Food Chemistry 418 (2023) 135992

Contents lists available at ScienceDirect

Food Chemistry
journal homepage: www.elsevier.com/locate/foodchem

AODB: A comprehensive database for antioxidants including small

molecules, peptides and proteins
Weiting Deng 1, Yihao Chen 1, Xinning Sun, Ling Wang *
Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, Joint International Research Laboratory of Synthetic Biology and Medicine, Ministry of
Education, Guangdong Provincial Engineering and Technology Research Center of Biopharmaceuticals, School of Biology and Biological Engineering, South China
University of Technology, Guangzhou 510006, China

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

Keywords: Antioxidants are widely used in the fields of food, medicine, nutraceuticals, and cosmetics. Given their important
Antioxidant roles in promoting and maintaining human health, a large number of antioxidants have been reported. Some
Online database antioxidant-related databases have been developed; however, the annotation of antioxidants and related infor­
Peptide
mation stored in existing databases is incomplete and requires more efficient retrieval methods. This study aimed
Protein
to develop a manually curated comprehensive antioxidant database (AODB). Currently, it stores 56,666 small
molecules tested for antioxidant activity, 1480 antioxidant peptides, and 998 antioxidant proteins, including
their structures, names, antioxidant assay records, computable physicochemical and ADMET properties, and
sources. AODB supports text search and mining, 2D and 3D chemical structure search, and BLAST-based protein
sequence search, enabling users to retrieve antioxidant data quickly and easily. AODB, as a one-stop antioxidant
database, can facilitate the exploration of antioxidants and potential applications. AODB is publicly available and
updated annually at https://aodb.idruglab.cn/.

1. Introduction which in turn can lead to oxidative stress. Progressively increasing

studies suggest that oxidative stress increases the risk of developing
Reactive oxygen species (ROS) are naturally produced in the meta­ cancer, diabetes, atherosclerosis, arthritis, and neurodegenerative dis­
bolic process of organisms through the oxidative reaction of respiration, eases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s
including hydrogen peroxide (H2O2), superoxide (O•– 2 ), singlet oxygen disease, and amyotrophic lateral sclerosis (Hwang & Bowen, 2007;
(1/2 O2), hydroxyl radical (•OH), peroxynitrite (ONOO–), nitric oxide Tangvarasittichai, 2015; Kattoor, Pothineni, Palagiri, & Mehta, 2017;
(NO⋅), and so forth (Carocho & Ferreira, 2013). These ROS can attack Heliövaara et al., 1994; Li, Li, Jiang, & Ghanbari, 2013). In addition, free
and damage the DNA, lipids, and proteins of an organism, as well as radicals participate in the oxidation of lipids, and the oxidative
cause cellular damage. Typically, the antioxidant systems such as decomposition of unsaturated fatty acids is closely related to rancidity in
endogenous antioxidant enzymes, including superoxide dismutase many foods (Peng, Xiong, & Kong, 2009). An antioxidant is a substance
(SOD), glutathione peroxidase (GPx), thioredoxin reductase (TR), and that can remove ROS and neutralize free radicals (Umamaheswari &
catalase (CAT) (Valko et al., 2007), are present in the organisms, which Chatterjee, 2008). Therefore, it is important to reduce the harm caused
can neutralize the harmful cellular damage caused by ROS. However, by excessive ROS by increasing the intake of antioxidants and adding
this limited efficacy and environmental factors such as pollution, ul­ oxidants to foods.
traviolet rays, and imbalanced diets can produce an excess of ROS, Currently, antioxidants have numerous applications in a wide range

Abbreviations: AODB, Antioxidants database; ROS, Reactive oxygen species; H2O2, hydrogen peroxide; O2•–, superoxide; 1/2 O2, singlet oxygen; •OH, hydroxyl
radical; ONOO–, peroxynitrite; NO⋅, nitric oxide; SOD, superoxide dismutase; GPx, glutathione peroxidase; TR, thioredoxin reductase; CAT, catalase; DFBP, food-
bioactive peptides; HTML, Hyper Text Markup Language; HAT, hydrogen atom transfer; ET, electron transfer; DPPH, 2,2-Diphenyl-1-picrylhydrazyl assay; ABTS,
ABTS radical cation decolorization assay; TEAC, trolox equivalent antioxidant capacity method; ORAC, oxygen radical absorbance capacity method; TBA, thio­
barbituric acid method; FRAP, ferric reducing- antioxidant power assay; AA, amino acids; FAQ, Frequently Asked Question.
* Corresponding author.
E-mail address: [email protected] (L. Wang).
1
These authors contributed equally to this work.

https://doi.org/10.1016/j.foodchem.2023.135992
Received 16 November 2022; Received in revised form 11 March 2023; Accepted 18 March 2023
Available online 25 March 2023
0308-8146/© 2023 Elsevier Ltd. All rights reserved.
W. Deng et al. Food Chemistry 418 (2023) 135992

of industries, including medicine, nutraceuticals, food, and cosmetics. databases such as PubChem (Kim et al., 2021) and ChEMBL (Mendez
Antioxidants approved for marketing in food and medicine are shown in et al., 2019). Obviously, quickly and accurately finding specific small-
Fig. 1. In the pharmaceutical industry, some antioxidant drugs, such as molecule antioxidants from among the tens of millions of compounds
acetylcysteine, pirfenidone, idebenone, and edaravone, have been is challenging due to insufficient annotation. Therefore, a comprehen­
approved for treating diseases related to oxidative stress (Firuzi, Miri, sive and complete professional antioxidant database to cover the
Tavakkoli, & Saso, 2011). In addition, antioxidants are also an impor­ mainstream types of antioxidants involving small molecules, peptides,
tant part of the nutrition market (Jain & Ramawat, 2013) People take and proteins is still lacking.
nutritional supplements, including glutathione, methionine, coenzyme To fill this gap, we developed a comprehensive database of antioxi­
Q10, and beta-carotene, to prevent the occurrence of various diseases. dants, termed AODB, which contained 56,666 small molecules tested for
In the food industry, oxidation is one of the main reasons for the antioxidant activity, 1480 antioxidant peptides, and 998 antioxidant
decline in food quality and the short shelf life (Lee, Jeon, & Byun, 2011). proteins, as well as their related data including 7781 antioxidant assay
Therefore, antioxidants are primarily used as food additives to prevent records, 643,184 physicochemical and 610,704 ADMET properties, 2D
or slow oxidation, improve food stability, and extend shelf life. Synthetic and 3D structural information, and 6802 published findings. Fig. 2
small-molecule antioxidants such as butylated hydroxyanisole, butyl­ displays a schematic diagram of the content, operation, and construction
ated hydroxytoluene, propyl gallate, and tert-butylhydroquinone, are of AODB. AODB aimed to provide researchers with a free database of
widely used in the food industry due to their excellent antioxidant ac­ antioxidants to promote antioxidant research and development.
tivity and low cost (Shahidi, 2015). As people become increasingly
concerned about the safety of synthetic antioxidants, they are turning to 2. Materials and methods
natural alternatives such as tocopherol, rosemary extract, and ascorbic
acid. Antioxidant peptides and proteins have emerged as promising 2.1. Data collection and processing
options for use as natural food additives due to their safety and effec­
tiveness. Skin damage and skin aging can also be accelerated by As shown in Table S1 and Fig. 2, all of the data in the AODB was
oxidative stress, the appearance of which is reflected in the formation of manually compiled from publicly accessible databases and published
superficial fine lines, wrinkles, atypical pigmentation, and skin inflam­ findings. First, the PubChem BioAssay (accessed April 2022) (Kim et al.,
mation (Masaki, 2010). Therefore, adding antioxidants, such as vitamin 2021) and ChEMBL Assay (accessed April 2022) (Mendez et al., 2019)
C, resveratrol, and ferulic acid in cosmetics can slow down skin aging, databases were searched to extract antioxidant assays using the keyword
protect the skin, and protect cosmetic formulas from oxidative damage “antioxidant”. The search results were further processed through
(Chen, Liu, Zhao, & Qiu, 2021). manual screening and verification, which ensured that information
The widespread use of antioxidants and their potential commercial related to small-molecule antioxidants was captured. Based on these
value have led more and more practitioners to engage in antioxidant confirmed antioxidant assays, information related to small-molecule
research, resulting in a large number of experimental data related to antioxidants, such as chemical structures, antioxidant assay methods,
various types of antioxidants. Currently, some databases related to an­ assay results, assay targets, and references, was collected. The 2D
tioxidants have been reported. In 2017, Feng et al. proposed an anti­ chemical structure of each compound was embedded into the website
oxidant protein database comprising 710 experimentally validated using the SVG vector map format generated using RDKit software (htt
antioxidant proteins (Feng, Ding, Lin, & Chen, 2017). In 2019, Min­ ps://www.rdkit.org). The 3D chemical structure of each compound
kiewicz and coworkers developed a BIOPEP-UWM database that stored was generated using RDKit and then integrated into the website using
4497 biologically active peptides, including 779 peptides with antioxi­ the 3Dmol.js (Rego & Koes, 2015).
dant activity (Minkiewicz, Iwaniak, & Darewicz, 2019). Very recently, a Second, we searched the DFBP database (accessed May 2022) (Qin
database of food-bioactive peptides (DFBP) for peptidomics research et al., 2022), BIOPEP-UWM Database (accessed May 2022) (Minkiewicz
was developed, which stored 6276 peptides and their bioactivity infor­ et al., 2019), and MBPDB (accessed May 2022) (Nielsen, Beverly, Qu, &
mation (Qin et al., 2022). Further analysis found that the database Dallas, 2017) to capture antioxidant peptides and related data. In
included 1032 antioxidant peptide entries. Small-molecule antioxidants addition, we conducted a PubMed (accessed May 2022) search using the
are distributed in the scattered literature and some pharmacy-related keywords “antioxidant peptide”, “antioxidation peptide”, and

Fig. 1. Antioxidants approved for marketing in food and medicine.

2
W. Deng et al. Food Chemistry 418 (2023) 135992

Fig. 2. Schematic diagram of the construction process of AODB.

“antioxidative peptide” to explore the literature on antioxidant peptides 2.3. Search tools
that might not have been identified in the aforementioned databases.
After manual inspection and examination, 334 published studies related Three data retrieval methods, including text mining, chemical
to antioxidant peptides were finally obtained. Accordingly, the structure search, and protein sequence search, were encoded in AODB
comprehensive information on these antioxidant peptides, including the for users to quickly capture the desired antioxidants and their associated
sequence, origin, and antioxidant activity of the peptides, was then data. The 2D similarity calculation method (Table S2) was employed for
mined manually from these peer-reviewed publications. The 2D and 3D small-molecule searching based on ECFP_4 fingerprints using RDKit
structures of each antioxidant peptide were displayed in a similar software, and the Tanimoto coefficient was used to quantify the simi­
manner to that of the compound. larity score between two molecules. LS-align was encoded in AODB for
We used the method described by Feng et al. (Feng et al., 2017) to 3D similarity search, which used a statistically significant scoring
collect antioxidant proteins and their related data by searching the function independent of the ligand size to evaluate the ligand similarity
UniProtKB/Swiss-Prot (release 2022_03) (The UniProt Consortium, (Hu, Liu, Yu, & Zhang, 2018) (Jiang, Xu, Yan, & Wang, 2021). In
2021) database using the keyword “antioxidant”. In data processing, the addition, the BLAST algorithm was used to search for protein sequence
sequences containing nonstandard letters (i.e., “B”, “X” or “Z”) outside similarity (Altschul, Gish, Miller, Myers, & Lipman, 1990).
of the standard amino acid alphabet were removed due to their unclear
meanings. Finally, the experimentally confirmed antioxidant proteins 2.4. Database and web interface implementation
and their associated information were obtained through further manual
inspection and verification. The 3D structure of the protein (mmCIF file) AODB was implemented as a relational database in SQLite. The web
was obtained from AlphaFold DB (Jumper, Evans, Pritzel, Green, Fig­ interface was built using Hyper Text Markup Language (HTML), Java­
urnov, Ronneberger, & Hassabis, 2021) and integrated into the web Script, Flask, and Nginx. The front-end page was built using a template
page through Mol* Viewer (Sehnal et al., 2021). called Mazer, while Bootstrap Table was used to present a user-friendly
database interface. The detailed tools involved in the construction of
2.2. Calculated properties and cluster AODB are provided in Table S2.

A series of properties of each antioxidant of small molecule, peptide, 3. Results and discussion
and protein were calculated and stored in the AODB. Specifically, 11
physicochemical properties and 11 ADMET pharmacokinetics (Table S1) 3.1. Database content and statistics
for each small molecule were calculated using RDKit and Discovery
Studio software package (version 3.5; Biovia, CA, USA), respectively; Currently, AODB contains 59,144 unique, experimentally deter­
(iv) the online tool NovoPro (https://www.novopro.cn/tools/rev_comp.
mined antioxidants, as well as the information associated with them
html) was used to determine the structure and physicochemical prop­ (Table S1). Among these, the proportions of small-molecule compounds,
erties of each peptide. Eleven physicochemical properties of each pro­
peptides, and proteins are 95.8%, 2.5%, and 1.7%, respectively. For
tein were calculated using ProtParam (http://www.expasy. antioxidant small-molecular compounds, 56,666 compounds involving
org/tools/protparam.html).
7015 antioxidant assay items (Table S1) were collected and then an­
For the convenience of users, we classified molecules according to notated according to the chemical principles of antioxidant capacity
the similarity described in the molecular assay method and used the
determination (Apak, Özyürek, Güçlü, & Çapanoğlu, 2016; Huang, Ou,
Discovery Studio software package to classify each type of molecule & Prior, 2005; López-Alarcón & Denicola, 2013). As shown in Fig. 3A,
based on ECFP_4 fingerprints for clustering.
such small molecules could be attributed to the following seven cate­
gories, depending on the types of reactions involved in their assays: (1)
hydrogen atom transfer (HAT) reaction-based assay (4.3%); (2) electron

3
W. Deng et al. Food Chemistry 418 (2023) 135992

Fig. 3. AODB data statistics. (A) Classification of antioxidant compound assays. (B) Top 10 antioxidant test methods. (C) Antioxidant peptide sequence length
distribution. (D) Antioxidant peptide amino acid composition. (E) Antioxidant proteins length analysis. (F) Antioxidant protein sequence length distribution.

transfer (ET) reaction-based assay (16.1%); (3) inhibition of lipid UniProtKB/Swiss-Prot, along with their sequences, structures, taxo­
peroxidation-based assay (3.7%); (4) assay based on antioxidant/pro- nomic lineages, source organisms, gene ontologies, catalytic activity,
oxidant enzymes (16.7%); (5) assay via targeting the Nrf2-antioxidant function, active site, kinetics, and published literature information.
response element signaling pathway (31.3%); (6) cell-based bioassays More importantly, AODB provided protein AA composition analysis and
(1.7%); and (7) others (26.2%). The results of this analysis not only 3D structure online display for antioxidant proteins. Currently, the
showed the diversity of current antioxidant testing methods but also length of the collected antioxidant proteins ranges from 8 to 2545 AAs,
reflected the attractiveness of antioxidant research. Further analysis with 41.9% of these AAs falling between 150 and 200 (Fig. 3E).
showed that the antioxidant activity of approximately 24.0% of small Isoleucine, alanine, and glycine represent the most prevalent AAs in the
molecules was determined using the following top 10 methods (Fig. 3B), collected antioxidant proteins (Fig. 3F).
including DPPH (2,2-Diphenyl-1-picrylhydrazyl assay), ABTS/TEAC
(ABTS radical cation decolorization assay/Trolox equivalent antioxidant
capacity method), ORAC (oxygen radical absorbance capacity method), 3.2. Web interface and usage
TBA (thiobarbituric acid method), superoxide radical scavenging ac­
tivity, FRAP (ferric reducing-antioxidant power assay), hydroxyl radical AODB can be accessed through a user-friendly web interface (https:
scavenging activity, metal chelating activity, nitric oxide scavenging //aodb.idruglab.cn/). The interface includes a homepage; a browse
activity, and hydrogen peroxide scavenging activity. In addition, function for compounds, peptides, and proteins; and search, document,
623,326 physicochemical properties and 610,704 ADMET data points download, and FAQ (Frequently Asked Questions) menus, allowing
were integrated into the AODB to assess the physicochemical, drug- users to quickly browse, search and obtain the desired antioxidants and
likeness, and pharmacokinetics profiles of the collected antioxidant related information.
compounds. Lipinski’s rule of five, the Veber rule, and the ADMET
properties of each small-molecule antioxidant were presented in online 3.2.1. Browse and search
radar charts using Apache ECharts (https://echarts.apache.org/en/i The antioxidant in AODB can be browsed by selecting a specific
ndex.html), which enabled users to visually determine the quality of a antioxidant type (e.g., compounds, peptides, and proteins) on the
given property (Li et al., 2019). Browse page and then clicking the corresponding AODB ID. For
For antioxidant peptides, the current version of AODB includes 1480 example, small-molecule antioxidants can be browsed by the assay
antioxidant peptides with unique sequences from 334 publications. As method, and the antioxidant peptides and proteins can be browsed by
shown in Table S1, much associated data from these peptides were also sequence length in a positive or reverse order.
collected and integrated into AODB, including 1480 peptide sequences, Quick search is available on the toolbar in the upper right corner of
310 organisms, 766 antioxidant activity data points, 7400 physico­ each module page of compounds, peptides, and proteins in the Browse
chemical property data points, 334 literature, and three cross-linked page. Free-text search allows the users to enter any term in AODB ID,
databases. The length distribution of antioxidant peptides ranged from sequence, source, or length without specifying a search entity. For
1 to 68 amino acids (AA), where the sequence length of 82.5% of the example, the users can enter “egg” in the search bar of the peptide
antioxidant peptides was within 10 AA (Fig. 3C). Further analysis of the browsing interface (Fig. 4A) and then click submit to display egg-related
AA composition of the collected antioxidant peptides found that proline, antioxidant peptides. The users can further click on the AODB ID of the
leucine, and glycine appeared most frequently (Fig. 3D). peptide to view its structure, properties, antioxidant activity, and other
In addition, AODB contained 998 antioxidant proteins from information (Fig. 4B).
In addition, AODB provides a protein sequence alignment search. In

4
W. Deng et al. Food Chemistry 418 (2023) 135992

Fig. 4. Text search and protein sequence search interface and cases in AODB. (A) Text search results for antioxidant peptides associated with egg. (B) The antioxidant
peptide with the sequence “AHK” and its basic, structural properties, and cross-database information. (C) BLAST was used for the sequence similarity of
peroxiredoxin-6. (D) Snapshot of peroxiredoxin-6 search results obtained using BLAST search. (E) Snapshot of basic, structural, and functional information of
peroxiredoxin-6.

the “Search” interface, the users can enter the protein sequence of in­ map related to these properties (Fig. 5E) can be further easily viewed by
terest into the BLAST toolbar (Fig. 4B). Peroxiredoxin-6 (UniProt ID: clicking on the AODB ID of the desired compound (Fig. 5C). In addition,
O35244) acts as a mercaptan-specific peroxidase, catalyzing the the user can view other molecules similar to the molecular assay
reduction of hydrogen peroxide and organic hydroperoxide to water and description in the clustering section (Fig. 5E) and click to jump to the
alcohol, respectively. The users can easily obtain a protein similar to the interface of the molecule of interest. Alternatively, the users can upload
peroxiredoxin-6 (Fig. 4C) and view the desired protein sequence and the 3D structure of ascorbic acid in MOL2 format in the 3D similarity
other information (Fig. 4D). search column (Fig. 5C) to obtain molecules similar to its 3D structure
The users can perform a 2D similarity search by drawing online or by (Fig. 5D).
entering SMILES or InChI of the molecule of interest. Taking ascorbic
acid (a commonly used antioxidant) as an example, the users can enter
ascorbic acid in SMILES format (Fig. 5A) and then click the “Submit” 3.3. Download and FAQ
button to get molecules similar to ascorbic acid (Fig. 5B). The structure,
antioxidant assay, physicochemical and ADMET properties, and radar All of the antioxidant data stored in AODB can be freely downloaded
from the “Download” page for noncommercial use. Meanwhile, the

5
W. Deng et al. Food Chemistry 418 (2023) 135992

Fig. 5. Chemical structure search interface and cases in AODB. (A) 2D similarity search interface and 2D case searching for ascorbic acid in SMILES format. (B)
Snapshot of search results for ascorbic acid using 2D similarity search. (C) 3D similarity search interface and 3D case searching for ascorbic acid in MOL2 format. (D)
Snapshot of search results for ascorbic acid using 3D similarity search. (E) Structure, representations, assay data, properties, and external link information of
ascorbic acid.

“FAQ” page provides detailed introductions and tutorials about AODB. antioxidant information of interest. To enhance its versatility as an
antioxidant database, AODB will undergo annual updates through
4. Conclusions extensive antioxidant data deposition and resource integration. In the
future, we will integrate machine learning-based predictive models to
Given the importance of antioxidants in human health and their explore and explain the relationships between the structures and anti­
potential to improve the quality of life, we created AODB in the present oxidant activity of compounds, peptides, and proteins, aiming to enable
study. To our best knowledge, AODB is a comprehensive database that the discovery of novel antioxidants. Collectively, we anticipate that
collects and annotates information on various types of antioxidants, AODB can serve as a powerful tool for antioxidant research and devel­
including small molecules, peptides, and proteins. A detailed compari­ opment, as well as for advancing the field of antioxidants for pharma­
son of AODB with other antioxidant-related databases (e.g., AOD, DFBP, cists, biologists, and food scientists.
BIOPEP-UWM, and MBPDB) is summarized in Table 1. Obviously,
compared with the existing databases, the antioxidant information Declaration of Competing Interest
stored in AODB is more comprehensive and targeted. In addition, the
multiple search tools in AODB can help users quickly retrieve the The authors declare that they have no known competing financial

6
W. Deng et al. Food Chemistry 418 (2023) 135992

Table 1
Detailed comparison of AODB and other antioxidant-related databases.
Category Feature Database

AOD DFBP BIOPEP-UWM MBPDB AODB (our)

Compound Chemical structure × × × × 56,666

Assay data point × × × × 98,313
Physicochemical property × × × × 623,326
ADMET property × × × × 610,704
Cross-linked databases × × × × 2

Peptide Peptide sequence × 1,008 773 80 1,480

Assay data point × √ × × √
Physicochemical property × √ × × √

Protein Protein Sequence 710 × × × 998

Organism √ × × × √
Taxonomic lineage √ × × × √
Subcellular location √ × × × √
Function √ × × × √
Catalytic activity √ × × × √
Gene Ontology √ × × × √
Structure √ × × × √
3D structure display × × × × √
Kinetics × × × × √
Active site × × × × √
Reference × × × × √
Physicochemical property × × × × √
Amino acid composition × × × × √

Search function Text search √ √ √ √ √

2D chemical structure search × × × × √
3D chemical structure search × × × × √
Blast × × × × √

interests or personal relationships that could have appeared to influence Firuzi, O., Miri, R., Tavakkoli, M., & Saso, L. (2011). Antioxidant therapy: Current status
and future prospects. Current Medicinal Chemistry, 18(25), 3871–3888. https://doi.
the work reported in this paper.
org/10.2174/092986711803414368
Heliövaara, M., Knekt, P., Aho, K., Aaran, R. K., Alfthan, G., & Aromaa, A. (1994). Serum
Data availability antioxidants and risk of rheumatoid arthritis. Annals of the Rheumatic Diseases, 53(1),
51–53.
Hu, J., Liu, Z., Yu, D.-J., & Zhang, Y. (2018). LS-align: An atom-level, flexible ligand
Data will be made available on request. structural alignment algorithm for high-throughput virtual screening. Bioinformatics,
34(13), 2209–2218. https://doi.org/10.1093/bioinformatics/bty081
Acknowledgments Huang, D., Ou, B., & Prior, R. L. (2005). The Chemistry behind Antioxidant Capacity
Assays. Journal of Agricultural and Food Chemistry, 53(6), 1841–1856. https://doi.
org/10.1021/jf030723c
This work was supported by the Natural Science Foundation of Hwang, E.-S., & Bowen, P. E. (2007). DNA Damage, a Biomarker of Carcinogenesis: Its
Guangdong Province (2023B1515020042), the National Natural Science Measurement and Modulation by Diet and Environment. Critical Reviews in Food
Science and Nutrition, 47(1), 27–50. https://doi.org/10.1080/10408390600550299
Foundation of China (81973241), and the transversal research program Jain, N., & Ramawat, K. G. (2013). Nutraceuticals and Antioxidants in Prevention of
(D8224910) of Guangdong Suntrap Life Technologies Ltd. Diseases. In K. G. Ramawat, & J.-M. Mérillon (Eds.), Natural Products: Phytochemistry,
Botany and Metabolism of Alkaloids, Phenolics and Terpenes (pp. 2559–2580).
Springer. https://doi.org/10.1007/978-3-642-22144-6_70.
Appendix A. Supplementary data Jiang, Z., Xu, J., Yan, A., & Wang, L. (2021). A comprehensive comparative assessment of
3D molecular similarity tools in ligand-based virtual screening. Briefings in
Supplementary data to this article can be found online at https://doi. Bioinformatics, 22(6), bbab231. https://doi.org/10.1093/bib/bbab231
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., … Hassabis,
org/10.1016/j.foodchem.2023.135992.
D. (2021). Highly accurate protein structure prediction with AlphaFold. Nature, 596
(7873), Article 7873. 10.1038/s41586-021-03819-2.
References Kattoor, A. J., Pothineni, N. V. K., Palagiri, D., & Mehta, J. L. (2017). Oxidative Stress in
Atherosclerosis. Current Atherosclerosis Reports, 19(11), 42. https://doi.org/10.1007/
Altschul, S. F., Gish, W., Miller, W., Myers, E. W., & Lipman, D. J. (1990). Basic local s11883-017-0678-6
alignment search tool. Journal of Molecular Biology, 215(3), 403–410. https://doi. Kim, S., Chen, J., Cheng, T., Gindulyte, A., He, J., He, S., … Bolton, E. E. (2021).
org/10.1016/S0022-2836(05)80360-2 PubChem in 2021: New data content and improved web interfaces. Nucleic Acids
Apak, R., Özyürek, M., Güçlü, K., & Çapanoğlu, E. (2016). Antioxidant Activity/Capacity Research, 49(D1), D1388–D1395. https://doi.org/10.1093/nar/gkaa971
Measurement. 2. Hydrogen Atom Transfer (HAT)-Based, Mixed-Mode (Electron Lee, W.-S., Jeon, J.-K., & Byun, H.-G. (2011). Characterization of a novel antioxidative
Transfer (ET)/HAT), and Lipid Peroxidation Assays. Journal of Agricultural and Food peptide from the sand eel Hypoptychus dybowskii. Process Biochemistry, 46(5),
Chemistry, 64(5), 1028–1045. https://doi.org/10.1021/acs.jafc.5b04743 1207–1211. https://doi.org/10.1016/j.procbio.2011.02.001
Carocho, M., & Ferreira, I. C. F. R. (2013). A review on antioxidants, prooxidants and Li, J. O. W., Li, W., Jiang, Z. G., & Ghanbari, H. A. (2013). Oxidative Stress and
related controversy: Natural and synthetic compounds, screening and analysis Neurodegenerative Disorders. International Journal of Molecular Sciences., 14(12),
methodologies and future perspectives. Food and Chemical Toxicology, 51, 15–25. 24438–24475. https://doi.org/10.3390/ijms141224438
https://doi.org/10.1016/j.fct.2012.09.021 Li, Y., Zhao, C., Zhang, J., Zhai, S., Wei, B., & Wang, L. (2019). HybridMolDB: A
Chen, J., Liu, Y., Zhao, Z., & Qiu, J. (2021). Oxidative stress in the skin: Impact and Manually Curated Database Dedicated to Hybrid Molecules for Chemical Biology and
related protection. International Journal of Cosmetic Science, 43(5), 495–509. https:// Drug Discovery. Journal of Chemical Information and Modeling, 59(10), 4063–4069.
doi.org/10.1111/ics.12728 https://doi.org/10.1021/acs.jcim.9b00314
Feng, P., Ding, H., Lin, H., & Chen, W. (2017). AOD: The antioxidant protein database. López-Alarcón, C., & Denicola, A. (2013). Evaluating the antioxidant capacity of natural
Scientific Reports, 7(1). Article 1. https://doi.org/10.1038/s41598-017-08115-6 products: A review on chemical and cellular-based assays. Analytica Chimica Acta,
763, 1–10. https://doi.org/10.1016/j.aca.2012.11.051

7
W. Deng et al. Food Chemistry 418 (2023) 135992

Masaki, H. (2010). Role of antioxidants in the skin: Anti-aging effects. Journal of Rego, N., & Koes, D. (2015). 3Dmol.js: Molecular visualization with WebGL.
Dermatological Science, 58(2), 85–90. https://doi.org/10.1016/j. Bioinformatics., 31(8), 1322–1324. https://doi.org/10.1093/bioinformatics/btu829
jdermsci.2010.03.003 Sehnal, D., Bittrich, S., Deshpande, M., Svobodová, R., Berka, K., Bazgier, V., …
Mendez, D., Gaulton, A., Bento, A. P., Chambers, J., De Veij, M., Félix, E., … Leach, A. R. Rose, A. S. (2021). Mol* Viewer: Modern web app for 3D visualization and analysis
(2019). ChEMBL: Towards direct deposition of bioassay data. Nucleic Acids Research, of large biomolecular structures. W437 Nucleic Acids Research, 49(W1), W431.
47(D1), D930–D940. https://doi.org/10.1093/nar/gky1075 https://doi.org/10.1093/nar/gkab314.
Minkiewicz, P., Iwaniak, A., & Darewicz, M. (2019). BIOPEP-UWM Database of Bioactive Shahidi, F. (2015). 1 - Antioxidants: Principles and applications. In F. Shahidi (Ed.),
Peptides: Current Opportunities. International Journal of Molecular Sciences, 20(23), Handbook of Antioxidants for Food Preservation (pp. 1–14). Woodhead Publishing.
5978. https://doi.org/10.3390/ijms20235978 https://doi.org/10.1016/B978-1-78242-089-7.00001-4.
Nielsen, S. D., Beverly, R. L., Qu, Y., & Dallas, D. C. (2017). Milk bioactive peptide Tangvarasittichai, S. (2015). Oxidative stress, insulin resistance, dyslipidemia and type 2
database: A comprehensive database of milk protein-derived bioactive peptides and diabetes mellitus. World Journal of Diabetes, 6(3), 456–480. https://doi.org/
novel visualization. Food Chemistry, 232, 673–682. https://doi.org/10.1016/j. 10.4239/wjd.v6.i3.456
foodchem.2017.04.056 The UniProt Consortium. (2021). UniProt: The universal protein knowledgebase in 2021.
Peng, X., Xiong, Y. L., & Kong, B. (2009). Antioxidant activity of peptide fractions from D489 Nucleic Acids Research, 49(D1), D480. https://doi.org/10.1093/nar/gkaa1100.
whey protein hydrolysates as measured by electron spin resonance. Food Chemistry, Umamaheswari M., Chatterjee T.K. (2008). In vitro antioxidant activities of the fractions
113(1), 196–201. https://doi.org/10.1016/j.foodchem.2008.07.068 of Coccinia grandis l. Leaf extract. African Journal of Traditional, Complementary and
Qin, D., Bo, W., Zheng, X., Hao, Y., Li, B., Zheng, J., & Liang, G. (2022). In DFBP: A Alternative Medicines. 5(1), Article 1. 10.4314/ajtcam.v5i1.31258.
Comprehensive Database of Food-Derived Bioactive Peptides for Peptidomics Research. Valko, M., Leibfritz, D., Moncol, J., Cronin, M. T. D., Mazur, M., & Telser, J. (2007). Free
England: Bioinformatics (Oxford). https://doi.org/10.1093/bioinformatics/btac323. radicals and antioxidants in normal physiological functions and human disease. The
btac323. International Journal of Biochemistry & Cell Biology, 39(1), 44–84. https://doi.org/
10.1016/j.biocel.2006.07.001