ABSTRACT
Objective: Network pharmacology combines drug and disease targets with biological information networks based on the integrity and systematicness of the interactions between drugs and disease targets. This study aims to explore the molecular basis of Hanshi Zufei formula for treatment of COVID-19 based on network pharmacology and molecular docking techniques. Methods: Using TCMSP, the chemical constituents and molecular targets of Atractylodis Rhizoma, Citri Reticulatae Pericarpium, Magnoliae Officinalis Cortex, Pogostemonis Herba, Tsaoko Fructus, Ephedrae Herba, Notopterygii Rhizoma et Radix, Zingiberis Rhizoma Recens, and Arecae Semen were investigated. The predicted targets of novel coronavirus were screened using the NCBI and GeneCards databases. To further screen the drug-disease core targets network, the corresponding target proteins were queried using multiple databases (Biogrid, DIP, and HPRD), a protein interaction network graph was constructed, and the network topology was analyzed. The molecular docking studies were also performed between the network's top 15 compounds and the coronavirus (SARS-CoV-2) 3CL hydrolytic enzyme and angiotensin conversion enzyme II (ACE2). Results: The herb-active ingredient-target network contained nine drugs, 86 compounds, and 49 drug-disease targets. Gene ontology (GO) enrichment analysis resulted in 1566 GO items (P < 0.05), among which 1438 were biological process items, 35 were cell composition items, and 93 were molecular function items. Fourteen signal pathways were obtained by enrichment screening of the KEGG pathway database (P < 0.05). The molecular docking results showed that the affinity of the core active compounds with the SARS-CoV-2 3CL hydrolase was better than for the other compounds. Conclusion: Several core compounds can regulate multiple signaling pathways by binding with 3CL hydrolase and ACE2, which might contribute to the treatment of COVID-19.
ABSTRACT
Glycyrrhizic acid (GA) is one of the main active components in licorice and has often been reported to have cardioprotective effects. However, the underlying cellular mechanisms remain unclear. The aim of this study is to verify the protective effects of GA against isoproterenol (ISO)-induced myocardial ischemia injury in rats. Another aim is to explore the cellular mechanisms based on the L-type Ca2+ channel, myocardial cell contraction, and intracellular Ca2+ ([Ca2+]i) transient. The results show that GA reduced the ST segment elevation, decreased the heart rate, prevented ISO-induced QT-interval shortening, improved heart morphology, and decreased the activity of CK and LDH. GA blocked ICa-L in a dose-dependent manner. The concentration for 50% of the maximal effect (EC50) of GA was 145.54 µg/mL, and the maximal inhibition was 47.43 ± 0.75% at 1000 µg/mL. However, GA did not affect the dynamical properties of the Ca2+ channel. GA reversibly reduced the amplitude of cell contraction in a dose-dependent manner and slowed down its deflection and recovery, as well as the [Ca2+]i transient. The data demonstrate that GA inhibits L-type Ca2+ channels, decreases the [Ca2+]i transient, and shows a negative cardiac inotropic effect in the ventricular myocardial cells of adult rats. It also protects the myocardia from ischemia injury induced by ISO.
