Elsevier

Phytomedicine

Volume 95, January 2022, 153784
Phytomedicine

Yindan Jiedu granules exhibit anti-inflammatory effect in patients with novel Coronavirus disease (COVID-19) by suppressing the NF-κB signaling pathway

https://doi.org/10.1016/j.phymed.2021.153784Get rights and content
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open access

Highlights

  • Yindan Jiedu Granules (YDJDG) is a new Chinese herbal formula for COVID-19.

  • YDJDG could shorten the course and delay the progression of COVID-19.

  • We provide clinical, bioinformatics and experiment basis for COVID-19 treatment with YDJDG.

  • YDJDG may suppressing inflammation via targeting the NF-κB pathway.

Abstract

Background

Coronavirus disease 2019 (COVID-19) is a pandemic that has caused a high number of deaths worldwide. Inflammatory factors may play important roles in COVID-19 progression. Yindan Jiedu granules (YDJDG) can inhibit the progression of COVID-19, but the associated mechanism is unclear.

Purpose

To evaluate the therapeutic effects of YDJDG on COVID-19 and explore its underlying mechanism.

Methods

We recruited 262 participants and randomly assigned 97 patients each to the YDJDG and control groups using one-to-one propensity score matching (PSM). Clinical effects were observed and serum inflammatory and immune indicators were measured. The target network model of YDJDG was established by predicting and determining the targets of identified compounds. The main constituents of the YDJDG extracts were identified and evaluated using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and molecular docking. Besides, the anti-inflammatory effects of YDJDG and its specific biological mechanism of action were studied.

Results

After PSM, the results showed that compared with the control group, the YDJDG group had a shorter time of dissipation of acute pulmonary exudative lesions (p < 0.0001), shorter time to negative conversion of viral nucleic acid (p < 0.01), more rapid decrease in serum amyloid A level and erythrocyte sedimentation rate (p < 0.0001), and a higher rate of increase in CD4+T cell count (p = 0.0155). By overlapping the genes of YDJDG and COVID-19, 213 co-targeted genes were identified. Metascape enrichment analysis showed that 25 genes were significantly enriched in the NF-κB pathway, which were mainly targets of luteolin, quercetin, and kaempferol as confirmed by MS analysis. Molecular docking revealed that the ligands of three compounds had strong interaction with NF-κB p65 and IκBα. In vivo, YDJDG significantly protected animals from lipopolysaccharide (LPS)-induced acute lung injury (ALI), decreasing the lung wet/dry weight ratio, ALI score, and lung histological damage. In LPS-treated RAW264.7 cells, YDJDG suppressed nuclear translocation of NF-κB p65. In vivo and in vitro, YDJDG exerted anti-inflammatory effects by inhibiting the production of inflammatory cytokines (IL-6, IL-1β, and TNF-α). These effects were accompanied by the inhibition of NF-ĸB activation and IκBα phosphorylation.

Conclusion

YDJDG may shorten the COVID-19 course and delay its progression by suppressing inflammation via targeting the NF-κB pathway.

Keywords

COVID-19
Yindan jiedugranules
Clinical research
Pharmacology analysis
Molecular docking
NF-κB signaling pathway

Abbreviations

ACE2
angiotensin-converting enzyme 2
ALI
acute lung injury
COVID-19
Coronavirus disease 2019
CRP
C-reactive protein
DL
drug-likeness property
ESR
erythrocyte sedimentation rate
GO
Gene Ontology
KEGG
Kyoto Encyclopedia of Genes and Genomes
LC
liquid chromatography
MS
mass spectrometry
NHC
National Health Commission
NLR
neutrophil-to-lymphocyte ratio
OB
satisfying oral bioavailability
PSM
propensity score matching
SAA
serum amyloid A
TCM
Traditional Chinese medicine
TCMSP
Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform
YDJDG
Yindan Jiedu granules.

Cited by (0)

1

The three authors contributed equally to this paper.