The important herbal pair for the treatment of COVID-19 and its possible mechanisms

Abstract

Background Coronavirus Disease 2019 (COVID-19) is an unprecedented disaster for people around the world. Many studies have shown that traditional Chinese medicine (TCM) are effective in treating COVID-19. However, it is difficult to find the most effective combination herbal pair among numerous herbs, as well as identifying its potential mechanisms. Herbal pair is the main form of a combination of TCM herbs, which is widely used for the treatment of diseases. It can also help us to better understand the compatibility of TCM prescriptions, thus improving the curative effects. The purpose of this article is to explore the compatibility of TCM prescriptions and identify the most important herbal pair for the treatment of COVID-19, and then analyze the active components and potential mechanisms of this herbal pair. Methods We first systematically sorted the TCM prescriptions recommended by the leading experts for treating COVID-19, and the specific herbs contained in these prescriptions across different stages of the disease. Next, the association rule approach was employed to examine the distribution and compatibility among these TCM prescriptions, and then identify 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, and analyzed the potential mechanisms against COVID-19. Finally, the main active compounds in the herbal pair were selected for molecular docking with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) 3CLpro and angiotensin converting enzyme II (ACE2) for further verification. Result We obtained 32 association rules for the herbal combinations in the selection of TCM treatment for COVID-19. The results showed 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 the stages of COVID-19, so ACV and ESS (AE) were selected as the most important herbal pair. There were 26 active ingredients and 44 potential targets, which might be related to the herbal pair of AE against COVID-19. The main active ingredients of AE against COVID-19 were quercetin, kaempferol, luteolin, while the potential targets were Interleukin 6 (IL-6), Mitogen-activated Protein Kinase 1 (MAPK)1, MAPK8, Interleukin-1β (IL-1β), and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) p65 subunit (RELA). 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 potential pathways mainly involved tumor necrosis factor (TNF), Toll-like receptor (TLR), hypoxia-inducible factor-1 (HIF-1), and nucleotide-binding oligomerization domain (NOD)-like receptor (NLRs). The molecular docking results showed that the main active ingredients of AE have good affinity with SARS-COV-2 3CLpro and ACE2, which are consistent with the above analysis. Conclusions There were 32 association rules in the TCM prescriptions recommended by experts for COVID-19. The combination of ACV and EAS was the most important herbal pair for the treatment of COVID-19. AE might have therapeutic effects against COVID-19 by affecting the inflammatory and immune responses, cell apoptosis, hypoxia damage and other pathological processes through multiple components, targets and pathways.

Differential Co-Expression Network Analysis Reveals Key Hub-High Traffic Genes as Potential Therapeutic Targets for COVID-19 Pandemic

“…Additionally, some of the purple module hub-high traffic genes, such as MAPK1 ( 189 , 374 ), CUL2 ( 210 ), CMTM6 ( 162 ), TXNRD1 ( 375 ), RAB1A ( 376 ), DICER1 ( 377 ), RAB5A ( 209 ), HSP90B1 ( 343 ), MAGT1 ( 378 ), ADAM10 ( 379 , 380 ), SNX2 ( 89 ), OLA1 ( 381 ), SPTLC1 ( 382 ), SH3GLB1 ( 383 ), TIMM10B ( 384 ), and CREB1 ( 385 ) hub-high traffic TF, which are central for information exchange in this module, are potential targets for development of COVID-19 therapeutic strategies. Among these, the mitogen-activated protein kinase 1 ( MAPK1 ) hub-high traffic gene is a potential core target for many anti-COVID-19 therapeutic strategies ( 189 , 374 , 386 – 390 ). Perhaps targeting the MAPK1 hub-high traffic gene with guanfacine or desipramine may be effective for treating COVID-19 associated comorbidities, such as diabetes, CVDs, and chronic kidney diseases (CKDs) ( 139 ).…”

Traditional Chinese Medicine, Qingfei Paidu Decoction and Xuanfei Baidu Decoction, Inhibited Cytokine Production via NF-κB Signaling Pathway in Macrophages: Implications for Coronavirus Disease 2019 (COVID-19) Therapy

“…We found that both QPD and XBD suppressed NF-κB signaling, to a striking degree. Moreover, network pharmacology studies ( Li et al, 2021 ; Niu et al, 2021 ; Xia et al, 2021 ) have revealed that numerous active compounds in TCM have significant molecular binding affinities with IL-6 or could block IL-6 mediated JAK-STAT signaling pathway, raising another possibility for the anti-inflammatory activity of TCM.…”

Possible Use of Phytochemicals for Recovery from COVID-19-Induced Anosmia and Ageusia

“…Anti-viral: COV2 by binding affinity to 3CL pro [421]; to 3pro and ACE2 [422] Cinnamon (Cinnamomum) Camphor: 60% in root bark [426] Anti-inflammation [278,296] Cinnamaldehyde: 65%-80% in bark [426] Anti-viral: [ Anti-inflammation [11,238,241,261,262,265,267,291,400] p-Cymene: 42.1% in leaf and 30.0% in fruit [438] Anti-inflammation [322,328] Limonene: 5.5% in leaf and none in fruit [438], 1.33% in E. lehmani leaves and 3.32% in E. sideroxylon leaves [300], from 0% to 28% depending on the species and location [439] Anti-inflammation [275,278,297] α-Pheliandrene: from 0% to 20.1% depending on the species and location [439] Anti-inflammation [278] α-Pinene: 12.7% in leaf and 9.0% in fruit [438], from 1.27% to 26.35% in 7 Eucalyptus species' leaves with highest in E. lehmani [300], from 0% to 52.7% depending on the species and location [439] Anti-inflammation [278,337] Spathulenol: 3.2% in leaf and none in fruit [438], 1.15% in E. astrengens leaves [300], from 0% to 41.5% depending on the species and location [439] Anti-inflammation [387] γ -Terpinene: none in leaf and 5.1% in fruit [438], from 0% to 29.2% depending on the species and location [439] Anti-inflammation [278,…”