{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T19:55:28Z","timestamp":1778356528315,"version":"3.51.4"},"reference-count":77,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T00:00:00Z","timestamp":1702598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministry of Education, Universities and Research","doi-asserted-by":"publisher","award":["PRIN 2017B9NCSX_005"],"award-info":[{"award-number":["PRIN 2017B9NCSX_005"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Hydrogen sulfide (H2S) is a signaling molecule endogenously produced within mammals\u2019 cells that plays an important role in inflammation, exerting anti-inflammatory effects. In this view, the research has shown a growing interest in identifying natural H2S donors. Herein, for the first time, the potential of marine extract as a source of H2S-releasing agents has been explored. Different fractions obtained by the Indonesian ascidian Polycarpa aurata were evaluated for their ability to release H2S in solution. The main components of the most active fraction were then characterized by liquid chromatography\u2013high-resolution mass spectrometry (LC-HRMS) and NMR spectroscopy. The ability of this fraction to release H2S was evaluated in a cell-free assay and J774 macrophages by a fluorimetric method, and its anti-inflammatory activity was evaluated in vitro and in vivo by using carrageenan-induced mouse paw edema. The anti-inflammatory effects were assessed by inhibiting the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), and interleukin-6 (IL-6), coupled with a reduction in nitric oxide (NO) and IL-6 levels. Thus, this study defines the first example of a marine source able to inhibit inflammatory responses in vivo through the release of H2S.<\/jats:p>","DOI":"10.3390\/md21120641","type":"journal-article","created":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T08:12:57Z","timestamp":1702627977000},"page":"641","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Searching for Novel Sources of Hydrogen Sulfide Donors: Chemical Profiling of Polycarpa aurata Extract and Evaluation of the Anti-Inflammatory Effects"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5037-712X","authenticated-orcid":false,"given":"Marcello","family":"Casertano","sequence":"first","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erika","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6103-8748","authenticated-orcid":false,"given":"Ivana","family":"Bello","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Indolfi","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9879-3293","authenticated-orcid":false,"given":"Masteria","family":"Putra","sequence":"additional","affiliation":[{"name":"Research Center for Vaccine and Drugs, Research Organisation for Healths, National Research and Innovation Agency (BRIN), Jalan Raya Jakarta-Bogor KM. 46, Cibinong 16911, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8374-4432","authenticated-orcid":false,"given":"Lorenzo","family":"Di Cesare Mannelli","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research and Child Health-NEUROFARBA-Pharmacology and Toxicology Section, University of Florence, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Ghelardini","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research and Child Health-NEUROFARBA-Pharmacology and Toxicology Section, University of Florence, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4515-3014","authenticated-orcid":false,"given":"Marialuisa","family":"Menna","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via D. 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Montesano 49, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7377-0653","authenticated-orcid":false,"given":"Concetta","family":"Imperatore","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0274-4671","authenticated-orcid":false,"given":"Elisabetta","family":"Panza","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Mitidieri","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via D. 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Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"C3","DOI":"10.1152\/ajpcell.00282.2016","article-title":"Hydrogen Sulfide, an Enhancer of Vascular Nitric Oxide Signaling: Mechanisms and Implications","volume":"312","author":"Szabo","year":"2017","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1111\/bph.14654","article-title":"L-cysteine\/Cystathionine-\u03b2-synthase-induced Relaxation in Mouse Aorta Involves a L-serine\/Sphingosine-1-phosphate\/NO Pathway","volume":"177","author":"Mitidieri","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/sj.bjp.0706906","article-title":"Regulation of Vascular Nitric Oxide in Vitro and in Vivo; a New Role for Endogenous Hydrogen Sulphide?","volume":"149","author":"Ali","year":"2006","journal-title":"Br. J. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1093\/cvr\/cvq248","article-title":"Hydrogen Sulfide Interacts with Nitric Oxide in the Heart: Possible Involvement of Nitroxyl","volume":"88","author":"Yong","year":"2010","journal-title":"Cardiovasc. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"22457","DOI":"10.1074\/jbc.M109.010868","article-title":"Relative Contributions of Cystathionine \u03b2-Synthase and \u03b3-Cystathionase to H2S Biogenesis via Alternative Trans-Sulfuration Reactions","volume":"284","author":"Singh","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1089\/ars.2010.3781","article-title":"The Quantitative Significance of the Transsulfuration Enzymes for H2S Production in Murine Tissues","volume":"15","author":"Kabil","year":"2011","journal-title":"Antioxid. Redox Signal"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1089\/ars.2013.5309","article-title":"Production and Physiological Effects of Hydrogen Sulfide","volume":"20","author":"Kimura","year":"2014","journal-title":"Antioxid. Redox Signal"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1093\/jb\/mvp111","article-title":"Vascular Endothelium Expresses 3-Mercaptopyruvate Sulfurtransferase and Produces Hydrogen Sulfide","volume":"146","author":"Shibuya","year":"2009","journal-title":"J. Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.niox.2014.05.014","article-title":"Hydrogen Sulfide and Nitric Oxide Interactions in Inflammation","volume":"41","author":"Fox","year":"2014","journal-title":"Nitric Oxide"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Rodkin, S., Nwosu, C., Sannikov, A., Tyurin, A., Chulkov, V.S., Raevskaya, M., Ermakov, A., Kirichenko, E., and Gasanov, M. (2023). The Role of Gasotransmitter-Dependent Signaling Mechanisms in Apoptotic Cell Death in Cardiovascular, Rheumatic, Kidney, and Neurodegenerative Diseases and Mental Disorders. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076014"},{"key":"ref_13","first-page":"1","article-title":"Hydrogen Sulfide Biochemistry and Interplay with Other Gaseous Mediators in Mammalian Physiology","volume":"2018","author":"Vicente","year":"2018","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4021","DOI":"10.1111\/bph.13815","article-title":"Nitric Oxide and Hydrogen Sulfide: The Gasotransmitter Paradigm of the Vascular System","volume":"174","author":"Cirino","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1089\/ars.2020.8211","article-title":"Hydrogen Sulfide in Inflammation: A Novel Mediator and Therapeutic Target","volume":"34","author":"Bhatia","year":"2021","journal-title":"Antioxid. Redox Signal"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1089\/ars.2011.4351","article-title":"Hydrogen Sulfide: An Endogenous Mediator of Resolution of Inflammation and Injury","volume":"17","author":"Wallace","year":"2012","journal-title":"Antioxid. Redox Signal"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1586\/ecp.10.134","article-title":"Hydrogen Sulfide and Inflammation: The Good, the Bad, the Ugly and the Promising","volume":"4","author":"Whiteman","year":"2011","journal-title":"Expert. Rev. Clin. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"R814","DOI":"10.1152\/ajpregu.90524.2008","article-title":"Leukocyte Trafficking and Pain Behavioral Responses to a Hydrogen Sulfide Donor in Acute Monoarthritis","volume":"295","author":"Andruski","year":"2008","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/srep00499","article-title":"Hydrogen Sulfide and Resolution of Acute Inflammation: A Comparative Study Utilizing a Novel Fluorescent Probe","volume":"2","author":"Dufton","year":"2012","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1111\/j.1476-5381.2010.01016.x","article-title":"Hydrogen Sulphide Induces Mouse Paw Oedema through Activation of Phospholipase A2","volume":"161","author":"Coletta","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4153","DOI":"10.4049\/jimmunol.179.6.4153","article-title":"Hydrogen Sulfide Up-Regulates Substance P in Polymicrobial Sepsis-Associated Lung Injury","volume":"179","author":"Zhang","year":"2007","journal-title":"J. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Vellecco, V., Esposito, E., Indolfi, C., Saviano, A., Panza, E., Bucci, M., Brancaleone, V., Cirino, G., d\u2019Emmanuele di Villa Bianca, R., and Sorrentino, R. (2023). Biphasic Inflammatory Response Induced by Intra-Plantar Injection of L-Cysteine: Role of CBS-Derived H2S and S1P\/NO Signaling. Biomed. Pharmacother., 167.","DOI":"10.1016\/j.biopha.2023.115536"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1042\/CS20110267","article-title":"Emerging Role of Hydrogen Sulfide in Health and Disease: Critical Appraisal of Biomarkers and Pharmacological Tools","volume":"121","author":"Whiteman","year":"2011","journal-title":"Clin. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.intimp.2016.07.020","article-title":"Hydrogen Sulfide Improves Colonic Barrier Integrity in DSS-Induced Inflammation in Caco-2 Cells and Mice","volume":"39","author":"Zhao","year":"2016","journal-title":"Int. Immunopharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Zhou, T., Qian, H., Zheng, N., Lu, Q., and Han, Y. (2022). GYY4137 Ameliorates Sepsis-Induced Cardiomyopathy via NLRP3 Pathway. Biochim. Biophys. Acta (BBA) Mol. Basis Dis., 1868.","DOI":"10.1016\/j.bbadis.2022.166497"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1089\/ars.2009.2899","article-title":"The Effect of Hydrogen Sulfide Donors on Lipopolysaccharide-Induced Formation of Inflammatory Mediators in Macrophages","volume":"12","author":"Whiteman","year":"2010","journal-title":"Antioxid. Redox Signal"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.phrs.2016.08.019","article-title":"The Novel Mitochondria-Targeted Hydrogen Sulfide (H 2 S) Donors AP123 and AP39 Protect against Hyperglycemic Injury in Microvascular Endothelial Cells in Vitro","volume":"113","author":"Torregrossa","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1089\/ars.2019.7841","article-title":"Activatable Small-Molecule Hydrogen Sulfide Donors","volume":"32","author":"Levinn","year":"2020","journal-title":"Antioxid. Redox Signal"},{"key":"ref_29","first-page":"296","article-title":"Prodrugs of Hydrogen Sulfide and Related Sulfur Species: Recent Development","volume":"18","author":"Yuan","year":"2020","journal-title":"Chin. J. Nat. Med."},{"key":"ref_30","first-page":"749","article-title":"The Effect of Hydrogen Sulfide-Releasing Naproxen (ATB-346) versus Naproxen on Formation of Stress-Induced Gastric Lesions, the Regulation of Systemic Inflammation, Hypoxia and Alterations in Gastric Microcirculation","volume":"68","author":"Magierowski","year":"2017","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_31","first-page":"1537","article-title":"Hydrogen Sulfide Releasing Naproxen Offers Better Anti-Inflammatory and Chondroprotective Effect Relative to Naproxen in a Rat Model of Zymosan Induced Arthritis","volume":"19","author":"Dief","year":"2015","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"17977","DOI":"10.1073\/pnas.0705710104","article-title":"Hydrogen Sulfide Mediates the Vasoactivity of Garlic","volume":"104","author":"Benavides","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1089\/ars.2019.7888","article-title":"Organic Isothiocyanates as Hydrogen Sulfide Donors","volume":"32","author":"Martelli","year":"2020","journal-title":"Antioxid. Redox Signal"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Micheli, L., Mitidieri, E., Turnaturi, C., Vanacore, D., Ciampi, C., Lucarini, E., Cirino, G., Ghelardini, C., Sorrentino, R., and Di Cesare Mannelli, L. (2022). Beneficial Effect of H2S-Releasing Molecules in an In Vitro Model of Sarcopenia: Relevance of Glucoraphanin. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23115955"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Bello, I., Smimmo, M., d\u2019Emmanuele di Villa Bianca, R., Bucci, M., Cirino, G., Panza, E., and Brancaleone, V. (2023). Erucin, an H2S-Releasing Isothiocyanate, Exerts Anticancer Effects in Human Triple-Negative Breast Cancer Cells Triggering Autophagy-Dependent Apoptotic Cell Death. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076764"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1111\/bph.14645","article-title":"Erucin Exhibits Vasorelaxing Effects and Antihypertensive Activity by H2S-releasing Properties","volume":"177","author":"Martelli","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.vph.2013.11.003","article-title":"Pharmacological Characterization of the Vascular Effects of Aryl Isothiocyanates: Is Hydrogen Sulfide the Real Player?","volume":"60","author":"Martelli","year":"2014","journal-title":"Vasc. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.1055\/s-0035-1560638","article-title":"Natural Products Containing Hydrogen Sulfide Releasing Moieties","volume":"26","author":"Pluth","year":"2015","journal-title":"Synlett"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1039\/C9NP00011A","article-title":"Synergy and Antagonism in Natural Product Extracts: When 1 + 1 Does Not Equal 2","volume":"36","author":"Caesar","year":"2019","journal-title":"Nat. Prod. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Genovese, M., Imperatore, C., Casertano, M., Aiello, A., Balestri, F., Piazza, L., Menna, M., del Corso, A., and Paoli, P. (2021). Dual Targeting of PTP1B and Aldose Reductase with Marine Drug Phosphoeleganin: A Promising Strategy for Treatment of Type 2 Diabetes. Mar. Drugs, 19.","DOI":"10.3390\/md19100535"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Casertano, M., Genovese, M., Piazza, L., Balestri, F., Del Corso, A., Vito, A., Paoli, P., Santi, A., Imperatore, C., and Menna, M. (2022). Identifying Human PTP1B Enzyme Inhibitors from Marine Natural Products: Perspectives for Developing of Novel Insulin-Mimetic Drugs. Pharmaceuticals, 15.","DOI":"10.3390\/ph15030325"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Casertano, M., Genovese, M., Santi, A., Pranzini, E., Balestri, F., Piazza, L., Del Corso, A., Avunduk, S., Imperatore, C., and Menna, M. (2023). Evidence of Insulin-Sensitizing and Mimetic Activity of the Sesquiterpene Quinone Avarone, a Protein Tyrosine Phosphatase 1B and Aldose Reductase Dual Targeting Agent from the Marine Sponge Dysidea Avara. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15020528"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1039\/D2NP00083K","article-title":"Marine Natural Products","volume":"40","author":"Carroll","year":"2023","journal-title":"Nat. Prod. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Haque, N., Parveen, S., Tang, T., Wei, J., and Huang, Z. (2022). Marine Natural Products in Clinical Use. Mar. Drugs, 20.","DOI":"10.3390\/md20080528"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Imperatore, C., Gimmelli, R., Persico, M., Casertano, M., Guidi, A., Saccoccia, F., Ruberti, G., Luciano, P., Aiello, A., and Parapini, S. (2020). Investigating the Antiparasitic Potential of the Marine Sesquiterpene Avarone, Its Reduced Form Avarol, and the Novel Semisynthetic Thiazinoquinone Analogue Thiazoavarone. Mar. Drugs, 18.","DOI":"10.3390\/md18020112"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.1021\/acs.jnatprod.7b00397","article-title":"Assignment of the Absolute Configuration of Phosphoeleganin via Synthesis of Model Compounds","volume":"80","author":"Luciano","year":"2017","journal-title":"J. Nat. Prod."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Casertano, M., Vito, A., Aiello, A., Imperatore, C., and Menna, M. (2023). Natural Bioactive Compounds from Marine Invertebrates That Modulate Key Targets Implicated in the Onset of Type 2 Diabetes Mellitus (T2DM) and Its Complications. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15092321"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Casertano, M., Imperatore, C., Luciano, P., Aiello, A., Putra, M.Y., Gimmelli, R., Ruberti, G., and Menna, M. (2019). Chemical Investigation of the Indonesian Tunicate Polycarpa Aurata and Evaluation of the Effects Against Schistosoma Mansoni of the Novel Alkaloids Polyaurines A and B. Mar. Drugs, 17.","DOI":"10.3390\/md17050278"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1021\/ol400791n","article-title":"New Cytotoxic 1,2,4-Thiadiazole Alkaloids from the Ascidian Polycarpa aurata","volume":"15","author":"Pham","year":"2013","journal-title":"Org. Lett."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1021\/jo960040e","article-title":"Alkaloids from the Tunicate Polycarpa aurata from Chuuk Atoll","volume":"61","author":"Abas","year":"1996","journal-title":"J. Org. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1021\/np000570c","article-title":"New 4-Methoxybenzoyl Derivatives from the Ascidian Polycarpa aurata","volume":"64","author":"Wessels","year":"2001","journal-title":"J. Nat. Prod."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1021\/acs.jnatprod.0c00166","article-title":"Synthesis of the 1,2,4-Thiadiazole Alkaloid Polyaurine B","volume":"83","author":"Anstis","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.imlet.2007.04.013","article-title":"Nitric Oxide, Chronic Inflammation and Autoimmunity","volume":"111","author":"Nagy","year":"2007","journal-title":"Immunol. Lett."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1021\/ml400239a","article-title":"Arylthioamides as H2S Donors: L-Cysteine-Activated Releasing Properties and Vascular Effects in Vitro and in Vivo","volume":"4","author":"Martelli","year":"2013","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1111\/j.1476-5381.2009.00611.x","article-title":"Markedly Reduced Toxicity of a Hydrogen Sulphide-Releasing Derivative of Naproxen (ATB-346)","volume":"159","author":"Wallace","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1016\/j.freeradbiomed.2009.09.018","article-title":"Making and Working with Hydrogen Sulfide","volume":"47","author":"Hughes","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1161\/CIRCULATIONAHA.107.753467","article-title":"Characterization of a Novel, Water-Soluble Hydrogen Sulfide\u2013Releasing Molecule (GYY4137)","volume":"117","author":"Li","year":"2008","journal-title":"Circulation"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Magli, E., Perissutti, E., Santagada, V., Caliendo, G., Corvino, A., Esposito, G., Esposito, G., Fiorino, F., Migliaccio, M., and Scognamiglio, A. (2021). H2S Donors and Their Use in Medicinal Chemistry. Biomolecules, 11.","DOI":"10.3390\/biom11121899"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.ejphar.2011.01.052","article-title":"Hydrogen Sulfide Gas Has Cell Growth Regulatory Role","volume":"656","author":"Baskar","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.3892\/ijmm.2015.2176","article-title":"Hydrogen Sulfide Attenuates Cytokine Production through the Modulation of Chromatin Remodeling","volume":"35","author":"Rios","year":"2015","journal-title":"Int. J. Mol. Med."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Hirayama, D., Iida, T., and Nakase, H. (2017). The Phagocytic Function of Macrophage-Enforcing Innate Immunity and Tissue Homeostasis. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010092"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Wang, Z., Guan, Y., Yang, R., Li, J., Wang, J., and Jia, A.-Q. (2020). Anti-Inflammatory Activity of 3-Cinnamoyltribuloside and Its Metabolomic Analysis in LPS-Activated RAW 264.7 Cells. BMC Complement. Med. Ther., 20.","DOI":"10.1186\/s12906-020-03115-y"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1007\/s10787-007-0013-x","article-title":"Role of Nitric Oxide in Inflammatory Diseases","volume":"15","author":"Sharma","year":"2007","journal-title":"Inflammopharmacology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.pupt.2007.08.003","article-title":"Inhibition of INOS Expression and NO Production by Anti-Inflammatory Steroids","volume":"21","author":"Lilja","year":"2008","journal-title":"Pulm. Pharmacol. Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/j.bbamcr.2011.01.034","article-title":"The Pro- and Anti-Inflammatory Properties of the Cytokine Interleukin-6","volume":"1813","author":"Scheller","year":"2011","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Cell Res."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Imperatore, C., Varriale, A., Rivieccio, E., Pennacchio, A., Staiano, M., D\u2019Auria, S., Casertano, M., Altucci, C., Valadan, M., and Singh, M. (2020). Spectroscopic Properties of Two 5\u2032-(4-Dimethylamino)Azobenzene Conjugated G-Quadruplex Forming Oligonucleotides. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197103"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Imperatore, C., Valadan, M., Tartaglione, L., Persico, M., Ramunno, A., Menna, M., Casertano, M., Dell\u2019Aversano, C., Singh, M., and d\u2019Aulisio Garigliota, M.L. (2020). Exploring the Photodynamic Properties of Two Antiproliferative Benzodiazopyrrole Derivatives. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041246"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.niox.2018.02.003","article-title":"Mercaptopyruvate Acts as Endogenous Vasodilator Independently of 3-Mercaptopyruvate Sulfurtransferase Activity","volume":"75","author":"Mitidieri","year":"2018","journal-title":"Nitric Oxide"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Benigno, D., Virgilio, A., Bello, I., La Manna, S., Vellecco, V., Bucci, M., Marasco, D., Panza, E., Esposito, V., and Galeone, A. (2022). Properties and Potential Antiproliferative Activity of Thrombin-Binding Aptamer (TBA) Derivatives with One or Two Additional G-Tetrads. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232314921"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.1016\/j.bmcl.2012.02.102","article-title":"Sinularioside, a Triacetylated Glycolipid from the Indonesian Soft Coral Sinularia Sp., Is an Inhibitor of NO Release","volume":"22","author":"Putra","year":"2012","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.ejphar.2003.09.071","article-title":"Pyrrolidine Dithiocarbamate Reduces Renal Dysfunction and Injury Caused by Ischemia\/Reperfusion of the Rat Kidney","volume":"482","author":"Chatterjee","year":"2003","journal-title":"Eur. J. Pharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1111\/j.1476-5381.2010.00872.x","article-title":"Animal Research: Reporting in Vivo Experiments: The ARRIVE Guidelines","volume":"160","author":"Kilkenny","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3611","DOI":"10.1111\/bph.15178","article-title":"ARRIVE 2.0 and the British Journal of Pharmacology: Updated Guidance for 2020","volume":"177","author":"Lilley","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1111\/bph.12740","article-title":"Crucial Role of Androgen Receptor in Vascular H2S Biosynthesis Induced by Testosterone","volume":"172","author":"Brancaleone","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1111\/dom.12750","article-title":"Vascular Effects of Linagliptin in Non-Obese Diabetic Mice Are Glucose-Independent and Involve Positive Modulation of the Endothelial Nitric Oxide Synthase (ENOS)\/Caveolin-1 (CAV-1) Pathway","volume":"18","author":"Vellecco","year":"2016","journal-title":"Diabetes Obes. Metab."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Montanaro, R., Vellecco, V., Torregrossa, R., Casillo, G.M., Manzo, O.L., Mitidieri, E., Bucci, M., Castaldo, S., Sorrentino, R., and Whiteman, M. (2023). Hydrogen Sulfide Donor AP123 Restores Endothelial Nitric Oxide-Dependent Vascular Function in Hyperglycemia via a CREB-Dependent Pathway. Redox Biol., 62.","DOI":"10.1016\/j.redox.2023.102657"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1047026","DOI":"10.3389\/fnut.2022.1047026","article-title":"Combination of Marine Bioactive Compounds and Extracts for the Prevention and Treatment of Chronic Diseases","volume":"9","author":"Ebrahimi","year":"2023","journal-title":"Front. 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