Prediction of Treatment Mechanisms of Scutellariae Radix on Viral Pneumonia Through Network Pharmacology: Focus on Hypoxic State Regulation Through HIF-1α and HSP90

Article information

J Korean Med. 2024;45(2):55-73

Publication date (electronic) : 2024 June 01

doi : https://doi.org/10.13048/jkm.24024

Jee-won Shon ¹^,^§

, Do Kyung Han ¹^,^§

, Youn Sook Kim ²^,

, Won Gun An ¹^,

¹Department of Korean Medicine, School of Korean Medicine, Pusan National University

²Research Institute for Longevity and Well-Being, Pusan National University

Correspondence to: Won Gun An, Department of Korean Medicine, School of Korean Medicine, Pusan National University, Tel: +82-51-510-8455, E-mail: wgan@pusan.ac.kr

Correspondence to: Youn Sook Kim, Research Institute for Longevity and Well-Being, Pusan National University, Tel: +82-51-510-8455, E-mail: younskim@pusan.ac.kr

^§

These authors contributed equally to this work.

Received 2024 April 15; Revised 2024 May 14; Accepted 2024 May 14.

Abstract

Objectives

In this study, we used network-based systems pharmacology analysis and molecular docking methods to predict the therapeutic mechanism of Scutellariae Radix on viral pneumonia.

Methods

We screened active components of Scutellariae Radix and its’ genes by TCMSP. Also, we extracted viral pneumonia related target genes through Gene Cards, CTD and DisGeNet. To construct Protein-protein Interaction, STRING database was used. For functional enrichment, using SRplot platform, genes were classified by 3 categories: cellular component (CC), molecular function (MF) and biological process (BP). Molecular docking was conducted by AutoDockTools (version 4.2.6).

Results

32 Network-based systematic pharmacology analysis identified 37 target genes associated with baicalein. Based on the network and gene ontology analysis of the active ingredient's target genes and disease target genes, we identified nine core genes (AKT1, BAX, BCL2, CASP3, HIF1A, PTGS2, RELA, TP53, VEGFA) and HSP90 as involved. Notably, HIF1A showed the highest relevance, overlapping with two or more utilized programs. Hypoxia-inducible factor 1-alpha (HIF-1α) has been implicated in the expression of inflammatory cytokines, the induction of hypoxia, and the triggering of cytokine storms. Baicalein, a major component of SR, binds to both HIF-1α and HSP90, suggesting that it may be a possible targeted treatment for viral pneumonia.

Conclusions

Baicalein may bind to HIF-1α to control inflammation caused by viral infectious diseases and may also regulate hypoxic conditions to prevent impairment of lung function caused by an overactive immune system. These findings suggest further research into the molecular mechanisms involved in hypoxia and provide a scientific basis for improving the treatment of viral infectious diseases.

Keywords: Baicalein; COVID-19; HIF-1α; Molecular docking; Scutellariae Radix

Fig. 1

Investigating overlaps between genes derived by applying four keywords related to viral pneumonia to three databases: GeneCards (G), DisGeNET (D), and CTD (C), and Baicalein's target genes.

(A) The keyword is 'Viral Pneumonia’. (B) The keyword is 'Pneumonia Influenza’. (C) The keyword is 'SARS’. (D) The keyword is 'Coronavirus Infection’. The number of genes overlapping between disease-related genes and Baicalein's target genes is represented by black circles.

Fig. 2

Nine Key Genes Common in Four Keywords.

Fig. 3

Protein-Protein Interaction of 26 Key Duplicated Genes Overlapping in Two or More Disease keywords. PPI enrichment p-value: < 1.0e-16.

Fig. 4

Protein-Protein Interaction (PPI) Involving 9 Key Duplicated Genes and HSP90, as Represented in STRING.

(A) 10 nodes connected by 36 edges, averaging 7.2 nodes interacting. PPI enrichment p-value: 0.00267. (B) Genes associated with lung tissue (green nodes). (C) Genes involved in host-virus interaction (blue nodes) and apoptosis (red nodes).

Fig. 5

Ten Compounds and Targets with a High Degree of Association Among the Compounds of Scutellariae Radix and Target genes.

Fig. 6

Gene Ontology Analysis of Scutellariae Radix and Baicalein.

The results for three ontologies, namely Biological Process (BP), Cellular Component (CC), and Molecular Function (MF), for both (A) Scutellariae Radix and (B) Baicalein.

Fig. 7

Predictive model of the binding of baicalein to HSP90 and HIF1A

(A) Gray: protein, HSP90 (PDB ID: 1YET), pink: ligand, baicalein, affinity: −6.7 kcal/mol. (B) Light green: van der waals, Green: conventional hydrogen bond, Pink: Pi-alkyl, Yellow: Pi-sulfur, Purple: Pi-sigma. (C) 3D structure of the intermolecular docking of baicalein and HSP90. (D) Gray: protein, HIF1A (PDB ID: 8HE3), Pink: ligand, baicalein, affinity: −6.6 kcal/mol. (E) Light green: van der waals, Green: conventional hydrogen bond, Pink: Pi-alkyl, Yellow: Pi-anion. (F) 3D detailed structure of the intermolecular docking of baicalein and HIF1A.

Table 1

Active Compounds of Scutellariae Radix

Table 2

Targets of Baicalein

Table 3

Common Genes between Baicalein Target Genes between Each Diseases Keyword.

Table 4

26 Genes Duplicated Two or More Times in Four Disease Names

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