The chemoprotective hormetic effects of rosmarinic acid

Abstract

Rosmarinic acid is a polyphenol found in numerous fruits and vegetables, consumed in supplement form, and tested in numerous clinical trials for therapeutic applications due to its putative chemopreventive properties. Rosmarinic acid has been extensively studied at the cellular, whole animal, and molecular mechanism levels, presenting a complex array of multi-system biological effects. Rosmarinic acid-induced hormetic dose responses are widespread, occurring in numerous biological models and cell types for a broad range of endpoints. Consequently, this article provides the first assessment of rosmarinic acid-induced hormetic concentration/dose responses, their quantitative features, mechanistic foundations, extrapolative strengths/limitations, and their biomedical, clinical, and public health implications.

Keywords: U-shaped dose–response; biphasic dose response; dose–response; hormesis; neuroprotection.

Figure 1

Dynamic features of the hormetic dose response.

Figure 2

Rosmarinic acid enhanced memory in ICR male mice in the Morris water maize (escape latency) (modified from Park et al. [27]) (*= statistical significance P = <0.05).

Figure 3

Effects of rosmarinic acid on forced swimming induced immobilization in ICR male mice (modified from Takeda et al. [31]) (*= statistical significance P = <0.05).

Figure 4

Effects of rosmarinic acid on the freezing behavior of male ddY mice exposed to conditioned fear stress (modified from Takeda et al. [32]) (*= statistical significance P = <0.05).

Figure 5

Effects of lemon peel oil on anxiety in SD rats (modified from Yousuf et al. [33]) (*= statistical significance P = <0.05).

Figure 6

Effects of rosmarinic acid on pain response in male ICR mice (modified from Boonyarikpunchai et al. [36]) (*= statistical significance P = <0.05).

Figure 7

Effects of rosmarinic acid on the generalized seizure incidence in female C57BL/6 mice (modified from Gruigoletto et al. [37]).

Figure 8

Effects of rosmarinic acid on cultured hippocampal neural stem cells (WST assay) (modified from Nie et al. [39]) (*= statistical significance P = <0.05).

Figure 9

Effects of Lavandula stoechas extract (with rosmarinic acid) on PC12 cells (modified from Tayarani-Najaran et al. [40]) (*= statistical significance P = <0.05).

Figure 10

Effects of rosmarinic acid cell viability (MTT assay) on the rat (Wistar adult males) adipose tissue-derived stem cells (modified from Ghorbani et al. [45]) (*= statistical significance P = <0.05).

Figure 11

Effects of rosemary extract (RE) on C2C12 myoblast differentiation (modified from Lee et al. [50]) (*= statistical significance P = <0.05).

Figure 12

Effect of rosmarinic acid on PCS cells, a normal human skin fibroblast cell strain, using MTT assay (modified from Sodagam et al. [52]) (*= statistical significance P = < 0.05).

Figure 13

Effects of rosmarinic acid pretreatment (24 h) on the toxicity of ultraviolet B on HDF and human keratinocytes (HaCaT) (MTT assay) (modified from Gupta et al. [56]) (*= statistical significance P = < 0.05).

Figure 14

Effects of rosmarinic acid on cell viability in direct exposure and in preconditioning studies to prevent H₂O₂ toxicity in MCF-7 cells (modified from Rahbardar et al. [58]) (*= statistical significance P = < 0.05).

Figure 15

Effects of rosmarinic acid on spotted halibut functional quality during cryopreservation (modified from Zidni et al. [64]) (*= statistical significance P = < 0.05).

Figure 16

Effects of rosmarinic acid on cell viability of human ovarian carcinoma cells (OVCAR3) (24 h) (modified from Sari and Zaman [69]) (*= statistical significance P = < 0.05).

Figure 17

Effects of rosmarinic acid on allium root growth (i.e., root length) (modified from Liman et al. [74]) (*= statistical significance P = < 0.05).

Figure 18

Effects of rosmarinic acid on the cell proliferation of CCC-HEL (hepatic stellate cells) (modified from Zhang et al. [75]).