ETCM: an encyclopaedia of traditional Chinese medicine (2024)

Table 1.

Content statistics of ETCM

The herb information

The herb section contains the general and drug effectiveness-related information of 403 commonly used Chinese herbs, including the name, type, species, collection time, property, flavor, meridian tropism, indication and specification of herbs. These information was collected from the Pharmacopoeia of the People's Republic of China (2015 version). The pictures and habitat map of herbs were obtained from the Fourth National Survey on Chinese Materia Medica Resources (http://www.zyzypc.com.cn/), which was initiated by the State Administration of Traditional Chinese Medicine in China and carried out a large-scale investigation on Chinese medicinal resources in 1345 counties of China. The colored provinces on the habitat maps are locations where the herbs can grow in China. The ingredients of herbs were mainly extracted from published papers, as well as from ChEMBL (https://www.ebi.ac.uk/chembl/) and PubChem (https://pubchem.ncbi.nlm.nih.gov/).

The formula information

A total of 3962 TCM prescriptions approved by China Food and Drug Administration (CFDA) were collected and stored in the formula section of ETCM. These prescriptions are the commonly used TCM formulas for treating various diseases or maintaining healthy body conditions in clinical practice. The information of formula name, type, dosage form, composition, applicable indications and syndromes, as well as route of administration were obtained from the Pharmacopoeia of the People's Republic of China (2015 version) and Drug Standard of Ministry of Public Health of the People's Republic of China (1993 version). The external links to CFDA are provided to search more detailed drug information by clicking the formula name.

Quality standard of herbs and TCM prescriptions

To facilitate quality evaluation of TCM, the quantitative standards of marker ingredients of herbs and formulas are provided in the herb and formula sections of ETCM. The quantitative standards are set according to the Pharmacopoeia of the People's Republic of China (2015 version), which are the official TCM quality evaluation standards in China.

The ingredient information

The ingredients of herbs and formulas reported in ETCM were collected manually according to the Pharmacopoeia of the People's Republic of China (2015 version) and other literatures. For each ingredient, its name, molecular formula, molecular weight, 2D structure, partition coefficient (ALogP), distribution coefficient (LogD), molecular solubility, molecular volume, surface area and polar surface area, as well as the number of rotatable bonds, H acceptors and H donors are included. These physico-chemical properties were calculated using the Pipeline Pilot software (version 7.5). External links to Public database sources, such as ChEMBL (https://www.ebi.ac.uk/chembl/) and PubChem (https://pubchem.ncbi.nlm.nih.gov/), are also provided for each ingredient.

To estimate drug-likeness of each ingredient, pharmacokinetic parameters were calculated based on models in Pipeline Pilot ADMET collection, such as aqueous solubility, blood brain barrier penetration, CYP450 2D6 inhibition, hepatotoxicity, human intestinal absorption and plasma protein binding. A quantitative metrics, known as the quantitative estimate of drug-likeness (QED), was used for assessing drug-likeness,and the estimated values range from 0 (all properties are unfavorable) to 1 (all properties are favorable). The reported mean QED values for attractive and unattractive components in drug development are 0.67 and 0.49, respectively (14–16). Thus, we classified all 7274 ingredients collected in ETCM into three groups according to their QED scores, good (QED>0.67), moderate (0.49≤QED≤ 0.67) and weak (QED<0.49).

The target information

We predicted potential targets for herbal ingredients in ETCM using MedChem Studio (version 3.0), an efficient drug similarity search tool to identify known drugs with high structural similarity (Tanimoto score > 0.8) to herbal ingredients. The Tanimoto Score is in the range of [0,1], where ‘0’ denotes completely different structures between ingredients and known drugs, and ‘1’ denotes identical structures of two components. The therapeutic targets in the DrugBank database (17) of known drugs are considered as the candidate targets of the herbal ingredients with Tanimoto Scores >0.8 to the known drugs. The biological functions and participated pathways of the candidate drug targets are investigated according to the Gene Ontology (18) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway database (19). Enrichment of Gene Ontology terms and KEGG pathways by target genes of each formula or herb is analyzed using in house python scripts with hypergeometric test.

The disease information

The disease section records the detailed information of diseases and their related genes, which were collected from Human Phenotype Ontology (HPO, March 2018 release), Online Mendelian Inheritance in Man (OMIM, April 2018 release), Database of gene–disease associations (DisGeNET, v5.0) and ORPHANET database. The inconsistent gene or protein IDs of different resources were manually inspected and converted into Official Gene Symbols and UniProt Accession Numbers. The diseases are linked to herbs and formulas according to the overlap of disease-causing genes and the putative target genes of herbs/formulas.

Network analysis

ETCM uses the network module of a dynamic browser based visualization library vis.js (v4.21.0, http://visjs.org/index.html) to construct user-friendly networks for multi-level interactions among herbs/formulas, targets and diseases. The gene-gene interaction data were collected from five existing molecular interaction databases, including Reactome (https://reactome.org/, version 65), Human Protein Reference Database (HPRD, http://www.hprd.org/, Release 9), the Molecular INTeraction Database (MINT, https://mint.bio.uniroma2.it/, updated in August 2011), IntAct Molecular Interaction Database (https://www.ebi.ac.uk/intact/, version: 4.2.12) and Database of Interacting Proteins (DIP, https://dip.doe-mbi.ucla.edu/dip/, updated in Feb 13, 2017). Connections among herbs, formulas, pathways and diseases are established by the ingredients of herbs/formulas and the putative targets of each ingredient.

TCM-specific functional features

TCM understands human bodies and diseases from a special systematic point of view, which is quite different from modern anatomy and medicines. For example, in TCM, herbs are classified according to their flavours (sour, salty, sweet, bitter and pungent), the properties of herbs are characterized according to their effects (cold, hot, warm, cool, and even), and the target organs of herbs are defined by meridian tropisms (lung meridian, liver meridian, etc.). All these information are presented in the ‘Herbs’ section of ETCM (Figure 2A). By clicking on the pie chart of each above mentioned category, users can obtain a full list of all herbs belonging to each category (Figure 2B).

Detailed information of each herb can be retrieved by clicking on its Chinese or Pinyin name, including the habitat, best collection time, property, flavor, meridian tropism, indications, and chemical components of the herb. The picture of each herb as well as its habitat map in China and quality control standard are provided (Figure 2C andD). Formulas containing each herb are also provided in the herb information page, clicking each formula name can link to the information page of the formula. It is worth to note that the herb indication information provided in the ‘Herbs’ section is described according to the records in the Pharmacopoeia of the People's Republic of China (2015 version), these indications are different from modern diseases, therefore we tried to use genes related to both TCM ingredients and modern diseases to build the links between TCM herb indications and modern diseases. Similarly, formulas collected in the ETCM database are also classified according to TCM syndromes, such as heart-clearing, blood-regulation, etc.

Links to molecular biology and modern diseases

To facilitate the understanding of TCM functions from the modern science point of view, we performed target prediction for ingredients of the collected herbs and formulas according to the 2D MACCS fingerprint similarity between TCM ingredients and known drugs in the DrugBank database, and considered the target genes of known drugs as the putative targets of TCM ingredients passed the fingerprint similarity test of the known drugs. The collective targets of all ingredients of a herb or formula are considered as the putative targets of the herb or formula. Diseases associated with those target genes are also considered as diseases that may be cured by the herbs or formulas. Gene Ontology terms or pathways enriched by genes targeted by certain ingredients, herbs, formulas or associated with certain diseases, are also included in ETCM (Figure 2E andF).

To better illustrate the relationships among ingredients, herbs, formulas, target genes, gene-involved pathways and diseases, ETCM provides a systematic analysis function, which allows users to build networks among two or more above mentioned items. By entering a query item and selecting one or more categories, users are capable to build herb-ingredient-target, ingredient-gene-pathway-disease, as well as many other networks (Figure 3). They can also mark or modify nodes and edges of a network to facilitate further researchers. All database contents and analysis results are available for download, and a clear user-manual is also provided.

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Data Availability Statement

All data of ETCM is available at http://www.nrc.ac.cn:9090/ETCM/.