Mechanism deconvolution of Qing Fei Pai Du decoction for treatment of Coronavirus Disease 2019 (COVID-19) by label-free integrative pharmacology assays

Abstract

Ethnopharmacological relevance Traditional Chinese medicine (TCM) has a long history in the prevention and treatment of pandemics. The TCM formula Lung Cleansing and Detoxifying Decoction (LCDD), also known as Qing Fei Pai Du Decoction, has been demonstrated effective against Coronavirus Disease 2019 (COVID-19). Aim of the study This work aimed to elucidate the active ingredients, targets and pathway mechanism of LCDD related to suppression of inflammatory, immunity regulation and relaxation of airway smooth muscle for the treatment of COVID-19. Materials and methods Mining chemical ingredients reported in LCDD, 144 compounds covering all herbs were selected and screened against inflammatory-, immunity- and respiratory-related GPCRs including GPR35, H1, CB2, B2, M3 and β2-adrenoceptor receptor using a label-free integrative pharmacology method. Further, all active compounds were detected using liquid chromatography-tandem mass spectrometry, and an herb-compound-target network based on potency and content of compounds was constructed to elucidate the multi-target and synergistic effect. Results Thirteen compounds were identified as GPR35 agonists, including licochalcone B, isoliquiritigenin, etc. Licochalcone B, isoliquiritigenin and alisol A exhibited bradykinin receptor B2 antagonism activities. Atractyline and shogaol showed as a cannabinoid receptor CB2 agonist and a histamine receptor H1 antagonist, respectively. Tectorigenin and aristofone acted as muscarinic receptor M3 antagonists, while synephrine, ephedrine and pseudoephedrine were β2-adrenoceptor agonists. Pathway deconvolution assays suggested activation of GPR35 triggered PI3K, MEK, JNK pathways and EGFR transactivation, and the activation of β2-adrenoceptor mediated MEK and Ca 2+ . The herb-compound-target network analysis found that some compounds such as licochalcone B acted on multiple targets, and multiple components interacted with the same target such as GPR35, reflecting the synergistic mechanism of Chinese medicine. At the same time, some low-abundance compounds displayed high target activity, meaning its important role in LCDD for anti-COVID-19. Conclusions This study elucidates the active ingredients, targets and pathways of LCDD. This is useful for elucidating multitarget synergistic action for its clinical therapeutic efficacy.

The potential role of ischaemia–reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications

“…Other drugs being studied for use in ME/CFS or Long COVID include metformin [ 735–737 ], fenofibrate (which is somewhat protective against reperfusion injury [ 738 , 739 ]), and low-dose naltrexone [ 740–742 ]. While we are no experts, and the mechanisms are normally not well understood [ 743 ], but as a segue to the following section on nutraceuticals, we also note the effective use of certain traditional Chinese and other traditional medicines in acute COVID-19 [ 744–749 ] and their potential for use in Long COVID [ 748–750 ]. This seems like an area well worth further study by those qualified to do so.…”

Therapeutic effects of herbal-medicine combined therapy for COVID-19: A systematic review and meta-analysis of randomized controlled trials

“…Take some formulas, which have been included in this meta-analysis, Lian Hua Qing Wen has been proved with regulating angiotensin converting enzyme 2 (ACE2) expression-disorder-caused symptoms and relieve the cytokine storm ( Zheng et al, 2020 ). Some study revealed that acacetin, wogonin, and isorhamnetin were the main active ingredients in Qing Fei Pai Du decoction, ( Li et al, 2022 ); while the target network model noted that some compounds such as licochalcone B acted on multiple targets, and multiple components interacted with the same target such as GPR35, reflecting the synergistic mechanism of Chinese medicine ( Xu F. et al, 2021 ). Another special agent which not included in this trial is a potential mucosal topical agent “Ankaferd hemostat (ABS)”, which was approved with effect of antagonizing proteinase-activated receptors (PARs), mainly PAR-1.…”

Exploring the mechanism of action of Xuanfei Baidu granule (XFBD) in the treatment of COVID-19 based on molecular docking and molecular dynamics

“…Therefore, molecular docking and molecular dynamics can be used to more deeply and objectively study the mechanism of action of small molecules in XFBD that coordinate and interact with each other to treat COVID-19. Some studies have used network pharmacology methods to enrich the targets and pathways of traditional Chinese medicines (such as: Lung Cleansing and Detoxifying Decoction (LCDD)) and explore their therapeutic effects on COVID-19 ( Xu et al., 2021 ). This study not only analyzed and drawed on relevant network pharmacology research results, but also used the supercomputer platform to simulate the relationship between small molecule drugs and protein targets through molecular dynamics.…”