Abstract
<title>Abstract</title> <p>Psoriasis is a long-lasting inflammatory skin disease in which skin cells grow too fast because the immune system is overactive. Interleukin-17 (IL-17) and tumour necrosis factor (TNF) are known to drive it, but much of the wider biology that keeps the disease going, and links it to other health problems, remains unclear. We aimed to map the gene activity behind psoriatic skin and to find plant compounds that could act on several disease pathways at once when applied to the skin. We compared gene activity in lesional and unaffected skin to identify genes that changed, and studied the affected pathways and their upstream regulators using Ingenuity Pathway Analysis. Protein interaction networks and chemical-gene maps were built to shortlist compounds, keeping those that reversed disease-linked gene changes; each was checked for suitability for skin delivery, and pairs were tested computationally for combined effects. Gene activity in psoriatic skin was shaped mainly by interferon responses, antiviral and antimicrobial programs, disturbed metabolism, and the regulators AP-1 and CREB1. Several genes and regulators not previously linked to psoriasis appeared among the inflammation and cell-movement groups. Seven plant compounds-mahanine, atractylon, protopine, annomontine, taraxasterol, tricin and tamarixetin-matched several disease pathways; protopine and atractylon were the most suited to skin use, and flavonoid-alkaloid pairs showed the strongest combined effects. These findings point to plant-based treatments that may act on several psoriasis pathways together, though testing in keratinocyte and organotypic skin models is still needed to confirm the effects.</p>