The functional role of sulforaphane in intestinal inflammation: a review

Wei, Liyang; Zhang, Jiukai; Chen, Ying

doi:10.1039/d1fo03398k

Cited by 34 publications

(24 citation statements)

References 119 publications

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“…Sulforaphane (Sfn), an aliphatic isothiocyanate found as a glucosinolate precursor in cruciferous vegetables, is highly investigated in the context of cancer prevention and inflammation-related disorders, including psoriasis, inflammatory bowel disease, neurodegeneration, or atherosclerosis (e.g., 8 – 13 ). Numerous in vitro and in vivo studies revealed the ubiquitin ligase adapter Keap1 as one of Sfn’s main targets ( 14 , 15 ).…”

Section: Introductionmentioning

confidence: 99%

Sulforaphane diminishes moonlighting of pyruvate kinase M2 and interleukin 1β expression in M1 (LPS) macrophages

et al. 2022

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Murine macrophages activated by the Toll-like receptor 4 agonist lipopolysaccharide (LPS) polarize to the M1 type by inducing proinflammatory marker proteins and changing their energy metabolism to increased aerobic glycolysis and reduced respiration. We here show that the aliphatic isothiocyanate sulforaphane (Sfn) diminishes M1 marker expression (IL-1β, IL-6, TNF-α, iNOS, NO, and ROS) and leads to highly energetic cells characterized by both high glycolytic and high respiratory activity as assessed by extracellular flux analysis. Focusing on a potential connection between high glycolytic activity and low IL-1β expression in M1 (LPS/Sfn) macrophages, we reveal that Sfn impedes the moonlighting function of pyruvate kinase M2 (PKM2) in M1 macrophages. Sfn limits mono/dimerization and nuclear residence of PKM2 accompanied by reduced HIF-1α levels, Stat3 phosphorylation at tyrosine 705, and IL-1β expression while preserving high levels of cytosolic PKM2 tetramer with high glycolytic enzyme activity. Sfn prevents glutathionylation of PKM2 in LPS-stimulated macrophages which may account for the reduced loss of PKM2 tetramer. Overall, we uncover PKM2 as a novel affected hub within the anti-inflammatory activity profile of Sfn.

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Section: Introductionmentioning

confidence: 99%

Sulforaphane diminishes moonlighting of pyruvate kinase M2 and interleukin 1β expression in M1 (LPS) macrophages

et al. 2022

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“…This metabolite has been broadly characterized revealing cutting edge information on its health benefits, specifically related to preventing the onset of diverse types of cancer [ 44 ], in addition to key physiological activities, such as anti-depressant/anxiolytic-like effects, hypoglycemic, and anti-inflammatory activities [ 45 , 46 , 47 ]. Related to the latter activity and closely related to the concentration of dietary SFN reached in the upper intestinal sections, SFN has been recently related to the prevention of the severity of intestinal bowel disease, an emerging epidemic disorder that needs new therapeutic agents contributing to lower the incidence and severity of the clinical symptoms [ 48 ]. In this frame, the current study showed that although all materials digested after processing by lyophilisation, low-temperature, and decreasing temperature gradient drying experienced an augment of the SFN concentration in the digestion process, the highest values were for broccoli stalk’s core independently of the treatment applied, achieving concentrations of 3.8–4.1 g/kg dw ( Figure 2 ).…”

Section: Resultsmentioning

confidence: 99%

A New Food Ingredient Rich in Bioaccessible (Poly)Phenols (and Glucosinolates) Obtained from Stabilized Broccoli Stalks

Costa-Pérez

Moreno

Periago

et al. 2022

Foods

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Broccoli (Brassica oleracea var. italica) stalks account for up to 35% of the broccoli harvest remains with the concomitant generation of unused waste that needs recovery to contribute to the sustainability of the system. However, due to its phytochemical composition, rich in bioactive (poly)phenols and glucosinolates, as well as other nutrients, the development of valorization alternatives as a source of functional ingredients must be considered. In this situation, the present work aims to develop/obtain a new ingredient rich in bioactive compounds from broccoli, stabilizing them and reducing their degradation to further guarantee a high bioaccessibility, which has also been studied. The phytochemical profile of lyophilized and thermally treated (low-temperature and descending gradient temperature treatments), together with the digested materials (simulated static in vitro digestion) were analysed by HPLC-PDA-ESI-MSn and UHPLC-3Q-MS/MS. Broccoli stalks and co-products were featured by containing phenolic compounds (mainly hydroxycinnamic acid derivatives and glycosylated flavonols) and glucosinolates. The highest content of organosulfur compounds corresponding to the cores of the broccoli stalks treated by applying a drying descendant temperature gradient (aliphatic 18.05 g/kg dw and indolic 1.61 g/kg dw, on average, while the breakdown products were more abundant in the bark ongoing low temperature drying 11.29 g/kg dw, on average). On the other hand, for phenolics, feruloylquinic, and sinapoylquinic acid derivatives of complete broccoli stalk and bark, were more abundant when applying low-temperature drying (14.48 and 28.22 g/kg dw, on average, respectively), while higher concentrations were found in the core treated with decreasing temperature gradients (9.99 and 26.26 g/kg dw, on average, respectively). When analysing the bioaccessibility of these compounds, it was found that low-temperature stabilization of the core samples provided the material with the highest content of bioactives including antioxidant phenolics (13.6 and 33.9 g/kg dw of feruloylquinic and sinapoylquinic acids, on average, respectively) and sulforaphane (4.1 g/kg dw, on average). These processing options enabled us to obtain a new product or ingredient rich in bioactive and bioaccessible compounds based on broccoli stalks with the potential for antioxidant and anti-inflammatory capacities of interest.

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“…Treatment of CPZ-intoxicated rats with SF counteracted the enhanced oxidative stress in both cardiac and hepatic tissues. SF exhibited the potential to enhance the expression of detoxification or defensive enzymes via the Keap1/Nrf2/ARE signaling pathway [ 30 ]. Immunohistochemical results demonstrated Nrf-2 activation upon treatment with SF; this could be ascribed to the potential of Nrf-2 to regulate the up-regulation of detoxification genes to activate a cytoprotective response, through mediating the inactivation of oxidants and favoring the synthesis of antioxidants [ 68 ].…”

Section: Discussionmentioning

confidence: 99%

“…Nrf-2 is vital for the maintenance of redox signaling in response to stress [ 71 ]. Under stress conditions such as CPZ-induced toxicity, Nrf-2 loses its DNA binding to ARE, however, this loss of Nrf-2/ARE binding could be reversed by using “Nrf-2 agonists” such as SF [ 72 , 73 ]; suggesting that Nrf-2-mediated survival pathways are reversible and responsive by using effective agonists of Nrf-2 such as SF, which act as “indirect antioxidant” with anti-inflammatory potential [ 30 , 74 ]. The inhibitory potential of SF on abnormally activated inflammation is related to the activation of Nrf-2-mediated signaling pathways [ 75 ].…”

Section: Discussionmentioning

confidence: 99%

“…Sulforaphane (SF) is a powerful phytochemical found in seeds and sprouts of cruciferous plants such as broccoli, SF is a pleiotropic agent that exhibited promising multifactorial functions against several chronic diseases, including neurodegenerative disorders and cancer [20][21][22][23][24], moreover, numerous studies showed the hepatoprotective and cardioprotective activities of SF [25][26][27][28][29]. SF is an activator of nuclear factor E2 related factor (Nrf-2) [30], which is a transcription factor involved in the adaptive response to several endogenous and exogenous stressors such as oxidative stress; SF targets the activation of the Nrf-2 pathway which regulates the expression of cytoprotective enzymes that exhibited anti-oxidative and detoxification activities [31].…”

Section: Introductionmentioning

confidence: 99%

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Sulforaphane, an Nrf-2 Agonist, Modulates Oxidative Stress and Inflammation in a Rat Model of Cuprizone-Induced Cardiotoxicity and Hepatotoxicity

Fouad

2023

Cardiovasc Toxicol

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Cuprizone (CPZ) is a neurotoxic agent that is used to induce demyelination and neurotoxicity in rats. This study aimed to investigate the protective potential of sulforaphane (SF), nuclear factor E2 related factor (Nrf-2) activator, against CPZ-induced cardiotoxicity and hepatotoxicity. Male adult Wistar rats (n = 18) were fed with a regular diet or a CPZ-contained diet (0.2%) for four weeks. The rats were divided into three groups (n = 6): negative control rats, CPZ-exposed rats, and CPZ + SF treated rats. SF was intraperitoneally administrated (2 mg/kg/day) for two weeks. The anti-inflammatory and anti-oxidative functions of SF were investigated biochemically, histologically, and immunohistochemically. CPZ increased serum levels of cardiac troponin 1 (CTn1), aspartate amino transaminase (AST), alanine amino transaminase (ALT), and alkaline phosphatase (ALP). In addition, serum levels of inflammatory interferon-gamma (IFN-γ), and pro-inflammatory interleukin 1β (IL-1β) were significantly elevated. Moreover, CPZ administration provoked oxidative stress as manifested by declined serum levels of total antioxidant capacity (TAC), as well as, stimulated lipid peroxidation and decreased catalase activities in both cardiac and hepatic tissues. SF treatment reversed all these biochemical alterations through exerting anti-oxidative and anti-inflammatory activities, and this was supported by histopathological investigations in both cardiac and hepatic tissues. This SF-triggered modulation of oxidative stress and inflammation is strongly associated with Nrf-2 activation, as evidenced by activated immunoexpression in both cardiac and hepatic tissues. This highlights the cardioprotective and hepatoprotective activities of SF via Nrf-2 activation and enhancing catalase function.

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The functional role of sulforaphane in intestinal inflammation: a review

Abstract: Intestinal inflammation represented by inflammatory bowel disease (IBD) has become a global epidemic disease and the number of patients is still increasing. This digestive tract disease not only affects the...

Cited by 34 publications

References 119 publications

Sulforaphane diminishes moonlighting of pyruvate kinase M2 and interleukin 1β expression in M1 (LPS) macrophages

Sulforaphane diminishes moonlighting of pyruvate kinase M2 and interleukin 1β expression in M1 (LPS) macrophages

A New Food Ingredient Rich in Bioaccessible (Poly)Phenols (and Glucosinolates) Obtained from Stabilized Broccoli Stalks

Sulforaphane, an Nrf-2 Agonist, Modulates Oxidative Stress and Inflammation in a Rat Model of Cuprizone-Induced Cardiotoxicity and Hepatotoxicity

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