Carnosic Acid as a Promising Agent in Protecting Mitochondria of Brain Cells

Abstract

Carnosic acid (CA; C₂₀H₂₈O₄), a phenolic diterpene characterized as an ortho-dihydroquinone-type molecule, is a pro-electrophile agent that becomes an electrophile after reacting with free radicals. The electrophile generated from CA interacts with and activates the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor, which is a major modulator of redox biology in mammalian cells. CA induces antioxidant and anti-inflammatory effects in several cell types, as observed in both in vitro and in vivo experimental models. In this context, CA has been viewed as a neuroprotective agent by activating signaling pathways associated with cell survival during stressful conditions. Indeed, CA exhibits the ability to promote mitochondrial protection in neural cells. Mitochondria are the main source of both ATP and reactive species in animal cells. Mitochondrial dysfunction plays a central role in the start and development of neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, among others. Therefore, the study of strategies aiming to reduce mitochondrial impairment in the case of neurodegeneration is of pharmacological interest. In the present review, it is described and discussed the effects of CA on brain mitochondria in experimental models of neural lesion. Based on the data discussed here, CA is a potential candidate to be listed as a neuroprotective agent by acting on the mitochondria of neural cells.

Keywords: Anti-apoptotic; Antioxidant; Brain; Carnosic acid; Mitochondria; Neuroprotection.