The synergistic anti-inflammatory effects of lycopene, lutein, β-carotene, and carnosic acid combinations via redox-based inhibition of NF-κB signaling

Hadad, Nurit; Lévy, Rachel

doi:10.1016/j.freeradbiomed.2012.07.078

Cited by 110 publications

(76 citation statements)

References 59 publications

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“…Activated NF-κB regulates iNOS expression and plays an important role in inflammation in LPS-stimulated macrophages [26,27]. In present study, LPS stimulation for 2 h caused a significant nuclear translocation of NF-κB p65, which was concentration-dependently attenuated by ZY-1A4 ( P < 0.05, Fig.…”

Section: Resultssupporting

confidence: 49%

Induction of Heme Oxygenase-1 by Sodium 9-Hydroxyltanshinone IIA Sulfonate Derivative Contributes to Inhibit LPS-Mediated Inflammatory Response in Macrophages

Liu

Wang

Xiao

et al. 2015

Cell Physiol Biochem

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Background/Aim: Sodium 9-acetoxyltanshinone IIA sulfonate (ZY-1A4), a novel compound derived from sodium 9-hydroxyltanshinone IIA sulfonate, was synthesized with potential biological activities. This study aimed to explore the effects of ZY-1A4 on lipopolysaccharide (LPS)-triggered inflammatory response and the underlying mechanisms. Methods: Activation of RAW264.7 macrophages was induced by LPS. The effects of ZY-1A4 on inducible nitric oxide synthase (iNOS) expression, nitric oxide (NO) generation, nuclear factor-κB (NF-κB) activation, heme oxygenase-1 (HO-1) expression, and nuclear factor-erythroid 2 related factor 2 (Nrf2) pathway were evaluated to elucidate its underlying mechanisms on inflammatory responses. Results: ZY-1A4 concentration-dependently reduced iNOS expression and NO production, and inhibited c-Jun-N-terminal kinase 1/2 (JNK1/2) phosphorylation and NF-κB activation in LPS-stimulated macrophages. In addition, ZY-1A4 concentration- and time-dependently induced HO-1 expression associated with degradation of Kelch-like ECH-associated protein 1 (Keap1) and nuclear translocation of Nrf2, while the effect of ZY-1A4 was abolished by a phosphoinositide 3-kinase (PI3K) inhibitor LY294002. Intriguingly, pharmacological inactivation of HO-1 with zinc protoporphyrin IX reversed anti-inflammatory effect of ZY-1A4, but the anti-inflammatory effect of ZY-1A4 was largely mimicked by HO-1 by-products carbon monoxide and bilirubin. Furthermore, the inhibitory effect of ZY-1A4 on LPS-induced iNOS expression and NO release was abolished by HO-1 siRNA or LY294002. Conclusion: Our results demonstrated that ZY-1A4 suppressed LPS-induced iNOS expression and NO generation via modulation of NF-κB activation and HO-1 expression. This new finding might shed light to the prevention and therapy of cardiovascular diseases.

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Section: Resultssupporting

confidence: 49%

Induction of Heme Oxygenase-1 by Sodium 9-Hydroxyltanshinone IIA Sulfonate Derivative Contributes to Inhibit LPS-Mediated Inflammatory Response in Macrophages

Liu

Wang

Xiao

et al. 2015

Cell Physiol Biochem

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“…In recent years, the anti-inflammatory effect of carotenoids was demonstrated in several in vitro and in vivo experimental systems [34][35][36][37][38][39][40]. Pretreatment with lycopene attenuated the proinflammatory phenotype as shown by the inhibition of NFkB activity, particularly in combination with other phytonutrients [34,39,40].…”

Section: Introductionmentioning

confidence: 99%

“…Pretreatment with lycopene attenuated the proinflammatory phenotype as shown by the inhibition of NFkB activity, particularly in combination with other phytonutrients [34,39,40]. Several studies indicate that carotenoids inhibit NFkB in experimental cancer models [35,36].…”

Section: Introductionmentioning

confidence: 99%

Carotenoid derivatives inhibit nuclear factor kappa B activity in bone and cancer cells by targeting key thiol groups

Linnewiel-Hermoni

Motro

Miller

et al. 2014

Free Radical Biology and Medicine

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“…The lycopene-rich TNC assessed in the current study contained 15 mg lycopene, 5.8 mg phytoene and phytofluene, 0.8 mg β-carotene, 5.6 mg tocopherols from tomato extract, and 4 mg carnosic acid from rosemary extract per day because previous in vitro studies/animal studies indicated a synergistic inhibition of LPS-induced NO production, TNFα-, superoxide and PGE 2 release in macrophages and in a mouse model of peritonitis by lycopene, β-carotene, and the phenolic carnosic acid [39]. Similarly, synergistic inhibition of oxidative stress in a mouse tumor model [40] or inhibition of androgen signaling and PSA secretion by lycopene and tocopherol [41] was determined.…”

Section: Resultsmentioning

confidence: 99%

Tomato Phytonutrients Balance UV Response: Results from a Double-Blind, Randomized, Placebo-Controlled Study

Groten

Marini

Jaenicke

et al. 2019

Skin Pharmacol Physiol

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Background: Our previous double-blinded, placebo-controlled cross-over study indicated that a nutritional supplement named lycopene-rich tomato nutrient complex (TNC) can protect from UVA1-induced (340–400 nm) and UVA- (320–400 nm)/UVB-induced (280–320 nm) upregulation of molecular markers associated with oxidative stress, inflammation, and ageing. Objectives: in the current double-blind, randomized, placebo-controlled multicenter study, we analyze whether a similar, synergistic carotenoid-rich TNC can protect from broadband UVB-induced threshold erythema formation assessed as increase in minimal erythemal dose (MED) reading, the intensity of erythema formation, and the upregulation of molecular markers associated with inflammation and immunosuppression, and whether this correlates with carotenoid blood levels. Methods: One hundred and forty-nine healthy volunteers were randomized to two groups and subjected to a 5-week washout phase, followed by a 12-week treatment phase receiving either 15 mg lycopene, 5.8 mg phytoene and phytofluene, 0.8 mg β-carotene, 5.6 mg tocopherols from tomato extract, and 4 mg carnosic acid from rosemary extract per day or placebo made from medium-chain triglycerides. At the end of each phase, MED determination, UVB irradiation, chromametry, biopsies, and blood samples were undertaken. Results: The active supplement was well tolerated. Interestingly, no significant difference was seen in the MED between the active-supplement and placebo groups, as determined by visual grading by expert assessors. Of note, the carotenoid-containing supplement significantly protected against UVB-induced erythema formation measured as Δa* after the intervention minus Δa* after the washout phase as compared to the placebo. Moreover, intake of the active supplement significantly protected against UVB-induced upregulation of IL6 and TNFα as compared with the intake of placebo. Lastly, carotenoid plasma levels were significantly increased. Conclusion: This well-tolerated carotenoid-containing supplement significantly protected against UVB-induced erythema formation and upregulation of proinflammatory cytokines in healthy volunteers.

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The synergistic anti-inflammatory effects of lycopene, lutein, β-carotene, and carnosic acid combinations via redox-based inhibition of NF-κB signaling

Cited by 110 publications

References 59 publications

Induction of Heme Oxygenase-1 by Sodium 9-Hydroxyltanshinone IIA Sulfonate Derivative Contributes to Inhibit LPS-Mediated Inflammatory Response in Macrophages

Induction of Heme Oxygenase-1 by Sodium 9-Hydroxyltanshinone IIA Sulfonate Derivative Contributes to Inhibit LPS-Mediated Inflammatory Response in Macrophages

Carotenoid derivatives inhibit nuclear factor kappa B activity in bone and cancer cells by targeting key thiol groups

Tomato Phytonutrients Balance UV Response: Results from a Double-Blind, Randomized, Placebo-Controlled Study

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