Molecular mechanisms revealed by network pharmacology of Xuebijing on the treatment of acute respiratory distress syndrome caused by novel coronavirus infection.

OBJECTIVE: The study aims to predict the target and molecular mechanism of Xuebijing injection in the treatment of novel coronavirus-induced acute respiratory distress syndrome (ARDS), based on network pharmacology. MATERIALS AND METHODS: Chinese and English studies were searched to obtain the main active components of Xuebijing injection. ETCM, TCMSP and Targetnet online databases were adopted used to predict Xuebijing therapeutic targets. GeneCards, CTD and OMIM databases were researched used to research for the novel coronavirus Disease-2019 (COVID-19) and ARDS-related targets. Integrate analysis was carried out to obtain the targets of Xuebijing injection in the treatment of ARDS caused by novel coronavirus. STRING was adopted to analyze the interaction of common target proteins. GO and KEGG enrichment analyses were carried out using Bioconductor bioinformatics software package based on R software. Network visualization was performed with Cytoscape software. RESULTS: A total of 30 main active components in Xuebijing injection were collected in this study, which can act on 615 targets. The core components of Xuebijing injection in treating the coronavirus-induced ARDS are Ferulic acid, Ethyl ferulate, Albiflorin, Caffeic acid, Rosmarinic acid, Naringenin, Quercetin. Xuebijing injection has 56 target points for the treatment of ARDS caused by the novel coronavirus, among which AKT1, TNF, CASP3 and STAT3 are the core ones. The main molecular mechanisms of Xuebijing injection in treating the coronavirus-induced ARDs include PI3K-Akt, TNF, STAT3, NF-κB and apoptosis-related pathways. CONCLUSIONS: Xuebijing mainly treats ARDS caused by the novel coronavirus through anti-inflammation, anti-apoptosis, and regulation of immunity since it has the characteristics of multi-component, multi-target and multi-pathway.

Alteration in transcripting the gene encoding the delta-opioid receptor in rat brain is not underlying the development of tolerance to [D-Ala2,D-Leu5] enkephalin.

Previous study has demonstrated that chronic treatment of [D-Ala2,D-Leu5] enkephalin (DADLE) induces profound down-regulation of delta opioid receptor in rat brain. We further examined whether this down-regulation of receptor was due to a decrease in the transcription of gene encoding delta-opioid receptor (DOR-1). Rats received daily i.c.v. injection of DADLE for 1, 3, or 5 days and developed significant tolerance to the antinociceptive effect of DADLE after one-day treatment. We measured the level of mRNA in rat brain tissues using in situ hybridization. No significant changes in the mRNA levels of the cortex, striatum, hippocampus, and thalamus on any examined days were found as compared to those of rats received sham operation only. There is only a transient decrease of DOR-1 mRNA level in midbrain region that occurred after a three-day treatment. Thus, the result of this study did not suggest that alteration in transcription of gene-encoding delta-opioid receptor was responsible for the down-regulation of delta-opioid receptor associated with the development of tolerance to DADLE.

[Effects of 5-HT on activity of arcuate neurons of rat hypothalamic slices].

Extracellular recordings were made from 176 spontaneous discharging units in the arcuate nucleus of rat hypothalamic slices. Depending on the patterns of discharge, the units were divided into three types; slow irregular (76%), fast continuous (26.5%) and phasic units (6.3%). The effect of 5-HT on the different types of units were observed. The results indicated that most of neurons were inhibited by 5-HT, and only a small portion of the cells showed excitation and a few of the slow irregular units showed "excitation after inhibition". With 5-HT 10(-6) mol/L we found that 12 units inhibited by 5-HT could not be reversed by CHD, while the 4 inhibited units could be partly or completely reversed by MSG. 4 of the 7 neurons inhibited by 5-HT were partly blocked by Pindobind-5-HT1A but not for the remaining 3 neurons. The results suggest that the inhibitory effect of 5-HT on arcuate neurons may be mediated by 5-HT1 receptor, while some by 5-HT1A receptor.

[The inhibitory effects of catechin derivatives on the activities of human immunodeficiency virus reverse transcriptase and DNA polymerases].

Catechin derivatives including (-)-epicatechin gallate (ECG), (-)-epigallocatechin gallate (EGCG), (-)-epigallocatechin (EGC) and green tea extract (GTE) were found to inhibit the activities of cloned human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT), duck hepatitis B virus replication complexes reverse transcriptase (DHBV RCs RT), herpes simplex virus 1 DNA polymerase (HSV-1 DNAP) and cow thymus DNA polymerase alpha (CT DNAP alpha). EGCG and ECG were shown to be very potent inhibitors of HIV-1 RT. According to the IC50 values for HIV-1 RT, these compounds can be ordered as EGCG 0.0066 mumol/L > ECG 0.084 mumol/L > GTE 0.1 microgram/ml > EGC 7.2 mumol/L. DHBV RCs RT was the least sensitive to these compounds. Kinetic study showed that EGCG exerts a mixed inhibition with respect to external template inducer poly (rA).oligo (dT) 12-18 and a noncompetitive inhibition with respect to substrate dTTP for HIV-1 RT. Bovine serum albumin significantly reduced the inhibitory effects of catechin analogues and GTE on HIV-1 RT. In tissue culture GTE inhibited the cytopathic effect of coxsackie B3 virus, but did not inhibit the cytopathic effects of HSV-1, HSV-2, influenza A or influenza B viruses.