Mutlidirectory inflammatory effect of thiopolysulfides in wild garlic (Allium ursinum L.): In silico, ex vivo and in vitro studies

• Applicant: Professorin Dr. Tuba Esatbeyoglu
• Subject Area: Food Chemistry ; Nutritional Sciences
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 563851351

Wild garlic (Allium ursinum L.) is a plant, which has been considered a natural remedy for numerous disorders. Mostly applied have been leaves of the plant, as they comprise thiopolysulfides (TPS) and polyphenols that act as detoxifying, antioxidant and antimicrobial agents. Moreover, the presence of the TPS creates a specific aroma and flavor. The key compounds of TPS are allicin (AL) and S-allyl-L-cysteine (SAL). The project assesses the anti-inflammatory potential of TPS. At first, SAL and AL will be investigated for their inhibition potency against angiotensin-converting enzyme (ACE) - responsible for hypertension and cardiovascular inflammation states, diabetic neuropathy, diabetes mellitus and cyclo-oxygenase-2 enzyme (COX-2), highly active in macrophages and in the epithelium. The results will be enriched by assessment of how TPS may inhibit inflammation in RAW264.7 murine macrophages previously exposed to lipopolysaccharides to trigger the inflammation and in an ex vivo assay to reduce skin inflammation and to improve the wound healing process. Wild garlic fractions will be tested under inflammation conditions, i.e. by inhibiting the activity of COX-2 and promoting the expression of interleukin by macrophages. Our finding will enable us to propose TPS or fractions of wild garlic to replace drugs currently recommended, e.g. salycilic acid. For the enzyme-inhibition experiments we will validate the molecular mechanisms of the effects observed by correlating the inhibition rate with the binding affinity and the loci of the modelled inhibitor to enzyme models using available computational software. Such information will deliver a comprehensive, holistic insight on future perspectives of the wild garlic application. The effect of the compounds on intestinal Caco-2 cells viability and TPS potential to inhibit oxidation of cellular DNA will be evaluated. The geno-protective effect observed in the cell model will be validated by electrochemical assessment, in which the isolated DNA from the Caco-2 cells will be measured under the changes in guanosine and adenosine electrochemical signals. The concept of the geno-protective effect of phytocompounds is relatively rare in food science and medicinal chemistry, even though such prevention could limit point mutations to cellular DNA and cancerogenesis. The DNA oxidation analysis will explain the inhibition of cancer cell proliferations by Allium extracts and their constituents. The samples will be evaluated for their antimicrobial effects against different pathogenic microflora and minimal inhibitory concentrations (MICs) will be determined. The most promising antimicrobial agents will be subjected to the last part of the study to examine wound protective effects against inflammation-induced presence of dermal microflora in a porcine ex vitro model.

• DFG Programme: Research Grants
• International Connection: Australia, Poland
• Cooperation Partners: Professor Dr. Oskar Szczepaniak; Dr. Zyta M. Ziora