NPCDR: natural product-based drug combination and its disease-specific molecular regulation

Abstract

Natural product (NP) has a long history in promoting modern drug discovery, which has derived or inspired a large number of currently prescribed drugs. Recently, the NPs have emerged as the ideal candidates to combine with other therapeutic strategies to deal with the persistent challenge of conventional therapy, and the molecular regulation mechanism underlying these combinations is crucial for the related communities. Thus, it is urgently demanded to comprehensively provide the disease-specific molecular regulation data for various NP-based drug combinations. However, no database has been developed yet to describe such valuable information. In this study, a newly developed database entitled 'Natural Product-based Drug Combination and Its Disease-specific Molecular Regulation (NPCDR)' was thus introduced. This database was unique in (a) providing the comprehensive information of NP-based drug combinations & describing their clinically or experimentally validated therapeutic effect, (b) giving the disease-specific molecular regulation data for a number of NP-based drug combinations, (c) fully referencing all NPs, drugs, regulated molecules/pathways by cross-linking them to the available databases describing their biological or pharmaceutical characteristics. Therefore, NPCDR is expected to have great implications for the future practice of network pharmacology, medical biochemistry, drug design, and medicinal chemistry. This database is now freely accessible without any login requirement at both official (https://idrblab.org/npcdr/) and mirror (http://npcdr.idrblab.net/) sites.

Graphical Abstract

NPCDR: natural product-based drug combination and its disease-specific molecular regulation.

Figure 1.

The unique contents and characteristics of NPCDR. The NPs were reported to enhance drug efficacy by augmenting drug sensitivity/achieve therapeutic synergy, decrease adverse drug reaction and reverse drug resistance. Thus, NPCDR is UNIQUE in providing the comprehensive NP-based drug combinations & describing their clinically/experimentally validated therapeutic effects, and describing the disease-specific regulations of molecules and pathways for a number of NP-based drug combinations.

Figure 2.

Combinatorial therapeutic effects that were clinically or experimentally validated. The NPs were reported able to enhance the drug efficacy by augmenting its sensitivity and achieving therapeutic synergy, decrease adverse drug reaction, and reverse drug resistance. The therapeutic effects of each NP-based drug combination were thus described in the bottom panel (highlighted using the green frame) of this figure.

Figure 3.

Regulation of molecules and pathways by NP-based drug combinations. Mechanisms of molecular regulation were explicitly described (including the induction of protein degradation, the up or down-regulation of molecule's cleavage, activity, phosphorylation, ubiquitination, and expression). The biological regulation of drug combinations was also provided (e.g. the induction of cell cycle arrest, inhibition of metabolite biosynthesis, etc.). These regulation data were linked to their in-vitro or in-vivo disease model, and an extended description on each regulated molecule could be accessed by clicking the ‘Molecule Info’ buttons.

Figure 4.

The natural product (NP) page of this database. The general information (upper orange panel) and the combinatorial therapeutic effects of this NP (lower blue panel) were provided in NPCDR. Particularly, the combinatorial therapeutic effects of this NP on a list of drugs that were clinically/experimentally validated were shown. These accompanied drugs were grouped based on three types of combinatorial effects of NP: (a) a list of drugs whose efficacy can be enhanced by this NP, (b) a list of drugs whose adverse effects can be decreased by this NP and (c) a list of drugs whose resistance can be reversed by this NP.