Persulfidation of mitoKv7.4 channels contributes to the cardioprotective effects of the H2S-donor Erucin against ischemia/reperfusion injury

Testai, Lara; Montanaro, Rosangela; Flori, L.; Pagnotta, Eleonora; Vellecco, Valentina; Gorica, Era; Ugolini, Luisa; Righetti, Laura; Brancaleone, Vincenzo; Bucci, Mariarosaria; Piragine, Eugenia; Martelli, Alma; Mannelli, Lorenzo Di Cesare; Ghelardini, Carla; Calderone, Vincenzo

doi:10.1016/j.bcp.2023.115728

Cited by 8 publications

(7 citation statements)

References 65 publications

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“…ERU (Figure 1) was produced by myrosinase-catalyzed hydrolysis of glucoerucin isolated from Eruca sativa Mill. defatted seed meals, as described in [33]. Briefly, the glucosinolate was extracted from E. sativa (Nemat) defatted seed meal in 70% ethanol and it was isolated by an ion exchange chromatography on a DEAE-Sephadex A-25 anion-exchange column (5 × 20 cm) (GE Healthcare Bioscience AB, Uppsala, Sweden) pre-conditioned with 50 mM acetate buffer, pH 4.2.…”

Section: Erucin Productionmentioning

confidence: 99%

“…Recently, our research group has demonstrated how the isothiocyanate moiety, characteristic of several compounds of natural origin, is capable of releasing H 2 S and exerts cardioprotective effects [27,32,33]. In this regard, erucin (ERU) is an isothiocyanate deriving from the enzymatic hydrolysis of the GSL glucoerucin, naturally occurring in the different cellular compartments of Eruca sativa Mill., a plant belonging to the Brassicaceae family.…”

Section: Introductionmentioning

confidence: 99%

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Erucin Exerts Cardioprotective Effects on Ischemia/Reperfusion Injury through the Modulation of mitoKATP Channels

Flori,

Montanaro,

Pagnotta

et al. 2023

Biomedicines

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Modulation of mitochondrial K channels represents a pharmacological strategy to promote cardioprotective effects. Isothiocyanates emerge as molecules capable of releasing hydrogen sulfide (H2S), an endogenous pleiotropic gasotransmitter responsible for anti-ischemic cardioprotective effects also through the involvement of mitoK channels. Erucin (ERU) is a natural isothiocyanate resulting from the enzymatic hydrolysis of glucosinolates (GSLs) present in Eruca sativa Mill. seeds, an edible plant of the Brassicaceae family. In this experimental work, the specific involvement of mitoKATP channels in the cardioprotective effect induced by ERU was evaluated in detail. An in vivo preclinical model of acute myocardial infarction was reproduced in rats to evaluate the cardioprotective effect of ERU. Diazoxide was used as a reference compound for the modulation of potassium fluxes and 5-hydroxydecanoic acid (5HD) as a selective blocker of KATP channels. Specific investigations on isolated cardiac mitochondria were carried out to evaluate the involvement of mitoKATP channels. The results obtained showed ERU cardioprotective effects against ischemia/reperfusion (I/R) damage through the involvement of mitoKATP channels and the consequent depolarizing effect, which in turn reduced calcium entry and preserved mitochondrial integrity.

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Section: Erucin Productionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Erucin Exerts Cardioprotective Effects on Ischemia/Reperfusion Injury through the Modulation of mitoKATP Channels

Flori,

Montanaro,

Pagnotta

et al. 2023

Biomedicines

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“…seed extract generated H 2 S in the same cell‐free assay (Testai et al, 2022). The H 2 S‐releasing properties of natural ITCs from Brassicaceae were then confirmed in different biological substrates (i.e., cultured cardiac (Testai et al, 2023), vascular (Martelli et al, 2020), and cancer cells (Citi et al, 2019). More recently, the thiol‐dependent H 2 S‐releasing capacity of both Moringa oleifera Lam.…”

Section: Natural H2s‐donorsmentioning

confidence: 91%

“…This is confirmed by a meta‐analysis of observational studies, which highlighted a significantly inverse association between consumption of Brassica vegetables and risk of colorectal cancer (Wu et al, 2013). In addition to chemoprevention (Ambrosone et al, 2004; Na et al, 2023; Novío Mallón et al, 2016), organosulfur‐containing plants and isolated sulfur compounds show many other biological effects: they induce vasorelaxation and lower blood pressure (Benavides et al, 2007; Martelli et al, 2020), promote cardioprotective properties (Bai et al, 2015; Testai et al, 2022; Testai et al, 2023), counteract vascular inflammation (Ciccone et al, 2022; Martelli et al, 2021), and contribute to the regulation of glucose and lipid metabolism (Piragine et al, 2022; Ried et al, 2013; Zandani et al, 2021). The impressive overlap of the beneficial effects of H 2 S and natural sulfur compounds has “unmasked” the hidden player in the pharmacology of polysulfides and ITCs, namely the gaseous molecule H 2 S. Regardless of the source and chemical structure, in fact, both polysulfides from Alliaceae and ITCs from Brassicaceae and Moringa oleifera Lam.…”

Section: Natural H2s‐donorsmentioning

confidence: 99%

Natural H₂S‐donors: A new pharmacological opportunity for the management of overweight and obesity

Spezzini,

Piragine,

Flori

et al. 2024

Phytotherapy Research

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The prevalence of overweight and obesity has progressively increased in the last few years, becoming a real threat to healthcare systems. To date, the clinical management of body weight gain is an unmet medical need, as there are few approved anti‐obesity drugs and most require an extensive monitoring and vigilance due to risk of adverse effects and poor patient adherence/persistence. Growing evidence has shown that the gasotransmitter hydrogen sulfide (H2S) and, therefore, H2S‐donors could have a central role in the prevention and treatment of overweight/obesity. The main natural sources of H2S‐donors are plants from the Alliaceae (garlic and onion), Brassicaceae (e.g., broccoli, cabbage, and wasabi), and Moringaceae botanical families. In particular, polysulfides and isothiocyanates, which slowly release H2S, derive from the hydrolysis of alliin from Alliaceae and glucosinolates from Brassicaceae/Moringaceae, respectively. In this review, we describe the emerging role of endogenous H2S in regulating adipose tissue function and the potential efficacy of natural H2S‐donors in animal models of overweight/obesity, with a final focus on the preliminary results from clinical trials. We conclude that organosulfur‐containing plants and their extracts could be used before or in combination with conventional anti‐obesity agents to improve treatment efficacy and reduce inflammation in obesogenic conditions. However, further high‐quality studies are needed to firmly establish their clinical efficacy.

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“…The remarkable potential of nutraceuticals extends far beyond their actions; it resides in their unique ability to orchestrate a symphony of benefits, harmoniously targeting multiple intricate pathways implicated in oxidative stress and inflammation [ 80 , 81 , 82 ]. The advent of personalized medicine has introduced a highly promising avenue for optimizing nutraceutical therapy within the realm of these medical conditions [ 83 ].…”

Section: Challenges In Metabolic Disorders and Nutraceuticals As A No...mentioning

confidence: 99%

Targeting Metabolic Diseases: The Role of Nutraceuticals in Modulating Oxidative Stress and Inflammation

Dama,

Shpati,

Daliu

et al. 2024

Nutrients

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The escalating prevalence of metabolic and cardiometabolic disorders, often characterized by oxidative stress and chronic inflammation, poses significant health challenges globally. As the traditional therapeutic approaches may sometimes fall short in managing these health conditions, attention is growing toward nutraceuticals worldwide; with compounds being obtained from natural sources with potential therapeutic beneficial effects being shown to potentially support and, in some cases, replace pharmacological treatments, especially for individuals who do not qualify for conventional pharmacological treatments. This review delves into the burgeoning field of nutraceutical-based pharmacological modulation as a promising strategy for attenuating oxidative stress and inflammation in metabolic and cardiometabolic disorders. Drawing from an extensive body of research, the review showcases various nutraceutical agents, such as polyphenols, omega-3 fatty acids, and antioxidants, which exhibit antioxidative and anti-inflammatory properties. All these can be classified as novel nutraceutical-based drugs that are capable of regulating pathways to mitigate oxidative-stress- and inflammation-associated metabolic diseases. By exploring the mechanisms through which nutraceuticals interact with oxidative stress pathways and immune responses, this review highlights their potential to restore redox balance and temper chronic inflammation. Additionally, the challenges and prospects of nutraceutical-based interventions are discussed, encompassing bioavailability enhancement, personalized treatment approaches, and clinical translation. Through a comprehensive analysis of the latest scientific reports, this article underscores the potential of nutraceutical-based pharmacological treatment modulation as a novel avenue to fight oxidative stress and inflammation in the complex landscape of metabolic disorders, particularly accentuating their impact on cardiovascular health.

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Persulfidation of mitoKv7.4 channels contributes to the cardioprotective effects of the H2S-donor Erucin against ischemia/reperfusion injury

Cited by 8 publications

References 65 publications

Erucin Exerts Cardioprotective Effects on Ischemia/Reperfusion Injury through the Modulation of mitoKATP Channels

Erucin Exerts Cardioprotective Effects on Ischemia/Reperfusion Injury through the Modulation of mitoKATP Channels

Natural H₂S‐donors: A new pharmacological opportunity for the management of overweight and obesity

Targeting Metabolic Diseases: The Role of Nutraceuticals in Modulating Oxidative Stress and Inflammation

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Persulfidation of mitoKv7.4 channels contributes to the cardioprotective effects of the H2S-donor Erucin against ischemia/reperfusion injury

Cited by 8 publications

References 65 publications

Erucin Exerts Cardioprotective Effects on Ischemia/Reperfusion Injury through the Modulation of mitoKATP Channels

Erucin Exerts Cardioprotective Effects on Ischemia/Reperfusion Injury through the Modulation of mitoKATP Channels

Natural H2S‐donors: A new pharmacological opportunity for the management of overweight and obesity

Targeting Metabolic Diseases: The Role of Nutraceuticals in Modulating Oxidative Stress and Inflammation

Contact Info

Product

Resources

About

Natural H₂S‐donors: A new pharmacological opportunity for the management of overweight and obesity