Network Pharmacology to Uncover Potential Anti-Inflammatory and Immunomodulatory Constituents in Curcuma Longa Rhizome As Complementary Treatment in COVID-19

The immune status of patients plays an essential role in COVID-19. Herbal medicine with immunomodulatory and anti-inflammatory effect could have potential as a complementary therapeutic along with modern medicine. This study aims to investigate the anti-inflammatory and immunomodulatory constituents of Curcuma longa (C. longa) and its possible mechanisms in COVID-19. We systematically sorted the biochemical of C. longa rhizome from literature and repository. Next, we investigated targets related to COVID-19 in the selected active phytochemical constituents and analyzed the possible mechanisms against COVID-19 and performed molecular docking with four essential target proteins in COVID-19 for further verification. Ten active phytochemical constituents of C. longa were predicted to interact with four protein targets. The epidermal growth factor was the most interacted protein targeted by Calebin A, curcumin, cyclocurcumin, demethoxycurcumin, turmeronol a, turmeronol b, caffeic acid, and quercetin. Interferon-gamma was performed as the most critical protein targeted by 4-hydroxycinnamic acid. Curcumin was also predicted to interact with toll-like receptor 4 and Ar-turmerone with angiotensin II receptor type 2. We also reported four signaling pathways associated with target proteins-active phytochemical constituents against COVID-19: cytokine-cytokine receptor interaction, toll-like receptor signaling pathway, Jak-STAT signaling pathway, and PI3K-Akt signaling pathway. In conclusion, multi compounds in C. longa might act synergistically against COVID-19 by affecting the inflammatory and immune responses, and other pathological processes through multiple targets and pathways.