{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:23:55Z","timestamp":1760243035267,"version":"build-2065373602"},"reference-count":45,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2015,8,28]],"date-time":"2015-08-28T00:00:00Z","timestamp":1440720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The exploitation of marine organisms for human nutritional and pharmaceutical purposes has revealed important chemical prototypes for the discovery of new drugs, stimulating compounds isolation and syntheses of new related compounds with biomedical application. Nowadays, it is well known that inflammatory processes are involved in many diseases and the interest in the search for marine natural products with anti-inflammatory potential has been increasing. The genus Aplysia belongs to the class Gastropoda, having  a wide geographical distribution and including several species, commonly known as sea hares. Aplysia depilans Gmelin is usually found in the Mediterranean Sea and in the Atlantic Ocean, from West Africa to the French coast. In these marine organisms, most of the digestion and nutrient absorption occurs in the digestive gland. This work aimed to explore the chemical composition and bioactivity of the methanol extract from A. depilans digestive gland. Therefore, fatty acids and carotenoids were determined by GC-MS and HPLC-DAD, respectively. Twenty-two fatty acids and eight carotenoids were identified for the first time in this species. The A. depilans digestive gland revealed to be essentially composed by polyunsaturated fatty acids (PUFA) and xanthophylls. Regarding the  anti-inflammatory potential in RAW 264.7 cells stimulated with lipopolysaccharide, it was observed that this matrix has capacity to reduce nitric oxide (NO) and L-citrulline levels, which suggests that its compounds may act by interference with inducible nitric oxide synthase. Taking into account the results obtained, A. depilans digestive gland may be  a good source of nutraceuticals, due to their richness in health beneficial nutrients, such as carotenoids and long-chain PUFA.<\/jats:p>","DOI":"10.3390\/molecules200915766","type":"journal-article","created":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T10:55:58Z","timestamp":1441104958000},"page":"15766-15780","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Digestive Gland from Aplysia depilans Gmelin: Leads for Inflammation Treatment"],"prefix":"10.3390","volume":"20","author":[{"given":"Andreia","family":"Oliveira","sequence":"first","affiliation":[{"name":"REQUIMTE\/LAQV, Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica,  Faculdade de Farm\u00e1cia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, No. 228,  4050-313 Porto, Portugal"}]},{"given":"Alexandre","family":"Lobo-da-Cunha","sequence":"additional","affiliation":[{"name":"Department of Microscopy, Institute of Biomedical Sciences Abel Salazar (ICBAS),  University of Porto, Rua de Jorge Viterbo Ferreira, No. 228, 4050-313 Porto, Portugal"},{"name":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), Rua dos Bragas 289, 4050-123 Porto, Portugal"}]},{"given":"Marcos","family":"Taveira","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica,  Faculdade de Farm\u00e1cia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, No. 228,  4050-313 Porto, Portugal"}]},{"given":"Marta","family":"Ferreira","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica,  Faculdade de Farm\u00e1cia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, No. 228,  4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0740-4396","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Valent\u00e3o","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica,  Faculdade de Farm\u00e1cia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, No. 228,  4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9764-3920","authenticated-orcid":false,"given":"Paula","family":"Andrade","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica,  Faculdade de Farm\u00e1cia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, No. 228,  4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2015,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3390\/md203123","article-title":"Biomedical compounds from marine organisms","volume":"2","author":"Jha","year":"2004","journal-title":"Mar. Drugs"},{"key":"ref_2","first-page":"266","article-title":"Revision of the world species of Aplysia (Gastropoda, Opisthobranchia)","volume":"5","author":"Eales","year":"1960","journal-title":"Bull. Br. Mus. Zool."},{"key":"ref_3","first-page":"167","article-title":"Aplysia: Its biology and ecology","volume":"25","author":"Carefoot","year":"1987","journal-title":"Oceanogr. Mar. Biol. Ann. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/j.1463-6395.2007.00268.x","article-title":"Ultrastructural, histochemical and cytochemical characterization of intestinal epithelial cells in Aplysia depilans (Gastropoda, Opisthobranchia)","volume":"88","year":"2007","journal-title":"Acta Zool. (Stockh.)"},{"key":"ref_5","first-page":"7","article-title":"The specialization of the Aplysiid gut","volume":"18","author":"Fretter","year":"1979","journal-title":"Malacologia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1021\/np50047a023","article-title":"Epidioxy sterols from the tunicates Dendrodoa grossularia and Ascidiella aspersa and the gastropoda Aplysia depilans and Aplysia punctata","volume":"49","author":"Castedo","year":"1986","journal-title":"J. Nat. Prod."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5471","DOI":"10.1021\/jo961805l","article-title":"Structure and stereochemistry of aplyolides A\u2013E, lactonized dihydroxy fatty acids from the skin of the marine mollusk Aplysia depilans","volume":"62","author":"Spinella","year":"1997","journal-title":"J. Org. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1021\/np500851w","article-title":"Dactylomelane diterpenes from the sea hare Aplysia depilans","volume":"78","author":"Petraki","year":"2015","journal-title":"J. Nat. Prod."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1054\/tice.1998.0014","article-title":"Ultrastructural and cytochemical aspects of the basophilic cells in the hepatopancreas of Aplysia depilans (Mollusca, Opisthobranchia)","volume":"31","year":"1999","journal-title":"Tissue Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1054\/tice.1999.0082","article-title":"The digestive cells of the hepatopancreas in Aplysia depilans (Mollusca, Opistobranchia): Ultrastructural and cytochemical study","volume":"32","year":"2000","journal-title":"Tissue Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.cell.2010.01.022","article-title":"Pattern recognition receptors and inflammation","volume":"140","author":"Takeuchi","year":"2010","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.biocel.2009.12.016","article-title":"The resolution of inflammation: Anti-inflammatory roles for NF-\u03baB","volume":"42","author":"Lawrence","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/nature07201","article-title":"Origin and physiological roles of inflammation","volume":"454","author":"Medzhitov","year":"2008","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"281","DOI":"10.2174\/1568010054022024","article-title":"Macrophages in inflammation","volume":"4","author":"Fujiwara","year":"2005","journal-title":"Curr. Drug Targets Inflamm. Allergy"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/nri915","article-title":"Anti-inflammatory lipid mediators and insights into the resolution of inflammation","volume":"2","author":"Lawrence","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1161\/hc0902.104353","article-title":"Inflammation and atherosclerosis","volume":"105","author":"Libby","year":"2002","journal-title":"Circulation"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1172\/JCI11830","article-title":"NF-kappaB: A key role in inflammatory diseases","volume":"107","author":"Tak","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1183\/09031936.98.11061218","article-title":"Pulmonary fibrosis: Cytokines in the balance","volume":"11","author":"Coker","year":"1998","journal-title":"Eur. Resp. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.lfs.2003.10.042","article-title":"iNOS-mediated nitric oxide production and its regulation","volume":"75","author":"Aktan","year":"2004","journal-title":"Life Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8981","DOI":"10.1039\/C4RA14333G","article-title":"Fatty acids from edible sea hares: Anti-inflammatory capacity in LPS-stimulated RAW 264.7 cells involves iNOS modulation","volume":"5","author":"Pereira","year":"2015","journal-title":"RSC Adv."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.1016\/j.foodchem.2013.04.120","article-title":"Amino acids, fatty acids and sterols profile of some marine organisms from Portuguese waters","volume":"141","author":"Pereira","year":"2013","journal-title":"Food Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"740","DOI":"10.2174\/138955708784912148","article-title":"Natural marine anti-inflammatory products","volume":"8","author":"Abad","year":"2008","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3998","DOI":"10.3390\/md11103998","article-title":"Biosynthesis of polyunsaturated fatty acids in marine invertebrates: Recent advances in molecular mechanisms","volume":"11","author":"Monroig","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"278","DOI":"10.3390\/md9020278","article-title":"Carotenoids in marine animals","volume":"9","author":"Maoka","year":"2011","journal-title":"Mar. Drugs"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.dyepig.2014.06.011","article-title":"Marine natural pigments: Chemistry, distribution and analysis","volume":"111","author":"Pereira","year":"2014","journal-title":"Dyes Pigment."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4667","DOI":"10.1021\/jf400819p","article-title":"Application of novel extraction technologies for bioactives from marine algae","volume":"61","author":"Kadam","year":"2013","journal-title":"J. Agric. Food Chem."},{"key":"ref_27","first-page":"259","article-title":"Investigations of carotenoids in some animals of Adriatic sea\u2014VI. Representatives of sponges, annelids, molluscs and echinodermates","volume":"78","author":"Czeczuga","year":"1984","journal-title":"Comp. Biochem. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.foodchem.2004.01.056","article-title":"Compositional characteristics of green crab (Carcinus maenas)","volume":"88","author":"Naczk","year":"2004","journal-title":"Food Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"147","DOI":"10.2174\/187221312800166886","article-title":"Phytochemicals to prevent inflammation and allergy","volume":"6","author":"Bellik","year":"2012","journal-title":"Recent Pat. Inflamm. Allergy Drug Discov."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S1505","DOI":"10.1093\/ajcn\/83.6.1505S","article-title":"N-3 Polyunsaturated fatty acids, inflammation, and inflammatory diseases","volume":"83","author":"Calder","year":"2006","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_31","first-page":"54","article-title":"Palmitic acid and ergosta-7,22-dien-3-ol contribute to the apoptotic effect and cell cycle arrest of an extract from Marthasterias glacialis L. in neuroblastoma cells","volume":"12","author":"Pereira","year":"2014","journal-title":"Molecules"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1016\/j.fct.2010.05.003","article-title":"Evaluation of anti-inflammatory effect of fucoxanthin isolated from brown algae in lipopolysaccharide-stimulated RAW 264.7 macrophages","volume":"48","author":"Heo","year":"2010","journal-title":"Food Chem. Toxicol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1002\/mnfr.200600170","article-title":"Dietary lutein modulates inducible nitric oxide synthase (iNOS) gene and protein expression in mouse macrophage cells (RAW 264.7)","volume":"51","author":"Rafi","year":"2007","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1111\/j.1753-4887.2010.00287.x","article-title":"Fatty acids from fish: The anti-inflammatory potential of long-chain omega-3 fatty acids","volume":"68","author":"Wall","year":"2010","journal-title":"Nutr. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s00394-009-0057-3","article-title":"Effect of polyunsaturated fatty acids on the reactive oxygen and nitrogen species production by Raw 264.7 macrophages","volume":"49","author":"Ambrozova","year":"2010","journal-title":"Eur. J. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.plefa.2006.05.012","article-title":"Polyunsaturated fatty acids and inflammation","volume":"75","author":"Calder","year":"2006","journal-title":"Prostagland. Leuk. Essent. Fatty Acids"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1021\/mp100199m","article-title":"Role of Nrf2 in suppressing LPS-induced inflammation in mouse peritoneal macrophages by polyunsaturated fatty acids docosahexaenoic acid and eicosapentaenoic acid","volume":"7","author":"Wang","year":"2010","journal-title":"Mol. Pharm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.3945\/jn.109.119768","article-title":"An \u03b1-linolenic acid-rich formula reduces oxidative stress and inflammation by regulating NF-\u03baB in rats with TNBS-induced colitis","volume":"140","author":"Hassan","year":"2010","journal-title":"J. Nutr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"16683","DOI":"10.1074\/jbc.M011695200","article-title":"Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4","volume":"276","author":"Lee","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"322","DOI":"10.3390\/molecules18010322","article-title":"Molecular mechanism underlying anti-inflammatory and anti-allergic activities of phytochemicals: An update","volume":"18","author":"Bellik","year":"2013","journal-title":"Molecules"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/emm.2005.42","article-title":"Beta-Carotene inhibits inflammatory gene expression in lipopolysaccharide-stimulated macrophages by suppressing redox-based NF-\u03baB activation","volume":"37","author":"Bai","year":"2005","journal-title":"Exp. Mol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.microc.2009.04.005","article-title":"Fatty acid composition of wild edible mushrooms species: A comparative study","volume":"93","author":"Ribeiro","year":"2009","journal-title":"Microchem. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.3390\/md10071498","article-title":"Further insights on the carotenoid profile of the echinoderm Marthasterias glacialis L.","volume":"10","author":"Mariutti","year":"2012","journal-title":"Mar. Drugs"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e31145","DOI":"10.1371\/journal.pone.0031145","article-title":"Can phlorotannins purified extracts constitute a novel pharmacological alternative for microbial infections with associated inflammatory conditions?","volume":"7","author":"Lopes","year":"2012","journal-title":"PLoS ONE"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e59131","DOI":"10.1371\/journal.pone.0059131","article-title":"Integrated analysis of COX-2 and iNOS derived inflammatory mediators in LPS-stimulated RAW macrophages pre-exposed to Echium plantagineum L. bee pollen extract","volume":"8","author":"Moita","year":"2013","journal-title":"PLoS ONE"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/20\/9\/15766\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:47:38Z","timestamp":1760215658000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/20\/9\/15766"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8,28]]},"references-count":45,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2015,9]]}},"alternative-id":["molecules200915766"],"URL":"https:\/\/doi.org\/10.3390\/molecules200915766","relation":{},"ISSN":["1420-3049"],"issn-type":[{"type":"electronic","value":"1420-3049"}],"subject":[],"published":{"date-parts":[[2015,8,28]]}}}