What Is Bioactivity? The Stages of Evidence in Research on Functional Compounds Such as Polyphenols and Flavonoids
Bioactivity and Functionality
Bioactivity means the measurable effect that a substance has on a biological system such as an enzyme, cell, tissue, or whole organism. Bioactivity research aims to establish through which targets and pathways that effect occurs and at what dose it appears.
Evidence builds in stages. Results at the test-tube and cell level (in vitro) are a starting point for forming hypotheses, and the level of evidence rises through animal models (in vivo) and human studies. In particular, the structure of natural products often changes during absorption, distribution, metabolism, and excretion (ADME), so activity in the laboratory cannot be assumed to carry over directly to effects in the body.
Main research topics
- 01Mechanism of action and target identification
Identifying the protein targets to which a compound binds and the signaling pathways involved
- 02Dose-response relationship
Comparing effective concentration and dose ranges with the concentrations that can be reached in the body
- 03Bioavailability and formulation
Absorption rate and metabolic stability, and formulation research to improve them
- 04Interaction with gut microbes
Metabolism of compounds by gut microbes and its biological significance
- 05Design of human studies
Study design and reporting with randomisation, control groups, and blinding
- 06Assay interference and reproducibility
Identifying possible false positives, such as compounds that interfere with assays (PAINS)
Overview of methods
Target enzyme activity and cellular responses are measured.
Pathways are traced through transcriptome, proteome, and metabolome analysis.
They are designed and reported according to the ARRIVE guidelines.
Randomised controlled trials are designed and reported according to the CONSORT guidelines.
Evidence is summarised through systematic reviews and meta-analyses (PRISMA).
- Atanasov AG, Zotchev SB, Dirsch VM, et al. Natural products in drug discovery: advances and opportunities. Nat Rev Drug Discov 2021;20:200–216.
- Baell JB, Holloway GA. New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays. J Med Chem 2010;53(7):2719–2740.
- Percie du Sert N, et al. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol 2020;18(7):e3000410.
- CONSORT (Consolidated Standards of Reporting Trials) Statement.
- Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71.