Food Chemistry: X 23 (2024) 101742

Contents lists available at ScienceDirect

Food Chemistry: X
journal homepage: www.sciencedirect.com/journal/food-chemistry-x

PungentDB: Bridging traditional Chinese medicine of medicine food

homology and modern food flavor chemistry
Zhao Chen a, b, * , Zhixin Wang b, d , Yanfeng Cao b, c , Xinyuan Shi b, c , Bing Xu b, c , Xi Li b, e ,
Jing Li b, c , Yanling Zhang b, c, * , Yanjiang Qiao b, c, *
a
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China
b
Research Center of TCM-Information Engineering, State Administration of Traditional Chinese Medicine of China, Beijing, 102488, China
c
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China
d
Institute of Traditional Chinese Medicine Health Industry, China Academy of Chinese Medical Sciences, Nanchang, 330115, China
e
School of Pharmacy, Tongji Medical college, Huazhong University of Science and Technology, Wuhan, 430000, China

A R T I C L E I N F O A B S T R A C T

Keywords: Merging traditional Chinese medicine’s (TCM) principles of medicine-food homology with modern flavor
PungentDB chemistry, this research unveils PungentDB (http://www.pungentdb.org.cn/home), a database documenting 205
Flavor chemistry unique pungent flavor compounds from 231 TCMs. It provides detailed insights into their chemical attributes,
Traditional Chinese medicine
biological targets (including IC50/EC50 values), and molecular structures (2D/3D), enriched with visualizations
Medicine food homology
Sensory science
of target organ distribution and protein structures, exploring the pungent flavor space with the help of a feature-
Food flavor enhancement rich visual interface. This collection, derived from over 3249 sources and highlighting 9129 targets, delves into
Chemical analysis of food the compounds’ unique pungent flavors—taste, aroma, and thermal sensations—and their interaction with taste
and olfactory receptors. PungentDB bridges ancient wisdom and culinary innovation, offering a nuanced
exploration of pungent flavors’ role in enhancing food quality, safety, and sensory experiences. This initiative
propels flavor chemistry forward, serving as a pivotal resource for food science advancement and the innovative
application of pungent flavors.

1. Introduction have revolutionized our ability to identify and quantify the complex
array of flavor compounds in foods (Weng et al., 2021). These meth-
The exploration of traditional Chinese medicine (TCM), particularly odologies provide a detailed understanding of the chemical foundations
the concept of medicine-food homology, offers a unique perspective on of flavor and its implications for food safety, quality, and sensory
the therapeutic and dietary value of natural products (Gong, Ji, Xu, properties. The advent of ‘omics’ technologies—metabolomics, prote-
Zhang, & Li, 2020; Zhang et al., 2023). This ancient wisdom posits that omics, and genomics—further enhances our capability to dissect the
food and medicine share common sources and effects, enhancing both molecular profiles of foods, offering insights into how these compounds
health and sensory attributes in culinary practices. Integrating these interact with human biology to influence taste, aroma, and health out-
traditional insights with modern scientific approaches, especially in comes (Datir & Regan, 2022; Li et al., 2021).
flavor chemistry, opens new avenues for understanding the complex Despite significant strides, the food industry faces ongoing chal-
interplay between diet and health. This convergence is reshaping dietary lenges in maintaining the balance between flavor enhancement and
practices and steering the development of functional foods that cater to nutritional integrity. Processing techniques often alter the flavor profile
both health efficacy and sensory appeal (Yin et al., 2021; Yin et al., of food, sometimes at the expense of nutritional value (Utpott, Rodri-
2023). gues, de Oliveira Rios, Mercali, & Flôres, 2022). Additionally, scaling
Advancements in analytical techniques, such as high-performance biotechnological methods such as microbial fermentation and enzymatic
liquid chromatography (HPLC), gas chromatography–mass spectrom- modification presents challenges in consistency and acceptability.
etry (GC–MS), and liquid chromatography-mass spectrometry (LC-MS), However, these methods hold promise for developing novel flavor

* Corresponding authors at: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China; Research Center
of TCM-Information Engineering, State Administration of Traditional Chinese Medicine of China, Beijing, 102488, China.
E-mail addresses: [email protected] (Z. Chen), [email protected] (Y. Zhang), [email protected] (Y. Qiao).

https://doi.org/10.1016/j.fochx.2024.101742
Received 13 April 2024; Received in revised form 19 July 2024; Accepted 13 August 2024
Available online 14 August 2024
2590-1575/© 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).
Z. Chen et al. Food Chemistry: X 23 (2024) 101742

compounds that can enhance health benefits without compromising com/), Science Online (http://www.sciencemag.org/), Springer
taste or safety (Soto-Vaca, Gutierrez, Losso, Xu, & Finley, 2012). (https://link.springer.com/), Wiley (http://onlinelibrary.wily.com).
Sensory science plays a crucial role in translating chemical profiles Notably, 20 % of these sources were published in Cell, Nature, Science
into perceptible sensory experiences, effectively bridging the gap be- journals and their sub-journals.
tween the biochemical properties of food compounds and their
perceived flavors. This field has evolved to encompass not only basic 2.2. Identification of the pungent flavor compounds
tastes but also the intricate sensations of aroma, texture, and mouthfeel
(Koehler et al., 2024). Sensory evaluations are essential for under- To identify the pungent compounds in TCMs, this study employed
standing how processing methods, storage conditions, and culinary two main approaches. The first approach involved cross-referencing
preparations impact the overall flavor profile of foods. This knowledge compounds from pungent TCMs with known databases of pungent
guides the optimization of processing techniques to preserve or enhance compounds. These databases included the GB2760–2014 National Food
the sensory quality of food products (Colbert, Triplett, & Maier, 2022). Safety Standard and Food Additives Use Standard (China), FlavorDB
In our study, we introduce PungentDB, a comprehensive database (Garg et al., 2018), FooDB (http://foodb.ca), Flavornet (Arn & Acree,
that integrates the principles of TCM with modern scientific methodol- 1998), and FEMA (Adams et al., 2004). By intersecting these databases,
ogies to explore the pungent flavors of foods and their medicinal cor- a comprehensive list of pungent compounds was compiled.
relations. PungentDB includes detailed chemical, biological, and sensory The second approach focused on identifying relevant compounds
information on pungent compounds identified from TCM sources, through extensive literature review. This involved gathering data on the
providing an innovative tool for researchers and practitioners alike to interactions of compounds with sensory receptors, specifically the
understand and leverage the health-promoting properties of these transient receptor potential (TRP) and olfactory receptor (OR) families.
compounds. Our research addresses the gap in systematic documenta- The pungency is attributable to chemicals that activate a specific tran-
tion and provides a platform for the scientific community to study the sient receptor potential (TRP) cation channel family and olfactory re-
complex interactions between pungent flavors and their sensory and ceptors (ORs). Moreover, the ligands of TRPs are for the most part spices
therapeutic effects. This approach supports the advancement of flavor and flavor molecules. Data collection was performed from journal arti-
science and contributes to the development of functional foods that are cles published by major publishers such as Elsevier ScienceDirect, Na-
both nutritious and appealing. ture, Science Online, Springer, and Wiley. This thorough literature
review ensured a robust dataset of pungent compounds linked to sensory
2. Material and methods receptors.
Through these methods, we ensure the comprehensive identification
2.1. Data acquisition of pungent compounds in TCMs, leveraging both established databases
and extensive literature to provide a thorough understanding of these
We collected compounds from pungent TCMs of medicine food ho- compounds and their sensory impacts.
mology and identified pungent compounds from various databases
including FlavorDB (Garg et al., 2018), FooDB (http://foodb.ca), and 2.3. Organ target location mapping and system distribution with gene
Flavornet (Arn & Acree, 1998), FEMA(Adams et al., 2004). Information organizer
of pungent TCMs of medicine food homology were extracted from
pharmacopoeia of the People’s Republic of China (2015), which consists In Traditional Chinese Medicine (TCM), meridian theory suggests
of 5608 different species of drugs, including herbs, plant oils and ex- that a TCM’s therapeutic efficacy is directed towards specific organs or
tracts. The pungent TCMs’ compounds were sourced from TCMSP (Ru meridians, indicating its target within the body. Due to the limitation of
et al., 2014), TCMID (Huang et al., 2018), BATMAN-TCM (Kong et al., most expression datasets, there is a strong bias towards certain organs
2024), TCM-Mesh (Zhang, Yu, Bai, & Ning, 2017), TCM Data- and tissues (e.g. brain, blood and skin), and many other body parts are
base@Taiwan (Chen, 2011). The 2D/3D chemical structures, physico- rare or completely absent. TCM theory focuses on the interaction of
chemical properties, and SDF/XML files for most pungent flavor TCMs with human body with a holistic view. To map these targets
molecules were obtained from PubChem (Wang et al., 2009). Users can accurately, we utilized Gene ORGANizer (Gokhman et al., 2017), a
download these files in either 2D or 3D formats. comprehensive and fully curated database containing over 150,000
We compiled a set of physical descriptors and identifiers for these gene-body part associations, covering more than 7000 human genes.
compounds, including PubChem CID, FEMA number, InChI, InChI Key, Gene ORGANizer provides robust evidence for understanding the organ
CAS registry number, molecular weight, logP, XlogP (XlogP-AA), Smiles target locations and system distribution of pungent compounds from
molecular solubility, water solubility, H-bond donors, H-bond acceptors TCMs, thus elucidating the concept of meridian tropism at the molecular
and Rotatable bonds, flavor profile, taste and odors, drawing from level.
PubChem (Wang et al., 2009), FlavorDB (Garg et al., 2018), FooDB The methodology involved mapping the targets of pungent TCM
(http://foodb.ca), FEMA (Adams et al., 2004). The water solubility de- compounds to organ-specific locations and human systems using Gene
scriptors for some pungent compounds were computed using the ORGANizer. This was achieved by analyzing the correlation between
ALOGPS 2.1 program (free resources available at http://www.vcclab. genes and their associated organs and systems based on phenotypic data.
org/lab/alogps/). The research aimed to establish a foundational understanding of the
The targets information of pungent compounds were extracted from relationship between TCM meridian theory and organ-specific targeting,
publications using Pubtator (Wei, Kao, & Lu, 2013) and several disease- focusing on phenotype-genotype relationships. This process is crucial for
gene databases including DrugBank (http://www.drugbank.ca/), accurate clinical diagnosis and treatment, as symptom phenotypes are
STITCH (http://stitch.embl.de/), ChEMBL (https://www.ebi.ac.uk/ch diligently observed by physicians.
embl/), BindingDB (http://www.bindingdb.org/bind/index.jsp). Ther-
apeutic Target Database (http://bidd.nus.edu.sg/ group/ttd/), and 2.4. Assay of pungent compounds
Comparative Toxicogenomics Database (CTD, http://ctdbase.org/).
Relevant pungent sensory taste receptors, including TRPs and ORs The assay data for pungent compounds in PungentDB were sourced
families, and their IC50 and EC50 values were derived from literatures from ChEMBL and peer-reviewed scientific publications. Data extraction
and ChEMBL (Gaulton et al., 2012) (https://www.ebi.ac.uk/chembl/). involved a meticulous manual curation process to ensure accuracy and
These sources span five major publishers: Elsevier ScienceDirect relevance. ChEMBL, a comprehensive bioactivity database, provided
(https://www.sciencedirect.com/), Nature (https://www.nature. detailed bioassay information, including IC50 and EC50 values, target

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names, assay organisms, and activity types (Gaulton et al., 2012). visualizations for quick access to desired information. PungentDB uses
Additionally, relevant data were manually extracted from various peer- Cytoscape.js (v3.5.0, http://js.cytoscape.org/) to construct dynamic,
reviewed journals, capturing detailed bioactivity profiles of pungent browser-based networks that display multilevel interactions among
compounds. pungent TCMs, pungent compounds, and their targets (TRPs and ORs).
Each compound’s assay data were annotated with its name, Pub- Additionally, D3.js (https://d3js.org/) is utilized to visualize the
Chem Identifier (PID), structure (2D and 3D), IC50 value, EC50 value, network of pungent flavor compound-pharmacological actions, illus-
assay organism, and target names. The data were organized to link each trating multiple pharmacological effects exerted by each pungent
compound with its respective assays and targets, creating a compre- compound.
hensive list that includes the PID, substance name, target name, and For 3D structure visualization, LiteMol Viewer (Sehnal et al., 2017)
assay references. This process ensured that each entry was cross- (https://litemol.org) provides efficient visualization of chemical struc-
referenced with relevant literature sources and ChEMBL entries, tures, including biological context annotations from resources such as
enabling users to access detailed bioactivity records and additional re- UniProt. 3Dmol.js (Rego & Koes, 2015) (http://3dmol.csb.pitt.edu) of-
sources through the ‘Target Report Card’ and ‘Document Report Card’ in fers a high-performance interactive viewer for 3D molecular data, while
ChEMBL. NGL Viewer (Rose & Hildebrand, 2015) (http://proteinformatics.ch
arite.de/) uses WebGL to display molecules with various representa-
2.5. Molecular structure search tions. For 2D/3D structure display, users can interactively sketch in a
structure or substructure of interest using JSME Molecule Editor (Bien-
To facilitate the identification of pungent compounds, we imple- fait & Ertl, 2013) (http://peter-ertl.com/jsme/), and perform structural
mented a 2D structure similarity search feature within PungentDB. This similarity searches with RDKit (Bento et al., 2020), using the Tanimoto
feature allows users to retrieve compounds similar to a given chemical coefficient to assess the degree of similarity between the query molecule
structure query. The JSME Molecule Editor (Bienfait & Ertl, 2013) (http and database entries.
://peter-ertl.com/jsme/), an advanced tool for drawing chemical The D3.js JavaScript library is also used to implement organ location
structures, was integrated into the database as an optional built-in edi- maps and system distributions for pungent compounds’ targets based on
tor. This interface enables users to sketch structures or substructures of gene phenotype, aiding in the visualization of how these compounds
interest for their queries. interact with different parts of the human body.
For the actual similarity search, we utilized RDKit (Bento et al.,
2020). The 2D structures of small molecules were converted into SMILES 2.8. Visualization and interaction of pungent compounds with TRP and
format, facilitating efficient chemical structure similarity searches. The OR receptor structures
similarity between the query molecule and database entries is measured
using the Tanimoto coefficient, a standard 2D similarity metric. The To support the visualization and interactive exploration of TRP and
Tanimoto coefficient ranges from 0 to 1, with 1 indicating maximum olfactory receptor (OR) family macromolecules, we implemented
similarity. The results of the similarity search depend on the user’s several advanced tools within PungentDB. We created a custom data-
specified threshold settings. base consisting of protein sequences from 71 TRP receptors and 33 ORs
(both human and other species). The sequences are searchable using
2.6. Advanced search PungentDB’s local BLAST service, powered by the NCBI BLAST package/
Webblast and ViroBLAST (Chen, Li, Hou, Zhang, & Qiao, 2021; Johnson
To enable refined searches, the ‘Advanced Search’ feature in Pun- et al., 2008). This service facilitates the search for sequence similarities
gentDB was developed to allow users to query the database based on a across multiple databases, aiding in the study of TCM genomics (Deng,
wide array of molecular properties and identifiers. The design process Nickle, Learn, Maust, & Mullins, 2007).
involved integrating multiple search parameters to facilitate complex We integrated high-performance interactive viewers such as 3Dmol.
queries. Key molecular properties included in the search criteria are js, LiteMol Viewer, and NGL. These tools enable users to view, manip-
molecular weight, hydrogen bond donors and acceptors, rotatable ulate, and analyze 3D molecular data directly within their web browsers.
bonds, LogP, water solubility, and XLogP3 (or XLogP3-AA). Addition- 3Dmol.js provides a full-featured API and a straightforward interface for
ally, the search functionality supports queries by various compound embedding molecular data (Rego & Koes, 2015). LiteMol Viewer offers
identifiers such as PungentDB ID, PubChem CID, SMILES, FEMA num- rapid 3D visualization and uses annotations from UniProt to map protein
ber, InChI, InChI Key, CAS registry number, IUPAC systematic name, functions and regulatory activities (Sehnal et al., 2017). NGL Viewer
and molecular formula. displays large molecular complexes using WebGL, supporting various
To construct this feature, the database schema was enhanced to representations like cartoon, spacefill, and licorice (Rose & Hildebrand,
index these properties efficiently. An intuitive user interface was 2015).
designed to allow users to specify search criteria easily, either by
entering textual data or using a chemical structure drawing tool. The 2.9. Webserver tech stack
backend processing uses advanced algorithms to match the search
criteria with the database entries, ensuring quick and accurate retrieval PungentDB has been designed as a Relational Database using SQLite
of relevant compounds. Moreover, the system supports the inclusion of (https://www.sqlite.org/index.html). The webserver has been built
receptor-specific searches, allowing users to filter compounds based on using the Python web development framework, flask (http://flask.
their interaction with specific pungent taste receptors (TRP family) and pocoo.org/). Flask has no database abstraction layer, form validation,
olfactory receptors (ORs). This was achieved by linking the molecular or any other components where pre-existing third-party libraries pro-
properties of compounds with known receptor interactions, compiled vide common functions (https://en.wikipedia.org/wiki/Flask(web_-
from extensive literature and database sources. framework)). However, Flask supports extensions that can add
application features as if they were implemented in Flask itself. More
2.7. Visualization tools/features specifically, this is done by means of a Flask micro-framework over a
Nginx reverse server and a Gunicorn server executing Flask (Mufid,
To facilitate the exploration of pungent flavor molecules and their Basofi, Al Rasyid, & Rochimansyah, 2019). The front-end has been built
interactions, PungentDB employs a suite of advanced visualization tools using HTML5, CSS and JavaScript. The jQuery, Bootstrap, D3.js and
and features. These tools enable users to search for structurally similar cytoscape.js were used to add to the functionality of PungentDB. Ningx
molecules within the database and provide interactive data (http://nginx.org/en/) is an HTTP and reverse proxy server, a mail

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proxy server, and a generic TCP/UDP proxy server. The basic HTTP 3.2. Compounds data acquisition results
server features are serving static and index files, accelerating reverse
proxying with caching and loading balancing and fault tolerance. We collected and identified more than 20,000 compounds from 231
Moreover, Ningx can limit the number of simultaneous connections or pungent TCMs of medicine food homology. The collected data include
requests coming from one address. The site is best viewed in latest 2D/3D chemical structures, physicochemical properties, and identifiers
versions of Firefox, Google Chrome, Opera, Internet Explorer, Safari and for each pungent compound, such as PubChem CID, FEMA number,
Microsoft Edge. InChI, InChI Key, CAS registry number, molecular weight, logP, and
XlogP (XlogP-AA). The water solubility for some pungent compounds
3. Results was computed using the ALOGPS 2.1 program. The targets information
of 205 pungent compounds was extracted from publications and several
3.1. Database overview disease-gene databases.

The database offers interactive tools for browsing, searching, and 3.3. Identification of pungent flavor compounds
visualizing pungent flavor compounds and their associated receptors,
facilitating research on the chemical and sensory attributes of these We identified a comprehensive list of pungent compounds present in
compounds. Traditional Chinese Medicines (TCMs) by integrating established data-
PungentDB combines different dimensions of pungent flavor bases and extensive literature. This approach provided a thorough un-
constituting the ‘Protein/DNA Blasting Layer’, ‘Entity Layer’, and derstanding of these compounds and their sensory impacts. The
‘Visualization Layer’ (Fig. 1). The former incorporates facets of in- identified pungent compounds were found to activate specific transient
gredients which are entities from plant sources often used in TCMs, receptor potential (TRP) cation channels and olfactory receptors. This
whereas the latter represents molecules responsible for pungent flavor finding highlights the interaction of flavor molecules with biological
sensation associated receptors and their descriptors. By bringing rele- sensory mechanisms, a phenomenon historically recognized by ancient
vant information from pungent TCMs of medicine food homology, Chinese medical practitioners through long-term clinical practice.
PungentDB provides a comprehensive dataset backed by a user-friendly PungentDB (http://www.pungentdb.org.cn/home/) compiles data
interface, creative visualizations, and pungent flavor compounds sour- on over 205 pungent compounds from 231 TCMs, including molecular
ces for exploring features that contribute to the potential medical effi- properties, biological targets, pharmacological actions, and compound
cacy. Thus, PungentDB paves the way for an improved understanding of identifiers. The dataset for further analysis includes identified pungent
pungent flavor perception from pungent TCMs of medicine food ho- flavor compounds from FlavorDB, FooDB, Flavornet, FEMA, and the
mology arising out of complex interplay of pungent flavor compounds pharmacopoeia of the People’s Republic of China. The GB2760–2014
with biological systems and medical applications in pungent TCMs of national standard of spice served as a reference for identifying these
medicine food homology. pungent flavor compounds. So the spices flavor molecules were
considered as the basis of pungent flavor. These compounds were
consistently found to activate specific TRP cation channels and olfactory
receptors, thus validating their roles as the fundamental elements of

Fig. 1. PungentDB is a seamless amalgamation of ‘Protein/DNA Blasting Layer’, ‘Entity Layer’, and ‘Visualization Layer’. The resource provides a comprehensive
dataset along with a userfriendly interface, visualization and interlinked search engines for exploring the pungent flavor universe from pungent TCMs of medicine
food homology.

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pungent flavor. The implementation of the ‘Advanced Search’ feature in PungentDB

significantly enhances the database’s functionality. Advanced Search
3.4. Organ target location mapping provides an option for refined search by querying PungentDB data on
the basis of a variety of molecular properties (Mol. Weight, Hydrogen
Using Gene ORGANizer (Gokhman et al., 2017), we mapped the Bond Donor, Hydrogen Bond Acceptor, Rotatable Bonds, LogP, Water
targets of pungent TCMs’ pungent flavor compounds into an organ solubility, XLogP3 or XLogP3-AA), compound identifiers (PungentDB
location map/human system level. The correlation of genes associated ID, PubChem CID, Smiles, FEMA number, InChI, InChI Key, CAS registry
with organs and human systems was analyzed based on phenotype. This number, IUPAC systematic name, Mol. Formula), associated pungent
mapping provides strong evidence for elucidating the connotation of taste receptors (TRPs family), and olfactory receptors (ORs), etc. Users
meridian tropism at the target level. can also perform detailed searches using a combination of molecular
The utilization of Gene ORGANizer allowed for the detailed mapping properties and identifiers, facilitating the identification of compounds
of pungent TCM compounds’ targets into specific organs and human that meet specific research criteria. For example, users can filter com-
systems. This mapping revealed significant correlations between genes pounds by molecular weight ranges, hydrogen bonding characteristics,
associated with particular organs and their phenotypic expressions, or specific identifiers like PubChem CID and SMILES (see Possible usage
providing strong evidence for the concept of meridian tropism at the 1 and Fig. S1 A (III)). This advanced querying capability allows re-
target level. searchers to pinpoint compounds with desired properties quickly. For
The results demonstrated that certain organs and tissues (e.g., brain, numeric fields either a range or discrete values can be provided as a
blood, and skin) are more frequently represented in the expression query and subsequently obtain details of the pungent flavor molecules.
datasets, while many other body parts are underrepresented or absent. Furthermore, the ability to search based on receptor interactions
This highlights the need for comprehensive datasets to achieve a holistic enables targeted studies on pungent taste and olfactory receptors. This
view of TCM interactions with the human body. By mapping these tar- feature provides comprehensive data on the association between com-
gets, we were able to provide a more nuanced understanding of how pounds and their receptor targets, aiding in the exploration of structure-
pungent compounds interact with various body systems, which is activity relationships. The search results are presented in a user-friendly
essential for elucidating the therapeutic mechanisms of TCM. format, with a comprehensive table listing all matching PungentDB
Overall, this research significantly contributes to the understanding compounds and their properties. Users can easily browse and analyze
of organ-specific targeting and the practical application of TCM merid- the detailed information on each compound, including its molecular
ian theory in modern medical practice. It lays the groundwork for future structure, physical properties, and bioactivity data.
studies aimed at exploring the intricate relationships between TCM Overall, the ‘Advanced Search’ functionality in PungentDB offers a
theories and contemporary biological evidence. powerful tool for researchers, enhancing the ability to perform complex
queries and retrieve detailed information on pungent flavor compounds
3.5. Assay results efficiently. This feature supports a wide range of research applications,
from basic science to applied studies in flavor chemistry and traditional
The activity data for the pungent compounds, including IC50 and medicine.
EC50 values, were extracted from ChEMBL and 4329 full-text peer-
reviewed publications. The data includes structures, annotations, assay 3.8. Visualization tools/features on pungent flavor compounds and their
organism, target names, and activity types. The assay list, with links to profiles
relevant pungent compounds and their targets, is accessible via Pun-
gentDB. The list of assays for pungent compounds is displayed with the PungentDB provides a range of visualization tools, including 2D/3D
links to the PID, Name (substances that have been tested for their chemical structure displays generated using LiteMol Viewer, Cytoscape.
bioactivity), Target Name (the proteins or systems being monitored by js, D3.js, 3Dmol.js, and NGL. These tools offer interactive ways to
an assay), Assay References (literature source for the assay) (Supple- explore the pungent compounds from TCMs, visualize their networks,
mentary Fig. S1). The ‘Target Name’ and ‘Assay References’ in this assay biological activities, organ location map and system distribution feature
list link to the ‘Target Report Card’ and ‘Document Report Card’ in and inspect features of associated receptors.
ChEMBL, providing users with comprehensive details and facilitating The visualization tools and features in PungentDB provide users with
deeper exploration of pungent compounds and their bioactivities. a comprehensive and interactive platform to explore the pungent flavor
universe from TCMs. The Cytoscape.js-based network module allows for
3.6. Molecular structure search the exploration of multilevel interactions among pungent TCMs, pun-
gent compounds, and their targets. Users can click on entities to view
The implementation of the 2D structure similarity search in Pun- their associations with TCMs and related pungent flavor compounds,
gentDB provides users with a powerful tool to identify compounds with facilitating an in-depth understanding of these relationships (Fig. 2A).
similar chemical structures. Users can easily sketch a structure or sub- The D3.js visualizations illustrate the multiple pharmacological effects
structure of interest using the JSME Molecule Editor. The RDKit- exerted by each pungent compound, providing insights into their diverse
powered search then converts these structures into SMILES format and biological activities (Fig. 2B).
calculates the Tanimoto coefficient to determine the similarity between For 3D structure visualization, LiteMol Viewer enables users to
the query molecule and database entries. This process allows for precise efficiently view and manipulate the 3D structures of pungent com-
identification of structurally similar pungent compounds, aiding in the pounds, including rotating the structures 360 degrees and capturing
exploration and analysis of the molecular landscape of pungent TCMs. screenshots. It also provides biological context annotations from Uni-
The feature supports a wide range of research applications, from basic Prot, enhancing the user’s understanding of the molecular basis of
research to more advanced pharmacological studies. pungency (Fig. 2C).
To make it easier to determine pungent compounds act on human
3.7. Advanced search body parts, organ location map/system distribution for pungent com-
pounds’ targets based on gene phenotype was implemented with the D3.
The advanced search feature allows for refined queries based on js JavaScript library (https://d3js.org) (Fig. 2D).
molecular properties, compound identifiers, and associated receptors. Overall, these visualization tools and features enhance the usability
Users can browse a table with all PungentDB compounds and their of PungentDB, enabling researchers to conduct detailed and interactive
properties, providing detailed information on pungent flavor molecules. explorations of pungent flavor compounds from TCMs, thereby

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Fig. 2. Visualization tools/features in PungentDB.

supporting their scientific inquiries and advancing the field of flavor pungent tab.
chemistry. 3Dmol.js is an high-performance interactive viewer for 3D molecular
data that requires no plugins to work in web browsers and it provides a
full featured API for developers as well as a straightforward declarative
3.9. Visualization and interactive analysis of TRP and OR receptor
interface that lets users easily share and embed molecular data in
structures
websites (Rego & Koes, 2015). This biomacromolecular consists of four
chains, which are shown in different representation and color modes
The entity details of particular human associated pungent taste re-
(Fig. 3A).
ceptors (TRPs family), olfactory receptors allows users to interactively
The web page enables visualization and manipulation with the 3D
inspect the features of receptors listed in the Receptors associated to

Fig. 3. Gallery of 3D molecular structures of TRPs family proteins visualizations showing various representations with three different molecular viewers. (A) The
structure of a TRPs ion channel (PDB ID: 6BQV). This molecule consists of four chains with 3Dmol.js, which are shown in different representation and color modes.
Chain A is presented as cartoon mode colored by spectrum; Chain B is presented as sphere mode colored by spectrum; Chain C is presented as cross mode colored by
yellow; Chain D is presented as line mode colored by green. (B) and (D) are generated biomacromolecular structure of TRPA1 (PDB ID: 3J9P) with NGL from different
perspectives. (C) The structure of a TRPs ion channel (PDB ID: 4DX2) is implemented with the molecular viewer LiteMol. (For interpretation of the references to color
in this figure legend, the reader is referred to the web version of this article.)

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Z. Chen et al. Food Chemistry: X 23 (2024) 101742

structure using LiteMol Viewer (Sehnal et al., 2017), which is powerful herbs as pungent flavor TCMs. The pungent flavor in TCM term was the
and blazing-fast tool for handling 3D macromolecular data in the objective expression of sensory taste (taste, olfaction, etc.) by Chinese
browser (https://litemol.org). LiteMol uses annotations from UniProt (e. ancient physicians. However, they didn’t know material basis and the
g. a function of protein as well as activity regulation) and maps them on pungent flavor’s molecular mechanism of pungent flavor TCMs (Z.
the protein annotations section (Fig. 3C). Chen, Cao, Zhang, & Qiao, 2019). PungentDB was created with the aim
Moreover, there were another optional Viewers NGL (http://pro of integrating multidimensional aspects of pungent flavor molecules and
teinformatics.charite.de/), 3Dmol (http://3dmol.csb.pitt.edu). NGL representing their molecular features, flavor profiles and details of
Viewer is a web application for molecular visualization. WebGL is related pungent flavor TCMs.
employed to display molecules like proteins and DNA/RNA with a va- To summarize, taste recognition is complexity and import for pun-
riety of representations. NGL can interactively display large molecular gent TCMs of medicine food homology sensing and odors. The pungent
complexes and is also unaffected by the retirement of third-party plug- recognition is possibly plays additional physiological roles and medical
ins like Flash and Java Applets (Rose & Hildebrand, 2015). It supports value. Characterizing molecules as pungent and assigning them to a
common structural fileformats (e.g. PDB, mmCIF) and a variety of mo- specific receptor represents a crucial step towards prediction and
lecular representations (e.g. ‘cartoon, spacefill, licorice’) (Fig. 3B, D). rational modulation of spiciness. Creating a database of known pungent
Users can visualize the 3D structures of these receptors, which are compounds, which, in addition to associations between pungent mole-
essential for understanding the molecular basis of their interactions with cules and their receptors, also contains the chemicophysical properties
pungent flavor compounds. The interface supports various representa- of the ligands and organ location/system distribution data relevant for
tions, providing a detailed view of the molecular architecture. pungent molecules’ targets, is an essential step to discover the potential
The integration of LiteMol Viewer allows for efficient manipulation efficacy in this direction.
of 3D structures, facilitating detailed analysis of ligand-receptor in-
teractions. Users can rotate structures, zoom in on specific areas, and 4.1. Integration of TCM and flavor chemistry
capture screenshots for further study. NGL Viewer supports interactive
display of large molecular complexes, unaffected by the limitations of Our database not only aggregates chemical data but also aligns it
traditional plug-ins, thus enhancing the user experience (Fig. 3B, D). with TCM principles, offering a unique synthesis not extensively covered
PungentDB’s local BLAST service, TCM-Blat (Chen et al., 2021), in current literature. Previous studies, such as those by Gong et al.(Gong
powered by the NCBI BLAST package/Webblast and ViroBLAST, allows et al., 2020) and Zhang et al. (K. Zhang et al., 2023), have separately
for searching TRP and olfactory receptor protein sequences. This service discussed the roles of TCM in food science and the chemical analysis of
supports TCM genomics research by providing sequence similarity flavors. PungentDB bridges these aspects by providing a platform that
searches against multiple databases. correlates pungent compounds with their historical and therapeutic
Overall, the visualization tools in PungentDB provide a compre- contexts in TCM, offering a holistic view that was previously
hensive and interactive platform for exploring the structural features of fragmented.
TRP and OR family receptors, significantly contributing to the under- The methodologies employed for data collection and analysis in
standing of their roles in sensory perception and pharmacological PungentDB improve upon traditional techniques by incorporating
effects. advanced computational tools that enhance the accuracy and granu-
larity of data on pungent flavors. Our database utilizes state-of-the-art
4. Discussion bioinformatics tools to systematically categorize and analyze pungent
compounds, thus providing more detailed insights into their potential
The food industry faces ongoing challenges in balancing flavor applications.
enhancement with nutritional integrity. Processing techniques often The comprehensive data compilation in PungentDB, particularly
modify the flavor profile of food, sometimes at the expense of nutritional regarding the interaction of pungent compounds with TRP and OR re-
value. Additionally, scaling up biotechnological methods like microbial ceptors as observed in our results, paves the way for future experimental
fermentation and enzymatic modification presents challenges in con- and clinical research. By providing a detailed biochemical context, our
sistency and acceptability (Nielsen, Tillegreen, & Petranovic, 2022). Yet, database supports the development of new hypotheses regarding the
these methods offer potential for developing novel flavor compounds sensory and therapeutic roles of pungent compounds. This aspect is
that enhance health benefits without compromising taste or safety (Hu slightly touched upon in existing databases but is extensively detailed in
et al., 2023; Yamamoto & Inui-Yamamoto, 2023). PungentDB, offering a robust foundation for advancing research in food
The simple perception of pungent TCMs of medicine food homology chemistry and pharmacology.
arises from the interaction of flavor molecules with the biological ma-
chinery by ancient medical practitioners’ human sensory system. Fla- 4.2. Comparison of database content and methodology
vors derived from TCMs have shaped the pungent flavor throughout
ancient long-term clinical practice in China. Our methods of data collection, particularly the integration of 2D/3D
Pungent flavor is an expression of pungent olfactory and gustatory/ chemical structures, physicochemical properties, and extensive meta-
taste sensations experienced through a multitude of chemical processes data for each compound, follow rigorous standards that surpass many
triggered by pungent molecules. Pungent compounds widely exist in existing databases. For instance, while databases such as PubChem (Kim
pungent Traditional Chinese Medicines (TCMs) of medicine food ho- et al., 2023) and FooDB (http://foodb.ca) provide similar types of data,
mology. Pungent flavor in TCM term (sour, salty, sweet, bitter and PungentDB incorporates specific TCM-related attributes that are often
pungent) serve specific functions in identifying materia medica com- overlooked, such as associations with pungent flavor and therapeutic
pounds found in long term clinical practice of traditional Chinese roles as highlighted by sources like the pharmacopoeia of the People’s
medicine (TCM), and are recognized by some specific pungent taste Republic of China and TCMID (Huang et al., 2018).
receptors (transient receptor potential cation channel subfamily, TRPs) The use of ALOGPS 2.1 (Tetko & Tanchuk, 2002) for computing
or olfactory receptors (ORs) in the oral cavity and nasal cavity. Inter- water solubility and gathering target information from multiple disease-
estingly, pungent flavor in TCMs indicate not only pungent taste but also gene databases demonstrates an advanced approach not typically
pungent odor. Due to the limitation of biomedical level in ancient times, employed in traditional databases. This methodological sophistication
ancient Chinese physicians could recognize and discover medicinal allows for a more accurate prediction of compound behavior in bio-
herbs through human basic perception (taste, smell, touch, etc.) (An logical systems, which is crucial for the practical application of these
et al., 2020). They defined pungent taste, spicy smell or aromatic odor compounds in food science and medicine.

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Z. Chen et al. Food Chemistry: X 23 (2024) 101742

By collating an extensive range of identifiers and properties (e.g., compounds, enhancing the database’s utility for pharmacological and
PubChem CID, FEMA number, molecular weight, logP), PungentDB flavor science research.
provides a more comprehensive tool for researchers. The database’s Unlike conventional databases that may offer limited search func-
focus on pungent TCMs fills a significant gap in existing literature by tionalities, PungentDB integrates the JSME Molecule Editor, enabling
linking these compounds’ sensory and chemical properties to their his- users to intuitively sketch structures or substructures (Bienfait & Ertl,
torical and medicinal use in TCM, which is rarely addressed together in 2013). This feature reflects advancements discussed by Zdrazil et al.
other databases. (Zdrazil et al., 2024) in ChEMBL, which similarly aims to provide
comprehensive access to chemical data for broader scientific
4.3. Identification techniques and database integration applications.
Building on this foundation, future enhancements to PungentDB will
Our methodology for identifying pungent flavor compounds through include the integration of 3D structure search capabilities and improved
the integration of established databases (e.g., FlavorDB, FooDB, Fla- algorithms for molecular similarity to accommodate more complex
vornet, FEMA) and literature enhances the depth of our analysis. This queries and diverse research needs. These developments are anticipated
approach aligns with the practices discussed in the pharmacopoeia of to align with emerging trends in database utility and accessibility,
the People’s Republic of China and is further supported by our use of the driving forward the fields of flavor chemistry and pharmacology.
GB2760–2014 national standard.
The compounds we identified were consistently found to activate 4.7. Integration of advanced search capabilities
specific transient receptor potential (TRP) cation channels and olfactory
receptors, validating their roles in pungent flavor perception. This PungentDB’s advanced search feature offers significant advance-
finding is critical as it underscores the biochemical basis of sensory ments over traditional database searches by allowing highly refined
perceptions discussed in studies like those by Chen et al. (Chen et al., queries based on a wide range of molecular properties and identifiers
2019), which explore the molecular mechanisms underlying the sensory such as molecular weight, LogP, and receptor associations. This feature
properties of pungent compounds. is crucial for researchers focusing on the specificity of interactions be-
tween pungent compounds and sensory receptors, which is less
4.4. Organ-specific target mapping emphasized in databases like ChEMBL or PubChem. By integrating these
functionalities, PungentDB provides a tailored tool for exploring pun-
Our approach with Gene ORGANizer provided a novel insight into gent compounds in Traditional Chinese Medicines (TCMs), enhancing
the organ-specific effects of pungent compounds, which aligns with and the research efficiency in pharmacological and flavor chemistry studies.
expands upon foundational studies in pharmacology and TCM, such as Unlike general chemical databases, PungentDB is specifically
those by Gokhman et al. (Gokhman et al., 2017) who developed the designed to address the unique aspects of pungent compounds in TCMs.
Gene ORGANizer tool. Our findings demonstrate a detailed correlation For instance, while tools like the RDKit and ChemSpider (Pence &
between gene expressions and organ-specific effects, supporting the Williams, 2010) offer chemical search capabilities, they do not provide
theory of meridian tropism in TCM at a molecular level. integration with TCM-specific receptor data. PungentDB fills this gap by
By analyzing the correlations between genes and phenotypic ex- combining chemical searches with detailed receptor information,
pressions associated with different organs, our study provides empirical particularly the TRP and OR families relevant to pungency perception.
evidence supporting traditional claims of TCM. These insights have This integration is supported by extensive literature on receptor-ligand
important implications for the development of targeted therapeutic interactions that influence the sensory perception of pungency, adding
strategies using TCM principles. Future research should focus on a layer of specificity that is crucial for the application of TCMs in both
expanding these organ-target mappings with more comprehensive medicinal and culinary contexts.
genomic data. Several studies underscore the importance of integrating chemical
properties with receptor data to enhance the understanding of flavor and
4.5. Bioactivity and assay data pharmacological profiles. For instance, research by Humbeck & Koch
(Humbeck & Koch, 2017) on bioactivity databases highlights the need
The assay results from ChEMBL and various peer-reviewed publica- for specialized tools that cater to specific scientific inquiries such as
tions provided detailed bioactivity data, including IC50 and EC50 values those provided by PungentDB. Moreover, the work by Gong et al. (Gong
for pungent compounds. This comprehensive collection mirrors the et al., 2020) on the sensory and health impacts of bioactive compounds
approach seen in large-scale bioactivity databases and studies such as aligns with our approach to enhance the usability of data for TCM
those by Gaulton et al. (Gaulton et al., 2012) and is in line with the applications.
methodologies employed in high-throughput screening in pharmaceu-
tical research. Our integration of this data into PungentDB enhances its 4.8. Visualization tools in PungentDB
utility for exploring pungent compounds’ pharmacological potentials.
Our approach to making these assay results accessible through PungentDB utilizes a variety of advanced visualization tools such as
PungentDB with links to PID, substance names, target names, and assay LiteMol Viewer, Cytoscape.js, D3.js, 3Dmol.js, and NGL. These tools
references allows users to explore the bioactivities of compounds in a facilitate an interactive exploration of the chemical structures and bio-
user-friendly manner. This method of data presentation and integration logical interactions of pungent compounds derived from TCMs. The
supports the emerging trend of combining cheminformatics tools with detailed visualization capabilities enable researchers to examine the
traditional databases to improve data accessibility and utility, as high- molecular interactions and network dynamics of these compounds,
lighted in the work by Johnson et al. (Johnson et al., 2008). providing a deeper understanding of their pharmacological and sensory
properties.
4.6. 2D/3D structure similarity search The application of visualization tools in PungentDB mirrors ad-
vancements in computational chemistry and bioinformatics, where such
Our implementation of the 2D structure similarity search in Pun- technologies have been pivotal. For instance, studies like those by
gentDB leverages the RDKit toolkit to compute Tanimoto coefficients for Sehnal et al. (Sehnal et al., 2017) and Rego et al. (Rego & Koes, 2015)
molecular similarity assessments, aligning with the practices described have highlighted the utility of LiteMol Viewer and 3Dmol.js in
in contemporary cheminformatics research (Bento et al., 2020).This enhancing the accessibility and understanding of complex molecular
approach allows for robust identification of structurally similar pungent data. Similarly, the network visualization capabilities of Cytoscape.js

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Z. Chen et al. Food Chemistry: X 23 (2024) 101742

align with the findings of Shannon et al. (Shannon et al., 2003), who species, and thus contributing to elucidating evolutionary aspects of
demonstrated its effectiveness in elucidating biological pathways and pungent sensory taste and olfactory perception. By leveraging the vast
protein interactions. potential of food-medicine homology and advanced analytical tools, the
The incorporation of these visualization tools in PungentDB not only food science community can innovate new product formulations that
corroborates the methodologies employed in existing research but also support both health and pleasure. This endeavor will require multidis-
extends their application to the study of pungent flavors in TCMs. By ciplinary collaborations spanning TCM, modern science, culinary arts,
providing a platform for detailed molecular and network analysis, and technology to fully realize the potential of flavor chemistry in
PungentDB enhances the existing knowledge base and supports the enhancing human health and well-being.
discovery of novel insights into the sensory and biological mechanisms As we proceed, it is crucial that the research community continues to
of pungent compounds. engage with these advanced methodologies to refine our understanding
of flavor chemistry and its impact on food quality and human health.
4.9. Enhancing flavor research with advanced visualization tools The insights garnered from combining traditional knowledge with
modern science will not only enrich our dietary patterns but also
The integration of advanced visualization tools such as 3Dmol.js and enhance the therapeutic potential of our meals, adhering to the ethos of
LiteMol Viewer in PungentDB significantly enhances our understanding medicine-food homology that has been recognized for centuries in TCM.
of the molecular mechanisms underlying pungent flavors. These tools The ongoing research efforts documented in this special issue are testi-
enable intricate examinations of the TRP and OR receptors, which play a mony to the dynamic and evolving field of flavor science, which remains
critical role in sensory perception by interacting with pungent com- at the forefront of scientific and culinary innovation.
pounds (Rego & Koes, 2015; Sehnal et al., 2017). By providing inter-
active 3D visualizations, researchers can better understand the 5. Conclusion
structural basis of receptor-ligand interactions, which is crucial for
designing compounds with optimized sensory profiles. PungentDB emerges as a pioneering resource, elucidating the intri-
Furthermore, the use of these tools allows for a detailed analysis of cate relationships between more than 205 pungent flavor compounds
the interactions between pungent molecules and their target receptors, extracted from 231 traditional Chinese medicines (TCMs) and their in-
offering insights into the diverse pharmacological effects of these com- teractions with taste and olfactory receptors. This database not only
pounds. The interactive tools and visualization capabilities of Pun- sheds light on the chemical essence of pungency but also highlights the
gentDB has set a new benchmark in the exploration of pungent flavors. potential of these compounds to significantly improve food quality,
Our approach enhances user interaction and data accessibility. How- safety, and sensory experiences. It provides a comprehensive platform
ever, PungentDB introduces specific enhancements in the visualization that combines detailed compound information, including bioactive
of flavor compound interactions with biological receptors, providing a profiles, pharmacological actions, and molecular structures, thereby
more intuitive understanding of chemical-sensory relationships. This enabling robust scientific inquiry and fostering innovation in the realm
advancement over existing databases is crucial for both academic re- of food flavor chemistry.
searchers and industry practitioners seeking deeper insights into flavor The fusion of traditional insights with modern scientific practices
dynamics. through PungentDB exemplifies the significance of adopting a multi-
Looking forward, the integration of TCM with modern flavor science disciplinary approach in food science research. By offering sophisticated
and food technology suggests a promising avenue for the development of visualization tools and extensive datasets, PungentDB enhances our
next-generation functional foods. By leveraging the vast potential of capacity to navigate the molecular landscape of flavors. This advance-
food-medicine homology and advanced analytical tools, the food science ment opens new avenues for the development and refinement of food
community can innovate new product formulations that support both flavors, leveraging both natural and biotechnological methodologies.
health and pleasure. This endeavor will require multidisciplinary col- The database stands at the forefront, propelling the food science field
laborations spanning TCM, modern science, culinary arts, and technol- towards groundbreaking discoveries in flavor enhancement and sensory
ogy to fully realize the potential of flavor chemistry in enhancing human analysis, underscoring the imperative of interdisciplinary collaboration
health and well-being. to tackle the complexities of flavor chemistry.
Despite our best efforts, PungentDB is not an exhaustive repository of Looking ahead, the anticipated expansion of PungentDB to include a
all pungent molecules and ingredients from pungent TCMs of medicine broader spectrum of pungent compounds from varied sources is set to
food homology. Our data on pungent molecules of an ingredient is widen the research domain in flavor chemistry further. Future iterations
limited by the availability of information about them from literature aim to integrate cutting-edge ‘omics’ analyses and sensory evaluation
survey and relevant databases. Similarly, the pungent compounds rep- studies, deepening our comprehension of flavor’s molecular foundations
resented in the database are not exhaustive in themselves as their choice and their practical implications in food science and technology. In
is limited by another pungent TCMs’ compounds from magnumopus essence, PungentDB represents a critical resource for both researchers
named Chinese Materia Medica. and practitioners, facilitating significant advancements in flavor science
In future, we intend to increase the coverage of pungent TCMs of that promise to have a lasting impact on both traditional and contem-
medicine food homology and extract the pungent compounds from these porary culinary practices.
sources. Our endeavor is to integrate aspects of pungent flavor profiles
with those of entities and molecules that has hitherto been unexplored Availability
based on TRPs and ORs family receptors from newly increased pungent
TCMs’ chemical constituents. Fundamental questions as well as poten- PungentDB is available at http://www.pungentdb.org.cn/home.
tial therapeutic applications of the modulation of pungent associated
sensory taste and olfactory receptors continue to motivate further Authors’ contributions
development of the PungentDB database. The number of TRPs and ORs
family receptors in a given species may relate to the receptors’ receptive ZC, YZ and YQ conceived the study. ZC drafted the manuscript. ZC,
range. The ability to understand and predict these effects relies on the YC, XL, and JL collected the data. ZC, XS, BX and ZW analyzed the data.
knowledge of what is ‘pungent’ (sensory taste and odor) to different ZC YC YZ and YQ wrote the codes, evaluated the software, and provided
species, and on the ability to cluster ligands based on their chemical scientific and conceptual interpretations.
similarity from more pungent TCMs of medicine food homology.
PungentDB will be extended in the future to include additional

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Z. Chen et al. Food Chemistry: X 23 (2024) 101742

Funding org/10.1016/j.fochx.2024.101742.

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