Exploration of molecular targets and mechanisms of Chinese medicinal formula Acacia Catechu -Scutellariae Radix in the treatment of COVID-19 by a systems pharmacology strategy.
Phytother Res
; 36(11): 4210-4229, 2022 Nov.
Article
in English
| MEDLINE | ID: covidwho-1935726
ABSTRACT
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In China, the Acacia catechu (AC)-Scutellariae Radix (SR) formula has been widely used for pulmonary infection in clinical practice for several centuries. However, the potential role and mechanisms of this formula against COVID-19 remains unclear. The present study was designed to dissect the active ingredients, molecular targets, and the therapeutic mechanisms of AC-SR formula in the treatment of COVID-19 based on a systems pharmacology strategy integrated by ADME screening, target prediction, network analysis, GO and KEGG enrichment analysis, molecular docking, and molecular dynamic (MD) simulations. Finally, Quercetin, Fisetin(1-), kaempferol, Wogonin, Beta-sitosterol, Baicalein, Skullcapflavone II, Stigmasterol were primarily screened to be the potentially effective active ingredients against COVID-19. The hub-proteins were TP53, JUN, ESR1, MAPK1, Akt1, HSP90AA1, TNF, IL-6, SRC, and RELA. The potential mechanisms of AC-SR formula in the treatment of COVID-19 were the TNF signaling pathway, PI3K-Akt signaling pathway and IL-17 signaling pathway, etc. Furthermore, virtual docking revealed that baicalein, (+)-catechin and fisetin(1-) exhibited high affinity to SARS-CoV-2 3CLpro, which has validated by the FRET-based enzymatic inhibitory assays with the IC50 of 11.3, 23.8, and 44.1 µM, respectively. And also, a concentration-dependent inhibition of baicalein, quercetin and (+)-catechin against SARS-CoV-2 ACE2 was observed with the IC50 of 138.2, 141.3, and 348.4 µM, respectively. These findings suggested AC-SR formula exerted therapeutic effects involving "multi-compounds and multi-targets." It might be working through directly inhibiting the virus, improving immune function, and reducing the inflammatory in response to anti-COVID-19. Ultimately, this study would provide new perspective for discovering potential drugs and mechanisms against COVID-19.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Drugs, Chinese Herbal
/
Catechin
/
Acacia
/
COVID-19 Drug Treatment
Type of study:
Diagnostic study
/
Prognostic study
/
Systematic review/Meta Analysis
Topics:
Traditional medicine
Limits:
Humans
Language:
English
Journal:
Phytother Res
Journal subject:
Complementary Therapies
Year:
2022
Document Type:
Article
Affiliation country:
Ptr.7554
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