# Exploring the patterns in traditional Chinese medicine for bipolar disorder: a data-driven network approach

**Authors:** Zhenshan Sun, Jiangbangrui Chu, Junjie Peng, Kefan Hu, Zhengyi Wang, Zhu Zhang, Ken Kin Lam Yung

PMC · DOI: 10.3389/fphar.2025.1524345 · Frontiers in Pharmacology · 2025-06-04

## TL;DR

This study uses data-driven methods to explore traditional Chinese medicine patterns for bipolar disorder, identifying key botanical drugs and their mechanisms.

## Contribution

A novel data-mining approach is used to uncover treatment patterns and active metabolite interactions in TCM for bipolar disorder.

## Key findings

- Five core botanical drugs were identified for bipolar disorder treatment in TCM.
- Botanical drug-metabolite-target networks were constructed to explain treatment mechanisms.
- In vitro experiments showed dose-dependent effects of palmitic and stearic acids on cell viability and gene expression.

## Abstract

Traditional Chinese Medicine offers a holistic approach that could provide complementary benefits for bipolar disorder treatment. However, the clinical cases in Traditional Chinese Medicine are highly dispersed, creating challenges for translational research. This study employs a novel data-mining-derived approach to identify treatment patterns and active metabolite interactions within these clinical cases.

Bipolar disorder-related targets were determined using DisGeNET and GeneCards databases. Active botanical drugs were extracted from the BATMAN-TCM 2.0 database. All terms for botanical drugs and diseases were confirmed via the Pharmacopoeia of the People’s Republic of China 2020 Edition and Medical Subject Headings. Networks were constructed using Cytoscape, with data analysis performed using Python. MTT cell viability and qRT-PCR analysis were used to perform in vitro experiments on SH-SY5Y neuroblastoma cells.

Five key botanical drugs—Glycyrrhizae Radix Et Rhizoma, Poria, Coptidis Rhizoma, Bupleuri Radix, and Polygalae Radix—were identified as core drugs in BD treatment formulas. The botanical drug-metabolite-target network was constructed. In vitro experiments using SH-SY5Y neuroblastoma cells demonstrated dose-dependent effects of palmitic acid (PA) and stearic acid (SA) on cell viability and gene expression. qRT-PCR analysis revealed bidirectional regulation of GABRA1 and ESR1 by these metabolites.

Five botanical drugs: Glycyrrhizae Radix Et Rhizoma, Poria, Coptidis Rhizoma, Bupleuri Radix, and Polygalae Radix, were identified as the core botanical drugs in bipolar disorder treatment. The main mechanism of these botanical drugs is their effects on the gamma-aminobutyric acid type A receptor and ESR1.

## Linked entities

- **Genes:** GABRA1 (gamma-aminobutyric acid type A receptor subunit alpha1) [NCBI Gene 2554], ESR1 (estrogen receptor 1) [NCBI Gene 2099]
- **Chemicals:** palmitic acid (PubChem CID 985), stearic acid (PubChem CID 5281)
- **Diseases:** bipolar disorder (MONDO:0004985)

## Full-text entities

- **Genes:** ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, GABRA1 (gamma-aminobutyric acid type A receptor subunit alpha1) [NCBI Gene 2554] {aka DEE19, ECA4, EIEE19, EJM, EJM5}
- **Diseases:** BD (MESH:D001528), neuroblastoma (MESH:D009447), Bipolar disorder (MESH:D001714)
- **Chemicals:** SA (MESH:C031183), PA (MESH:D019308), Bupleuri Radix (-), MTT (MESH:C070243)
- **Cell lines:** SH-SY5Y — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_0019)

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12174447/full.md

## References

31 references — full list in the complete paper: https://tomesphere.com/paper/PMC12174447/full.md

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Source: https://tomesphere.com/paper/PMC12174447