Inflammation is a hot topic in medical research, because it plays a key role in inflammatory diseases: rheumatoid arthritis (RA) and other forms of arthritis, diabetes, heart diseases, irritable bowel syndrome, Alzheimer’s disease, Parkinson’s disease, allergies, asthma, even cancer and many others. Over the past few decades, it was realized that the process of inflammation is virtually the same in different disorders, and a better understanding of inflammation may lead to better treatments for numerous diseases. Inflammation is the activation of the immune system in response to infection, irritation, or injury, with an influx of white blood cells, redness, heat, swelling, pain, and dysfunction of the organs involved. Although the pathophysiological basis of？these conditions？is not yet fully understood, reactive oxygen species (ROS) have often been implicated in their？pathogenesis. In fact, in inflammatory diseases the antioxidant defense system is compromised, as evidenced by increased markers of oxidative stress, and decreased levels of protective antioxidant enzymes in patients with rheumatoid arthritis (RA). An enriched diet containing antioxidants, such as vitamin E, vitamin C, β-carotene and phenolic substances, has been suggested to improve symptoms by reducing disease-related oxidative stress. In this respect, the marine world represents a largely untapped reserve of bioactive ingredients, and considerable potential exists for exploitation of these bioactives as functional food ingredients. Substances such as n-3 oils, carotenoids, vitamins, minerals and peptides provide a myriad of health benefits, including reduction of cardiovascular diseases, anticarcinogenic and anti-inflammatory activities. New marine bioactives are recently gaining attention, since they could be helpful in combating chronic inflammatory degenerative conditions. The aim of this review is to examine the published studies concerning the potential pharmacological properties and application of many marine bioactives against inflammatory diseases.
References
[1]
Wu, M.L.; Ho, Y.C.; Lin, C.Y.; Yet, S.F. Heme oxygenase-1 in inflammation and cardiovascular disease. Am. J. Cardiovasc. Dis. 2011, 1, 150–158. 22254194
[2]
Thelle, D.S.; Arnesen, E. CRP level as risk marker of cardiovascular disease? Tidsskr. Nor. Laegeforen. 2010, 130, 512–514, doi:10.4045/tidsskr.09.1002.
[3]
Tas, S.W.; Remans, P.H.; Reedguist, K.A.; Tak, P.P. Signal transduction pathways and transcription factors as therapeutic targets in inflammatory disease: towards innovative antirheumatic therapy. Curr. Pharm. Des. 2005, 11, 581–611, doi:10.2174/1381612053381918. 15720277
[4]
Namazi, N.; Esfanjani, A.T.; Heshmati, J.; Bahrami, A. The effect of hydro alcoholic Nettle (Urtica dioica) extracts on insulin sensitivity and some inflammatory indicators in patients with type 2 diabetes: A randomized double-blind control trial. Pak. J. Biol. Sci. 2011, 14, 775–779, doi:10.3923/pjbs.2011.775.779. 22303583
[5]
Kowalski, J.; Samojedny, A.; Paul, M.; Pietsz, G.; Wilczok, T. Effect of apigenin, kaempferol and resveratrol on the expression of interleukin-1 beta and tumor necrosis factor-alpha genes in J774.2 macrophages. Pharmacol. Rep. 2005, 57, 390–394. 15985724
[6]
Yeramian, A.; Santacana, M.; Sorolla, A.; Llobet, D.; Encinas, M.; Velasco, A.; Bahi, N.; Eritja, N.; Domingo, M.; Oliva, E.; Dolcet, X.; Matias-Guiu, X. Nuclear factor-κB2/p100 promotes endometrial carcinoma cell survival under hypoxia in a HIF-1α independent manner. Lab. Invest. 2011, 91, 859–871, doi:10.1038/labinvest.2011.58.
[7]
Honkanen, P. Consumer acceptance of (marine) functional food. In Marine Functional Food, 1st ed.; Wageningen Academic Publishers: Wageningen, The Netherlands, 2009; Volume 1, pp. 141–154.
[8]
Wall, R.; Ross, R.P.; Fitzgerald, G.F.; Stanton, C. Fatty acids from fish: The anti-inflammatory potential of long-chain omega-3 fatty acids. Nutr. Rev. 2010, 68, 280–289, doi:10.1111/j.1753-4887.2010.00287.x. 20500789
[9]
Goldberg, R.J.; Katz, J. A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain. Pain 2007, 129, 210–223, doi:10.1016/j.pain.2007.01.020. 17335973
[10]
Moskowitz, R.W. Role of collagen hydrolysate in bone and joint disease. Semin. Arthritis Rheum. 2000, 30, 87–99, doi:10.1053/sarh.2000.9622. 11071580
Stamp, L.K.; James, M.J.; Cleland, L.G. Diet and rheumatoid arthritis: a review of the literature. Semin. Arthritis Rheum. 2005, 35, 77–94, doi:10.1016/j.semarthrit.2005.05.001. 16194694
[13]
Lordan, S.; Ross, R.P.; Stanton, C. Marine Bioactives as Functional Food Ingredients: Potential to Reduce the Incidence of Chronic Diseases. Mar. Drugs 2011, 9, 1056–1100, doi:10.3390/md9061056. 21747748
[14]
Gambhir, J.K.; Lali, P.; Jain, A.K. Correlation between blood antioxidant levels and lipid peroxidation in rheumatoid arthritis. Clin. Biochem. 1997, 30, 351–355, doi:10.1016/S0009-9120(96)00007-0. 9209794
[15]
Halliwell, B. Free radicals, antioxidants, and human disease: curiosity, cause, or consequence? Lancet 1994, 344, 721–724, doi:10.1016/S0140-6736(94)92211-X.
[16]
Sarban, S.; Kocyigit, A.; Yazar, M.; Isikan, U.E. Plasma total antioxidant capacity, lipid peroxidation, and erythrocyte antioxidant enzyme activities in patients with rheumatoid arthritis and osteoarthritis. Clin. Biochem. 2005, 11, 981–986.
[17]
Darlington, L.G.; Stone, T.W. Antioxidants and fatty acids in the amelioration of rheumatoid arthritis and related disorders. Br. J. Nutr. 2001, 85, 251–269, doi:10.1079/BJN2000239. 11299072
[18]
Comstock, G.W.; Burke, A.E.; Hoffman, S.C.; Heizlsouer, K.J.; Bendich, A; Masi, A.T.; Norkus, E.P.; Malamet, R.L.; Gershiwin, M.E. Serum concentrations of alpha tocopherol, beta carotene, and retinol preceding the diagnosis of rheumatoid arthritis and systemic lupus erythematosus. Ann. Rheum. Dis. 1997, 56, 323–325, doi:10.1136/ard.56.5.323.
[19]
Edmonds, S.E.; Winyard, P.G.; Guo, R.; Kidd, B.; Merry, P.; Lnagrish-Smith, A.; Hansen, C.; Ramm, S.; Blake, D.R. Putative analgesic activity of repeated oral doses of vitamin E in the treatment of rheumatoid arthritis. Results of a prospective placebo controlled double blind trial. Ann. Rheum. Dis. 1997, 56, 649–655, doi:10.1136/ard.56.11.649. 9462166
[20]
？imen, M.Y.B.; ？imen, O.O.B.; Ka？maz, M.; Ooztürk, J.S.; Yorgancio？lu, I.; Durak, I. Oxidant/antioxidant status of the erythrocytes from patients with rheumatoid arthritis. Clin. Rheumatol. 2000, 19, 275–277, doi:10.1007/PL00011172. 10941807
[21]
Brown, A.A; Hu, F.B. Dietary modulation of endothelial function: implications for cardiovascular disease. Am. J. Clin. Nutr. 2001, 73, 673–686. 11273841
[22]
Ford, E.S.; Liu, S.; Mannino, D.M.; Giles, W.H.; Smith, S.J. C-reactive protein concentration and concentrations of blood vitamins, carotenoids, and selenium among United States adults. Eur. J. Clin. Nutr. 2003, 57, 1157–1163, doi:10.1038/sj.ejcn.1601667. 12947436
[23]
Kritchevsky, S.B.; Bush, A.J.; Pahor, M.; Gross, M.D. Serum carotenoids and markers of inflammation in non smokers. Am. J. Epidemiol. 2000, 152, 1065–1071, doi:10.1093/aje/152.11.1065. 11117616
[24]
Erlinger, T.P.; Guallar, E.; Miller, E.R.; Stolzenberg-Solomon, R.; Appel, L.J. Relationship between systemic markers of inflammation and serum beta-carotene levels. Arch. Intern. Med. 2001, 161, 1903–1908, doi:10.1001/archinte.161.15.1903. 11493133
[25]
Rowley, K.; Walker, K.Z.; Cohen, J. Inflammation and vascular endothelial activation in an Aboriginal population: relationships to coronary disease risk factors and nutritional markers. Med. J. Aust. 2003, 178, 495–500. 12741936
[26]
Paredes, S.; Girona, J.; Hurt-Camejo, E. Antioxidant vitamins and lipid peroxidation in patients with rheumatoid arthritis: association with inflammatory markers. J. Rheumatol. 2002, 29, 2271–2277. 12415581
[27]
Terracciano, S.; Aquino, M.; Rodriguez, M.; Monti, M.C.; Casapullo, A.; Riccio, R.; Gomez-Paloma, L. Chemistry and biology of anti-inflammatory marine natural products: molecule interfering with cyclooxygenase, NF-κB and other unidentified targets. Curr. Med. Chem. 2006, 13, 1947–1969, doi:10.2174/092986706777585095. 16842204
[28]
Ferreira, S.H.; Vane, J.R. New aspects of the mode of action of Non steroid antiinflammatory drugs. Ann. Rev. Pharmacol. 1974, 14, 57–73, doi:10.1146/annurev.pa.14.040174.000421.
[29]
López, J.E.T.; Soto, V.G. Participación de la ciclooxigenasa-1 en el dolor inflamatorio. Universidad Juarez Autonoma de Tabasco Mexico 2001, 17, 73–81.
[30]
Bjorkman, D.J. The effect of aspirin and non steroidal anti-inflammatory drugs on prostaglandins. Am. J. Med. 1998, 105, 8–12, doi:10.1016/S0002-9343(98)00069-2.
[31]
Takei, M.; Burgoyne, D.L.; Andersen, R.J. Effect of contignasterol on histamine release induced by anti-immunoglobulin E from rat peritoneal mast cells. J. Pharm. Sci. 1994, 83, 1234–1235, doi:10.1002/jps.2600830909. 7530301
[32]
Sims, J.; Fenical, W.; Wing, R.; Radlick, P. Marine Natural Products, Pacifenol, a rare sesquiterpene containing bromine and chlorine from the red alga, Laurencia pacifica. J. Am. Chem. Soc. 1971, 93, 3774–3775, doi:10.1021/ja00744a041.
[33]
Baker, J.T. Some metabolites from australian, marine organisms. Pure Appl. Chem. 1976, 48, 35–44, doi:10.1351/pac197648010035.
[34]
Clifford, W.; Chang, J. Marine Natural Products Other Than Pigments. J. Chem. Educ. 1973, 50, 260–262, doi:10.1021/ed050p260. 4690239
[35]
Dembitsky, V.M.; Tolstkov, G.A. Natural Halogenated sesquiterpenes from marine organisms. Chem. Sustain. Dev. 2004, 12, 1–12, doi:10.1002/sd.225.
[36]
San Martín, A.; Rovirosa, J.; Astudillo, L.; Sepúlveda, B.; Ruiz, D.; San Martín, C. Biotransformation of the marine sesquiterpene pacifenol by a facultative marine fungus. Nat. Prod. Res. 2008, 22, 1627–1632, doi:10.1080/14786410701869440. 19085420
[37]
Areche, C.; San Martin, A.; Rovirosa, J.; Munoz, M.A.; Barragan, A.H.; Bucio, M.A.; Nathan, P.J. Stereostructure Reassignment and Absolute Configuration of Isoepitaondiol, a Meroditerpenoid from Stypopodium flabelliforme. J. Nat. Prod. 2010, 73, 79–82, doi:10.1021/np900553p. 20000452
[38]
Areche, C.; Vaca, I.; Labbe, P.; Delgado, J.S.; Astudillo, L.; Silva, M.; Rovirosa, J.; San Martin, A. Biotransformation of Stypotriol triacetate by Aspergillus niger. J. Mol. Structure 2011, 998, 167–170, doi:10.1016/j.molstruc.2011.05.026.
[39]
Martinez, J.L.; Sepulveda, S.P.; Rovirosa, J.; San Martin, A. Efectos en aorta y auricula aisladas de rata de diacetil epitaondiol, diterpenoide del alga Stypopodium flabelliforme. An. Asoc. Quim. Argent 1997, 85, 69–75.
[40]
Gil, B.; Ferrandiz, M.L.; Sanz, M.J.; Terencio, M.C.; Ubeda, A.; Rovirosa, J.; San Martin, A.; Alcaraz, M.J.; Payá, M. Inhibition of inflammatory responses by epitaondiol and other marine natural products. Life Sci. 1995, 57, 25–30.
[41]
Llanio, M.; Fernández, M.D.; Cabrera, B.; Bermejo, P.; Abad, M.J.; Payá, M.; Alcaraz, M.J. The marine plant thalassia testudinum possesses anti-inflammatory and analgesic properties. Pharmacologyonline 2006, 3, 594–600.
[42]
Areche, C.; San Martín, A.; Rovirosa, J.; Sepúlveda, B. Gastroprotective activity of epitaondiol and sargaol. Nat. Prod. Commun. 2011, 6, 1073–1074. 21922901
[43]
Rovirosa, J.; San Martin, A. Antimicrobial activity of the brown alga Stypopodium flabelliformeconstituents. Fitoterapia 1997, 68, 473–475.
[44]
Soares, A.R.; Abrantes, J.L.; Souza, T.M.L.; Fontes, C.F.L.; Pereira, R.C.; Frugulhetti, I.C.D.P.P.; Teixeira, V.L. In vitro antiviral effect of meroditerpenes isolated from the Brazilian seaweed Stypopodium zonale (Dictyotales). Planta Med. 2007, 73, 1221–1224, doi:10.1055/s-2007-981589. 17713872
[45]
Pereira, D.M.; Cheel, J.; Areche, C.; San Martin, A.; Rovirosa, J.; Silva, L.R.; Valentao, P.; Andrade, P.B. Anti-Proliferative Activity of Meroditerpenoids Isolated from the Brown Alga Stypopodium flabelliforme against Several Cancer Cell Lines. Mar. Drugs 2011, 9, 852–862, doi:10.3390/md9050852. 21673894
[46]
Al Sabi, A.; McArthur, J.; Ostroumov, V.; French, R.J. Marine Toxins That Target Voltage-gated Sodium Channels. Mar. Drugs 2006, 4, 157–192, doi:10.3390/md403157.
Ferrando, F.S.; San Martin, A. Epitaondiol: The First Polycyclic Meroditerpenoid Containing Two Fused Six-Membered Rings Forced into the Twist-Boat Conformation. J. Org. Chem. 1995, 60, 1475–1478, doi:10.1021/jo00110a062.
[49]
Mu？oz, M.A.; Areche, C.; San Martin, A.; Rovirosa, J.; Nathan, P.J. VCD determination of the absolute configuration of stypotriol. Nat. Prod. Commun. 2009, 4, 1037–1040. 19768979
[50]
Bramley, A.M.; Langlands, J.M.; Jones, A.K.; Burgoyne, D.L.; Li, Y.; Andersen, R.J.; Salari, H. Effects of IZP-94005 (contignasterol) on antigen induced bronchial responsiveness in ovalbumin-sensitized guinea-pigs. Br. J. Pharmacol. 1995, 115, 1433–1438, doi:10.1111/j.1476-5381.1995.tb16634.x. 8564202
[51]
Tan, A.S.; Berridge, M.V. Superoxide produced by activated neutrophils efficiently reduces the tetrazolium salt, WST-1 to produce a soluble formazan: a simple colorimetric assay for measuring respiratory burst activation and for screening anti-inflammatory agents. J. Immunol. Methods 2000, 238, 59–68, doi:10.1016/S0022-1759(00)00156-3. 10758236
[52]
Izzo, I.; Pironti, V.; Della Monica, C.; Sodano, G.; De Riccardis, F. Stereocontrolled synthesis of contignasterol’s side chain. Tetrahedron Lett. 2001, 42, 8977–8980, doi:10.1016/S0040-4039(01)01964-5.
[53]
Burgoyne, D.L.; Andersen, R.J.; Alle, T.M. Contignasterol, a highly oxygenated steroid with the unnatural 14-beta configuration from the marine sponge Petrosia contignata Thiele, 1899. J. Org. Chem. 1992, 57, 525–528, doi:10.1021/jo00028a024.
[54]
Gross, H.; Conig, G.M. Terpenoids from marine organisms: unique structures and their pharmacological potential. Phytochem. Rev. 2006, 5, 115–141, doi:10.1007/s11101-005-5464-3.
[55]
Andersen, R.J.; Allen, T.M.; Burgoyne, D.L. Contignasterol,and related 3-alpha hydroxy-6-alpha hydroxy-7-beta hydroxy-15-keto-14-beta steroids useful as anti-inflammatory and anti-thrombosis agents. U.S. Patent 5,506,221, 9 April 1996.
[56]
Kobayashi, J.; Shinonaga, H.; Shigemori, H. Xestobergsterol C, a New Pentacyclic Steroid from the Okinawan Marine Sponge Ircinia sp. and Absolute Stereochemistry of Xestobergsterol A. J. Nat. Prod. 1995, 58, 312–318, doi:10.1021/np50116a029.
[57]
Nakamura, A.; Kaji, Y.; Saida, K.; Ito, M.; Nagatoshi, Y.; Hara, N.; Fujimoto, Y. Synthesis of xestobergsterol A from dehydroepiandrosterone. Tetrahedron Lett. 2005, 46, 6373–6376, doi:10.1016/j.tetlet.2005.07.042.
[58]
Takei, M.; Umeyama, A.; Shoji, N.; Arihara, S.; Endo, K. Mechanism of inhibition of IgE-dependent histamine release from rat mast cells by xestobergsterol A from the Okinawan marine sponge Xestospongia bergquistia. Experientia 1993, 49, 145–149, doi:10.1007/BF01989419. 7680004
[59]
Jung, M.E.; Johnson, T.W. First total synthesis of xestobergsterol A and active structural analogues of the xestobergsterols. Tetrahedron 2001, 57, 1449–1481, doi:10.1016/S0040-4020(00)01086-3.
[60]
Keyzers, R.A.; Northcote, P.T.; Berridge, M.V. Clathriol B, a new 14 beta marine sterol from the New Zealand sponge Clathria lissosclera. Aust. J. Chem. 2003, 56, 279–282, doi:10.1071/CH02167.
[61]
Mayer, A.M.S.; Lehmann, V.K.B. Marine pharmacology in 1998: marine compounds with antibacterial, anticoagulant, antifungal, anti-inflammatory, anthelmintic, antiplatelet, antiprotozoal, and antiviral activities; with actions on the cardiovascular, endocrine, immune, and nervous systems; and other miscellaneous mechanisms of action. Pharmacologist 2000, 42, 62–69.
[62]
Joseph, B.; Sujatha, S. Pharmacologically Important Natural products from Marine Sponges. J. Nat. Prod. 2011, 4, 5–12.
[63]
Mayer, A.M.S.; Rodriguez, A.D.; Berlinck, R.G.S.; Hamann, M.T. Marine pharmacology in 2003–4: Marine Compounds with Anthelminthic, Antibacterial, Anticoagulant, Antifungal, Anti-inflammatory, Antimalarial, Antiplatelet, Antiprotozoal, Antituberculosis, and Antiviral Activities affecting the Cardiovascular, Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action. Comp. Biochem. Physiol. C. Toxicol. Pharmacol. 2007, 145, 553–581, doi:10.1016/j.cbpc.2007.01.015. 17392033
[64]
Lattasch, H.; Thomson, R.H. A revised structure for cycloprodigiosin. Tetrahedron Lett. 1983, 24, 2701–2704, doi:10.1016/S0040-4039(00)87981-2.
[65]
Lee, J.S.; Kim, Y.S.; Park, S.; Kim, J.; Kang, S.J.; Lee, M.H.; Ryu, S.; Choi, J.M.; Oh, T.K.; Yoon, J.H. Exceptional Production of both Prodigiosin and Cycloprodigiosin as Major Metabolic Constituents by a Novel Marine Bacterium, Zooshikella rubidus S1-1. Appl. Environ. Microbiol. 2011, 77, 4967–4973, doi:10.1128/AEM.01986-10. 21642414
[66]
Kitahara, J.; Sakamoto, H.; Tsujimoto, M.; Nakagawa, Y. Involvement of NF-κB in the protection of cell death by tumor necrosis factor in L929 derived TNF resistant C12 cells. Biol. Pharm. Bull. 2000, 23, 397–401, doi:10.1248/bpb.23.397. 10784415
[67]
Yamamoto, D.; Kiyozuka, Y.; Uemura, Y.; Yamamoto, C.; Takemoto, H.; Hirata, H.; Tanaka, K.; Hioki, K.; Tsubura, A. Cycloprodigiosin hydrochloride, a H+/Cl？ symporter, induces apoptosis in human breast cancer cell lines. J. Cancer Res. Clin. Oncol. 2000, 126, 191–197, doi:10.1007/s004320050032. 10782891
[68]
Yamamoto, C.; Takemoto, H.; Kuno, K.; Yamamoto, D.; Nakai, K.; Baden, T.; Kamata, K.; Hirata, H.; Watanabe, T.; Inoue, K. Cycloprodigiosin hydrochloride, a H+/Cl？ symporter, induces apoptosis in human colon cancer cell lines in vitro. Oncol. Rep. 2001, 8, 821–824. 11410791
[69]
Yamamoto, D.; Uemura, Y.; Tanaka, K.; Nakai, K.; Yamamoto, C.; Takemoto, H.; Kamata, K.; Hirata, H.; Hioki, K. Cycloprodigiosin hydrochloride, H+/CL- symporter, induces apoptosis and differentiation in HL-60 cells. Int. J. Cancer 2000, 88, 121–128, doi:10.1002/1097-0215(20001001)88:1<121::AID-IJC19>3.0.CO;2-C. 10962449
Kawauchi, K.; Shibutani, K.; Yagisawa, H.; Kamata, H.; Nakatsuji, S.; Anzai, H.; Yokoyama, Y.; Ikegami, Y.; Moriyama, Y.; Hirata, H. A Possible Immunosuppressant, Cycloprodigiosin Hydrochloride, Obtained from Pseudoalteromonas denitrificans. Biochem. Biophys. Res. Commun. 1997, 237, 543–547, doi:10.1006/bbrc.1997.7186. 9299400
[72]
Teshima, S.; Nakanishi, H.; Kamata, K.; Kaibori, M.; Kwon, A.H.; Kamiyama, Y.; Nishizawa, M.; Ito, S.; Okumura, T. Cycloprodigiosin up-regulates inducible nitric oxide synthase gene expression in hepatocytes stimulated by interleukin-1β. Nitric Oxide 2004, 11, 9–16, doi:10.1016/j.niox.2004.07.009. 15350552
[73]
Dijkstra, G.; Moshage, H.; Jansen, P.L. Blockade of NF-kappaB activation and donation of nitric oxide: new treatment options in inflammatory bowel disease? Scand. J. Gastroenterol. Suppl. 2002, 236, 37–41. 12408502
[74]
Ban, J.O.; Oh, J.H.; Kim, T.M.; Kim, D.J.; Jeong, H.S.; Han, S.B.; Hong, J.T. Anti-inflammatory and arthritic effects of thiacremonone, a novel sulfurcompound isolated from garlic via inhibition of NF-κB. Arthritis Res. Ther. 2009, 11, 145–149, doi:10.1186/ar2819.
[75]
Tasdemir, D.; Mallon, R.; Greenstein, M.; Feldberg, L.; Kim, S.; Collins, K.; Wojciechowicz, D.; Mangalindan, G.; Concepcion, G.; Harper, M.K.; Ireland, C.M. Aldisine alkaloids from the Philippine sponge Stylissa massa are potent inhibitors of mitogen-activated protein kinase-1 (MEK-1). J. Med. Chem. 2002, 45, 529–532, doi:10.1021/jm0102856. 11784156
[76]
Skropeta, D.; Pastro, N.; Zivanovic, A. Kinase Inhibitors from Marine Sponges. Mar. Drugs 2011, 9, 2131–2154, doi:10.3390/md9102131. 22073013
[77]
Meijer, L.; Thunnissen, A.M.; White, A.W.; Garnier, M.; Nikolic, M.; Tsai, L.H.; Walter, J.; Cleverley, K.E.; Salinas, P.C.; Wu, Y.Z.; Biernat, J.; Mandelkow, E.M.; Kim, S.H.; Pettit, G.R. Inhibition of cyclin-dependent kinases, GSK-3beta and CK1 by hymenialdisine, a marine sponge constituent. Chem. Biol. 2000, 7, 51–63, doi:10.1016/S1074-5521(00)00063-6. 10662688
[78]
Di Martino, M.; Wolff, C.; Patil, A.; Nambi, P. Effects of a protein kinase C inhibitor (PKCI) on the development of adjuvant-induced arthritis (AA) in rats. Inflamm. Res. 1995, 2, 123–124.
[79]
Roshak, A.; Jackson, J.R.; Fletcher, M.C.; Marshall, L.A. Inhibition of NFkB-mediated interleukin-1b-stimulated prostaglandin E2 formation by the marine natural product hymenialdisine. J. Pharmacol. Exp. Ther. 1997, 283, 955–960. 9353419
[80]
Breton, J.J.; Fletcher, M.C. The natural product hymenialdisine inhibits interleukin-8 production in U937 cells by inhibition of nuclear factor-B. J. Pharmacol. Exp. Ther. 1997, 282, 459–466. 9223588
[81]
Badger, A.M.; Cook, M.N.; Swift, B.A.; Newman-Tarr, T.M.; Gowen, M.; Lark, M. Inhibition of interleukin-1-induced proteoglycan degradation and nitric oxide production in bovine articular cartilage/chondrocyte cultures by the natural product, hymenialdisine. J. Pharmacol. Exp. Ther. 1999, 290, 587–593. 10411566
[82]
Higa, T.; Tanaka, J. Studies in Natural Products Chemistry: bioactive marine macrolides. Structure Chem. 1996, 19, 549–626.
[83]
Qi, Y.; Ma, S. The medicinal potential of promising marine macrolides with anticancer activity. Chem. Med. Chem. 2011, 6, 399–409. 21302362
[84]
Napolitano, J.G.; Daranas, A.H.; Norte, M.; Fernández, J.J. Marine macrolides, a promising source of antitumor compounds. Anticancer Agents Med. Chem. 2009, 9, 122–137, doi:10.2174/187152009787313800. 19199861
[85]
Jacobson, P.B.; Jacobs, R.S. Fuscoside: An anti-inflammatory marine natural product which selectively inhibits 5-lipoxigenase. Part I: physiological and biochemical studies in murine inflammatory models. J. Pharmacol. Exp. Ther. 1992, 262, 866–873. 1501127
[86]
Spector, I.; Shochet, N.R.; Blasberger, D.; Kashman, Y. Latrunculins, novel marine macrolides that disrupt microfilament organization and affect cell growth: comparison with cytochalasin D. Cell. Motil. Cytoskeleton 1989, 13, 127–144, doi:10.1002/cm.970130302. 2776221
[87]
Yamada, K.; Ojika, M.; Ishigaki, T.; Yoshida, Y.; Ekimoto, H.; Arakawa, M. Aplyronine A, a potent antitumor substance, and the congeners Aplyronines B and C isolated from the sea hare Aplysia kurodai. J. Am. Chem. Soc. 1993, 115, 11020–11021, doi:10.1021/ja00076a082.
[88]
Paterson, I.; Findlay, A.D. Total synthesis of cytotoxic marine macrolides: callipeltoside A, aurisides A and B, and dolastatin 19. Pure Appl. Chem. 2008, 80, 1773–1782, doi:10.1351/pac200880081773.
[89]
Ishibashi, M.; Moore, R.E.; Patterson, G.M.L.; Xu, C.F.; Clardy, J. Scytophycins, cytotoxic and antimitotic agents from the cyanophyte Scytonema pseudohofinanni. J. Org. Chem. 1986, 51, 5300–5306, doi:10.1021/jo00376a047.
[90]
D’Auria, M.V.; Paloma, L.G.; Minale, L.; Zampella, L. Superstolide A: a potent cytotoxic macrolide of a new type from the New Caledonian deep water marine sponge Neosiphonia superstes. J. Am. Chem. Soc. 1994, 116, 6658–6663, doi:10.1021/ja00094a022.
[91]
Paterson, I.; Britton, R.; Ashton, K.; Knust, H.; Stafford, J. Synthesis of antimicrofilament marine macrolides: synthesis and configurational assignment of a C5–C16 degradation fragment of reidispongiolide A. Proc. Natl. Acad. Sci. USA 2004, 101, 11986–11991, doi:10.1073/pnas.0401548101. 15201432
[92]
Jensen, P.R.; Williams, P.G.; Oh, D.C.; Zeigler, L.; Fenical, W. Species specific secondary metabolite production in marine actinomycetes of the Genus Salinispora. Appl. Environ. Microbiol. 2007, 73, 1146–1152, doi:10.1128/AEM.01891-06. 17158611
[93]
Trischman, J.A.; Tapiolas, D.M.; Jensen, P.R.; Dwight, R.; Fenical, W.; McKee, T.C.; Ireland, C.M.; Stout, T.J.; Clardy, J. Salinamides A and B: anti-inflammatory depsipeptides from a marine Streptomycetes. J. Am. Chem. Soc. 1994, 116, 757–758, doi:10.1021/ja00081a042.
[94]
Renner, M.K.; Shen, Y.C.; Cheng, X.C.; Jensen, P.R.; Frankmoelle, W.; Kauffman, C.A.; Fenical, W.; Lobkovsky, E.; Clardy, J. Cyclomarins A–C, New Antiinflammatory Cyclic Peptides Produced by a Marine Bacterium (Streptomyces sp.). J. Am. Chem. Soc. 1999, 121, 11273–11276, doi:10.1021/ja992482o.
[95]
Schmitt, E.K.; Riwanto, M.; Sambandamurthy, V.; Roggo, S.; Miault, C.; Zwingelstein, C.; Krastel, P.; Noble, C.; Beer, D.; Rao, S.P.S.; Au, M.; Niyomrattanakit, P.; Lim, V.; Zheng, J.; Jeffery, D.; Pethe, K.; Camacho, L.R. The Natural Product Cyclomarin Kills Mycobacterium Tuberculosis by Targeting the Clp-C1 Subunit of the Caseinolytic Protease. Angew. Chem. Int. Ed. 2011, 50, 5889–5891, doi:10.1002/anie.201101740.
[96]
Wen, S.J.; Hu, T.S.; Yao, Z.J. Macrocyclization studies and total synthesis of cyclomarin C, an anti-inflammatory marine cyclopeptide. Tetrahedron 2005, 61, 4931–4938, doi:10.1016/j.tet.2005.03.058.
[97]
Pietra, F. Secondary metabolites from marine microorganisms: bacteria, protozoa, algae and fungi. Achievements and prospects. Nat. Prod. Rep. 1997, 14, 453–464, doi:10.1039/np9971400453.
[98]
Moore, B.S.; Trischman, J.A.; Seng, D.; Kho, D.; Jensen, P.R.; Fenical, W. Salinamides, Antiinflammatory peptides from a Marine Streptomycete. J. Org. Chem. 1999, 64, 1145–1150, doi:10.1021/jo9814391.
[99]
Randazzo, A.; Bifulco, G.; Giannini, C.; Bucci, M.; Debitus, C.; Cirino, G.; Paloma, G.L. Halipeptins A and B: two novel potent anti-inflammatory cyclic depsipeptides from the Vanuatu marine sponge Haliclona species. J. Am. Chem. Soc. 2001, 123, 10870–10876, doi:10.1021/ja010015c. 11686688
[100]
Sousuke, H.; Kazuishi, M.; Yasumasa, H. Synthetic Studies on Halipeptins, Anti-Inflammatory Cyclodepsipeptides. Pept. Sci. 2006, 2005, 39–42.
[101]
Nicolaou, K.C.; Lizos, D.E.; Kim, D.W.; Schlawe, D.; De Noronha, R.G.; Longbottom, D.A.; Rodriquez, M.; Bucci, M.; Cirino, G. Total Synthesis and Biological Evaluation of Halipeptins A and D and Analogues. J. Am. Chem. Soc. 2006, 128, 4460–4470, doi:10.1021/ja060064v. 16569024
[102]
Yu, X.; Pan, X.; Lin, D. Total Synthesis of Halipeptin A: A Potent Antiinflammatory Cyclic Depsipeptide. Angew. Chem. 2005, 117, 137–140, doi:10.1002/ange.200461239.
[103]
Kim, J.S.; Lim, Y.J.; Im, K.S.; Jung, J.H.; Shim, C.J.; Lee, C.O.; Hong, J.; Lee, H. Cytotoxic polyacetylenes from the marine sponge Petrosia sp. J. Nat Prod. 1999, 62, 554–559, doi:10.1021/np9803427.
[104]
Shin, J.; Seo, Y.; Cho, K.W. Five new polyacetylenes from a sponge of the genus petrosia. J. Nat. Prod. 1998, 61, 1268–1273, doi:10.1021/np9802015. 9784165
[105]
Hong, S.; Kim, S.H.; Rhee, M.H.; Kim, A.R.; Jung, J.H.; Chun, T.; Yoo, E.S.; Cho, J.Y. In vitro anti-inflammatory and pro-aggregative effects of a lipid compound, petrocortyne A, from marine sponges. Naunyn Schmiedeberg’s Arch. Pharmacol. 2003, 368, 448–456, doi:10.1007/s00210-003-0848-7.
[106]
Eigler, A.; Sinha, B.; Hartmann, G.; Endres, S. Taming TNF: strategies to restrain this proinflammatory cytokine. Immunol. Today 1997, 18, 487–492, doi:10.1016/S0167-5699(97)01118-3. 9357141
[107]
Sui, B.; Yeh, E.A.H.; Dennis, P. Curran Assignment of the structure of petrocortyne A by mixture syntheses of four candidate stereoisomers. J. Org. Chem. 2010, 75, 2942–2954, doi:10.1021/jo100115h. 20394446
[108]
Ekebergh, A.; Karlsson, I.; Mete, R.; Pan, Y.; Borje, A.; Martensson, J. Oxidative coupling as a biomimetic approach to the synthesis of scytonemin. Org. Lett. 2011, 13, 4458–4461, doi:10.1021/ol201812n. 21786790
[109]
Stevenson, C.S.; Capper, E.A.; Roshak, A.K.; Marquez, B.; Eichman, C.; Jackson, J.R.; Mattern, M.; Gerwick, W.H.; Jacobs, R.S. The identification and characterization of the marine natural product scytonemin as a novel antiproliferative pharmacophore. J. Pharmacol. Exp. Ther. 2002, 303, 858–866, doi:10.1124/jpet.102.036350. 12388673
[110]
Soule, T.; Stoute, V.; Swingley, W.D.; Meeks, J.C.; Pichel, F.G. Molecular genetics and genomic analysis of scytonemin biosynthesis in Nostoc punctiforme ATCC 29133. J. Bacteriol. 2007, 189, 4465–4472, doi:10.1128/JB.01816-06. 17351042
[111]
Ninomiya, M.; Satoh, H.; Yamaguchi, Y.; Takenaka, H.; Koketsu, M. Antioxidative activity and chemical constituents of edible terrestrial alga Nostoc commune Vauch. Biosci. Biotechnol. Biochem. 2011, 75, 2175–2177, doi:10.1271/bbb.110466. 22056440
[112]
United States Department of Agriculture (USDA) and United States Department of Health and Human Services (HHS). Dietary Guidelines for Americans, 5th; Home and Garden Bulletin No. 232; USDA: Washington, DC, USA, 2000; pp. 10–12.
[113]
Lichtenstein, A.H. Nutrient supplements and cardiovascular disease: A heartbreaking story. J. Lipid Res. 2009, 50, 429–433.
[114]
Riccioni, G.; D’Orazio, N.; Palumbo, N.; Bucciarelli, V.; Ilio, E.; Bazzano, L.A.; Bucciarelli, T. Relationship between plasma antioxidant concentrations and carotid intima-media thickness: the asymptomatic carotid atherosclerotic disease in Manfredonia study. Eur. J. Cardiovasc. Prev. Rehabil. 2009, 3, 351–357.
Allen, R.G.; Tresini, M. Oxidative stress and gene regulation. Free Radic. Biol. Med. 2000, 28, 463–499, doi:10.1016/S0891-5849(99)00242-7. 10699758
[117]
Zaccaroni, A.; Perugini, M.; D’Orazio, N.; Manera, M.; Giannella, B.; Zucchini, M.; Giammarino, A.; Riccioni, G.; Ficoneri, C.; Naccari, C.; Amorena, M. Investigation of total arsenic in fish from the central adriatic sea (Italy) in relation to levels found in fishermen’s hair. J. Vet. Pharmacol. Ther. 2006, 29, 178–179.
[118]
Perugini, M.; D’Orazio, N.; Manera, M.; Giannella, B.; Zaccaroni, A.; Zucchini, M.; Giammarino, A.; Riccioni, G.; Ficoneri, C.; Amorena, M. Total mercury in fish from the central adriatic sea in relation to levels found in fishermen’s hair. J. Vet. Pharmacol. Ther. 2006, 29, 176–177.
[119]
Jackson, H.; Braun, C.L.; Ernst, H. The chemistry of novel xanthophyll carotenoids. Am. J. Cardiol. 2008, 101, 50–57, doi:10.1016/j.amjcard.2008.02.008.
[120]
Miyashita, K. Function of marine carotenoids. Forum Nutr. 2009, 61, 136–146. 19367118
[121]
Higuera-Ciapara, I.; Valenzuela, L.F.; Goycoolea, F.M. Astaxanthin: a review of its chemistry and applications. Crit. Rev. Food Sci. Nutr. 2006, 46, 185–196, doi:10.1080/10408690590957188. 16431409
[122]
Shimidzu, N. Carotenoids as singlet oxygen quenchers in marine organisms. Fish. Sci. 1996, 62, 134–137, doi:10.2331/suisan.62.134.
[123]
Naguib, Y.M.A. Antioxidant acitivities of astaxanthin and related carotenoids. J. Agric. Food Chem. 2000, 48, 1150–1154, doi:10.1021/jf991106k. 10775364
[124]
Bennedsen, M.; Wang, X.; Willén, R.; Wadstr？m, T.; Andersen, L.P. Treatment of H. pylori infected mice with antioxidant astaxanthin reduces gastric inflammation, bacterial load and modulates cytokine release by splenocytes. Immunol. Lett. 1999, 70, 185–189. 10656672
[125]
Riccioni, G.; D’Orazio, N.; Franceschelli, S.; Speranza, L. Marine carotenoids and cardiovascular risk markers. Mar. Drugs 2011, 9, 1166–1175, doi:10.3390/md9071166. 21822408
[126]
Yuan, J.P.; Peng, J.; Yin, K.; Wang, J.H. Potential health-promoting effects of astaxanthin: A high-value carotenoid mostly from microalgae. Mol. Nutr. Food Res. 2011, 55, 150–165, doi:10.1002/mnfr.201000414. 21207519
[127]
Pashkow, F.J.; Watumull, D.G.; Campbell, C.L. Astaxanthin: A novel potential treatment for oxidative stress and inflammation in cardiovascular disease. Am. J.Cardiol. 2008, 101, 58–68, doi:10.1016/j.amjcard.2007.07.049. 18157966
[128]
Guerin, M.; Huntley, M.E.; Olaizola, M. Haematococcus astaxanthin: applications for human health and nutrition. Trends Biotechnol. 2003, 21, 210–216, doi:10.1016/S0167-7799(03)00078-7. 12727382
[129]
Hu, T.; Liu, D.; Chen, Y.; Wu, J.; Wang, S. Antioxidant activity of sulfated polysaccharide fractions extracted from Undaria pinnitafida in vitro. Int. J. Biol. Macromol. 2010, 46, 193–198, doi:10.1016/j.ijbiomac.2009.12.004. 20025899
[130]
Nomura, T.; Kikuchi, M.; Kubodera, A.; Kawakami, Y. Proton-donative antioxidant activity of fucoxanthin with 1,1-diphenyl-2-picrylhydrazyl (DPPH). Biochem. Mol. Biol. Int. 1997, 42, 361–370. 9238535
[131]
Woo, M.N.; Jeon, S.M.; Shin, Y.C.; Lee, M.K.; Kang, M.A.; Choi, M.S. Anti-obese property of fucoxanthin is partly mediated by altering lipid-regulating enzymes and uncoupling proteins of visceral adipose tissue in mice. Mol. Nutr. Food Res. 2009, 53, 1603–1611, doi:10.1002/mnfr.200900079. 19842104
[132]
Kim, K.N.; Heo, S.J.; Kang, S.M.; Ahn, G.; Jeon, Y.J. Fucoxanthin induces apoptosis in human leukemia HL-60 cells through a ROS-mediated Bcl-xL pathway. Toxicol. In Vitro 2010, 24, 1648–1654, doi:10.1016/j.tiv.2010.05.023. 20594983
[133]
Jeon, S.M.; Kim, H.J.; Woo, M.N.; Lee, M.K.; Shin, Y.C.; Park, Y.B.; Choi, M.S. Fucoxanthin-rich seaweed extract suppresses body weight gain and improves lipid metabolism in high-fat-fed C57BL/6J mice. Biotechnol. J. 2010, 5, 961–969, doi:10.1002/biot.201000215. 20845386
[134]
Shiratori, K.; Okgami, K.; Ilieva, I.; Jin, X.H.; Koyama, Y.; Miyashita, K.; Yoshida, K.; Kase, S.; Ohno, S. Effects of fucoxanthin on lipopolysaccharide-induced inflammation in vitro and in vivo. Exp. Eye Res. 2005, 81, 422–428, doi:10.1016/j.exer.2005.03.002. 15950219
[135]
Newman, D.; Cragg, G. Marine natural products and related compounds in clinical and advanced preclinical trials. J. Nat. Prod. 2004, 67, 1216–1238, doi:10.1021/np040031y. 15332835
[136]
Pallela, R.; Na-Young, Y.; Kim, S.K. Anti-photoaging and photoprotective compounds derived from marine organisms. Mar. Drugs 2010, 8, 1189–1202, doi:10.3390/md8041189. 20479974
[137]
Kadam, S.; Prabhasankar, P. Marine foods as functional ingredients in bakery and pasta products. Food Res. Int. 2010, 43, 1975–1980, doi:10.1016/j.foodres.2010.06.007.
[138]
Helmy, M.; Shohayeb, M.; Helmy, M.H.; El-Bassiouni, E.A. Antioxidants as adjuvant therapy in rheumatoid disease. Arzneim-Forsch Drug Res. 2001, 51, 293–298.
