Network Pharmacological Analysis of TCM Formulae Based on the Syndrome Ontology and Multidimensional Quantitative Association Computing Platform

Summary

We propose a "Formula-Ingredient-Target-Pathway-Syndrome-Disease" network construction method based on the SoFDA platform, network pharmacology, and Traditional Chinese Medicine (TCM). Compared to the currently popular network pharmacology methods, this network incorporates the critical element of syndrome, which embodies the fundamental principle of syndrome differentiation in TCM.

Abstract

Current network pharmacology methods for TCM formulae predict potential active ingredients and mechanisms of action for specific diseases by constructing a formula-ingredient-target-pathway-disease network.

Syndrome differentiation and treatment, a core principle of TCM, embodies its holistic and dynamic approach, emphasizing individual variability and disease progression. By integrating syndrome characteristics into this network, researchers can develop multi-target drugs tailored to each disease stage, enabling precise and personalized treatment. The TCM Syndrome Ontology and Multidimensional Quantitative Association Computing Platform (SoFDA) allow the incorporation of TCM syndromes into network pharmacology analysis.

In this study, we used Lingguizhugan Decoction (formula) as an example to demonstrate its application in treating obesity with Yang Deficiency Syndrome and Dampness-Phlegm Syndrome (syndromes). We first identified key active ingredients from the TCMSP database. We then constructed a network linking diseases, syndromes, target genes, and signaling pathways using SoFDA. Finally, we integrated these data to build a formula-ingredient-target-pathway-syndrome-disease network.

Introduction

By integrating the concept of dialectical treatment in Chinese medicine and using the SoFDA^1,2 platform, we have explored a novel network pharmacology approach, namely, integrative pharmacology, to construct a formula-drug-target-pathway-syndrome-disease network diagram of Chinese medicine formulations.

Compared with the popular network pharmacology methods in recent years, this method incorporates the element of syndrome in TCM. Evidence, or Syndrome, is one of the unique concepts of TCM, and is a generalization of the pathological properties of a disease at a certain stage in its ....

Protocol

Taking Lingguizhugan decoction to treat "Yang deficiency Syndrome" and "Dampness-Phlegm Syndrome" of abdominal obesity as an example. Lingguizhugan decoction comprises 4 herbs: Poria cocos (Fuling), Cinnamomi ramulus (Guizhi), Rhizoma Atractylodis macrocephalae (Baizhu), Glycyrrhizae radix et Rhizoma (Gancao). The website of SoFDA platform is http://www.tcmip.cn/Syndrome/front/#/. The website of the traditional Chinese medicine systems pharmacology (TCMSP) database is https://old.tcmsp-e.com/tcmsp.php

1. Screening out the active ingredients of the formula

1. ....

Results

We selected 103 active ingredients of four Chinese herbs in the Lingguizhugan decoction by the criteria of bioavailability ≥30% and pharmacophore ≥0.18%. The main active ingredients were quercetin, kaempferol, naringenin, β-sitosterol, isorhamnetin. It is consistent with the laboratory extraction and screening components of Jiang et al.¹⁴.

For Dampness-Phlegm Syndrome and Yang Deficiency Syndrome of Lingguizhugan decoction (Figure 1), 328 t.......

Discussion

SoFDA is the first open-source ontology database for TCM syndromes, with its data and analysis results fully accessible to the public. This open-source nature provides researchers with greater flexibility. The platform employs a similarity-based association evaluation system, utilizing Jaccard or cosine similarity measures to quantitatively assess the relationships among disease-syndrome, and formula-syndrome associations. This dynamic modeling capability allows SoFDA to better simulate the dynamic changes in diseases an.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Cytoscape(type 3.9.1)	National Human Genome Rearch Institute (NHGRI)	https://cytoscape.org/
Gene Ontology (GO) knowledgebase	Global Core Biodata Resources	https://www.geneontology.org/
KEGG: Kyoto Encyclopedia of Genes and Genomes	Kanehisa Laboratories	https://www.genome.jp/kegg/
SoFDA platform	China Academy of Chinese Medical Science	http://www.tcmip.cn/Syndrome/front/#/
STRING12.0 website	Global Biodata Coalition?ELIXIR	https://cn.string-db.org/
TCMSP platform	Zhejiang Jiuwei Health Co., LTD	https://old.tcmsp-e.com/tcmsp.php
Wei Sheng Xin online website	NEWCORE	https://www.bioinformatics.com.cn/