ABSTRACT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic in 2019—coronavirus disease (COVID-19). More and more Western medicine (WM) and Chinese herbal medicine (CHM) treatments have been used to treat COVID-19 patients, especially among Asian populations. However, the interactions between WM and CHM have not been studied. This study aims at using the network pharmacology approach to explore the potential complementary effects among commonly used CHM and WM in a clinical setting from a biomolecular perspective. Three well-published and widely used CHM formulas (National Research Institute of Chinese Medicine 101 (NRICM101), Qing-Fei-Pai-Du-Tang (QFPDT), Hua-Shi-Bai-Du-Formula (HSBDF)) and six categories of WM (Dexamethasone, Janus kinase inhibitors (JAKi), Anti-Interleukin-6 (Anti-IL6), anticoagulants, non-vitamin K antagonist oral anticoagulants (NOAC), and Aspirin) were included in the network pharmacology analysis. The target proteins on which these CHM and WM had direct effects were acquired from the STITCH database, and the potential molecular pathways were found in the REACTOME database. The COVID-19-related target proteins were obtained from the TTD database. For the three CHM formulas, QFPDT covered the most proteins (714), and 27 of them were COVID-19-related, while HSBDF and NRICM101 covered 624 (24 COVID-19-related) and 568 (25 COVID-19-related) proteins, respectively. On the other hand, WM covered COVID-19-related proteins more precisely and seemed different from CHM. The network pharmacology showed CHM formulas affected several inflammation-related proteins for COVID-19, including IL-10, TNF-α, IL-6, TLR3, and IL-8, in which Dexamethasone and Aspirin covered only IL-10 and TNF-α. JAK and IL-6 receptors were only inhibited by WM. The molecular pathways covered by CHM and WM also seemed mutually exclusive. WM had advantages in cytokine signaling, while CHM had an add-on effect on innate and adaptive immunity, including neutrophil regulation. WM and CHM could be used together to strengthen the anti-inflammation effects for COVID-19 from different pathways, and the combination of WM and CHM may achieve more promising results. These findings warrant further clinical studies about CHM and WM use for COVID-19 and other diseases.
