Hormetic effects of curcumin: What is the evidence?

Abstract

Curcumin (diferuloylmethane), a component of the yellow powder prepared from the roots of Curcuma longa or Zingiberaceae (known as turmeric) is not only widely used to color and flavor food but also used as a pharmaceutical agent. Curcumin demonstrates anti‐inflammatory, anticarcinogenic, antiaging, and antioxidant activity, as well as efficacy in wound healing. Notably, curcumin is a hormetic agent (hormetin), as it is stimulatory at low doses and inhibitory at high doses. Hormesis by curcumin could be also a particular function at low doses (i.e., antioxidant behavior) and another function at high dose (i.e., induction of autophagy and cell death). Recent findings suggest that curcumin exhibits biphasic dose–responses on cells, with low doses having stronger effects than high doses; examples being activation of the mitogen‐activated protein kinase signaling pathway or antioxidant activity. This indicates that many effects induced by curcumin are dependent on dose and some effects might be greater at lower doses, indicative of a hormetic response. Despite the consistent occurrence of hormetic responses of curcumin in a wide range of biomedical models, epidemiological and clinical trials are needed to assess the nature of curcumin’s dose–response in humans. Fortunately, more than one hundred clinical trials with curcumin and curcumin derivatives are ongoing. In this review, we provide the first comprehensive analysis supportive of the hormetic behavior of curcumin and curcumin derivatives.

Pursuing the Elixir of Life: In Vivo Antioxidative Effects of Manganosalen Complexes

“…The antioxidant activity observed in cells can even decrease with increasing concentration [ 23 ], leading to curves that are not dose dependent. This behavior has been also reported in natural compounds such as curcumin or resveratrol, which present antioxidant effects at low doses but induce oxidative stress and cell death at high concentrations [ 166 , 167 ]. In this way, in vitro studies indicate that manganosalen complexes could also interact with other cellular pathways at high concentrations or with a receptor that could be suffering a threshold effect, that is, it would present higher affinity at low concentrations and would be desensitized at higher doses [ 168 ].…”

Biphasic Dose-Response Induced by Phytochemicals: Experimental Evidence

“…However, many reports provide evidence that low doses/concentrations of these compounds have the potential for adverse effects, such as enhancement of the proliferation of tumor cells [1,2]. Various phytochemicals demonstrate nonmonotonic dose/concentration-response termed biphasic dose-response and are considered to be hormetic compounds, for example, resveratrol [2,3] curcumin [4], sulforaphane [1]. The term hormesis described the phenomenon in which a chemical is able to induce biologically opposite effects at different doses; as dose decreases, there are not only quantitative changes in measured responses but also qualitative changes with reference to control and high dose level [5].…”

“…We have excluded curcumin from this work since its hormetic properties were recently reviewed elsewhere [4]. As data on the biphasic concentration/dose-response displayed by resveratrol were extensively reviewed in 2010 [2,3], we presented here reports concerning this subject published from 2010 until 2019.…”

Curcumin Inhibits the Proteolytic Process of SREBP-2 by First Inhibiting the Expression of S1P rather than Directly Inhibiting SREBP-2 Expression.

“…Curcumin is a chemical component extracted from the rhizome of Zingiberaceae and Araceae. Studies have described various effects of curcumin including reducing blood fat, choleretic actions, and antitumor, anti-inflammatory, and anti-oxidation effects [13][14][15][16] . Several studies have indicated that the effect of curcumin on SREBPs is related to the mechanism of curcumin regulating blood lipid metabolism [4,5,[8][9][10][11][12] .…”