Anti-eczema Mechanism of Action of Nigella sativa for Atopic Dermatitis: Computer-aided Prediction and Pathway Analysis Based on Protein-chemical Interaction Networks

Introduction: Black cumin (Nigella sativa) is widely used to treat various diseases. It is also believed to relief skin conditions accompanied by itching symptom, such as atopic dermatitis (AD) or eczema. However, the anti-eczema mechanism of action is still unclear. The aims of this syudy was to  identify anti-eczema mechanism of action of N. sativa for AD using computer aided prediction and pathway analysis based on protein-chemical networks. Methods: We utilized dataset consisting chemical compounds of N. sativa from KNApSAcK. It is a comprehensive species-metabolite relationship database. Using canonical SMILES strings that encode molecular structures of each compound, we predicted the probabilities of activity (Pa) for anti-eczema effect based on PASS algorithms. The compounds with Pa >0.7 were included for pathway analysis based on protein-chemical interaction networks in STITCH database. We selected interactomes built by experimental data, gene co-expression, closest gene position, fusion, co-occurence, computational prediction, and other secondary data. Results: Thirty-five active compounds of N. sativa have been utilized and 19 of them have potential anti-eczema effects. Oleic acid and lauric acid were predicted with Pa-value of 0.947 and 0.920 for anti-eczema effect, respectively. However, only lauric acid was confirmed having a plausible mechanism of action via LY96-TLR4- PIK3R1 pathway for lipopolysaccharide receptor activity (false discovery rate [FDR] = 0.0243) and low-density lipoprotein particle receptor binding (FDR = 0.0118). Conclusion: Lauric acid in N. sativa has potential antieczema effect to prevent relaps in AD patients by controlling opportunistic bacterial infection that aggravates itching symptom in this condition.