Native medicinal plants from Togo: defining anti-inflammatory and anti-helminthic properties of bioactive components

• Applicant: Dr. Manuel Ritter, since 5/2024
• Subject Area: Immunology ; Clinical Infectiology and Tropical Medicine ; Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: since 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 279018521

Emerging resistance and reaching the unreachable with anthelmintics makes it difficult to control helminth infections in endemic areas. The focus of this study is to determine the potential immune-modulatory and anti-helminthic properties of native medicinal plants from Togo which would essentially lead to affordable effective therapies for low income communities. We are particularly interested in identifying novel natural molecules that can suppress or deviate Th17 inflammatory responses since these are emphasized in individuals suffering from helminth infections presenting severe symptoms. During the first funding period, we were able to confirm that lack of Th17 pathways during Litomosoides sigmodontis (Ls) in IL-17A-/- C57BL/6 mice provides an environment that supports worm development. In Togo, during an ethnobotanical survey with traditional healers, it was revealed that they are aware of chronic helminth infections such as filariasis and schistosomiasis and treated them with specific herbal remedies. These stemmed from tree trunk bark of Khaya senegalensis (Ks), grains of Aframomum melegueta (Am) and fruits of Xylopia aethiopica (Xa). We then investigated the potential of plant extracts to suppress Th17 cell responses using both clinical and pre-clinical models of filariasis. We found that hydroethanolic but not macerated, infused or decoction methods resulted in extracts that were non-cytotoxic and could suppress Th17 responses in vitro using PBMCs from hyper-reactive onchocerciasis patients (those with dermal manifestations). Interestingly these suppressive effects were lost when samples were deproteinised. In pre-clinical studies, we have substantiated these observations since plant extracts were able to modulate cytokine release from CD4+ T cells isolated from Ls-infected BALB/c mice upon filarial-specific activation. Since anti-helminthic and anti-inflammatory properties were also observed with the hydroethanolic extracts, this funding period will focus on determining bioactive components and performing quantitative plant metabolomics. We shall use in vitro culture assays, mouse models and mass spectrometry and analytical tools with computational and statistical treatments (MetaboAnalyst and GNPS platforms), to annotate the active from non-active compounds in different extracts/fractions of the targeted plants. Bio-guided isolation will be subsequently performed to confirm compound activity. Alongside establishing a mouse facility in Lomé, these platforms will provide a large capacity building programme for Togo students. These extracts will then be tested in our established in vitro anti-helminthic assays and in vivo using the Ls model to see effects on worm development and fecundity using our embryogenesis assays. Comprehensive immune-profiling and functional assays will then be performed in complimentary mouse and human studies to determine the modulatory capacity of these compounds.

• DFG Programme: Research Grants
• International Connection: Togo
• International Co-Applicant: Gnatoulma Katawa, Ph.D.
• Ehemalige Antragstellerin: Dr. Laura Elizabeth Layland-Heni, until 5/2024