H2S Donors and Their Use in Medicinal Chemistry

Magli, Elisa; Perissutti, Elisa; Santagada, Vincenzo; Caliendo, Giuseppe; Corvino, Angela; Esposito, Gianluca; Esposito, Giovanna; Fiorino, Ferdinando; Migliaccio, Marianna; Scognamiglio, Antonia; Severino, Beatrice; Sparaco, Rosa; Frecentese, Francesco

doi:10.3390/biom11121899

Cited by 50 publications

(33 citation statements)

References 259 publications

(321 reference statements)

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“…To further explore the roles of CTH/H 2 S in the inflammation process, β-cyano- l -Alanine (BCA), a CTH-specific reversible inhibitor [ 21 , 22 ], and NaHS, a H 2 S donor to trigger H 2 S release in cells [ 23 ], were introduced to uncover the CTH/H 2 S function. CTH and CBS expression was evaluated by qRT-PCR and WB assays.…”

Section: Resultsmentioning

confidence: 99%

CTH/H2S Regulates LPS-Induced Inflammation through IL-8 Signaling in MAC-T Cells

Lin

Bai

Gao

et al. 2022

IJMS

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Hydrogen sulfide (H2S), as an endogenous gaseous signaling molecule, plays an important role in the inflammatory process. Our previous study found that Cystathionine-γ-lyase (CTH) and H2S are correlated with the occurrence and development of Clinical Mastitis (CM) in Holstein cows. However, the functions and regulatory mechanisms of CTH/H2S are still unknown. In this study, the inflammatory mammary cell model based on the MAC-T cell line was established by Lipopolysaccharide (LPS)-induced manner to further explore the function and regulatory mechanism of CTH/H2S in cows with CM. In the inflammatory MAC-T cell, the CTH expression and H2S production were both repressed in an LPS-dose dependent manner, which demonstrated that CTH/H2S is related to the progression of inflammation. The inhibition of CTH/H2S using a selective CTH inhibitor, β-cyano-L-Alanine (BCA), promoted LPS-induced inflammation response and the expression of inflammatory cytokines. However, this was reversed by the H2S donor NaHS, demonstrating that H2S can protect cells from inflammatory damage. Intriguingly, interleukin-8 (IL-8) showed an inverse expression pattern correlated with the H2S-mediated cell protection effect during the inflammation process, and the inhibition test using a selective IL-8 receptor antagonist, SB225002, showed that IL-8 signaling plays a critical role in mediating endogenous H2S synthesis, and CTH/H2S exerts its anti-inflammation via IL-8-mediated signaling. This study provided support for the prevention and treatment of CM and the development of a novel anti-inflammatory strategy.

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Section: Resultsmentioning

confidence: 99%

CTH/H2S Regulates LPS-Induced Inflammation through IL-8 Signaling in MAC-T Cells

Lin

Bai

Gao

et al. 2022

IJMS

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“…Previous studies have revealed that some OSCs could exert their anti-inflammatory effect through the inhibition of the MAPK and NF-κB pathways, but their detailed mechanisms are still unclear ( Rodrigues and Percival, 2019 ). A large amount of literature has indicated that the benefits of OSCs are associated with the number of sulfur atoms in their structure, which is closely related to its potential to increase endogenous hydrogen sulfide (H 2 S) ( Benavides et al, 2007 ; Magli et al, 2021 ). H 2 S has been shown to play an important regulatory role in the inflammatory processes and inhibit the activation of NF-κB and MAPKs ( Stuhlmeier et al, 2009 ; Wu et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Allyl methyl trisulfide protected against LPS-induced acute lung injury in mice via inhibition of the NF-κB and MAPK pathways

et al. 2022

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Allyl methyl trisulfide (AMTS) is one major lipid-soluble organosulfur compound of garlic. Previous studies have reported the potential therapeutic effect of garlic on acute lung injury (ALI) or its severe condition acute respiratory distress syndrome (ARDS), but the specific substances that exert the regulatory effects are still unclear. In this study, we investigate the protective effects of AMTS on lipopolysaccharide (LPS)-induced ALI mice and explored the underlying mechanisms. In vivo experiments, ICR mice were pretreated with 25–100 mg/kg AMTS for 7 days and followed by intratracheal instillation of LPS (1.5 mg/kg). The results showed that AMTS significantly attenuated LPS-induced deterioration of lung pathology, demonstrated by ameliorative edema and protein leakage, and improved pulmonary histopathological morphology. Meanwhile, the expression of inflammatory mediators and the infiltration of inflammation-regulation cells induced by LPS were also inhibited. In vitro experiments also revealed that AMTS could alleviate inflammation response and inhibit the exaggeration of macrophage M1 polarization in LPS-induced RAW264.7 cells. Mechanistically, we identified that AMTS treatment could attenuate the LPS-induced elevation of protein expression of p-IκBα, nuclear NF-κB-p65, COX2, iNOS, p-P38, p-ERK1/2, and p-JNK. Collectively, these data suggest that AMTS could attenuate LPS-induced ALI and the molecular mechanisms should be related to the suppression of the NF-κB and MAPKs pathways.

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“…In particular, there was a significant decrease of lipid and protein oxidation products and a substantial increment in the total antioxidant capacity and total thiol levels in the plasma samples from the study group as compared to the control group [ 47 ]. Some recent reviews of available H 2 S donors that serve as a platform for the release of H 2 S have underlined their considerable promise as favorable drugs in the clinical treatment of many diseases [ 48 , 49 , 50 ]. However, a series of experiment on numerous types of animals, including lamprey, trout, mouse, rat, pig, and cow, reported an essentially undetectable basal level of H 2 S gas (<100 nM total sulfide) in blood in all animals.…”

Section: Antioxidant Activities: a Conventional Anti-aging Paradigm O...mentioning

confidence: 99%

The Potential Implications of Hydrogen Sulfide in Aging and Age-Related Diseases through the Lens of Mitohormesis

Huynh

Wang

et al. 2022

Antioxidants

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The growing increases in the global life expectancy and the incidence of chronic diseases as a direct consequence have highlighted a demand to develop effective strategies for promoting the health of the aging population. Understanding conserved mechanisms of aging across species is believed helpful for the development of approaches to delay the progression of aging and the onset of age-related diseases. Mitochondrial hormesis (or mitohormesis), which can be defined as an evolutionary-based adaptive response to low-level stress, is emerging as a promising paradigm in the field of anti-aging. Depending on the severity of the perceived stress, there are varying levels of hormetic response existing in the mitochondria called mitochondrial stress response. Hydrogen sulfide (H2S) is a volatile, flammable, and toxic gas, with a characteristic odor of rotten eggs. However, H2S is now recognized an important gaseous signaling molecule to both physiology and pathophysiology in biological systems. Recent studies that elucidate the importance of H2S as a therapeutic molecule has suggested its protective effects beyond the traditional understanding of its antioxidant properties. H2S can also be crucial for the activation of mitochondrial stress response, postulating a potential mechanism for combating aging and age-related diseases. Therefore, this review focuses on highlighting the involvement of H2S and its sulfur-containing derivatives in the induction of mitochondrial stress response, suggesting a novel possibility of mitohormesis through which this gaseous signaling molecule may promote the healthspan and lifespan of an organism.

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H2S Donors and Their Use in Medicinal Chemistry

Cited by 50 publications

References 259 publications

CTH/H2S Regulates LPS-Induced Inflammation through IL-8 Signaling in MAC-T Cells

CTH/H2S Regulates LPS-Induced Inflammation through IL-8 Signaling in MAC-T Cells

Allyl methyl trisulfide protected against LPS-induced acute lung injury in mice via inhibition of the NF-κB and MAPK pathways

The Potential Implications of Hydrogen Sulfide in Aging and Age-Related Diseases through the Lens of Mitohormesis

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