Astaxanthin as a Modulator of Nrf2, NF-κB, and Their Crosstalk: Molecular Mechanisms and Possible Clinical Applications

Abstract

Astaxanthin (AST) is a dietary xanthophyll predominantly found in marine organisms and seafood. Due to its unique molecular features, AST has an excellent antioxidant activity with a wide range of applications in the nutraceutical and pharmaceutical industries. In the past decade, mounting evidence has suggested a protective role for AST against a wide range of diseases where oxidative stress and inflammation participate in a self-perpetuating cycle. Here, we review the underlying molecular mechanisms by which AST regulates two relevant redox-sensitive transcription factors, such as nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor κB (NF-κB). Nrf2 is a cellular sensor of electrophilic stress that coordinates the expression of a battery of defensive genes encoding antioxidant proteins and detoxifying enzymes. Likewise, NF-κB acts as a mediator of cellular stress and induces the expression of various pro-inflammatory genes, including those encoding cytokines, chemokines, and adhesion molecules. The effects of AST on the crosstalk between these transcription factors have also been discussed. Besides this, we summarize the current clinical studies elucidating how AST may alleviate the etiopathogenesis of oxidative stress and inflammation.

Thymoquinone Prevents Doxorubicin-induced Hepatic-injury by Mitigating the Impairment of Mitochondrial Respiration and Electron Transport

“…Our results showed that tissue SOD levels were lower in rats given DOX than in rats in the control group. This was in line with other studies [30,31]. However, THY pre-treatment reversed the observed change in SOD levels.…”

Ambroxol, a mucolytic agent, boostsHO‐1, suppressesNF‐κB, and decreases the susceptibility of the inflamed rat colon to apoptosis: A new treatment option for treating ulcerative colitis

“…The latter findings impose the anti‐inflammatory potential of ambroxol (200 mg/kg) in the injured rat colons. It has been well delineated that NF‐κB/Nrf2 crosstalk is a significant player in the interplay between oxidative stress and inflammation 58 . In this context, ambroxol proved to modulate NF‐κB/Nrf2 crosstalk.…”

“…It has been well delineated that NF-κB/Nrf2 crosstalk is a significant player in the interplay between oxidative stress and inflammation. 58 In this context, ambroxol proved to modulate NF-κB/Nrf2 crosstalk. As indicated by the alterations in the levels of Nrf2, Nrf2 activity, HO-1, the ratio of phospho p65/p65, NF-κB p65 binding activity, and increased levels of IκBα as well as the consequent elevations in the activity of catalase and the total antioxidant capacity.…”

Recent Advances and the Mechanism of Astaxanthin in Ophthalmological Diseases

“…In addition, another survey showed that AST can significantly increase the activity of GPx and SOD, protecting mouse hepatocytes from oxidative damage by using hydrogen peroxide [24]. Fakhri et al also found that AST can increase the expression of glutathione S-transferase α1 (GST-α1), which enhances the biological defense against oxidative stress damage via the activation of the extracellular signal-regulated protein kinase (ERK) signaling pathway in vitro and in vivo [10].…”

“…Due to the speci c biological structure, AST can play an important role in a variety of biological processes, such as antioxidant, anti-in ammatory, antiapoptotic, and anticancer processes; it has a series of biological functions, such as protecting the cardiovascular system, delaying diabetic nephropathy and liver injury, having antiobesity properties, and improving immunity [10]. Currently, AST has become a hot research topic, and several recent studies have highlighted the potential protective role of AST in eye diseases.…”