Cytoprotective Effects of Natural Compounds against Oxidative Stress

Abstract

Oxidative stress, an imbalance between reactive oxygen species and antioxidants, has been witnessed in pathophysiological states of many disorders. Compounds identified from natural sources have long been recognized to ameliorate oxidative stress due to their inherent antioxidant activities. Here, we summarize the cytoprotective effects and mechanisms of natural or naturally derived synthetic compounds against oxidative stress. These compounds include: caffeic acid phenethyl ester (CAPE) found in honey bee propolis, curcumin from turmeric roots, resveratrol abundant in grape, and 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl] imidazole (CDDO-Im), a synthetic triterpenoid based on naturally occurring oleanolic acid. Cytoprotective effects of these compounds in diseases conditions like cardiovascular diseases and obesity to decrease oxidative stress are discussed.

Keywords: CAPE; CDDO-Im; cardiovascular diseases; curcumin; cytoprotection; obesity; oxidative stress; resveratrol.

Figure 1

Structures of CAPE (caffeic acid phenethyl ester), Curcumin, Resveratrol, and CDDO-Im (1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl] imidazole).

Figure 2

Mechanism of action of resveratrol to reduce inflammation, oxidative stress and obesity. AMPK: AMP-activated protein kinase; ERK: extracellular signal-regulated kinase; NF-κB: nuclear factor - kappa B; Nrf2: nuclear erythroid 2 - related factor; SIRT1: sirtuin 1.

Figure 3

Overview of the cytoprotective mechanisms of CAPE, CDDO-Im, curcumin and resveratrol. All the four compounds inhibit NFκB [12,26,46,59] and trigger Nrf2 nuclear translocation to activate HO-1 expression. Induction of HO-1 by curcumin and CDDO-Im is mediated in part through the activation of MAPK signaling which in turn translocates Nrf2 [59]. The cytoprotective mechanism of resveratrol and CAPE include Nrf2-medaited HO-1 induction coupled with the activation of ERK signaling pathway [34,142]. CAPE: caffeic acid phenethyl ester; CDDO-Im: 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl] imidazole; ERK: extracellular signal-regulated kinase; GPx: glutathione peroxidase; HO-1: heme oxygenase-1; MAPK: mitogen-activated protein kinase; NF-κB: nuclear factor - kappa B; Nrf2: nuclear erythroid 2 - related factor; PI₃K/Akt: phosphatidylinositol 3-kinase/ protein kinase B; SOD: superoxide dismutase.