The immune condition of individuals is a key factor influencing the progression of COVID-19. Herbal remedies possessing immunomodulatory and anti-inflammatory properties may serve as effective complementary options alongside conventional treatments. This research aimed to identify and explore the immunomodulatory and anti-inflammatory components of Curcuma longa (C. longa) and elucidate their potential mechanisms of action in COVID-19. Biochemical constituents of C. longa rhizomes were systematically compiled from published studies and databases. Subsequently, targets associated with COVID-19 were identified for the selected bioactive phytochemicals, and their possible mechanisms of action were examined through network analysis and molecular docking against four major COVID-19-related proteins for validation. Ten active compounds from C. longa were predicted to interact with these protein targets. Among them, epidermal growth factor showed the highest level of interaction, being targeted by Calebin A, curcumin, cyclocurcumin, demethoxycurcumin, turmeronol A, turmeronol B, caffeic acid, and quercetin. Interferon-gamma emerged as another critical protein influenced by 4-hydroxycinnamic acid. Moreover, curcumin was predicted to interact with toll-like receptor 4, while Ar-turmerone targeted angiotensin II receptor type 2. Four signaling pathways—cytokine-cytokine receptor interaction, toll-like receptor signaling, Jak-STAT, and PI3K-Akt pathways—were identified as key mechanisms linking these phytochemicals to their targets against COVID-19. In summary, the diverse bioactive compounds in C. longa may exert synergistic effects against COVID-19 by modulating immune and inflammatory responses and influencing multiple molecular pathways involved in the disease.
