Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Jun 26:15:1359890.
doi: 10.3389/fphar.2024.1359890. eCollection 2024.

Quest for malaria management using natural remedies

Qura Tul Ain  1   2 , Nida Saleem  1 , Nayla Munawar  3 , Rukhsana Nawaz  4 , Faiza Naseer  1   5 , Sagheer Ahmed  1
Affiliations
Review

Quest for malaria management using natural remedies

Qura Tul Ain et al. Front Pharmacol. .

Abstract

Malaria, transmitted through the bite of a Plasmodium-infected Anopheles mosquito, remains a significant global health concern. This review examines the complex life cycle of Plasmodium, emphasizing the role of humans and mosquitoes in its transmission and proliferation. Malarial parasites are transmitted as sporozoites to the human body by biting an infected female Anopheles mosquito. These sporozoites then invade liver cells, multiply, and release merozoites, which infect red blood cells, perpetuating the cycle. As this cycle continues, the affected person starts experiencing the clinical symptoms of the disease. The current treatments for malaria, including chloroquine, artemisinin-based combination therapy, and quinine, are discussed alongside the challenges of drug resistance and misdiagnosis. Although efforts have been made to develop a malarial vaccine, they have so far been unsuccessful. Additionally, the review explores the potential of medicinal plants as remedies for malaria, highlighting the efficacy of compounds derived from Artemisia annua, Cinchona species, and Helianthus annuus L., as well as exploration of plants and phytocompounds like cryptolepine, and isoliquiritigenin against drug-resistant Plasmodium species. Moreover, studies from Pakistan further highlight the diverse vegetal resources utilized in malaria treatment, emphasizing the need for further research into natural remedies. Despite the advantages of herbal medicines, including cost-effectiveness, and fewer side effects; their limitations must be taken into account, including variations in potency and potential drug interactions. The review concludes by advocating for a balanced approach to malaria treatment and prevention, emphasizing the importance of early detection, accurate diagnosis, and integrated efforts to combat the disease in the endemic regions.

Keywords: Artemisia; Cinchona; drug resistance; malaria; natural products.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
During its asexual blood stage, the P. falciparum parasite, surrounded by its parasitophorous vacuole membrane (PVM), develops within the host RBCs. (❶) Quinoline-based antimalarials, including chloroquine (CQ), amodiaquine (ADQ), and piperaquine (PPQ), concentrate from the parasitic cytosol (pH ∼7) into the digestive vacuole (DV) (pH ∼5.2). (❷) Once inside the DV, weak-base drugs are protonated, unable to passively diffuse out through the DV membrane. (❸) Protonated drug molecules bind to toxic heme by-products and grooves on hemozoin crystals in the DV, resulting in >1,000-fold drug accumulation due to pH trapping and heme-binding. (❹) The DV membrane protein PfCRT is believed to be involved in transporting peptides released from hemoglobin digestion into the parasite cytosol. (❺) In drug-resistant parasites, mutations in PfCRT enable the efflux of protonated drug molecules out of the DV, away from their heme target. (❻) DV membrane transporter PfMDR1 mutations influence parasite susceptibility by redirecting drugs such as halofantrine (HF), lumefantrine (LMF), and mefloquine (MFQ) into the DV, away from their primary site of action.
FIGURE 2
FIGURE 2
(❶) Artemisinin-based (ART) drugs are activated by cleavage of their endoperoxide by iron protoporphyrin IX (Fe2+-heme), a product of parasite-digested hemoglobin. (❷) The Fe2+-heme- ART carbon-centered radicals alkylate and damage a multitude of parasite proteins, heme, and lipids and inhibit proteasome-mediated protein degradation. PfK13 mutations, located primarily in the β-propeller kelch domain, confer ART resistance. (❸) The loss of PfK13 function provided by mutations has been shown to cause reduced endocytosis of host Hb and (❹) to extend the duration of ring-stage development, perhaps via PK4-mediated eIF2α phosphorylation, resulting in lowered levels of Hb catabolism and availability of Fe2+-heme as the drug activator, reducing ART activation (❺) PfK13 mutations activate the unfolded protein response, maintain proteasome-mediated degradation of polyubiquitinated proteins in the presence of ART, (❻) remove drugs and damaged proteins through an increase in PI3K-mediated vesicular trafficking. (❼) PfK13 may also help regulate mitochondrial physiology and maintain membrane potential during drug-induced ring-stage quiescence. The asterisk signifies the activated form of ART (Wicht, Mok, and Fidock, 2020).
FIGURE 3
FIGURE 3
Geographical distribution of malaria (Centre for Disease Control and Prevention).
FIGURE 4
FIGURE 4
The life cycle of Plasmodium in humans and Anopheles mosquito.
FIGURE 5
FIGURE 5
Structure of 3 common plant-derived anti-malaria drugs.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Abrantes P., George D., Grosso A. R., Rosario V. E. do, Silveira H. (2008). Chloroquine mediated modulation of Anopheles gambiae gene expression. PLoS One 3 (7), e2587. 10.1371/journal.pone.0002587 - DOI - PMC - PubMed
    1. Acosta M. M., Bram J. T., Sim D., Read A. F. (2020). Effect of drug dose and timing of treatment on the emergence of drug resistance in vivo in a malaria model. Evol. Med. Public Health 2020 (1), 196–210. 10.1093/emph/eoaa016 - DOI - PMC - PubMed
    1. Adedeji W. A., Balogun T., Fehintola F. A., Morse G. D. (2018). Drug-drug interactions of antimalarial drugs. Drug Interact. Infect. Dis. Antimicrob. Drug Interact., 503–514. 10.1007/978-3-319-72416-4_12 - DOI
    1. Aderinto N., Olatunji G., Kokori E., Sikirullahi S., Aboje J. E., Ojabo R. E. (2024). A perspective on Oxford’s R21/Matrix-M™ malaria vaccine and the future of global eradication efforts. Malar. J. 23 (1), 16. 10.1186/s12936-024-04846-w - DOI - PMC - PubMed
    1. Afzal H. S., Khan W., Nawaz S., Malik Utra A., Ahmad T. (2022). Investigation of the diuretic potential of diosmetin, a flavonoid from citrus lemon in sprague-dawley rat model. Phytopharm. Commun. 2 (02), 115–126. 10.55627/ppc.002.02.0151 - DOI

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The authors thank the United Arab Emirates University for financing this research under UPAR project G00003696, grant code 12S094.

LinkOut - more resources