance than the pure drug in mice (Elfawal et al., 2015). These results demonstrate the need to identify other plants with antimalarial activity, preferably those growing locally in endemic areas, as additional options for effective and sustainable malaria control. Notably, Cymbopogon citratus, a tropical plant belonging to the Poaceae (Gramineae) family, has been used in traditional medicine as an anti-inflammatory, antipyretic, antiprotozoal and particularly antimalarial agent (Adebayo and Krettli, 2011, Avoseh et al., 2015, Ginsburg and Deharo, 2011, Santoro et al., 2007). In fact, the essential oils isolated from C. citratus have been reported to exhibit antimalarial activity in mice in vivo (Akono Ntonga et al., 2014, Tchoumbougnang et al., 2005). C. citratus has been classified as a safe herb for human consumption (Ekpenyong et al., 2015, Koh et al., 2012); however, the antimalarial activity of the whole C. citratus plant has not been experimentally assessed. Thus, we evaluated the antimalarial activity of the whole C. citratus plant compared with that of and herbal infusion. We also tested the whole C. citratus plant antimalarial activity using two different Plasmodium species, P. chabaudi AS and P. berghei ANKA. The whole plant was administered either as a single dose after establishment of parasitaemia or as a prophylactic treatment prior to infection.
Section snippets
Plant material collection sites
C. citratus was collected in Zafra, Putla Villa de Guerrero, México. (latitude: N16°58′52″, longitude: W97°53′34″) and was identified by Dr. Eloy Solano-Camacho from the Facultad de Estudios Superiores (FES) Zaragoza of the Universidad Nacional Autónoma de México (UNAM), where the voucher specimen was deposited under number FEZA: 1607. The plant was dried for 10 days at room temperature, ground in an electric blender, and passed through brass sieves to obtain a 0.3 mm particle size. The plant
Titration of the antimalarial dose of the whole-plant treatment
The whole C. citratus plant significantly suppressed parasitaemia (by 47.99–99.89%) in a dose-dependent manner. The highest antimalarial activity was detected in the group treated with 1600 mg/kg body weight of the whole plant (99.89%), and it was slightly higher than that observed in the group treated with 10 mg/kg CLQ (98.61%). A remarkable outcome is that in spite of the low concentration administered, the combined treatment of C. citratus (800 mg/kg) with chloroquine (5 mg/kg) generated 99.99%
Discussion
In the search for new approaches to treat malaria, scientists have focused their research on medicinal plants (Nandakumar et al., 2006, Rasoanaivo et al., 2011, Willcox et al., 2011). Our results demonstrated that the whole C. citratus plant exhibited antimalarial activity against both P. chabaudi AS and P. berghei ANKA. The results of the 4 day suppressive test demonstrated that the antimalarial activity of the whole C. citratus plant was dose dependent, and increased suppression of
Conclusions
Our study demonstrated the antimalarial efficacy of the whole C. citratus plant against P. chabaudi AS and P. berghei ANKA. The antimalarial activity of C. citratus was dose-dependent; a dose of 1600 mg/kg exhibited higher antimalarial activity than that of 3200 mg/kg. As a prophylactic treatment, the whole plant showed higher antimalarial activity than CLQ and the herbal infusion. This study provides evidence that the whole C. citratus plant has potential for use as an alternative therapy
Conception and design
Uchechukwu M. Chukwuocha and Martha Legorreta-Herrera.
Collection and assembly of data
All authors.
Analysis and interpretation of data
All authors.
Obtaining of funding and critical revision of the article for intellectual content
Martha Legorreta-Herrera.
Conflicts of interest
The authors declare that they have no conflict of interest.
Acknowledgements
We are grateful to the World Academy of Sciences (TWAS) and Mexican Council on Science and Technology (CONACYT) (CONACYT-TWAS Postdoctoral fellowship award FR number 3240280381) for awarding Chukwuocha U.M. a one-year postdoctoral fellowship. This study was funded by the DGAPA, Grant PAPIIT IN216914, UNAM. The authors thank Dr. Eloy Solano-Camacho for his assistance with the collection and identification of C. citratus and Dr. Antonio Valencia-Hernández for critical reading of the manuscript.
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