Future antimalarials from<i>Artemisia</i>? A rationale for natural product mining against drug-refractory<i>Plasmodium</i>stages

Maciuk, Alexandre; Mazier, Dominique; Duval, Romain

doi:10.1039/d3np00001j

Cited by 7 publications

(3 citation statements)

References 195 publications

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“…As a direct consequence, a renewed interest in self-medicating in heavily affected regions is growing. Most commonly employed are infusions of Artemisia annua in Asia and Artemisia afra in Africa [ 37 ]. Self-medicating with natural products can be risky as plants can produce unexpected secondary metabolites that can be dangerous, highlighting the necessity to exploit these products and identify metabolites that are strictly active against the parasite and not the host [ 34 ].…”

Section: From Natural Remedies To Synthetic Molecules and Back Againmentioning

confidence: 99%

The Paradigm Shift of Using Natural Molecules Extracted from Northern Canada to Combat Malaria

Bourgeois,

Lemos,

Roucheray

et al. 2024

Infectious Disease Reports

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Parasitic diseases, such as malaria, are an immense burden to many low- and middle-income countries. In 2022, 249 million cases and 608,000 deaths were reported by the World Health Organization for malaria alone. Climate change, conflict, humanitarian crises, resource constraints and diverse biological challenges threaten progress in the elimination of malaria. Undeniably, the lack of a commercialized vaccine and the spread of drug-resistant parasites beg the need for novel approaches to treat this infectious disease. Most approaches for the development of antimalarials to date take inspiration from tropical or sub-tropical environments; however, it is necessary to expand our search. In this review, we highlight the origin of antimalarial treatments and propose new insights in the search for developing novel antiparasitic treatments. Plants and microorganisms living in harsh and cold environments, such as those found in the largely unexploited Northern Canadian boreal forest, often demonstrate interesting properties that are not found in other environments. Most prominently, the essential oil of Rhododendron tomentosum spp. Subarcticum from Nunavik and mortiamides isolated from Mortierella species found in Nunavut have shown promising activity against Plasmodium falciparum.

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Section: From Natural Remedies To Synthetic Molecules and Back Againmentioning

confidence: 99%

The Paradigm Shift of Using Natural Molecules Extracted from Northern Canada to Combat Malaria

Bourgeois,

Lemos,

Roucheray

et al. 2024

Infectious Disease Reports

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“…1500 records for the genus Artemisia. This genus of over 500 species is a source of important bioactive compounds, the most famous of which is artemisinin, the noted antimalarial produced by Artemisia annua L. [5][6][7] While both Artemisia species contain a plethora of specialty molecules, A. afra typically contains no detectable artemisinin. 8 Also similar to A. annua, A. afra has a long history of ethnobotanical medicinal use, primarily in southern Africa instead of South Asia.…”

Section: Introductionmentioning

confidence: 99%

A methoxylated flavone fromArtemisia afrakillsMycobacterium tuberculosis

Kellogg,

Alonso,

Jordan

et al. 2023

Preprint

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Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is a deadly and debilitating disease globally affecting millions annually. Emerging drug-resistant Mtb strains endanger the efficacy of the current combination therapies employed to treat tuberculosis; therefore, there is an urgent need to develop novel drugs to combat this disease. Artemisia afra is used traditionally in southern Africa to treat malaria and recently has shown anti tuberculosis activity. This genus synthesizes a prodigious number of phytochemicals, many of which have demonstrated human health effects. Transcriptomic analysis revealed that A. afra exerts different effects on Mtb compared to A. annua or the well-known antimalarial artemisinin, suggesting other phytochemicals present in A. afra with unique modes of action. A biochemometric study of A. afra resulted in the isolation of a methoxylated flavone (1), which displayed considerable activity against Mtb strain mc26230. Compound 1 had an MIC of 312.5 μg/mL and yielded no viable colonies after 6 days of treatment. In addition, 1 was effective in killing hypoxic Mtb cultures, with no viable cultures after 2 days of treatment. This suggested that A. afra is a source of potentially powerful anti-Mtb phytochemicals with novel mechanisms of action.

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“…Currently, approximately 60% of newly discovered small molecule drugs are sourced from natural products or their derivatives (Kalkreuter et al, 2020). Notably, a significant portion of these natural products can be found in the human diet, encompassing vegetables, fruits, and certain herbs (Maciuk et al, 2023;Sofi & Tabassum, 2022). In recent years, the field of biological sciences and phytochemistry has witnessed significant advancements, leading to the identification and utilization of various food-derived natural products.…”

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confidence: 99%

Human diet‐derived polyphenolic compounds and hepatic diseases: From therapeutic mechanisms to clinical utilization

Hu,

Zhang,

Wei

et al. 2023

Phytotherapy Research

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This review focuses on the potential ameliorative effects of polyphenolic compounds derived from human diet on hepatic diseases. It discusses the molecular mechanisms and recent advancements in clinical applications. Edible polyphenols have been found to play a therapeutic role, particularly in liver injury, liver fibrosis, NAFLD/NASH, and HCC. In the regulation of liver injury, polyphenols exhibit anti‐inflammatory and antioxidant effects, primarily targeting the TGF‐β, NF‐κB/TLR4, PI3K/AKT, and Nrf2/HO‐1 signaling pathways. In the regulation of liver fibrosis, polyphenolic compounds effectively reverse the fibrotic process by inhibiting the activation of hepatic stellate cells (HSC). Furthermore, polyphenolic compounds show efficacy against NAFLD/NASH by inhibiting lipid oxidation and accumulation, mediated through the AMPK, SIRT, and PPARγ pathways. Moreover, several polyphenolic compounds exhibit anti‐HCC activity by suppressing tumor cell proliferation and metastasis. This inhibition primarily involves blocking Akt and Wnt signaling, as well as inhibiting the epithelial‐mesenchymal transition (EMT). Additionally, clinical trials and nutritional evidence support the notion that certain polyphenols can improve liver disease and associated metabolic disorders. However, further fundamental research and clinical trials are warranted to validate the efficacy of dietary polyphenols.

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Future antimalarials fromArtemisia? A rationale for natural product mining against drug-refractoryPlasmodiumstages

Abstract: Non-artemisinin phytochemicals from Artemisia annua and A. afra infusions may explain their activity against the drug-refractory hypnozoite and mature gametocyte stages of Plasmodium parasites, potentially constituting invaluable antimalarial hits.

Cited by 7 publications

References 195 publications

The Paradigm Shift of Using Natural Molecules Extracted from Northern Canada to Combat Malaria

The Paradigm Shift of Using Natural Molecules Extracted from Northern Canada to Combat Malaria

A methoxylated flavone fromArtemisia afrakillsMycobacterium tuberculosis

Human diet‐derived polyphenolic compounds and hepatic diseases: From therapeutic mechanisms to clinical utilization

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