New therapeutic strategies are now crucial for combating microbial infections given the recurring threat of antibiotic resistance. A new approach involves using molecules from natural pharmacopoeia, i.e. derived from medicinal plants used in traditional Chinese medicine for instance. The antimicrobial properties of these molecules have recently been studied by Institut Pasteur scientists.
Microbial infections represent a major health challenge for emerging and industrialized countries, and alternative or additional approaches are now needed to tackle growing pathogen resistance to current antibiotic therapies. A new therapeutic strategy, which no longer targets growth of the pathogen but its environment, and which stimulates host innate immune defenses, would prevent and more rapidly tackle infections from a broad spectrum of microorganisms, including bacteria, viruses and fungi. In this context, the Institut Pasteur Molecular Microbial Pathogenesis Unit has focused on immunomodulatory molecules. These molecules are capable of:
- inducing expression of antimicrobial peptides, i.e. antibiotics naturally produced by human epithelia – the tissue lining the body's internal cavities,
- limiting the secretion of pro-inflammatory substances to preserve mucosal integrity.
Three molecules derived from medicinal plants
By screening a bank of natural compounds, "we have identified three molecules derived from medicinal plants that selectively induce transcription of the gene coding for beta-defensin 3, one of the peptides with the largest spectrum of antimicrobial activity", explains Brice Sperandio from the Molecular Microbial Pathogenesis Unit at the Institut Pasteur. These molecules are derived from three plants, described below.
- Andrographolide (a labdane diterpenoid) is the main active component of Andrographis paniculata, a plant also known as king of bitters or green chirayta, which is native to India and Sri Lanka, and used to treat fever.
- Oridonin (a purified diterpenoid) is derived from Rabdosia rubescens, a plant found in China and East Asia, and used to treat some cancers thanks to its properties that inhibit the growth of new blood vessels.
- Isoliquiritigenin (a flavonoid) is present in the root of Glycyrrhiza glabra, the scientific name for licorice, which is commonly found in Europe and Asia, and used for its anti-inflammatory properties.
Effective against known pathogens
Through systematic analysis, scientists have unraveled the molecular mechanism supporting the induction of this gene following treatment of intestinal epithelial cells with these molecules, and they have shown an increase in their bactericidal and bacteriostatic effect against pathogens such as Listeria monocytogenes, Salmonella enterica and Pseudomonas aeruginosa.
This research demonstrates the existence of pharmacologically-active molecules derived from plants used in traditional Chinese medicine and capable of stimulating human antimicrobial defenses.
Natural molecules induce and synergize to boost expression of the human antimicrobial peptide β-defensin-3, Proceedings of the National Academy of Sciences, October 16, 2018
Emmanuel Secheta,b,1, Erica Telfordab,1, Clément Bonamya,b, Philippe J. Sansonettia,b,c,2, and Brice Sperandioa,b,2
a. Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, 75015 Paris, France ;
b. Unité INSERM U1202, Institut Pasteur, 75015 Paris, France ;
c. Chaire de Microbiologie et Maladies Infectieuses, Collège de France, 75005 Paris, France.