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"Mamede, Lúcia"
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Metabolomics, Molecular Networking and Phytochemical Investigation of Psiadia dentata (Cass.) DC., Endemic to Reunion Island: Discovery of Novel Bioactive Molecules
by
Kodja, Hippolyte
,
Frederich, Michel
,
Gauvin-Bialecki, Anne
in
Animals
,
Anti-Inflammatory Agents - chemistry
,
Anti-Inflammatory Agents - pharmacology
2026
The genus Psiadia (Asteraceae), widely distributed in Madagascar and the Mascarene Islands (Mauritius, La Réunion, Rodrigues), is traditionally used to treat bronchitis, asthma, colds, abdominal pain, and other inflammatory disorders. However, few studies have scientifically validated these traditional medicinal uses. To assess P. dentata as a valuable source of bioactive natural products, a combined 1H NMR-based metabolomic, molecular networking, and phytochemical study was conducted. Multivariate analysis (PLS-DA) of crude extracts from Psiadia species collected on Reunion Island enabled rapid discrimination of active extracts from P. dentata and revealed two methoxylated flavonoids and one coumarin as metabolites correlated with its antiplasmodial and anti-inflammatory activities. Additionally, UHPLC-DAD-ESI-QTOF-MS/MS molecular networking approach enabled detailed chemical profiling of this species, allowing the annotation of 25 compounds (1–25) in this species. Subsequent phytochemical investigation of P. dentata leaves led to the isolation and identification of 25 metabolites, including nine new diterpenes (26–34), one new coumarin (35), and 15 known compounds (1–8, 11, 18, 19 and 36–39) from the diterpenoid, flavonoid, and coumarin families. The structures of the new compounds were elucidated using spectroscopic methods, including extensive 1D and 2D NMR and HRESIMS analyses. Biological evaluation of the isolated compounds showed that compounds 1, 7, 26 and 27 showed antiplasmodial activity against Plasmodium falciparum (3D7 strain, IC50 = 7.25–13.46 μM). Compounds 7, 26, 27, 31 and 32 inhibited nitric oxide production (IC50 = 0.87–27.71 μM), indicating potential anti-inflammatory effects. Only compound 1 displayed moderate cytotoxicity against HepG2 and HT29 cancer cell lines (IC50 = 25.67 and 18.35 μM, respectively).
Journal Article
Secondary metabolites isolated from Artemisia afra and Artemisia annua and their anti-malarial, anti-inflammatory and immunomodulating properties-pharmacokinetics and pharmacodynamics: a review
by
Loe, Gisèle E.
,
Frederich, Michel
,
Ghogomu, Stephen Mbigha
in
Artemisia afra
,
Artemisia annua
,
Artemisinin
2023
There are over 500 species of the genus Artemisia in the Asteraceae family distributed over the globe, with varying potentials to treat different ailments. Following the isolation of artemisinin (a potent anti-malarial compound with a sesquiterpene backbone) from Artemisia annua, the phytochemical composition of this species has been of interest over recent decades. Additionally, the number of phytochemical investigations of other species, including those of Artemisia afra in a search for new molecules with pharmacological potentials, has increased in recent years. This has led to the isolation of several compounds from both species, including a majority of monoterpenes, sesquiterpenes, and polyphenols with varying pharmacological activities. This review aims to discuss the most important compounds present in both plant species with anti-malarial properties, anti-inflammatory potentials, and immunomodulating properties, with an emphasis on their pharmacokinetics and pharmacodynamics properties. Additionally, the toxicity of both plants and their anti-malaria properties, including those of other species in the genus Artemisia, is discussed. As such, data were collected via a thorough literature search in web databases, such as ResearchGate, ScienceDirect, Google scholar, PubMed, Phytochemical and Ethnobotanical databases, up to 2022. A distinction was made between compounds involved in a direct anti-plasmodial activity and those expressing anti-inflammatory and immunomodulating activities or anti-fever properties. For pharmacokinetics activities, a distinction was made between compounds influencing bioavailability (CYP effect or P-Glycoprotein effect) and those affecting the stability of pharmacodynamic active components.
Journal Article
Natural triterpenic phenolic esters target PfA-M17 in Plasmodium falciparum
by
Schmitt, Marjorie
,
Rangel, Gabriel W.
,
Spichty, Martin
in
Aminopeptidase
,
Analysis
,
Antimalarial agents
2026
Background
Malaria is a deadly parasitic disease for which innovative treatments are urgently needed. A mixture of eight triterpenic esters (8TTE) was previously identified as important for the antiplasmodial activity of
Keetia leucantha
twigs
,
a plant used in traditional medicine in Benin. Despite the reported in vitro and in vivo activity, the targets of 8TTE are unknown.
Methods
The present study investigated the mode of action of 8TTE on
Plasmodium falciparum
by a multi-scale integrative study from phenotype to metabolome, including: phenotypic analysis, enzymatic tests, molecular docking and metabolomic profiling.
Results
This study identified a unique antiplasmodial profile with activity onset in the early-ring stage of the parasite, the inhibition of aminopeptidase PfA-M17 (PlasmoDB PF3D7_1446200) and perturbations in parasite haemoglobin metabolism.
Conclusions
Further structure–activity and medicinal chemistry studies are warranted to elaborate on these findings and the potential for 8TTE-related molecules to serve as future antimalarial drugs.
Journal Article
Exploring the Phytochemical Diversity and Anti-Plasmodial Potential of Artemisia annua and Artemisia afra from Different Geographical Locations in Cameroon
by
Loe, Gisèle E.
,
Bonnet, Olivier
,
Nchang, Abenwie S.
in
Antimalarials - chemistry
,
Antimalarials - pharmacology
,
Artemisia - chemistry
2025
In Cameroon, like in other African countries, infusions of Artemisia afra and Artemisia annua are widely used for the management of health-related problems, including malaria. The secondary metabolite contents of medicinal plants vary between different geographical regions and seasons, directly influencing their effectiveness in treating ailments. This study explores the phytochemical diversity and anti-plasmodial potential of A. annua and A. afra from distinct geographical locations within Cameroon, aiming to define the optimal chemical composition in terms of anti-plasmodial activity. Extracts were prepared from plants collected from diverse regions in Cameroon during both the rainy and dry seasons, and their metabolic contents were analyzed using Thin-Layer Chromatography (TLC), High Performance Liquid Chromatography (HPLC), and Gas Chromatography (GC). Their anti-plasmodial potential was assessed on a chloroquine-sensitive 3D7 Plasmodium falciparum strain. Additionally, the environmental parameters of the collecting sites were retrieved from multispectral satellite imagery. The activity profiles of the samples were associated with their environment, with distinct phytochemical compositions observed for each sample based on its geographical origin and season. Traces of artemisinin were detected in some of the A. afra samples, but it was present in the A. annua samples at a significantly higher concentration, especially in the rainy season samples (highest concentration in the Adamawa region, at 8.9% m/m artemisinin in the dry extract). Both plants are active at different levels, with A. annua more active due to the presence of artemisinin and A. afra probably active due to the presence of polyphenols. Both season and geographical location influence both plants’ metabolic contents and hence their antimalaria activity. These findings suggest that the selection of a suitable Artemisia sample for use as a potential antimalarial treatment should take into consideration its geographical origin and the period of collection.
Journal Article
Ethical and Clinical Boundaries in Genomics & Newborn Screening: A Brief Report from IPIC2025
by
Rivers, Elizabeth
,
Fisher, Rosalind
,
Booth, Claire
in
Ataxia
,
ataxia–telangiectasia
,
Conference Report
2026
The Ethics Session of the International Primary Immunodeficiency Congress (IPIC), held in November 2025 and organised by the International Patient Organisation for Primary Immunodeficiencies (IPOPI), examined one of the most challenging developments emerging from genomic-enhanced newborn screening: the identification of serious, non-treatable disorders as incidental detection in programmes originally designed to detect severe combined immunodeficiency (SCID). Using a fictionalised clinical scenario based on the recent literature, the session explored the early diagnosis of ataxia-telangiectasia (AT) detected through TREC-based screening. The discussion highlighted the clinical value and psychological risks associated with presymptomatic detection, the persistent shortcomings in parental consent processes, the systemic pressures created by expanding genomic testing, and the ethical challenges surrounding the reporting and management of incidental findings in screening. The debate underscored the need for internationally coordinated frameworks to guide the management of incidental detection in newborn screening as genomic technologies become more deeply embedded in routine public health practice.
Journal Article
Navigating disruption in the PID landscape: embracing opportunities and anticipating threats in the next ten years
by
Prévot, Johan
,
Mahlaoui, Nizar
,
Barasa, Anne
in
Artificial Intelligence
,
Clinical trials
,
Cost analysis
2025
The International Patient Organisation for Primary Immunodeficiencies (IPOPI) held its third edition of the Global Multi-Stakeholders' Summit, gathering key primary immunodeficiencies (PID) stakeholders and experts to discuss and foment global collaboration.
This edition focused on the impact of genomic medicine in PID treatment, the role of digital health, including artificial intelligence, in PID care, and how to anticipate and minimise risks to ensure optimal patient access to care.
These discussions aimed to examine current hurdles and brainstorm feasible solutions and priorities for the PID community in these areas in the next ten years.
These discussions led to recommendations for comprehensive approaches to care and access to treatment for PID patients, suggesting actions that will bring the community closer to treatments based on real-world evidence and adjusted to patient's needs. To accomplish this, collaboration between academia, industry, regulatory authorities, and patients is crucial.
Journal Article
Natural Alkaloids as Antiviral Agents Against RNA Viruses: A Comprehensive and Mechanistic Review
by
Vandeberg, Elyn
,
Garigliany, Mutien-Marie
,
Ledoux, Allison
in
Alkaloids
,
Alkaloids - chemistry
,
Alkaloids - pharmacology
2026
RNA viruses pose a persistent global threat due to their high mutation rates, zoonotic potential, and rapid adaptability. Emergence events have risen steadily, as demonstrated by major outbreaks caused by Influenza A, Ebola, Zika, and Chikungunya viruses, followed by the coronavirus epidemics of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-1) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and culminating in the COVID-19 pandemic. These characteristics frequently compromise the durability of existing vaccines and antiviral therapies, highlighting the urgent need for new antiviral agents. Alkaloids, a structurally diverse class of nitrogen-containing natural compounds, have gained attention for their ability to interfere with multiple stages of the viral life cycle, including entry, replication, protein synthesis, and host immune modulation. To our knowledge, this review compiles all currently reported alkaloids with antiviral activity against RNA viruses and summarizes their proposed mechanisms of action, distinguishing evidence from in vitro, in vivo, and in silico studies. Quaternary alkaloids are discussed separately because their permanent ionic charge enables distinctive interactions with membranes and host pathways. Although many findings are promising, clinical translation remains limited by incomplete mechanistic validation, scarce in vivo data, suboptimal bioavailability, narrow therapeutic windows, and inconsistent experimental methodologies. To advance the field, future research should prioritize RT-qPCR–based antiviral evaluation to accurately quantify viral replication, incorporate mechanistic assays to clarify modes of action, apply structure–activity relationship (SAR) approaches for rational optimization, and expand in vivo pharmacokinetic and efficacy studies to assess therapeutic feasibility. Overall, alkaloids represent a promising yet underdeveloped reservoir for next-generation antiviral discovery against rapidly evolving RNA viruses.
Journal Article
Recent metabolomic developments for antimalarial drug discovery
by
Schoumacher, Matthieu
,
De Tullio, Pascal
,
Ledoux, Allison
in
Antimalarial agents
,
Antiparasitic agents
,
Antiprotozoal agents
2022
Malaria is a parasitic disease that remains a global health issue, responsible for a significant death and morbidity toll. Various factors have impacted the use and delayed the development of antimalarial therapies, such as the associated financial cost and parasitic resistance. In order to discover new drugs and validate parasitic targets, a powerful omics tool, metabolomics, emerged as a reliable approach. However, as a fairly recent method in malaria, new findings are timely and original practices emerge frequently. This review aims to discuss recent research towards the development of new metabolomic methods in the context of uncovering antiplasmodial mechanisms of action in vitro and to point out innovative metabolic pathways that can revitalize the antimalarial pipeline.
Journal Article
Trypanosoma brucei: Metabolomics for analysis of cellular metabolism and drug discovery
by
Michels, Paul
,
Quetin-Leclercq Joëlle
,
Ledoux, Allison
in
Acute toxicity
,
African trypanosomiasis
,
Drug metabolism
2022
BackgroundTrypanosoma brucei is the causative agent of Human African Trypanosomiasis (also known as sleeping sickness), a disease causing serious neurological disorders and fatal if left untreated. Due to its lethal pathogenicity, a variety of treatments have been developed over the years, but which have some important limitations such as acute toxicity and parasite resistance. Metabolomics is an innovative tool used to better understand the parasite’s cellular metabolism, and identify new potential targets, modes of action and resistance mechanisms. The metabolomic approach is mainly associated with robust analytical techniques, such as NMR and Mass Spectrometry. Applying these tools to the trypanosome parasite is, thus, useful for providing new insights into the sleeping sickness pathology and guidance towards innovative treatments.Aim of reviewThe present review aims to comprehensively describe the T. brucei biology and identify targets for new or commercialized antitrypanosomal drugs. Recent metabolomic applications to provide a deeper knowledge about the mechanisms of action of drugs or potential drugs against T. brucei are highlighted. Additionally, the advantages of metabolomics, alone or combined with other methods, are discussed.Key scientific concepts of reviewCompared to other parasites, only few studies employing metabolomics have to date been reported on Trypanosoma brucei. Published metabolic studies, treatments and modes of action are discussed. The main interest is to evaluate the metabolomics contribution to the understanding of T. brucei’s metabolism.
Journal Article
Secondary Metabolites Isolated from IArtemisia afra/I and IArtemisia annua/I and Their Anti-Malarial, Anti-Inflammatory and Immunomodulating Properties—Pharmacokinetics and Pharmacodynamics: A Review
by
Loe, Gisèle E
,
Frederich, Michel
,
Ghogomu, Stephen Mbigha
in
Analysis
,
Malaria
,
Plant metabolites
2023
There are over 500 species of the genus Artemisia in the Asteraceae family distributed over the globe, with varying potentials to treat different ailments. Following the isolation of artemisinin (a potent anti-malarial compound with a sesquiterpene backbone) from Artemisia annua, the phytochemical composition of this species has been of interest over recent decades. Additionally, the number of phytochemical investigations of other species, including those of Artemisia afra in a search for new molecules with pharmacological potentials, has increased in recent years. This has led to the isolation of several compounds from both species, including a majority of monoterpenes, sesquiterpenes, and polyphenols with varying pharmacological activities. This review aims to discuss the most important compounds present in both plant species with anti-malarial properties, anti-inflammatory potentials, and immunomodulating properties, with an emphasis on their pharmacokinetics and pharmacodynamics properties. Additionally, the toxicity of both plants and their anti-malaria properties, including those of other species in the genus Artemisia, is discussed. As such, data were collected via a thorough literature search in web databases, such as ResearchGate, ScienceDirect, Google scholar, PubMed, Phytochemical and Ethnobotanical databases, up to 2022. A distinction was made between compounds involved in a direct anti-plasmodial activity and those expressing anti-inflammatory and immunomodulating activities or anti-fever properties. For pharmacokinetics activities, a distinction was made between compounds influencing bioavailability (CYP effect or P-Glycoprotein effect) and those affecting the stability of pharmacodynamic active components.
Journal Article