Biphasic Dose-Response Induced by Phytochemicals: Experimental Evidence.

Area of Science:

• Pharmacology
• Biochemistry
• Toxicology

Background:

• Phytochemicals can exhibit hormesis, a nonmonotonic dose-response where effects reverse at different concentrations.
• While often declared, experimental proof for phytochemical hormesis is scarce.
• Biphasic dose-response (BDR) is a key characteristic of hormetic compounds.

Purpose of the Study:

• To review and present experimental evidence of phytochemical-induced biphasic dose-response.
• To identify specific phytochemicals and compound classes demonstrating BDR.
• To highlight the documented reversal of effects at low versus high doses/concentrations.

Main Methods:

• Systematic literature review focusing on studies with experimentally proven BDR.
• Inclusion criteria: documented reversal of a single endpoint's response between low and high phytochemical doses/concentrations.
• Data extraction on phytochemicals, endpoints, and experimental models.

Main Results:

• Phytoestrogens showed the most data regarding BDR.
• Other compounds with BDR include resveratrol, sulforaphane, berberine, falcarinol, glyceollin1, plumbagin, naphazarin, and panaxatriol saponins.
• Most studies utilized cell cultures, with cell proliferation being the most common endpoint; animal model studies were rare.

Conclusions:

• Experimental evidence confirms biphasic dose-response for various phytochemicals.
• Phytochemicals like phytoestrogens, resveratrol, and sulforaphane demonstrate hormetic properties.
• Understanding phytochemical BDR has potential therapeutic and preventive implications.