Immunomodulatory and skin-compatible effects of Amaranthus retroflexus volatile compounds: An in-silico network and pathway-based approach

Background This study investigated the phytochemical profile, in silico skin sensitization, cosmetic toxicity, and endocrine-disrupting potential of compounds from Amaranthus retroflexus identified through GC-MS analysis. Methods Volatile constituents were identified using gas chromatography–mass spectrometry (GC–MS) analysis. The safety profiles of the major compounds were evaluated through in silico toxicity prediction models, including keratinosens, local lymph node assay (LLNA) and human cell line activation test (h-CLAT), along with molecular docking analysis to assess their endocrine-disrupting potential. Results A total of 39 distinct compounds were identified, with a predominant presence of unsaturated fatty acid methyl esters, including 9,12-octadecenoic acid, methyl ester (47.275 %) and 9-octadecenoic acid, methyl ester (22.790 %). Other notable compounds included methyl stearate (3.063 %), Squalene (9.687 %), and various alkanes. In silico skin sensitization analysis demonstrated that all five key compounds, including hexadecenoic acid methyl ester, methyl stearate, and squalene, fell within the applicability domain of the predictive models. High predictive confidence was observed in both the KeratinoSens and LLNA models, whereas the h-CLAT model exhibited lower predictive reliability . Cosmetic toxicity predictions revealed moderate to high risks for skin and eye irritation, particularly with Squalene, but the compounds were considered safe regarding systemic toxicity and photo-related effects. Furthermore, endocrine-disrupting potential was evaluated via in silico binding affinity analysis, which revealed minimal interaction with nuclear receptors. Conclusion These findings highlight the potential of the plant extract for dermatological applications, while emphasizing the need for further evaluation of its safety in topical use.