Berberine induces pleiotropic beneficial effects via hormesis

Berberine is a phytochemical that has been shown to prevent a spectrum of serious ailments, to slow aging, and to extend lifespans and health spans of animals, demonstrating its pleiotropic effectiveness. Like sulforaphane, metformin, resveratrol, and many other phytochemicals, berberine suppresses the expression of critical etiological factors-particularly oxidative stress, inflammation, and cellular damage-involved in the progression of many diseases (e.g., diabetes, cardiovascular diseases, cancers, and neurodegenerative disorders) and the aging process. Since the salutary responses elicited by many phytochemicals have already been reported to be biphasic and hormetic, this study examined whether berberine and its salutary responses are mediated by hormesis. To address these questions, it was necessary to mine data from across the biomedical research literature, utilize anti-biasing data-selection criteria, and apply conservative statistical methods to evaluate, identify, and validate the occurrence of a biphasic hormetic response. Results show berberine, at low nontoxic doses and/or concentrations, routinely induces responses across a broad range of biological models and medical endpoints that are not only hormetic (biphasic) and salutary but of biomedical/clinical importance. This study is the first to report that the many pleiotropic and beneficial effects induced by berberine are clearly hormetic. These results underscore the positive relationship between a strong experimental design and the likelihood of eliciting an hormetic response. This means that the experimental endpoints, the sample sizes, and the numbers, ranges, and temporal spacings of applied doses must be judiciously selected to increase the likelihood of inducing an unambiguous hormetic response.