Background: Corona Virus Disease 2019 (COVID-19) is an unprecedented disaster for people around the world. Many studies have shown that traditional Chinese medicines(TCM) are indeed effective in treating COVID-19. However, it is a hard work to find the most effective combination laws among numerous herbs as well as its potential mechanisms. The purpose of this article is to explore the combination laws of traditional Chinses medicine(TCM) prescriptions and pick out the most important herbal pair for treating COVID-19 and analyze the active components and potential mechanisms.
Methods: We first systematically sorted out the TCM prescriptions recommended by leading experts for treating COVID-19 and the specific herbs they contained in different stages of disease. Next, the association rule approach was employed to examine the distribution and combination laws among these TCM prescription, and then picked out the most important herbal pair. On this basis, we further investigated the active ingredients and potential targets in the selected herbal pair by a network pharmacology approach.
Result: We obtained 32 association rules for herb combinations in the process of TCM treatment for COVID-19. It was found that the combination of Amygdalus Communis Vas(ACV) and Ephedra sinica Stapf (ESS) had the highest confidence degree and lift value as well as high support degree, which can be used in almost all stages of COVID-19, so ACV and ESS (AE) was selected as the most important herbal pair. There were 26 active ingredients and 44 potential targets, which may be relate to the herbal pair of AE against COVID-19. The main active ingredients of AE against COVID-19 are quercetin, kaempferol, luteolin and the potential important targets are Interleukin 6 (IL-6), Mitogen-activated Protein Kinase 1 (MAPK)1, MAPK8, Interleukin-1β (IL-1β), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) p65 subunit (RELA) and so on. The protein-protein interaction (PPI) cluster demonstrated that IL-6 was the seed in the cluster, which plays an important role in connecting other nodes in the PPI network. The significant pathways mainly involved in tumor necrosis factor (TNF), Toll-like receptor (TLR), hypoxia-inducible factor-1 (HIF-1), nucleotide-binding oligomerization domain (NOD)-like receptor(NLRs).
Conclusion: Amygdalus Communis Vas and Ephedra sinica Stapf was the most important herbal pair in the treatment of COVID-19. The main active ingredients of AE against COVID-19 were quercetin, kaempferol, luteolin and the important targets were IL-6，MAPK1, MAPK8, IL-1β, RELA and so on. AE may have therapeutic effects against COVID-19 by affecting the pathological processes such as inflammatory and immune responses, cell apoptosis, hypoxia damage and other pathological processes through multiple components, multiple targets and multiple pathways.