Carnosic Acid Suppresses the H2O2-Induced Mitochondria-Related Bioenergetics Disturbances and Redox Impairment in SH-SY5Y Cells: Role for Nrf2

Abstract

The phenolic diterpene carnosic acid (CA, CHO) exerts antioxidant, anti-inflammatory, anti-apoptotic, and anti-cancer effects in mammalian cells. CA activates the nuclear factor erythroid 2-related factor 2 (Nrf2), among other signaling pathways, and restores cell viability in several in vitro and in vivo experimental models. We have previously reported that CA affords mitochondrial protection against various chemical challenges. However, it was not clear yet whether CA would prevent chemically induced impairment of the tricarboxylic acid cycle (TCA) function in mammalian cells. In the present work, we found that a pretreatment of human neuroblastoma SH-SY5Y cells with CA at 1 μM for 12 h prevented the hydrogen peroxide (HO)-induced impairment of the TCA enzymes (aconitase, α-ketoglutarate dehydrogenase (α-KGDH), succinate dehydrogenase (SDH)) and abolished the inhibition of the complexes I and V and restored the levels of ATP by a mechanism associated with Nrf2. CA also exhibited antioxidant abilities by enhancing the levels of reduced glutathione (GSH) and decreasing the content oxidative stress markers (cellular 8-oxo-2'-deoxyguanosine (8-oxo-dG), and mitochondrial malondialdehyde (MDA), protein carbonyl, and 3-nitrotyrosine). Silencing of Nrf2 by small interfering RNA (siRNA) abrogated the protective effects elicited by CA in mitochondria of SH-SY5Y cells. Therefore, CA prevented the HO-triggered mitochondrial impairment by an Nrf2-dependent mechanism. The specific role of Nrf2 in ameliorating the function of TCA enzymes function needs further research.

Carnosic acid improves porcine early embryonic development by inhibiting the accumulation of reactive oxygen species

“…4A). The main mechanism may involve regulation of ERK, Keap1/Nrf2, PI3K/Akt, and the c-fos signaling pathway [37][38][39][40].…”

Maresin 1 Ameliorates Lung Ischemia/Reperfusion Injury by Suppressing Oxidative Stress via Activation of the Nrf‐2‐Mediated HO‐1 Signaling Pathway

“…Yang et al verified that HO-1, upregulated by pterostilbene, suppressed mitochondrial oxidative stress in vitro and in vivo in an experimental model of cerebral ischemia reperfusion injury [40]. Marcos et al demonstrated that inhibition of HO-1 or silencing of Nrf-2 blocked the protective effects of Carnosic acid on mitochondria-related redox parameters and function, which explicated a role of the Nrf-2/HO-1 axis in the maintenance of mitochondrial function during oxidative stress [41]. Our present study showed that MaR 1 increased nuclear Nrf-2 and cytosolic HO-1 expression in lung tissue after ischemic reperfusion.…”

Chemical Composition and Pharmacological Effects of Geopropolis Produced by Melipona quadrifasciata anthidioides

“…Naringenin, one of the flavonoids identified in HEG, has been described as modulating the activity of the enzymes superoxide dismutase, glutathione peroxidase, and catalase, in addition to protecting the cell membrane against the lipid peroxidation process by inhibiting the production of malondialdehyde and increasing the content of thiol-SH groups [ 43 ]. In turn, diterpenes promote the scavenging of free radicals, which results in the inhibition of lipid peroxidation [ 46 , 47 ].…”