Herbal plants produce an astonishing number of ingredients, namely bioactive phytochemicals. These ingredients not only function as crucial signaling molecules in plants, but also pose effects in other species such as humans by regulating relevant protein targets. Artemisinin has not only been approved by Food and Drug Administration (FDA) as anti-malarial drug against plasmodium, but also used as a tool for discovery of the protein target, PDGFRA, the cell-surface receptor in regulation of embryonic development (Li, et al., 2017). Meanwhile, artemisinin has been reported to target PF3D7_0802200, the protein involved in heme detoxification in plasmodium (Gao, et al., 2023), whereas the RPD3, the protein involved in histone deacetylase, was identified to be regulated by artemisinin in yeast (Jensen, et al., 2014). Thus, collection, integration, biocuration, and annotation of experimentally identified herbal ingredient-target interactions (ITIs) will be helpful for better understanding the functional impacts of herbal ingredients and serve as a resource for further pharmaceutical consideration.
Here, we report a comprehensive database of protein targets of herbal ingredients (dbPTH), containing 165,967 reported ITIs between 4,856 ingredients and 27,981 protein targets across 8 species. The potential orthologs of these protein targets were computationally identified in up to 1,138 species, containing 36,594,449 highly potential ITIs for 2,657,336 potential targets. Compared to four mainstream herbal ingredient-target databases, TCMSP, HERB, HIT 2.0 and BATMAN-TCM 2.0, dbPTH 1.0 achieved 41.81-, 34.47-, 16.55- and 9.72-fold increase in maintaining known ITIs, respectively. For convenience, we classified the herbal ingredients and corresponding protein targets into 65 chemical subtypes and 9 protein subgroups, respectively.
Protein targets were categorized from ChEMBL (Mendez, et al., 2019):
(i) Enzyme;
(ii) Epigenetic regulator;
(iii) Ion channel;
(iv) Membrane receptor;
(v) Other cytosolic protein;
(vi) Secreted protein;
(vii) Transcription factor;
(viii) Transporter and
(ix) Other.
Herbal Ingredients catalog from ClassyFire (Djoumbou Feunang, et al., 2016).
Also, we carefully annotated the data, especially for human data, using the knowledge from 110 public resources that cover 14 aspects:
(i) Genetic variation & mutation;
(ii) Disease-associated information;
(iii) Protein-protein interaction;
(iv) Protein functional annotation;
(v) Post-translational modification;
(vi) Target-herb relation;
(vii) Protein structural annotation;
(viii) Subcellular localization;
(ix) Biological pathway;
(x) Protein expression/Proteomics;
(xi) Domain annotation;
(xii) Physicochemical property;
(xiii) mRNA expression;
(xiv) DNA & RNA element.
All datasets and annotations are free for use.
