Multivariate Analysis Reveals That Unsubstituted β-Ring and C8-Keto Structures Are Important Factors for Anti-Inflammatory Activity of Carotenoids.

Yuki Manabe,Tatsuya Sugawara,Nami Tomonaga,Takashi Maoka

doi:10.3390/nu13113699

Abstract

Carotenoids are natural lipophilic pigments with substantial health benefits. Numerous studies have demonstrated the anti-inflammatory activities of carotenoids, especially toward lipopolysaccharide-induced inflammatory responses. As such, there are few reports on the evaluation and comparison of the anti-inflammatory activities of carotenoids against inflammation induced by other stimuli. In this study, we used pathogen-associated molecular patterns, proinflammatory cytokines, degenerated proteins, and chemical irritants as inflammatory inducers to evaluate the anti-inflammatory activities of eight different carotenoids. Each carotenoid showed characteristic anti-inflammatory activities; thus, we conducted a multivariate analysis to clarify the differences among them. Unsubstituted β-ring (i.e., provitamin A) and C8-keto structures of carotenoids were found to be crucial for their inhibitory effects on the activation of nuclear factor-kappa B and interferon regulatory factors, respectively. Furthermore, we found that β-carotene and echinenone treatment increased intracellular retinoid levels in monocytes and that the retinoids showed the similar activities to β-carotene and echinenone. Taken together, the intake of both provitamin A and C8-keto carotenoids (e.g., siphonaxanthin and fucoxanthin) might be effective in improving the inflammatory status of individuals. A multivariate analysis of anti-inflammatory activities is a useful method for characterizing anti-inflammatory compounds.

Highlights

Inflammation is a physiological response to external assaults, such as pathogen invasion
A TLR4 antagonist is used for the treatment of sepsis, and advanced glycation end products (AGEs)—a group of degenerated proteins—and a receptor for AGEs (RAGE) have received attention as therapeutic targets for atherosclerosis [1]
We previously evaluated the effect of carotenoids on inof carotenoids; most of the studies used lipopolysaccharides (LPSs) to evoke flammatory responses induced by another stimulant, AGEs, and found for the first time inflammatory responses

Summary

Introduction

Inflammation is a physiological response to external assaults, such as pathogen invasion. Multiple inflammatory stimuli and their respective receptors are involved in the body’s response to external assaults. Invading pathogens are detected by pattern recognition receptors such as Toll-like receptors (TLRs) that induce inflammatory responses, including proinflammatory cytokine production. Proinflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and interferon (IFN)-γ, evoke inflammatory responses. In addition to pathogenderived molecules, degenerated proteins and chemical irritants are known to induce the production of proinflammatory cytokines. A TLR4 antagonist is used for the treatment of sepsis, and advanced glycation end products (AGEs)—a group of degenerated proteins—and a receptor for AGEs (RAGE) have received attention as therapeutic targets for atherosclerosis [1]

Methods

Results

Conclusion