# Network Pharmacology-Based Exploration of the Mechanism of Action of Shugan Hewei Recipe in the Treatment of Gastroesophageal Reflux Disease with Anxiety and Depression

**Authors:** Tingting Xu, Chunfang Liu, Xiulian Zhang, Lin Geng, Hongwei Wang, Li Li, Shengliang Zhu

PMC · DOI: 10.1155/2022/3957084 · 2022-09-27

## TL;DR

This study explores how a traditional Chinese medicine recipe works to treat gastroesophageal reflux disease along with anxiety and depression.

## Contribution

The study identifies key compounds and molecular targets of SHR using network pharmacology and validates its therapeutic effects in animal models.

## Key findings

- SHR's active compounds include quercetin, kaempferol, and luteolin.
- SHR targets TGF-β1, IL-1β, and GABA receptors to treat GERD and mental disorders.
- Animal experiments showed SHR repairs esophageal mucosa and improves behavior in rats.

## Abstract

The Shugan Hewei recipe (SHR) is a well-recognized traditional Chinese medicine (TCM) prescription that has been shown to significantly improve chest pain, acid regurgitation, and the mood of GERD. Nonetheless, the underlying mechanisms remain unclear. In this study, the active compounds and targets of SHR were predicted using network pharmacology. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were utilized to explore the therapeutic mechanism of SHR. Combined with the drug target obtained from network pharmacology, the therapeutic effect and mechanism of SHR were observed. SHR's main active compounds included quercetin, kaempferol, and luteolin. The core targets of SHR and GERD were TGF-β1, IL-1β, IL-4, CXCL10, MAPK1, MAPK3, CXCL8, IL-10, IL-2, and FOS, involving virus infection, inflammatory response, and body immunity. The core targets of SHR during the treatment of mental disorders were GABRA1, GABRA2, GABRA3, GABRA5, and GABRA6, involving synaptic transmission and transmembrane movement. Animal experiments revealed that SHR could repair the lower esophageal mucosa, mediate inflammatory factors, and GABA receptors and improve the behavior of rats. Overall, our results substantiate that SHR has huge prospects for widespread application in treating GERD subjects with anxiety and depression.

## Linked entities

- **Genes:** TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040], IL1B (interleukin 1 beta) [NCBI Gene 3553], IL4 (interleukin 4) [NCBI Gene 3565], CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627], MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594], MAPK3 (mitogen-activated protein kinase 3) [NCBI Gene 5595], CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576], IL10 (interleukin 10) [NCBI Gene 3586], IL2 (interleukin 2) [NCBI Gene 3558], FOS (Fos proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 2353], GABRA1 (gamma-aminobutyric acid type A receptor subunit alpha1) [NCBI Gene 2554], GABRA2 (gamma-aminobutyric acid type A receptor subunit alpha2) [NCBI Gene 2555], GABRA3 (gamma-aminobutyric acid type A receptor subunit alpha3) [NCBI Gene 2556], GABRA5 (gamma-aminobutyric acid type A receptor subunit alpha5) [NCBI Gene 2558], GABRA6 (gamma-aminobutyric acid type A receptor subunit alpha6) [NCBI Gene 2559]
- **Chemicals:** quercetin (PubChem CID 5280343), kaempferol (PubChem CID 5280863), luteolin (PubChem CID 5280445)
- **Diseases:** gastroesophageal reflux disease (MONDO:0007186), anxiety (MONDO:0005618), depression (MONDO:0002050)

## Full-text entities

- **Genes:** IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, GABRA3 (gamma-aminobutyric acid type A receptor subunit alpha3) [NCBI Gene 2556] {aka EPILX2}, GABRA1 (gamma-aminobutyric acid type A receptor subunit alpha1) [NCBI Gene 2554] {aka DEE19, ECA4, EIEE19, EJM, EJM5}, GABRA6 (gamma-aminobutyric acid type A receptor subunit alpha6) [NCBI Gene 2559], GABRA5 (gamma-aminobutyric acid type A receptor subunit alpha5) [NCBI Gene 2558] {aka DEE79, EIEE79}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627] {aka C7, IFI10, INP10, IP-10, SCYB10, crg-2}, GABRA2 (gamma-aminobutyric acid type A receptor subunit alpha2) [NCBI Gene 2555] {aka DEE78, EIEE78}, MAPK3 (mitogen-activated protein kinase 3) [NCBI Gene 5595] {aka ERK-1, ERK1, ERT2, HS44KDAP, HUMKER1A, P44ERK1}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, FOS (Fos proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 2353] {aka AP-1, C-FOS, p55}
- **Diseases:** chest pain (MESH:D002637), mental disorders (MESH:D001523), inflammatory (MESH:D007249), Anxiety (MESH:D001007), Depression (MESH:D003866), acid regurgitation (MESH:D008944), GERD (MESH:D005764), infection (MESH:D007239)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11401718/full.md

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Source: https://tomesphere.com/paper/PMC11401718