Complementary Molecular Targets and Pathways of Curcumin and Methotrexate in Psoriasis: Insights from Network Pharmacology

Psoriasis is a chronic immune-mediated skin disease that often requires long-term systemic therapy. Methotrexate is a first-line systemic therapy for moderate-to-severe psoriasis, but its use is limited by adverse effects and monitoring requirements. Curcumin, a bioactive polyphenol from Curcuma longa, has anti-inflammatory and antioxidant activity, but its translation remains limited by poor bioavailability and formulation dependence. This study aimed to examine the complementary molecular targets and pathways of curcumin and methotrexate in psoriasis using a network pharmacology approach. Targets of both compounds were identified from the Similarity Ensemble Approach (SEA) and the Comparative Toxicogenomics Database (CTD) and intersected with psoriasis-related genes. Functional enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID), while protein-protein interaction network analysis was conducted using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). In addition, in silico drug-likeness and toxicity assessments were performed. A total of 273 overlapping targets were identified and were enriched in inflammatory, apoptotic, and immune-regulatory pathways. Key hub proteins included TNF, IL6, TP53, AKT1, STAT3, and NFKB1. Methotrexate was more closely linked to central inflammatory nodes, whereas curcumin showed broader regulatory activity. Curcumin also showed lower predicted toxicity. These findings support partial network overlap with possible functional complementarity in psoriasis and provide a prioritized set of shared hubs and pathways for mechanistic and preclinical investigation. As these results are based on in silico analyses, experimental validation is required to confirm their biological relevance.