Study on mechanism of matrine in treatment of COVID-19 combined with liver injury by network pharmacology and molecular docking technology

Abstract

The aim of the present study was to investigate the pharmacological mechanism of matrine in treatment of COVID-19 combined with liver injury. Potential targets related to matrine, COVID-19 and liver injury were identified from several databases. We constructed PPI network and screened the core targets according to the degree value. Then, GO and KEGG enrichment were carried out. Molecular docking technology was used to verify the affinity between matrine and the crystal structure of core target protein. Finally, real-time RT-PCR was used to detect the effects of matrine on hub gene expression in liver tissue of liver injury mice and lung tissue of lung injury mice to further confirm the results of network pharmacological analysis. The results show that six core targets including AKT1, TP53, TNF, IL6, BCL2L1 and ATM were identified. The potential therapeutic mechanism of matrine on COVID-19 combined with liver injury is closely related to regulate antiviral process, improve immune system and regulate the level of inflammatory factors. Molecular docking showed that matrine could spontaneously bind to the receptor protein and had strong binding force. Real-time RT-PCR demonstrated that matrine could significantly reduce the expression of AKT1, TP53, TNF, IL6 and ATM in mice with liver injury or lung injury (P < 0.05), and increase the expression of BCL2L1 to a certain extent (P > 0.05). Our results indicate that matrine can achieve simultaneous intervention of COVID-19 combined with liver injury by multi-dimensional pharmacological mechanism.

Network pharmacology and experimental investigation of Rhizoma polygonati extract targeted kinase with herbzyme activity for potent drug delivery

“…In summary, using network pharmacology we may identify the pathways that drug delivery carriers induced signaling and potent enzyme activity. The bioinformatics tool can provide an efficient approach to expedite the biochemical analysis to target the potent signaling and applying the drug delivery platform especially at nanoscale for enhanced efficiency (Liu et al, 2021 ), by the dual function of interface effect and herbzyme effect.…”

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

“…We also identified tumor protein p53 ( TP53 ) hub-high traffic TF in the turquoise module, with an important role in the pathogenesis of COVID-19 ( 415 ). Moreover, in an animal model of COVID-19, ALI in the infected group was associated with an increase in TP53 expression ( 416 ). Besides, 1 study reported that an increase in the expression of TP53 led to the induction of apoptosis in PBMCs and thus reduced their frequencies in COVID-19 patients ( 97 ).…”

Sustained Release of Co-Amorphous Matrine-Type Alkaloids and Resveratrol with Anti-COVID-19 Potential

“…Furthermore, the mortality rate among hospitalized COVID-19 patients strongly correlated with the autoimmunity level to annexin A2 [ 10 ], suggesting its importance in SARS-CoV-2 pathogenicity [ 11 ]. Matrine was shown to directly target annexin A2 by a photo-affinity labeling approach [ 12 ], while very recent network pharmacological studies suggested that matrine may also have varying targets in cellular signaling pathways [ 13 , 14 , 15 ]. Oxymatrine (OMAR) and sophoridine (SPD, Scheme 1 ) are matrine-type alkaloids isolated from S. flavescens Ait with promising biological activities [ 16 , 17 ], including antiviral activity [ 18 , 19 ].…”