An Integrative Network Pharmacology and Bioinformatics Approach for Deciphering the Multi-target Effect of Nyctanthes arbortristis L. against COVID-19

Introduction: The COVID-19 pandemic represents a significant challenge across scientific, medical, and societal dimensions. The unpredictability of the disease progression, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), underscores the urgent need for identifying compounds that target multiple aspects of the virus to ensure swift and effective treatment. Nyctanthes arbortristis L., a delicate, perennial, deciduous shrub found across various Asian regions, has been recognized for its wide range of pharmacological benefits, including hepatoprotective, antimalarial, antibacterial, anti-inflammatory, antioxidant, and antiviral properties. Methods: Various in vitro studies revealed the therapeutic significance of Nyctanthes arbortristis against COVID-19. However, the exact molecular mechanism remains unclarified. In the present study, a network pharmacology approach was employed to uncover the active ingredients, their potential targets, and signaling pathways in Nyctanthes arbortristis for the treatment of COVID-19. In the framework of this study, we explored the active ingredient–target–pathway network and figured out that naringetol, ursolic acid, beta-sitosterol, and daucosterol decisively contributed to the development of COVID-19 by affecting IL6, MAPK3, and MDM2 genes. Results: The results of molecular docking analysis indicated that Nyctanthes arbortristis exerted effective binding capacity in COVID-19. Further, we disclosed the targets, biological functions, and signaling pathways of Nyctanthes arbortristis in COVID-19. The analysis indicated that Nyctanthes arbortristis could help treat COVID-19 through the enhancement of immunologic functions, inhibition of inflammatory reactions and regulation of the cellular microenvironment. In short, the current study used a series of network pharmacology-based and computational analyses to understand and characterize the binding capacity, biological functions, pharmacological targets and therapeutic mechanisms of Nyctanthes arbortristis in COVID-19. Conclusion: However, the findings were not validated in actual COVID-19 patients, so further investigation is needed to confirm the potential use of Nyctanthes arbortristis for treating COVID-19.