Review pubs.acs.org/JAFC
Marine Algae-Derived Bioactive Peptides for Human Nutrition and Health Xiaodan Fan, Lu Bai, Liang Zhu, Li Yang, and Xuewu Zhang* College of Light Industry and Food Sciences, South China University of Technology, Guangzhou, China ABSTRACT: Within the parent protein molecule, most peptides are inactive, and they are released with biofunctionalities after enzymatic hydrolysis. Marine algae have high protein content, up to 47% of the dry weight, depending on the season and the species. Recently, there is an increasing interest in using marine algae protein as a source of bioactive peptides due to their health promotion and disease therapy potentials. This review presents an overview of marine algae-derived bioactive peptides and especially highlights some key issues, such as in silico proteolysis and quantitative structure−activity relationship studies, in vivo fate of bioactive peptides, and novel technologies in bioactive peptides studies and production. KEYWORDS: marine algae, enzymatic hydrolysis, peptides, bioactivity, novel technologies
■
INTRODUCTION Bioactive peptides are usually composed of 2−20 amino acid residues and have received much attention due to their biological activities and health benefits. Generally, there are three ways to release bioactive peptides, such as solvent extraction, enzymatic hydrolysis, and microbial fermentation. However, due to the lack of residual chemicals in the final peptide products, enzymatic hydrolysis is preferred, especially in the pharmaceutical and food industries.1 After enzymatic hydrolysis, the most widely used peptide fractionation methods include ultrafiltration with different pore sizes (3, 5, 10, and 30 kDa), sequential chromatography (i.e., gel filtration chromatography and ion-exchange chromatography), and reverse-phase liquid chromatography.2 Then, the molecular structures of bioactive peptides can be characterized by mass spectrometry such as liquid chromatography−mass spectrometry (LC-MS) and mass−mass spectrometry (MS-MS) (Figure 1).3 Marine organisms produce a variety of bioactive molecules, which can be developed as nutraceuticals and pharmaceuticals for human nutrition supplementation and disease therapy.4−9 Marine algae include unicellular microalgae and multicellular macroalgae. High protein contents exist in marine algae, generally 5−15% of the dry weight in brown algae and 10−47% of the dry weight in red and green algae.10 Recently, there is an enormous interest in using marine alga proteind as a source of bioactive peptides.11−13 Depending on the amino acid sequence, marine algae-derived biopeptides may be involved in various biological functions, including antioxidant, anticancer, antihypertensive, antiatherosclerotic, and immunomodulatory effects. This review presents an overview of bioactive peptides from marine algae and discusses future challenges.
Figure 1. Schematic diagram for the preparation of marine algaederived bioactive peptides.
aging, hypertension, and neurodegenerative and inflammatory diseases.14,15 The use of synthetic antioxidants including butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and tert-butylhydroquinone (TBHQ) in humans is associated with some side effects such as carcinogenesis and liver damage.16 Hence, it is important to search for safe and
■
OVERVIEW OF BIOACTIVE PEPTIDES FROM MARINE ALGAE Antioxidant Biopeptides. There exist various reactive oxygen species (ROS), such as peroxyl radicals (ROO−), nitric oxide radicals (NO−), hydroxyl radicals (−OH), and superoxide radicals (O2−). The unlimited accumulation of ROS may lead to many health disorders such as cancer, diabetes mellitus, © 2014 American Chemical Society
Received: Revised: Accepted: Published: 9211
May 25, 2014 August 31, 2014 September 1, 2014 September 1, 2014 dx.doi.org/10.1021/jf502420h | J. Agric. Food Chem. 2014, 62, 9211−9222
Journal of Agricultural and Food Chemistry
9212
24 peroxyl, DPPH and hydroxyl radicals
23 free radicals/antihepatotoxicity
in vitro (HepG2/ CYP2E1 cells) in vitro
22
Chlorella ellipsoidea
Navicula incerta
0.02−1.42 mM
102−196 μg/mL
alcalase, Pronase-E, α-chymotrypsin, Neutrase, papain, pepsin, and trypsin alcalase, α-chymotrypsin, Neutrase, papain, pepsin, Pronase-E, and trypsin papain, trypsin, pepsin, and α-chymotrypsin Navicula incerta
enzymatic hydrolysates PGWNQWFL, VEVLPPAEL LNGDVW
in vitro
hydroxyl, alkyl and DPPH radical hydrogen peroxide hydroxyl radical, superoxide radical, peroxyl radical, DPPH radical and ABTS radicals hydroxyl, superoxide, DPPH in vitro in vitro in vitro C1 for TEAC, C3 > C4 > C1 for ORAC, and C4 > C1 > N1 for SOR. Bulky hydrophobic amino acids at the C-terminal are related to the antioxidant activity of peptides in the three free radical systems. Several publications explore the potential of in silico methods for the screening of bioactive peptides. For example, by in silico digestion of egg white protein and QSAR analysis of more than 20000 peptides generated from 75 in silico hydrolysates, Majumder and Wu82 found that thermolysin−pepsin digestion of ovotransferrin was the best condition, and three novel antihypertensive peptides were identified. Sargadia et al.83 identified six novel peptides with ACE-inhibitory activity (IC50 values = 4−32 μM) from 231 peptides of milk proteins, using matrix-assisted laser desorption/ionization tandem time-of-flight (MALDI-TOFTOF) mass spectrometry and QSAR modeling on ACEinhibitory peptides with an amino acid length larger >5. In Vivo Fate of Bioactive Peptides. Due to the susceptibility of peptides to protease degradation, the fate of bioactive peptides during gastrointestinal transit is a major problem. In fact, the antihypertensive peptide β-LG f(142− 148) obtained from β-lactoglobulin could not be detected in the sera of human volunteers following its oral ingestion; that is, the peptide is not sufficiently stable to gastrointestinal and serum proteases.84 To enhance the stability of peptides, one solution is chemical modification of peptides and the incorporation of unnatural amino acids (including D-amino acids). For example, at the carboxyl terminal end of a peptide, the presence of a proline residue has been shown to increase the peptide’s resistance to degradation by digestive enzymes.85 Shen et al.86 developed a new chemical method of peptide synthesis to generate cyclic peptides by incorporating unnatural amino acids into a peptide chain, hence increasing stability. Another solution is encapsulation of peptides with polymers or particles such as dendrimers, liposomes, and polyectrolyte microspheres. For example, Wang and Zhang35 investigated the micro- and nanoencapsulation of a Chlorella pyrenoidosa antitumor polypeptide (CPAP) by complex coacervation and ionotropic gelation. The in vitro release tests showed that CPAP was well preserved against gastric enzymatic degradation after micro/nanoencapsulation, and the slowly controlled release in the intestine could be potentially achieved. On the other hand, due to the existence of intestinal bacterial communities, it is necessary to consider whether or not potential toxic metabolites could be generated by fermentation of gut microbiota on bioactive peptides.87 For example, the increased protein fermentation and decreased carbohydrate fermentation by gut microbiota was shown to cause a significant decrease in fecal cancer protective metabolites (e.g., butyrate) and the greatest formation of hazardous metabolites such as Nnitroso compounds, which is probably detrimental to colonic health.88 9217
dx.doi.org/10.1021/jf502420h | J. Agric. Food Chem. 2014, 62, 9211−9222
Journal of Agricultural and Food Chemistry
Review
peptide mixtures with similar molecular weights. The most frequently used technologies include chromatography and pressure-driven filtration processes.107,108 However, some drawbacks, such as the high cost of chromatographic technology and membrane fouling formation for pressuredriven processes, limit their wide application.2 Recently, a patented electrodialysis with ultrafiltration membranes (EDUF) was developed to replace traditional separation methods for peptide recovery.109 The driving force of EDUF is the electric field; hence, there is no significant fouling formation at the membrane interface due to the absence of pressure.110 EDUF technology has been applied to the isolation of peptides from various hydrolysates.111−114 The third challenge is to understand the mechanisms of action of bioactive peptides. Fluorescence lifetime imaging (FLIM) technique is able to distinguish interacting and noninteracting fractions and to resolve changes in the binding, conformation, and composition of biologically relevant compounds in live cells.115 Therefore, FLIM has become an inevitable technique for spatially resolving cellular processes and physical interactions of cellular components in real time.116 Thus, it offers the opportunity to understand the mechanism of action for increasingly generated bioactive peptides, such as the interaction mechanisms of antimicrobial peptide (melittin) with live bacterial cells.117 However, FLIM is unable to determine the detailed molecular changes in such an interaction process. In this respect, omics technologies (transcriptomics, proteomics, and metabolomics) could make contributions. For instance, proteomics is a promising technology in understanding mechanism of action for bioactive peptides. By twodimensional electrophoresis (2DE) coupled to mass spectrometry, Huang and Chen118 profiled proteome changes in antibacterial peptide epinecidin-1-treated zebrafish. A possible protein−protein interacting network regulated by epinecidin-1 was constructed, suggesting a potential role of epinecindin-1 in cytoskeletal assembly and organization to promote resistance to bacterial infection. Currently, these novel methods are rarely applied to the production and study of marine algae peptides, but should be promising. Specifically, EAE and SWE technologies are first employed to extract proteins from marine algal biomass. On the one hand, the extracted proteins are subject to fermentation by probiotics such as lactic acid bacteria and bifidobacteria for peptide production. On the other hand, the extracted proteins are enzymatically hydrolyzed under the condition of immobilized enzymes or in a continuous enzyme membrane reactor system. Then, EDUF technology is employed to simultaneously isolate bioactive peptides from the complex peptides mixture. Finally, the mechanisms of action of bioactive peptides are investigated by FLIM and omics such as proteomics techniques (Figure 8). In conclusion, bioactive peptides generated by enzymatic hydrolysis of algae protein or algae processing waste exhibit diverse biofunctionalities, which are promising in applications of functional foods, pharmaceuticals, and cosmeceuticals. However, there are still many challenges before bioactive peptides can be translated into practical use for human nutrition and health. In silico proteolysis and QSAR modeling can accelerate the discovery of bioactive peptides. Innovative technologies need to be developed for transferring laboratoryscale preparations to industrial-scale production. Extensive research is highly required to explore metabolic products of bioactive peptides during gastrointestinal digestion and to
Figure 8. Proposed applications of novel technologies to produce and study marine algae-derived bioactive peptides.
elucidate the detailed mechanisms of action in vivo. It is envisaged that the bioactive peptides market will become a selfstanding industry in the next few decades. Hence, some regulations and standards that govern the production, utilization, and marketing of bioactive peptides should be set.
■
AUTHOR INFORMATION
Corresponding Author
*(X.Z.) Mail: College of Light Industry and Food Sciences, South China University of Technology, 381 Wushan Road, Guangzhou 510640, China. Phone/fax: 86 20 87113848. Email: [email protected]. Funding
This study was supported by an Ocean and Fisheries Development Project (A201301B04) from the Administration of Ocean and Fisheries of Guangdong Province and a National High-Tech Research and Development Project (863 Program) (2014AA022004). This study was supported by Key Laboratory of Enhanced Heat Transfer and Energy Conservation of the Ministry of Education, South China University of Technology, Guangzhou, China. 9218
dx.doi.org/10.1021/jf502420h | J. Agric. Food Chem. 2014, 62, 9211−9222
Journal of Agricultural and Food Chemistry
Review
Notes
(21) Sheih, I. C.; Wu, T. K.; Fang, T. J. Antioxidant properties of a new antioxidative peptide from algae protein hydrolysate in different oxidation systems. Bioresour. Technol. 2009, 100, 3419−3425. (22) Kang, K. H.; Qian, Z. J.; Ryu, B.; Kim, S. K. Characterization of growth and protein contents from microalgae Navicula incerta with the investigation of antioxidant activity of enzymatic hydrolysates. Food Sci. Biotechnol. 2011, 20 (1), 183−191. (23) Kang, K. H.; Qian, Z. J.; Ryu, B.; Karadeniz, F.; Kim, D.; Kim, S. K. Antioxidant peptides from protein hydrolysate of microalgae Navicula incerta and their protective effects in HepG2/CYP2E1 cells induced by ethanol. Phytother. Res. 2012, 26 (10), 1555−1563. (24) Ko, S. C.; Kim, D.; Jeon, Y. J. Protective effect of a novel antioxidative peptide purified from a marine Chlorella ellipsoidea protein against free radical-induced oxidative stress. Food Chem. Toxicol. 2012, 50 (7), 2294−2302. (25) Power, O.; Jakeman, P.; FitzGerald, R. J. Antioxidative peptides: enzymatic production, in vitro and in vivo antioxidant activity and potential applications of milk-derived antioxidative peptides. Amino Acids 2013, 44 (3), 797−820. (26) Ou, B.; Hampsch-Woodill, M.; Prior, R. Development and validation of an improved oxygen radical absorbance capacity assay using fluorescein as the fluorescent probe. J. Agric. Food Chem. 2001, 49 (10), 4619−4626. (27) Haytowitz, D.; Bhagwat, S. USDA Database for the Oxygen Radical Absorbance Capacity (ORAC) of Selected Foods, release 2; U.S. Department of Agriculture: Washington, DC, USA, 2010. (28) Manso, M. A.; Miguel, M.; Even, J.; Hernández, R.; Aleixandre, A.; López Fandinõ, R. Effect of the long-term intake of an egg white hydrolysate on the oxidative status and blood lipid profile of spontaneously hypertensive rats. Food Chem. 2008, 109 (2), 361−367. (29) Wang, D.; Wang, L.; Zhu, F.; Zhu, J.; Chen, X. D.; Zou, L.; Saito, M.; Li, L. In vitro and in vivo studies on the antioxidant activities of the aqueous extracts of Douchi (a traditional Chinese salt-fermented soybean food). Food Chem. 2008, 107 (4), 1421−1428. (30) Chidambara Murthy, K. N.; Vanitha, A.; Rajesha, J.; Mahadeva Swamy, M.; Sowmya, P. R.; Ravishankar, G. A. In vivo antioxidant activity of carotenoids from Dunaliella salina − a green microalga. Life Sci. 2005, 76 (12), 1381−1390. (31) Vijayavel, K.; Anbuselvam, C.; Balasubramanian, M. P. Antioxidant effect of the marine algae Chlorella vulgaris against naphthalene-induced oxidative stress in the albino rats. Mol. Cell. Biochem. 2007, 303 (1−2), 39−44. (32) Gad, A. S.; Khadrawy, Y. A.; El-Nekeety, A. A.; Mohamed, S. R.; Hassan, N. S.; Abdel-Wahhab, M. A. Antioxidant activity and hepatoprotective effects of whey protein and Spirulina in rats. Nutrition 2011, 27 (5), 582−589. (33) Kang, K. H.; Kim, S. K. Beneficial effect of peptides from microalgae on anticancer. Curr. Protein Pept. Sci. 2013, 14 (3), 212− 217. (34) Sheih, I. C.; Fang, T. J.; Wu, T. K.; Lin, P. H. Anticancer and antioxidant activities of the peptide fraction from algae protein in waste. J. Agric. Food Chem. 2010, 58, 1202−1207. (35) Wang, X.; Zhang, X. Separation, antitumor activities, and encapsulation of polypeptide from Chlorella pyrenoidosa. Biotechnol. Prog. 2013, 29 (3), 681−687. (36) Zhang, B.; Zhang, X. Separation and nanoencapsulation of antitumor polypeptide from Spirulina platensis. Biotechnol. Prog. 2013, 29, 1230−1238. (37) Zheng, L. H.; Wang, Y. J.; Sheng, J.; Wang, F.; Zheng, Y.; Lin, X. K.; Sun, M. Antitumor peptides from marine organisms. Mar. Drugs 2011, 9 (10), 1840−1859. (38) Gupta, S.; Kass, G. E.; Szegezdi, E.; Joseph, B. The mitochondrial death pathway: a promising therapeutic target in diseases. J. Cell. Mol. Med. 2009, 13, 1004−1033. (39) Zheng, L.; Lin, X.; Wu, N.; Liu, M.; Zheng, Y.; Sheng, J.; Ji, X.; Sun, M. Targeting cellular apoptotic pathway with peptides from marine organisms. Biochim. Biophys. Acta 2013, 1836 (1), 42−48. (40) Verdecchia, P.; Angeli, F.; Mazzotta, G.; Gentile, G.; Reboldi, G. The rennin angiotensin system in the development of cardiovascular
The authors declare no competing financial interest.
■
REFERENCES
(1) Korhonen, H.; Pihlanto, A. Bioactive peptides: production and functionality. Int. Dairy J. 2006, 16 (9), 945−960. (2) Chabeaud, A.; Vandanjon, L.; Bourseau, P.; Jaouen, P.; Guérard, F. Fractionation by ultrafiltration of a saithe protein hydrolysate (Pollachius virens): effect of material and molecular weight cut-off on the membrane performances. J. Food Eng. 2009, 91, 408−414. (3) Samarakoon, K.; Jeon, Y. J. Bio-functionalities of proteins derived from marine algae − a review. Food Res. Int. 2012, 48, 948−960. (4) Cheung, R. C.; Wong, J. H.; Pan, W. L.; Chan, Y. S.; Yin, C. M.; Dan, X. L.; Wang, H. X.; Fang, E. F.; Lam, S. K.; Ngai, P. H.; Xia, L. X.; Liu, F.; Ye, X. Y.; Zhang, G. Q.; Liu, Q. H.; Sha, O.; Lin, P.; Ki, C.; Bekhit, A. A.; Bekhit, A.-D.; Wan, D. C.; Ye, X. J.; Xia, J.; Ng, T. B. Antifungal and antiviral products of marine organisms. Appl. Microbiol. Biotechnol. 2014, 98 (8), 3475−3494. (5) Glaser, K. B.; Mayer, A. M. A renaissance in marine pharmacology: from preclinical curiosity to clinical reality. Biochem. Pharmacol. 2009, 78 (5), 440−448. (6) Hughes, C. C.; Fenical, W. Antibacterials from the sea. Chem. Eur. J. 2010, 16 (42), 12512−12525. (7) Mayer, A. M.; Gustafson, K. R. Marine pharmacology in 2005− 2006: antitumour and cytotoxic compounds. Eur. J. Cancer 2008, 44 (16), 2357−2387. (8) Mayer, A. M.; Rodríguez, A. D.; Taglialatela-Scafati, O.; Fusetani, N. Marine pharmacology in 2009−2011: marine compounds with antibacterial, antidiabetic, antifungal, anti-inflammatory, antiprotozoal, antituberculosis, and antiviral activities; affecting the immune and nervous systems, and other miscellaneous mechanisms of action. Mar. Drugs 2013, 11, 2510−2573. (9) Wijesekara, I.; Kim, S. K. Angiotensin-I-converting enzyme (ACE) inhibitors from marine resources: prospects in the pharmaceutical industry. Mar. Drugs 2010, 8 (4), 1080−1093. (10) Ibanez, E.; Cifuentes, A. Benefits of using algae as natural sources of functional ingredients. J. Sci. Food Agric 2013, 93, 703−709. (11) Kim, S. K.; Kang, K. H. Medicinal effects of peptides from marine microalgae. Adv. Food Nutr. Res. 2011, 64, 313−323. (12) Kim, S. K.; Wijesekara, I. Development and biological activities of marine-derived bioactive peptides: a review. J. Funct Foods 2010, 2, 1−9. (13) Kim, J. A.; Kim, S. K. Bioactive peptides from marine sources as potential anti-inflammatory therapeutics. Curr. Protein Pept. Sci. 2013, 14 (3), 177−182. (14) Butterfield, D. A.; Castenga, A.; Pocernich, C. B.; Drake, J.; Scapagnini, G.; Calabrese, V. Nutritional approaches to combat oxidative stress in Alzheimer’s disease. J. Nutr. Biochem. 2002, 13, 444−461. (15) Valko, M.; Leibfritz, D.; Mancol, J.; Cronin, M. T. D.; Mazur, M.; Telser, J. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol. 2007, 39, 44− 84. (16) Lindenschmidt, R. C.; Trika, A. F.; Guard, M. E.; Witschi, H. P. The effect of dietary butylated hydroxyl toluene on liver and colon tumor development in mice. Toxicology 1986, 38, 151−160. (17) Guedes, A. C.; Amaro, H. M.; Malcata, X. F. Microalgae as source of high added-value compounds a brief review of recent work. Biotechnol. Prog. 2011, 27, 597−613. (18) Ngo, D. H.; Wijesekara, I.; Vo, T. S.; Ta, Q. V.; Kim, S. K. Marine food-derived functional ingredients as potential antioxidants in the food industry: an overview. Food Res. Int. 2011, 44, 523−529. (19) Ahn, C. B.; Jeon, Y. J.; Kang, D. S.; Shin, T. S.; Jung, B. M. Free radical scavenging activity of enzymatic extracts from a brown seaweed Scytosiphon lomentaria by electron spin resonance spectrometry. Food Res. Int. 2004, 37, 253−258. (20) Heo, S. J.; Jeon, Y. J. Radical scavenging capacity and cytoprotective effect of enzymatic digests of Ishige okumurae. J. Appl. Phycol. 2008, 20, 1087−1095. 9219
dx.doi.org/10.1021/jf502420h | J. Agric. Food Chem. 2014, 62, 9211−9222
Journal of Agricultural and Food Chemistry
Review
disease: role of aliskiren in risk reduction. Vasc. Health Risk Manage. 2008, 4, 971−981. (41) Suetsuna, K.; Maekawa, K.; Chen, J. R. Antihypertensive effects of Undaria pinnatif ida (wakame) peptide on blood pressure in spontaneously hypertensive rats. J. Nutr Biochem. 2004, 15, 267−272. (42) Cha, S. H.; Ahn, G. N.; Heo, S. J.; Kim, K. N.; Lee, K. W.; Song, C. B.; et al. Screening of extracts from marine green and brown algae in Jeju for potential marine angiotensin-I converting enzyme (ACE) inhibitory activity. J. Korean Soc. Food Sci. Nutr. 2006, 35, 307−314. (43) Sheih, I. C.; Fang, T. J.; Wu, T. K. Isolation and characterization of a novel angiotensin-I converting enzyme (ACE) inhibitory peptide from the algae protein waste. Food Chem. 2009, 115, 279−284. (44) Ko, S. K.; Nalae, K.; Kim, E. A.; Kang, M. C.; Lee, S. H.; Kang, S. M.; et al. A novel angiotensin I-converting enzyme (ACE) inhibitory peptide from a marine Chlorella ellipsoidea and its antihypertensive effect in spontaneously hypertensive rats. Process Biochem. 2012, 45, 2005−2011. (45) Samarakoon, K. W.; et al. Purification and identification of novel angiotensin-I converting enzyme (ACE) inhibitory peptides from cultured marine microalgae (Nannochloropsis oculata) protein hydrolysate. J. Appl. Phycol 2013, 25, 1595−1606. (46) Fitzgerald, C.; Mora-Soler, L.; Gallagher, E.; O’Connor, P.; Prieto, J.; Soler-Vila, A.; Hayes, M. Isolation and characterization of bioactive pro-peptides with in vitro renin inhibitory activities from the macroalga Palmaria palmata. J. Agric. Food Chem. 2012, 60 (30), 7421−7427. (47) Chen, Z. Y.; Peng, C.; Jiao, R.; Wong, Y. M.; Yang, N.; Huang, Y. Anti-hypertensive nutraceuticals and functional foods. J. Agric. Food Chem. 2009, 57 (11), 4485−4499. (48) Huang, P. L.; Huang, Z. H.; Mashimo, H.; Bloch, K. D.; Moskowitz, M. A.; Bevan, J. A.; Fishman, M. C. Hypertension in mice lacking the gene for endothelia metric oxide synthase. Nature 1995, 377, 239−242. (49) Thomas, G. D.; Zhang, W.; Victor, R. G. Nitric oxide deficiency as a cause of clinical hypertension. JAMA−J. Am. Med. Assoc. 2008, 285, 2055−2057. (50) Udenigwe, C. C.; Mohan, A. Mechanisms of food proteinderived antihypertensive peptides other than ACE inhibition. J. Funct. Foods 2014, 8, 45−52. (51) Shih, M. F.; Chen, L. C.; Cherng, J. Y. Chlorella 11-peptide inhibits the production of macrophage-induced adhesion molecules and reduces endothelin-1 expression and endothelial permeability. Mar. Drugs 2013, 11 (10), 3861−3874. (52) Fitzgerald, C.; Gallagher, E.; O’Connor, P.; Prieto, J.; MoraSoler, L.; Grealy, M.; Hayes, M. Development of a seaweed derived platelet activating factor acetylhydrolase (PAF-AH) inhibitory hydrolysate, synthesis of inhibitory peptides and assessment of their toxicity using the zebrafish larvae assay. Peptides 2013, 50, 119−124. (53) Vo, T. S.; Kim, S. K. Down-regulation of histamine-induced endothelial cell activation as potential anti-atherosclerotic activity of peptides from Spirulina maxima. Eur. J. Pharm. Sci. 2013, 50 (2), 198− 207. (54) Vo, T. S.; Ryu, B. M.; Kim, S. K. Purification of novel antiinflammatory peptides from enzymatic hydrolysate of the edible microalgal Spirulina maxima. J. Funct. Foods 2013, 5, 1336−1346. (55) Huber, S. A.; Sakkinen, P.; Conze, D.; Hardin, N.; Tracy, R. Interleukin-6 exacerbates early atherosclerosis in mice. Arterioscler. Thromb. Vasc. Biol. 1999, 19, 2364−2367. (56) Takaishi, H.; Taniguchi, T.; Takahashi, A.; Ishikawa, Y.; Yokoyama, M. High glucose accelerates MCP-1 production via p38 MAPK in vascular endothelial cells. Biochem. Biophys. Res. Commun. 2003, 305, 22−28. (57) Little, P. J.; Ivey, M. E.; Osman, N. Endothelin-1 actions on vascular smooth muscle cell functions as a target for the prevention of atherosclerosis. Curr. Vasc. Pharmacol. 2008, 6, 195−203. (58) Sheikine, Y.; Hansson, G. K. Chemokines and atherosclerosis. Ann. Med. 2004, 36, 98−118. (59) Winkles, J. A.; Alberts, G. F.; Brogi, E.; Libby, P. Endothelin-1 and endothelin receptor mRNA expression in normal and athero-
sclerotic human arteries. Biochem. Biophys. Res. Commun. 1993, 191, 1081−1088. (60) Ross, R. Atherosclerosis − an inflammatory disease. N. Engl. J. Med. 1999, 340, 115−126. (61) Rozenberg, I.; Sluka, S. H.; Rohrer, L.; Hofmann, J.; Becher, B.; Akhmedov, A.; Soliz, J.; Mocharla, P.; Borén, J.; Johansen, P.; Steffel, J.; Watanabe, T.; Lüscher, T. F.; Tanner, F. C. Histamine H1 receptor promotes atherosclerotic lesion formation by increasing vascular permeability for low-density lipoproteins. Arterioscler. Thromb. Vasc. Biol. 2010, 30, 923−930. (62) Blaschke, F.; Bruemmer, D.; Law, R. E. Egr-1 is a major vascular pathogenic transcription factor in atherosclerosis and restenosis. Rev. Endocr. Metab. Disord. 2004, 5, 249−254. (63) Morris, H. J.; Carrillo, O.; Almarales, A.; Berm’udez, R. C.; Lebeque, Y.; Fontaine, R.; et al. Immunostimulant activity of an enzymatic protein hydrolysate from green microalga Chlorella vulgaris on undernourished mice. Enzyme Microb. Technol. 2007, 40, 456−460. (64) Ahn, G.; Hwang, I.; Park, E. J.; Kim, J. H.; Jeon, Y. J.; Lee, J. H.; et al. Immunomodulatory effects of an enzymatic extracts from Ecklonia cava on murine splenocytes. Mar. Biotechnol. 2008, 10, 278− 289. (65) Cian, R. E.; Martínez-Augustin, O.; Drago, S. R. Bioactive properties of peptides obtained by enzymatic hydrolysis from protein byproducts of Porphyra columbina. Food Res. Int. 2012, 49, 364−372. (66) Watanabe, H.; Shimizu, T.; Nishihira, J.; Abe, R.; Nakayama, T.; Taniguchi, M.; Sabe, H.; Ishibashi, T.; Shimizu, H. Ultraviolet Ainduced production of matrix metalloproteinase-1 is mediated by macrophage migration inhibitory factor (MIF) in human dermal fibroblasts. J. Biol. Chem. 2004, 279, 1676−1683. (67) Quan, T.; He, T.; Kang, S.; Voorhees, J. J.; Fisher, G. J. Elevated cysteine-rich 61 mediates aberrant collagen homeostasis in chronologically aged and photoaged human skin. Am. J. Pathol. 2006, 169, 482−490. (68) Chen, C. L.; Liou, S. F.; Chen, S. J.; Shih, M. F. Protective effects of Chlorella-derived peptide on UVB-induced production of MMP-1 and degradation of procollagen genes in human skin fibroblasts. Regul. Toxicol. Pharmacol. 2011, 60 (1), 112−119. (69) Shih, M. F.; Cherng, J. Y. Potential protective effect of fresh grown unicellular green algae component (resilient factor) against PMA- and UVB-induced MMP1 expression in skin fibroblasts. Eur. J. Dermatol. 2008, 18 (3), 303−307. (70) Fazzalari, N. L. Bone remodeling: a review of the bone microenvironment perspective for fragility fracture (osteoporosis) of the hip. Semin. Cell Dev. Biol. 2008, 19, 467−472. (71) Cao, X.; Chen, D. The BMP signaling and in vivo bone formation. Gene 2005, 357, 1−8. (72) Ge, C.; Xiao, G.; Jiang, D.; Franceschi, R. T. Critical role of the extracellular signal regulated kinase-MAPK pathway in osteoblast differentiation and skeletal development. J. Cell Biol. 2007, 176, 709− 718. (73) Novack, D. V. Role of NF-κB in the skeleton. Cell Res. 2011, 21, 169−182. (74) Rey, A.; Manen, D.; Rizzoli, R.; Ferrari, S. L.; Caverzasio, J. Evidences for a role of p38 MAP kinase in the stimulation of alkaline phosphatase and matrix mineralization induced by parathyroid hormone in osteoblastic cells. Bone 2007, 41, 59−67. (75) Miyazono, K.; Maeda, S.; Imamura, T. BMP receptor signaling: transcriptional targets, regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev. 2005, 16, 251−263. (76) Nguyena, M. H. T.; Qian, Z. J.; Nguyen, V. T.; Choic, I. W.; Heo, S. J.; Ohd, C. H.; Kang, D. H.; Kime, G. H.; Jung, W. K. Tetrameric peptide purified from hydrolysates of biodiesel byproducts of Nannochloropsis oculata induces osteoblastic differentiation through MAPK and Smad pathway on MG-63 and D1 cells. Process Biochem. 2013, 48, 1387−1394. (77) Martínez-Maqueda, D.; Miralles, B.; Recio, I.; HernandezLedesma, B. Antihypertensive peptides from food proteins: a review. Food Funct. 2012, 3, 350−361. 9220
dx.doi.org/10.1021/jf502420h | J. Agric. Food Chem. 2014, 62, 9211−9222
Journal of Agricultural and Food Chemistry
Review
(78) Carrasco-Castilla, J.; Hernandez-Alvarez, A. J.; JimenezMartınez, C.; Gutierrez-Lopez, G. F.; Davila-Ortiz, G. Use of proteomics and peptidomics methods in food bioactive peptide science and engineering. Food Eng. Rev. 2012, 4, 224−243. (79) Agyei, D.; Danquah, K. Industrial-scale manufacturing of pharmaceutical-grade bioactive peptides. Biotechnol. Adv. 2011, 29, 272−277. (80) Hancock, R. E. W.; Sahl, H.-G. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat. Biotechnol. 2006, 24 (12), 1551−1557. (81) Li, Y. W.; Li, B. Characterization of structure-antioxidant activity relationship of peptides in free radical systems using QSAR models: key sequence positions and their amino acid properties. J. Theor. Biol. 2013, 318, 29−43. (82) Majumder, K.; Wu, J. A new approach for identification of novel antihypertensive peptides from egg proteins by QSAR and bioinformatics. Food Res. Int. 2010, 43 (5), 1371−1378. (83) Sagardia, I.; Iloro, I.; Elortza, F.; Bald, C. Quantitative structureactivity relationship based screening of bioactive peptides identified in ripened cheese. Int. Dairy J. 2013, 33, 184−190. (84) Walsh, D. J.; Bernard, H.; Murray, B. A.; MacDonald, J.; Pentzien, A. K.; Wright, G. A.; et al. In vitro generation and stability of the lactokinin β-lactoglobulin fragment (142−148). J. Dairy Sci. 2004, 87 (11), 3845−3857. (85) Yamamoto, N.; Ejiri, M.; Mizuno, S. Biogenic peptides and their potential use. Curr. Pharm. Des. 2003, 9 (16), 1345−1355. (86) Shen, B.; Makley, D. M.; Johnston, J. N. Umpolung reactivity in amide and peptide synthesis. Nature 2010, 465 (7301), 1027−1032. (87) Xu, X. F.; He, S. J.; Zhang, X. W. New food safety concerns associated with gut microbiota. Trends Food Sci. Technol. 2013, 34, 62− 66. (88) Russell, W. R.; Gratz, S. W.; Duncan, S. H.; Holtrop, G.; Ince, J.; Scobbie, L.; Duncan, G.; Johnstone, A. M.; Lobley, G. E.; Wallace, R. J.; Duthie, G. G.; Flint, H. J. High-protein, reduced carbohydrate weight-loss diets promote metabolite profiles likely to be detrimental to colonic health. Am. J. Clin. Nutr. 2011, 93 (5), 1062−1072. (89) Doi, R. H.; Kosugi, A. Cellulosomes: plant-cell-wall-degrading enzyme complexes. Nat. Rev. Microbiol. 2004, 2, 541−551. (90) Heo, S. J.; Park, E. J.; Lee, K. W.; Jeon, Y. J. Antioxidant activities of enzymatic extracts from brown seaweeds. Bioresour. Technol. 2005, 96, 1613−1623. (91) Wijesinghe, W. A.; Jeon, Y. J. Enzyme-assistant extraction (EAE) of bioactive components: a useful approach for recovery of industrially important metabolites from seaweeds: a review. Fitoterapia 2012, 83, 6−12. (92) Park, P. J.; Shahidi, F.; Jeon, Y. J. Antioxidant activities of enzymatic extracts from an edible seaweed Sargassum horneri using ESR spectrometry. J. Food Lipids 2004, 11, 15−27. (93) Cian, R. E.; Alaiz, M.; Vioque, J.; Drago, S. R. Enzyme proteolysis enhanced extraction of ACE inhibitory and antioxidant compounds (peptides and polyphenols) from Porphyra columbina residual cake. J. Appl. Phycol. 2013, 25, 1197−1206. (94) Klingler, D.; Berg, J.; Vogel, H. Hydrothermal reactions of alanine and glycine insub- and supercritical water. J. Supercrit. Fluids 2007, 43, 112−119. (95) Sereewatthanawut, I.; Prapintip, S.; Watchiraruji, K.; Goto, M.; Sasaki, M.; Shotipruk, A. Extraction of protein and amino acids from deoiled rice bran by subcritical water hydrolysis. Bioresour. Technol. 2008, 99 (3), 555−561. (96) Möller, M.; Nilges, P.; Harnisch, F.; Schroder, U. Subcritical water as reaction environment: fundamentals of hydrothermal biomass transformation. ChemSusChem 2011, 4, 566−579. (97) Garcia-Moscoso, J. L.; Obeid, W.; Kumar, S.; Hatcher, P. G. Flash hydrolysis of microalgae (Scenedesmus sp.) for protein extractionand production of biofuels intermediates. J. Supercrit. Fluids 2013, 82, 183−190. (98) Rios, G. M.; Belleville, M. P.; Paolucci, D.; Sanchez, J. Progress in enzymatic membrane reactors − a review. J. Membr. Sci. 2004, 242, 189−196.
(99) Pedroche, J.; Just, M. M.; Lqari, H.; Megias, C.; Giron- Calle, J.; Alaiz, M. Obtaining of Brassica carinata protein hydrolysates enriched in bioactive peptides using immobilized digestive proteases. Food Res. Int. 2007, 40 (7), 931−938. (100) Cui, J.; Kong, X.; Hua, Y.; Zhou, H.; Liu, K. Continuous hydrolysis of modified wheat gluten in an enzymatic membrane reactor. J. Sci. Food Agric 2011, 91, 2799−2805. (101) Kapel, R.; Chabeau, A.; Lesage, J.; Riviere, G.; Ravallec-Ple, R.; Lecouturier, D.; Wartelle, M.; Guillochon, D.; Dhulster, P. Production, in continuous enzymatic membrane reactor, of an anti-hypertensive hydrolysate from an industrial alfalfa white protein concentrate exhibiting ACE inhibitory and opioid activities. Food Chem. 2006, 98 (1), 120−126. (102) Hayes, M.; Stanton, C.; Fitzgerald, G. F.; Ross, R. P. Putting microbes to work: dairy fermentation, cell factories and bioactive peptides. Part II: Bioactive peptide functions. Biotechnol. J. 2007, 2 (4), 435−49. (103) Liu, C.; Hu, B.; Liu, Y.; Chen, S. Stimulation of nisin production from whey by a mixed culture of Lactococcus lactis and Saccharomyces cerevisiae. Appl. Biochem. Biotechnol. 2006, 131 (1−3), 751−761. (104) Chang, O. K.; Seol, K. H.; Jeong, S. G.; Oh, M. H.; Park, B. Y.; Perrin, C.; Ham, J. S. Casein hydrolysis by Bif idobacterium longum KACC91563 and antioxidant activities of peptides derived therefrom. J. Dairy Sci. 2013, 96 (9), 5544−5555. (105) Renye, J. R.; Somkuti, G. A. Cloning of milk-derived bioactive peptides in Streptococcus thermophilus. Biotechnol. Lett. 2007, 30 (4), 723−730. (106) Poulin, J. F.; Amiot, J.; Bazinet, L. Simultaneous separation of acid and basic bioactive peptides by electrodialysis with ultrafiltration membrane. J. Biotechnol. 2006, 123, 314−328. (107) Butylina, S.; Luque, S.; Nyström, M. Fractionation of wheyderived peptides using a combination of ultrafiltration and nanofiltration. J. Membr. Sci. 2006, 280, 418−426. (108) Hsu, K. C. Purification of antioxidative peptides prepared from enzymatic hydrolysates of tuna dark muscle by-product. Food Chem. 2010, 122, 42−48. (109) Bazinet, L.; Amiot, J.; Poulin, J.-F.; Labbé, D.; Tremblay, D. Process and system for separation of organic charged compounds. WO 2005082495A1, 2012. (110) Firdaous, L.; Dhulster, P.; Amiot, J.; Gaudreau, A.; Lecouturier, D.; Kapel, R.; et al. Concentration and selective separation of bioactive peptides from an alfalfa white protein hydrolysate by electrodialysis with ultrafiltration membranes. J. Membr. Sci. 2009, 329, 60−67. (111) Firdaous, L.; Dhulster, P.; Amiot, J.; Doyen, A.; Lutin, F.; Vézina, L.-P.; et al. Investigation of the large-scale bioseparation of an antihypertensive peptide from alfalfa white protein hydrolysate by an electromembrane process. J. Membr. Sci. 2010, 355, 175−181. (112) Doyen, A.; Beaulieu, L.; Saucier, L.; Pouliot, Y.; Bazinet, L. Demonstration of in vitro anticancer properties of peptide fractions from a snow crab by-products hydrolysate after separation by electrodialysis with ultrafiltration membranes. Sep. Purif. Technol. 2011, 78, 321−329. (113) Doyen, A.; Husson, E.; Bazinet, L. Use of an electrodialytic reactor for the simultaneous β-lactoglobulin enzymatic hydrolysis and fractionation of generated bioactive peptides. Food Chem. 2013, 136, 1193−1202. (114) Doyen, A.; Udenigwe, C. C.; Mitchell, P. L.; Marette, A.; Aluko, R. E.; Bazinet, L. Anti-diabetic and antihypertensive activities of two flaxseed protein hydrolysate fractions revealed following their simultaneous separation by electrodialysis with ultrafiltration membranes. Food Chem. 2014, 145, 66−76. (115) Becker, W. Fluorescence lifetime imaging − techniques and applications. J. Microsc. 2012, 247 (2), 119−136. (116) Ebrecht, R.; Don Paul, C.; Wouters, F. S. Fluorescence lifetime imaging microscopy in the medical sciences. Protoplasma 2014,251 (2), 293−295. (117) Gee, M. L.; Burton, M.; Grevis-James, A.; Hossain, M. A.; McArthur, S.; Palombo, E. A.; Wade, J. D.; Clayton, A. H. Imaging the 9221
dx.doi.org/10.1021/jf502420h | J. Agric. Food Chem. 2014, 62, 9211−9222
Journal of Agricultural and Food Chemistry
Review
action of antimicrobial peptides on living bacterial cells. Sci. Rep. 2013, 3, 1557. (118) Huang, T. C.; Chen, J. Y. Proteomic and functional analysis of zebrafish after administration of antimicrobial peptide epinecidin-1. Fish Shellfish Immunol. 2013, 34 (2), 593−598.
9222
dx.doi.org/10.1021/jf502420h | J. Agric. Food Chem. 2014, 62, 9211−9222
Marine Algae-Derived Bioactive Peptides for Human Nutrition and Health Xiaodan Fan, Lu Bai, Liang Zhu, Li Yang, and Xuewu Zhang* College of Light Industry and Food Sciences, South China University of Technology, Guangzhou, China ABSTRACT: Within the parent protein molecule, most peptides are inactive, and they are released with biofunctionalities after enzymatic hydrolysis. Marine algae have high protein content, up to 47% of the dry weight, depending on the season and the species. Recently, there is an increasing interest in using marine algae protein as a source of bioactive peptides due to their health promotion and disease therapy potentials. This review presents an overview of marine algae-derived bioactive peptides and especially highlights some key issues, such as in silico proteolysis and quantitative structure−activity relationship studies, in vivo fate of bioactive peptides, and novel technologies in bioactive peptides studies and production. KEYWORDS: marine algae, enzymatic hydrolysis, peptides, bioactivity, novel technologies
■
INTRODUCTION Bioactive peptides are usually composed of 2−20 amino acid residues and have received much attention due to their biological activities and health benefits. Generally, there are three ways to release bioactive peptides, such as solvent extraction, enzymatic hydrolysis, and microbial fermentation. However, due to the lack of residual chemicals in the final peptide products, enzymatic hydrolysis is preferred, especially in the pharmaceutical and food industries.1 After enzymatic hydrolysis, the most widely used peptide fractionation methods include ultrafiltration with different pore sizes (3, 5, 10, and 30 kDa), sequential chromatography (i.e., gel filtration chromatography and ion-exchange chromatography), and reverse-phase liquid chromatography.2 Then, the molecular structures of bioactive peptides can be characterized by mass spectrometry such as liquid chromatography−mass spectrometry (LC-MS) and mass−mass spectrometry (MS-MS) (Figure 1).3 Marine organisms produce a variety of bioactive molecules, which can be developed as nutraceuticals and pharmaceuticals for human nutrition supplementation and disease therapy.4−9 Marine algae include unicellular microalgae and multicellular macroalgae. High protein contents exist in marine algae, generally 5−15% of the dry weight in brown algae and 10−47% of the dry weight in red and green algae.10 Recently, there is an enormous interest in using marine alga proteind as a source of bioactive peptides.11−13 Depending on the amino acid sequence, marine algae-derived biopeptides may be involved in various biological functions, including antioxidant, anticancer, antihypertensive, antiatherosclerotic, and immunomodulatory effects. This review presents an overview of bioactive peptides from marine algae and discusses future challenges.
Figure 1. Schematic diagram for the preparation of marine algaederived bioactive peptides.
aging, hypertension, and neurodegenerative and inflammatory diseases.14,15 The use of synthetic antioxidants including butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and tert-butylhydroquinone (TBHQ) in humans is associated with some side effects such as carcinogenesis and liver damage.16 Hence, it is important to search for safe and
■
OVERVIEW OF BIOACTIVE PEPTIDES FROM MARINE ALGAE Antioxidant Biopeptides. There exist various reactive oxygen species (ROS), such as peroxyl radicals (ROO−), nitric oxide radicals (NO−), hydroxyl radicals (−OH), and superoxide radicals (O2−). The unlimited accumulation of ROS may lead to many health disorders such as cancer, diabetes mellitus, © 2014 American Chemical Society
Received: Revised: Accepted: Published: 9211
May 25, 2014 August 31, 2014 September 1, 2014 September 1, 2014 dx.doi.org/10.1021/jf502420h | J. Agric. Food Chem. 2014, 62, 9211−9222
Journal of Agricultural and Food Chemistry
9212
24 peroxyl, DPPH and hydroxyl radicals
23 free radicals/antihepatotoxicity
in vitro (HepG2/ CYP2E1 cells) in vitro
22
Chlorella ellipsoidea
Navicula incerta
0.02−1.42 mM
102−196 μg/mL
alcalase, Pronase-E, α-chymotrypsin, Neutrase, papain, pepsin, and trypsin alcalase, α-chymotrypsin, Neutrase, papain, pepsin, Pronase-E, and trypsin papain, trypsin, pepsin, and α-chymotrypsin Navicula incerta
enzymatic hydrolysates PGWNQWFL, VEVLPPAEL LNGDVW
in vitro
hydroxyl, alkyl and DPPH radical hydrogen peroxide hydroxyl radical, superoxide radical, peroxyl radical, DPPH radical and ABTS radicals hydroxyl, superoxide, DPPH in vitro in vitro in vitro C1 for TEAC, C3 > C4 > C1 for ORAC, and C4 > C1 > N1 for SOR. Bulky hydrophobic amino acids at the C-terminal are related to the antioxidant activity of peptides in the three free radical systems. Several publications explore the potential of in silico methods for the screening of bioactive peptides. For example, by in silico digestion of egg white protein and QSAR analysis of more than 20000 peptides generated from 75 in silico hydrolysates, Majumder and Wu82 found that thermolysin−pepsin digestion of ovotransferrin was the best condition, and three novel antihypertensive peptides were identified. Sargadia et al.83 identified six novel peptides with ACE-inhibitory activity (IC50 values = 4−32 μM) from 231 peptides of milk proteins, using matrix-assisted laser desorption/ionization tandem time-of-flight (MALDI-TOFTOF) mass spectrometry and QSAR modeling on ACEinhibitory peptides with an amino acid length larger >5. In Vivo Fate of Bioactive Peptides. Due to the susceptibility of peptides to protease degradation, the fate of bioactive peptides during gastrointestinal transit is a major problem. In fact, the antihypertensive peptide β-LG f(142− 148) obtained from β-lactoglobulin could not be detected in the sera of human volunteers following its oral ingestion; that is, the peptide is not sufficiently stable to gastrointestinal and serum proteases.84 To enhance the stability of peptides, one solution is chemical modification of peptides and the incorporation of unnatural amino acids (including D-amino acids). For example, at the carboxyl terminal end of a peptide, the presence of a proline residue has been shown to increase the peptide’s resistance to degradation by digestive enzymes.85 Shen et al.86 developed a new chemical method of peptide synthesis to generate cyclic peptides by incorporating unnatural amino acids into a peptide chain, hence increasing stability. Another solution is encapsulation of peptides with polymers or particles such as dendrimers, liposomes, and polyectrolyte microspheres. For example, Wang and Zhang35 investigated the micro- and nanoencapsulation of a Chlorella pyrenoidosa antitumor polypeptide (CPAP) by complex coacervation and ionotropic gelation. The in vitro release tests showed that CPAP was well preserved against gastric enzymatic degradation after micro/nanoencapsulation, and the slowly controlled release in the intestine could be potentially achieved. On the other hand, due to the existence of intestinal bacterial communities, it is necessary to consider whether or not potential toxic metabolites could be generated by fermentation of gut microbiota on bioactive peptides.87 For example, the increased protein fermentation and decreased carbohydrate fermentation by gut microbiota was shown to cause a significant decrease in fecal cancer protective metabolites (e.g., butyrate) and the greatest formation of hazardous metabolites such as Nnitroso compounds, which is probably detrimental to colonic health.88 9217
dx.doi.org/10.1021/jf502420h | J. Agric. Food Chem. 2014, 62, 9211−9222
Journal of Agricultural and Food Chemistry
Review
peptide mixtures with similar molecular weights. The most frequently used technologies include chromatography and pressure-driven filtration processes.107,108 However, some drawbacks, such as the high cost of chromatographic technology and membrane fouling formation for pressuredriven processes, limit their wide application.2 Recently, a patented electrodialysis with ultrafiltration membranes (EDUF) was developed to replace traditional separation methods for peptide recovery.109 The driving force of EDUF is the electric field; hence, there is no significant fouling formation at the membrane interface due to the absence of pressure.110 EDUF technology has been applied to the isolation of peptides from various hydrolysates.111−114 The third challenge is to understand the mechanisms of action of bioactive peptides. Fluorescence lifetime imaging (FLIM) technique is able to distinguish interacting and noninteracting fractions and to resolve changes in the binding, conformation, and composition of biologically relevant compounds in live cells.115 Therefore, FLIM has become an inevitable technique for spatially resolving cellular processes and physical interactions of cellular components in real time.116 Thus, it offers the opportunity to understand the mechanism of action for increasingly generated bioactive peptides, such as the interaction mechanisms of antimicrobial peptide (melittin) with live bacterial cells.117 However, FLIM is unable to determine the detailed molecular changes in such an interaction process. In this respect, omics technologies (transcriptomics, proteomics, and metabolomics) could make contributions. For instance, proteomics is a promising technology in understanding mechanism of action for bioactive peptides. By twodimensional electrophoresis (2DE) coupled to mass spectrometry, Huang and Chen118 profiled proteome changes in antibacterial peptide epinecidin-1-treated zebrafish. A possible protein−protein interacting network regulated by epinecidin-1 was constructed, suggesting a potential role of epinecindin-1 in cytoskeletal assembly and organization to promote resistance to bacterial infection. Currently, these novel methods are rarely applied to the production and study of marine algae peptides, but should be promising. Specifically, EAE and SWE technologies are first employed to extract proteins from marine algal biomass. On the one hand, the extracted proteins are subject to fermentation by probiotics such as lactic acid bacteria and bifidobacteria for peptide production. On the other hand, the extracted proteins are enzymatically hydrolyzed under the condition of immobilized enzymes or in a continuous enzyme membrane reactor system. Then, EDUF technology is employed to simultaneously isolate bioactive peptides from the complex peptides mixture. Finally, the mechanisms of action of bioactive peptides are investigated by FLIM and omics such as proteomics techniques (Figure 8). In conclusion, bioactive peptides generated by enzymatic hydrolysis of algae protein or algae processing waste exhibit diverse biofunctionalities, which are promising in applications of functional foods, pharmaceuticals, and cosmeceuticals. However, there are still many challenges before bioactive peptides can be translated into practical use for human nutrition and health. In silico proteolysis and QSAR modeling can accelerate the discovery of bioactive peptides. Innovative technologies need to be developed for transferring laboratoryscale preparations to industrial-scale production. Extensive research is highly required to explore metabolic products of bioactive peptides during gastrointestinal digestion and to
Figure 8. Proposed applications of novel technologies to produce and study marine algae-derived bioactive peptides.
elucidate the detailed mechanisms of action in vivo. It is envisaged that the bioactive peptides market will become a selfstanding industry in the next few decades. Hence, some regulations and standards that govern the production, utilization, and marketing of bioactive peptides should be set.
■
AUTHOR INFORMATION
Corresponding Author
*(X.Z.) Mail: College of Light Industry and Food Sciences, South China University of Technology, 381 Wushan Road, Guangzhou 510640, China. Phone/fax: 86 20 87113848. Email: [email protected]. Funding
This study was supported by an Ocean and Fisheries Development Project (A201301B04) from the Administration of Ocean and Fisheries of Guangdong Province and a National High-Tech Research and Development Project (863 Program) (2014AA022004). This study was supported by Key Laboratory of Enhanced Heat Transfer and Energy Conservation of the Ministry of Education, South China University of Technology, Guangzhou, China. 9218
dx.doi.org/10.1021/jf502420h | J. Agric. Food Chem. 2014, 62, 9211−9222
Journal of Agricultural and Food Chemistry
Review
Notes
(21) Sheih, I. C.; Wu, T. K.; Fang, T. J. Antioxidant properties of a new antioxidative peptide from algae protein hydrolysate in different oxidation systems. Bioresour. Technol. 2009, 100, 3419−3425. (22) Kang, K. H.; Qian, Z. J.; Ryu, B.; Kim, S. K. Characterization of growth and protein contents from microalgae Navicula incerta with the investigation of antioxidant activity of enzymatic hydrolysates. Food Sci. Biotechnol. 2011, 20 (1), 183−191. (23) Kang, K. H.; Qian, Z. J.; Ryu, B.; Karadeniz, F.; Kim, D.; Kim, S. K. Antioxidant peptides from protein hydrolysate of microalgae Navicula incerta and their protective effects in HepG2/CYP2E1 cells induced by ethanol. Phytother. Res. 2012, 26 (10), 1555−1563. (24) Ko, S. C.; Kim, D.; Jeon, Y. J. Protective effect of a novel antioxidative peptide purified from a marine Chlorella ellipsoidea protein against free radical-induced oxidative stress. Food Chem. Toxicol. 2012, 50 (7), 2294−2302. (25) Power, O.; Jakeman, P.; FitzGerald, R. J. Antioxidative peptides: enzymatic production, in vitro and in vivo antioxidant activity and potential applications of milk-derived antioxidative peptides. Amino Acids 2013, 44 (3), 797−820. (26) Ou, B.; Hampsch-Woodill, M.; Prior, R. Development and validation of an improved oxygen radical absorbance capacity assay using fluorescein as the fluorescent probe. J. Agric. Food Chem. 2001, 49 (10), 4619−4626. (27) Haytowitz, D.; Bhagwat, S. USDA Database for the Oxygen Radical Absorbance Capacity (ORAC) of Selected Foods, release 2; U.S. Department of Agriculture: Washington, DC, USA, 2010. (28) Manso, M. A.; Miguel, M.; Even, J.; Hernández, R.; Aleixandre, A.; López Fandinõ, R. Effect of the long-term intake of an egg white hydrolysate on the oxidative status and blood lipid profile of spontaneously hypertensive rats. Food Chem. 2008, 109 (2), 361−367. (29) Wang, D.; Wang, L.; Zhu, F.; Zhu, J.; Chen, X. D.; Zou, L.; Saito, M.; Li, L. In vitro and in vivo studies on the antioxidant activities of the aqueous extracts of Douchi (a traditional Chinese salt-fermented soybean food). Food Chem. 2008, 107 (4), 1421−1428. (30) Chidambara Murthy, K. N.; Vanitha, A.; Rajesha, J.; Mahadeva Swamy, M.; Sowmya, P. R.; Ravishankar, G. A. In vivo antioxidant activity of carotenoids from Dunaliella salina − a green microalga. Life Sci. 2005, 76 (12), 1381−1390. (31) Vijayavel, K.; Anbuselvam, C.; Balasubramanian, M. P. Antioxidant effect of the marine algae Chlorella vulgaris against naphthalene-induced oxidative stress in the albino rats. Mol. Cell. Biochem. 2007, 303 (1−2), 39−44. (32) Gad, A. S.; Khadrawy, Y. A.; El-Nekeety, A. A.; Mohamed, S. R.; Hassan, N. S.; Abdel-Wahhab, M. A. Antioxidant activity and hepatoprotective effects of whey protein and Spirulina in rats. Nutrition 2011, 27 (5), 582−589. (33) Kang, K. H.; Kim, S. K. Beneficial effect of peptides from microalgae on anticancer. Curr. Protein Pept. Sci. 2013, 14 (3), 212− 217. (34) Sheih, I. C.; Fang, T. J.; Wu, T. K.; Lin, P. H. Anticancer and antioxidant activities of the peptide fraction from algae protein in waste. J. Agric. Food Chem. 2010, 58, 1202−1207. (35) Wang, X.; Zhang, X. Separation, antitumor activities, and encapsulation of polypeptide from Chlorella pyrenoidosa. Biotechnol. Prog. 2013, 29 (3), 681−687. (36) Zhang, B.; Zhang, X. Separation and nanoencapsulation of antitumor polypeptide from Spirulina platensis. Biotechnol. Prog. 2013, 29, 1230−1238. (37) Zheng, L. H.; Wang, Y. J.; Sheng, J.; Wang, F.; Zheng, Y.; Lin, X. K.; Sun, M. Antitumor peptides from marine organisms. Mar. Drugs 2011, 9 (10), 1840−1859. (38) Gupta, S.; Kass, G. E.; Szegezdi, E.; Joseph, B. The mitochondrial death pathway: a promising therapeutic target in diseases. J. Cell. Mol. Med. 2009, 13, 1004−1033. (39) Zheng, L.; Lin, X.; Wu, N.; Liu, M.; Zheng, Y.; Sheng, J.; Ji, X.; Sun, M. Targeting cellular apoptotic pathway with peptides from marine organisms. Biochim. Biophys. Acta 2013, 1836 (1), 42−48. (40) Verdecchia, P.; Angeli, F.; Mazzotta, G.; Gentile, G.; Reboldi, G. The rennin angiotensin system in the development of cardiovascular
The authors declare no competing financial interest.
■
REFERENCES
(1) Korhonen, H.; Pihlanto, A. Bioactive peptides: production and functionality. Int. Dairy J. 2006, 16 (9), 945−960. (2) Chabeaud, A.; Vandanjon, L.; Bourseau, P.; Jaouen, P.; Guérard, F. Fractionation by ultrafiltration of a saithe protein hydrolysate (Pollachius virens): effect of material and molecular weight cut-off on the membrane performances. J. Food Eng. 2009, 91, 408−414. (3) Samarakoon, K.; Jeon, Y. J. Bio-functionalities of proteins derived from marine algae − a review. Food Res. Int. 2012, 48, 948−960. (4) Cheung, R. C.; Wong, J. H.; Pan, W. L.; Chan, Y. S.; Yin, C. M.; Dan, X. L.; Wang, H. X.; Fang, E. F.; Lam, S. K.; Ngai, P. H.; Xia, L. X.; Liu, F.; Ye, X. Y.; Zhang, G. Q.; Liu, Q. H.; Sha, O.; Lin, P.; Ki, C.; Bekhit, A. A.; Bekhit, A.-D.; Wan, D. C.; Ye, X. J.; Xia, J.; Ng, T. B. Antifungal and antiviral products of marine organisms. Appl. Microbiol. Biotechnol. 2014, 98 (8), 3475−3494. (5) Glaser, K. B.; Mayer, A. M. A renaissance in marine pharmacology: from preclinical curiosity to clinical reality. Biochem. Pharmacol. 2009, 78 (5), 440−448. (6) Hughes, C. C.; Fenical, W. Antibacterials from the sea. Chem. Eur. J. 2010, 16 (42), 12512−12525. (7) Mayer, A. M.; Gustafson, K. R. Marine pharmacology in 2005− 2006: antitumour and cytotoxic compounds. Eur. J. Cancer 2008, 44 (16), 2357−2387. (8) Mayer, A. M.; Rodríguez, A. D.; Taglialatela-Scafati, O.; Fusetani, N. Marine pharmacology in 2009−2011: marine compounds with antibacterial, antidiabetic, antifungal, anti-inflammatory, antiprotozoal, antituberculosis, and antiviral activities; affecting the immune and nervous systems, and other miscellaneous mechanisms of action. Mar. Drugs 2013, 11, 2510−2573. (9) Wijesekara, I.; Kim, S. K. Angiotensin-I-converting enzyme (ACE) inhibitors from marine resources: prospects in the pharmaceutical industry. Mar. Drugs 2010, 8 (4), 1080−1093. (10) Ibanez, E.; Cifuentes, A. Benefits of using algae as natural sources of functional ingredients. J. Sci. Food Agric 2013, 93, 703−709. (11) Kim, S. K.; Kang, K. H. Medicinal effects of peptides from marine microalgae. Adv. Food Nutr. Res. 2011, 64, 313−323. (12) Kim, S. K.; Wijesekara, I. Development and biological activities of marine-derived bioactive peptides: a review. J. Funct Foods 2010, 2, 1−9. (13) Kim, J. A.; Kim, S. K. Bioactive peptides from marine sources as potential anti-inflammatory therapeutics. Curr. Protein Pept. Sci. 2013, 14 (3), 177−182. (14) Butterfield, D. A.; Castenga, A.; Pocernich, C. B.; Drake, J.; Scapagnini, G.; Calabrese, V. Nutritional approaches to combat oxidative stress in Alzheimer’s disease. J. Nutr. Biochem. 2002, 13, 444−461. (15) Valko, M.; Leibfritz, D.; Mancol, J.; Cronin, M. T. D.; Mazur, M.; Telser, J. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol. 2007, 39, 44− 84. (16) Lindenschmidt, R. C.; Trika, A. F.; Guard, M. E.; Witschi, H. P. The effect of dietary butylated hydroxyl toluene on liver and colon tumor development in mice. Toxicology 1986, 38, 151−160. (17) Guedes, A. C.; Amaro, H. M.; Malcata, X. F. Microalgae as source of high added-value compounds a brief review of recent work. Biotechnol. Prog. 2011, 27, 597−613. (18) Ngo, D. H.; Wijesekara, I.; Vo, T. S.; Ta, Q. V.; Kim, S. K. Marine food-derived functional ingredients as potential antioxidants in the food industry: an overview. Food Res. Int. 2011, 44, 523−529. (19) Ahn, C. B.; Jeon, Y. J.; Kang, D. S.; Shin, T. S.; Jung, B. M. Free radical scavenging activity of enzymatic extracts from a brown seaweed Scytosiphon lomentaria by electron spin resonance spectrometry. Food Res. Int. 2004, 37, 253−258. (20) Heo, S. J.; Jeon, Y. J. Radical scavenging capacity and cytoprotective effect of enzymatic digests of Ishige okumurae. J. Appl. Phycol. 2008, 20, 1087−1095. 9219
dx.doi.org/10.1021/jf502420h | J. Agric. Food Chem. 2014, 62, 9211−9222
Journal of Agricultural and Food Chemistry
Review
disease: role of aliskiren in risk reduction. Vasc. Health Risk Manage. 2008, 4, 971−981. (41) Suetsuna, K.; Maekawa, K.; Chen, J. R. Antihypertensive effects of Undaria pinnatif ida (wakame) peptide on blood pressure in spontaneously hypertensive rats. J. Nutr Biochem. 2004, 15, 267−272. (42) Cha, S. H.; Ahn, G. N.; Heo, S. J.; Kim, K. N.; Lee, K. W.; Song, C. B.; et al. Screening of extracts from marine green and brown algae in Jeju for potential marine angiotensin-I converting enzyme (ACE) inhibitory activity. J. Korean Soc. Food Sci. Nutr. 2006, 35, 307−314. (43) Sheih, I. C.; Fang, T. J.; Wu, T. K. Isolation and characterization of a novel angiotensin-I converting enzyme (ACE) inhibitory peptide from the algae protein waste. Food Chem. 2009, 115, 279−284. (44) Ko, S. K.; Nalae, K.; Kim, E. A.; Kang, M. C.; Lee, S. H.; Kang, S. M.; et al. A novel angiotensin I-converting enzyme (ACE) inhibitory peptide from a marine Chlorella ellipsoidea and its antihypertensive effect in spontaneously hypertensive rats. Process Biochem. 2012, 45, 2005−2011. (45) Samarakoon, K. W.; et al. Purification and identification of novel angiotensin-I converting enzyme (ACE) inhibitory peptides from cultured marine microalgae (Nannochloropsis oculata) protein hydrolysate. J. Appl. Phycol 2013, 25, 1595−1606. (46) Fitzgerald, C.; Mora-Soler, L.; Gallagher, E.; O’Connor, P.; Prieto, J.; Soler-Vila, A.; Hayes, M. Isolation and characterization of bioactive pro-peptides with in vitro renin inhibitory activities from the macroalga Palmaria palmata. J. Agric. Food Chem. 2012, 60 (30), 7421−7427. (47) Chen, Z. Y.; Peng, C.; Jiao, R.; Wong, Y. M.; Yang, N.; Huang, Y. Anti-hypertensive nutraceuticals and functional foods. J. Agric. Food Chem. 2009, 57 (11), 4485−4499. (48) Huang, P. L.; Huang, Z. H.; Mashimo, H.; Bloch, K. D.; Moskowitz, M. A.; Bevan, J. A.; Fishman, M. C. Hypertension in mice lacking the gene for endothelia metric oxide synthase. Nature 1995, 377, 239−242. (49) Thomas, G. D.; Zhang, W.; Victor, R. G. Nitric oxide deficiency as a cause of clinical hypertension. JAMA−J. Am. Med. Assoc. 2008, 285, 2055−2057. (50) Udenigwe, C. C.; Mohan, A. Mechanisms of food proteinderived antihypertensive peptides other than ACE inhibition. J. Funct. Foods 2014, 8, 45−52. (51) Shih, M. F.; Chen, L. C.; Cherng, J. Y. Chlorella 11-peptide inhibits the production of macrophage-induced adhesion molecules and reduces endothelin-1 expression and endothelial permeability. Mar. Drugs 2013, 11 (10), 3861−3874. (52) Fitzgerald, C.; Gallagher, E.; O’Connor, P.; Prieto, J.; MoraSoler, L.; Grealy, M.; Hayes, M. Development of a seaweed derived platelet activating factor acetylhydrolase (PAF-AH) inhibitory hydrolysate, synthesis of inhibitory peptides and assessment of their toxicity using the zebrafish larvae assay. Peptides 2013, 50, 119−124. (53) Vo, T. S.; Kim, S. K. Down-regulation of histamine-induced endothelial cell activation as potential anti-atherosclerotic activity of peptides from Spirulina maxima. Eur. J. Pharm. Sci. 2013, 50 (2), 198− 207. (54) Vo, T. S.; Ryu, B. M.; Kim, S. K. Purification of novel antiinflammatory peptides from enzymatic hydrolysate of the edible microalgal Spirulina maxima. J. Funct. Foods 2013, 5, 1336−1346. (55) Huber, S. A.; Sakkinen, P.; Conze, D.; Hardin, N.; Tracy, R. Interleukin-6 exacerbates early atherosclerosis in mice. Arterioscler. Thromb. Vasc. Biol. 1999, 19, 2364−2367. (56) Takaishi, H.; Taniguchi, T.; Takahashi, A.; Ishikawa, Y.; Yokoyama, M. High glucose accelerates MCP-1 production via p38 MAPK in vascular endothelial cells. Biochem. Biophys. Res. Commun. 2003, 305, 22−28. (57) Little, P. J.; Ivey, M. E.; Osman, N. Endothelin-1 actions on vascular smooth muscle cell functions as a target for the prevention of atherosclerosis. Curr. Vasc. Pharmacol. 2008, 6, 195−203. (58) Sheikine, Y.; Hansson, G. K. Chemokines and atherosclerosis. Ann. Med. 2004, 36, 98−118. (59) Winkles, J. A.; Alberts, G. F.; Brogi, E.; Libby, P. Endothelin-1 and endothelin receptor mRNA expression in normal and athero-
sclerotic human arteries. Biochem. Biophys. Res. Commun. 1993, 191, 1081−1088. (60) Ross, R. Atherosclerosis − an inflammatory disease. N. Engl. J. Med. 1999, 340, 115−126. (61) Rozenberg, I.; Sluka, S. H.; Rohrer, L.; Hofmann, J.; Becher, B.; Akhmedov, A.; Soliz, J.; Mocharla, P.; Borén, J.; Johansen, P.; Steffel, J.; Watanabe, T.; Lüscher, T. F.; Tanner, F. C. Histamine H1 receptor promotes atherosclerotic lesion formation by increasing vascular permeability for low-density lipoproteins. Arterioscler. Thromb. Vasc. Biol. 2010, 30, 923−930. (62) Blaschke, F.; Bruemmer, D.; Law, R. E. Egr-1 is a major vascular pathogenic transcription factor in atherosclerosis and restenosis. Rev. Endocr. Metab. Disord. 2004, 5, 249−254. (63) Morris, H. J.; Carrillo, O.; Almarales, A.; Berm’udez, R. C.; Lebeque, Y.; Fontaine, R.; et al. Immunostimulant activity of an enzymatic protein hydrolysate from green microalga Chlorella vulgaris on undernourished mice. Enzyme Microb. Technol. 2007, 40, 456−460. (64) Ahn, G.; Hwang, I.; Park, E. J.; Kim, J. H.; Jeon, Y. J.; Lee, J. H.; et al. Immunomodulatory effects of an enzymatic extracts from Ecklonia cava on murine splenocytes. Mar. Biotechnol. 2008, 10, 278− 289. (65) Cian, R. E.; Martínez-Augustin, O.; Drago, S. R. Bioactive properties of peptides obtained by enzymatic hydrolysis from protein byproducts of Porphyra columbina. Food Res. Int. 2012, 49, 364−372. (66) Watanabe, H.; Shimizu, T.; Nishihira, J.; Abe, R.; Nakayama, T.; Taniguchi, M.; Sabe, H.; Ishibashi, T.; Shimizu, H. Ultraviolet Ainduced production of matrix metalloproteinase-1 is mediated by macrophage migration inhibitory factor (MIF) in human dermal fibroblasts. J. Biol. Chem. 2004, 279, 1676−1683. (67) Quan, T.; He, T.; Kang, S.; Voorhees, J. J.; Fisher, G. J. Elevated cysteine-rich 61 mediates aberrant collagen homeostasis in chronologically aged and photoaged human skin. Am. J. Pathol. 2006, 169, 482−490. (68) Chen, C. L.; Liou, S. F.; Chen, S. J.; Shih, M. F. Protective effects of Chlorella-derived peptide on UVB-induced production of MMP-1 and degradation of procollagen genes in human skin fibroblasts. Regul. Toxicol. Pharmacol. 2011, 60 (1), 112−119. (69) Shih, M. F.; Cherng, J. Y. Potential protective effect of fresh grown unicellular green algae component (resilient factor) against PMA- and UVB-induced MMP1 expression in skin fibroblasts. Eur. J. Dermatol. 2008, 18 (3), 303−307. (70) Fazzalari, N. L. Bone remodeling: a review of the bone microenvironment perspective for fragility fracture (osteoporosis) of the hip. Semin. Cell Dev. Biol. 2008, 19, 467−472. (71) Cao, X.; Chen, D. The BMP signaling and in vivo bone formation. Gene 2005, 357, 1−8. (72) Ge, C.; Xiao, G.; Jiang, D.; Franceschi, R. T. Critical role of the extracellular signal regulated kinase-MAPK pathway in osteoblast differentiation and skeletal development. J. Cell Biol. 2007, 176, 709− 718. (73) Novack, D. V. Role of NF-κB in the skeleton. Cell Res. 2011, 21, 169−182. (74) Rey, A.; Manen, D.; Rizzoli, R.; Ferrari, S. L.; Caverzasio, J. Evidences for a role of p38 MAP kinase in the stimulation of alkaline phosphatase and matrix mineralization induced by parathyroid hormone in osteoblastic cells. Bone 2007, 41, 59−67. (75) Miyazono, K.; Maeda, S.; Imamura, T. BMP receptor signaling: transcriptional targets, regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev. 2005, 16, 251−263. (76) Nguyena, M. H. T.; Qian, Z. J.; Nguyen, V. T.; Choic, I. W.; Heo, S. J.; Ohd, C. H.; Kang, D. H.; Kime, G. H.; Jung, W. K. Tetrameric peptide purified from hydrolysates of biodiesel byproducts of Nannochloropsis oculata induces osteoblastic differentiation through MAPK and Smad pathway on MG-63 and D1 cells. Process Biochem. 2013, 48, 1387−1394. (77) Martínez-Maqueda, D.; Miralles, B.; Recio, I.; HernandezLedesma, B. Antihypertensive peptides from food proteins: a review. Food Funct. 2012, 3, 350−361. 9220
dx.doi.org/10.1021/jf502420h | J. Agric. Food Chem. 2014, 62, 9211−9222
Journal of Agricultural and Food Chemistry
Review
(78) Carrasco-Castilla, J.; Hernandez-Alvarez, A. J.; JimenezMartınez, C.; Gutierrez-Lopez, G. F.; Davila-Ortiz, G. Use of proteomics and peptidomics methods in food bioactive peptide science and engineering. Food Eng. Rev. 2012, 4, 224−243. (79) Agyei, D.; Danquah, K. Industrial-scale manufacturing of pharmaceutical-grade bioactive peptides. Biotechnol. Adv. 2011, 29, 272−277. (80) Hancock, R. E. W.; Sahl, H.-G. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat. Biotechnol. 2006, 24 (12), 1551−1557. (81) Li, Y. W.; Li, B. Characterization of structure-antioxidant activity relationship of peptides in free radical systems using QSAR models: key sequence positions and their amino acid properties. J. Theor. Biol. 2013, 318, 29−43. (82) Majumder, K.; Wu, J. A new approach for identification of novel antihypertensive peptides from egg proteins by QSAR and bioinformatics. Food Res. Int. 2010, 43 (5), 1371−1378. (83) Sagardia, I.; Iloro, I.; Elortza, F.; Bald, C. Quantitative structureactivity relationship based screening of bioactive peptides identified in ripened cheese. Int. Dairy J. 2013, 33, 184−190. (84) Walsh, D. J.; Bernard, H.; Murray, B. A.; MacDonald, J.; Pentzien, A. K.; Wright, G. A.; et al. In vitro generation and stability of the lactokinin β-lactoglobulin fragment (142−148). J. Dairy Sci. 2004, 87 (11), 3845−3857. (85) Yamamoto, N.; Ejiri, M.; Mizuno, S. Biogenic peptides and their potential use. Curr. Pharm. Des. 2003, 9 (16), 1345−1355. (86) Shen, B.; Makley, D. M.; Johnston, J. N. Umpolung reactivity in amide and peptide synthesis. Nature 2010, 465 (7301), 1027−1032. (87) Xu, X. F.; He, S. J.; Zhang, X. W. New food safety concerns associated with gut microbiota. Trends Food Sci. Technol. 2013, 34, 62− 66. (88) Russell, W. R.; Gratz, S. W.; Duncan, S. H.; Holtrop, G.; Ince, J.; Scobbie, L.; Duncan, G.; Johnstone, A. M.; Lobley, G. E.; Wallace, R. J.; Duthie, G. G.; Flint, H. J. High-protein, reduced carbohydrate weight-loss diets promote metabolite profiles likely to be detrimental to colonic health. Am. J. Clin. Nutr. 2011, 93 (5), 1062−1072. (89) Doi, R. H.; Kosugi, A. Cellulosomes: plant-cell-wall-degrading enzyme complexes. Nat. Rev. Microbiol. 2004, 2, 541−551. (90) Heo, S. J.; Park, E. J.; Lee, K. W.; Jeon, Y. J. Antioxidant activities of enzymatic extracts from brown seaweeds. Bioresour. Technol. 2005, 96, 1613−1623. (91) Wijesinghe, W. A.; Jeon, Y. J. Enzyme-assistant extraction (EAE) of bioactive components: a useful approach for recovery of industrially important metabolites from seaweeds: a review. Fitoterapia 2012, 83, 6−12. (92) Park, P. J.; Shahidi, F.; Jeon, Y. J. Antioxidant activities of enzymatic extracts from an edible seaweed Sargassum horneri using ESR spectrometry. J. Food Lipids 2004, 11, 15−27. (93) Cian, R. E.; Alaiz, M.; Vioque, J.; Drago, S. R. Enzyme proteolysis enhanced extraction of ACE inhibitory and antioxidant compounds (peptides and polyphenols) from Porphyra columbina residual cake. J. Appl. Phycol. 2013, 25, 1197−1206. (94) Klingler, D.; Berg, J.; Vogel, H. Hydrothermal reactions of alanine and glycine insub- and supercritical water. J. Supercrit. Fluids 2007, 43, 112−119. (95) Sereewatthanawut, I.; Prapintip, S.; Watchiraruji, K.; Goto, M.; Sasaki, M.; Shotipruk, A. Extraction of protein and amino acids from deoiled rice bran by subcritical water hydrolysis. Bioresour. Technol. 2008, 99 (3), 555−561. (96) Möller, M.; Nilges, P.; Harnisch, F.; Schroder, U. Subcritical water as reaction environment: fundamentals of hydrothermal biomass transformation. ChemSusChem 2011, 4, 566−579. (97) Garcia-Moscoso, J. L.; Obeid, W.; Kumar, S.; Hatcher, P. G. Flash hydrolysis of microalgae (Scenedesmus sp.) for protein extractionand production of biofuels intermediates. J. Supercrit. Fluids 2013, 82, 183−190. (98) Rios, G. M.; Belleville, M. P.; Paolucci, D.; Sanchez, J. Progress in enzymatic membrane reactors − a review. J. Membr. Sci. 2004, 242, 189−196.
(99) Pedroche, J.; Just, M. M.; Lqari, H.; Megias, C.; Giron- Calle, J.; Alaiz, M. Obtaining of Brassica carinata protein hydrolysates enriched in bioactive peptides using immobilized digestive proteases. Food Res. Int. 2007, 40 (7), 931−938. (100) Cui, J.; Kong, X.; Hua, Y.; Zhou, H.; Liu, K. Continuous hydrolysis of modified wheat gluten in an enzymatic membrane reactor. J. Sci. Food Agric 2011, 91, 2799−2805. (101) Kapel, R.; Chabeau, A.; Lesage, J.; Riviere, G.; Ravallec-Ple, R.; Lecouturier, D.; Wartelle, M.; Guillochon, D.; Dhulster, P. Production, in continuous enzymatic membrane reactor, of an anti-hypertensive hydrolysate from an industrial alfalfa white protein concentrate exhibiting ACE inhibitory and opioid activities. Food Chem. 2006, 98 (1), 120−126. (102) Hayes, M.; Stanton, C.; Fitzgerald, G. F.; Ross, R. P. Putting microbes to work: dairy fermentation, cell factories and bioactive peptides. Part II: Bioactive peptide functions. Biotechnol. J. 2007, 2 (4), 435−49. (103) Liu, C.; Hu, B.; Liu, Y.; Chen, S. Stimulation of nisin production from whey by a mixed culture of Lactococcus lactis and Saccharomyces cerevisiae. Appl. Biochem. Biotechnol. 2006, 131 (1−3), 751−761. (104) Chang, O. K.; Seol, K. H.; Jeong, S. G.; Oh, M. H.; Park, B. Y.; Perrin, C.; Ham, J. S. Casein hydrolysis by Bif idobacterium longum KACC91563 and antioxidant activities of peptides derived therefrom. J. Dairy Sci. 2013, 96 (9), 5544−5555. (105) Renye, J. R.; Somkuti, G. A. Cloning of milk-derived bioactive peptides in Streptococcus thermophilus. Biotechnol. Lett. 2007, 30 (4), 723−730. (106) Poulin, J. F.; Amiot, J.; Bazinet, L. Simultaneous separation of acid and basic bioactive peptides by electrodialysis with ultrafiltration membrane. J. Biotechnol. 2006, 123, 314−328. (107) Butylina, S.; Luque, S.; Nyström, M. Fractionation of wheyderived peptides using a combination of ultrafiltration and nanofiltration. J. Membr. Sci. 2006, 280, 418−426. (108) Hsu, K. C. Purification of antioxidative peptides prepared from enzymatic hydrolysates of tuna dark muscle by-product. Food Chem. 2010, 122, 42−48. (109) Bazinet, L.; Amiot, J.; Poulin, J.-F.; Labbé, D.; Tremblay, D. Process and system for separation of organic charged compounds. WO 2005082495A1, 2012. (110) Firdaous, L.; Dhulster, P.; Amiot, J.; Gaudreau, A.; Lecouturier, D.; Kapel, R.; et al. Concentration and selective separation of bioactive peptides from an alfalfa white protein hydrolysate by electrodialysis with ultrafiltration membranes. J. Membr. Sci. 2009, 329, 60−67. (111) Firdaous, L.; Dhulster, P.; Amiot, J.; Doyen, A.; Lutin, F.; Vézina, L.-P.; et al. Investigation of the large-scale bioseparation of an antihypertensive peptide from alfalfa white protein hydrolysate by an electromembrane process. J. Membr. Sci. 2010, 355, 175−181. (112) Doyen, A.; Beaulieu, L.; Saucier, L.; Pouliot, Y.; Bazinet, L. Demonstration of in vitro anticancer properties of peptide fractions from a snow crab by-products hydrolysate after separation by electrodialysis with ultrafiltration membranes. Sep. Purif. Technol. 2011, 78, 321−329. (113) Doyen, A.; Husson, E.; Bazinet, L. Use of an electrodialytic reactor for the simultaneous β-lactoglobulin enzymatic hydrolysis and fractionation of generated bioactive peptides. Food Chem. 2013, 136, 1193−1202. (114) Doyen, A.; Udenigwe, C. C.; Mitchell, P. L.; Marette, A.; Aluko, R. E.; Bazinet, L. Anti-diabetic and antihypertensive activities of two flaxseed protein hydrolysate fractions revealed following their simultaneous separation by electrodialysis with ultrafiltration membranes. Food Chem. 2014, 145, 66−76. (115) Becker, W. Fluorescence lifetime imaging − techniques and applications. J. Microsc. 2012, 247 (2), 119−136. (116) Ebrecht, R.; Don Paul, C.; Wouters, F. S. Fluorescence lifetime imaging microscopy in the medical sciences. Protoplasma 2014,251 (2), 293−295. (117) Gee, M. L.; Burton, M.; Grevis-James, A.; Hossain, M. A.; McArthur, S.; Palombo, E. A.; Wade, J. D.; Clayton, A. H. Imaging the 9221
dx.doi.org/10.1021/jf502420h | J. Agric. Food Chem. 2014, 62, 9211−9222
Journal of Agricultural and Food Chemistry
Review
action of antimicrobial peptides on living bacterial cells. Sci. Rep. 2013, 3, 1557. (118) Huang, T. C.; Chen, J. Y. Proteomic and functional analysis of zebrafish after administration of antimicrobial peptide epinecidin-1. Fish Shellfish Immunol. 2013, 34 (2), 593−598.
9222
dx.doi.org/10.1021/jf502420h | J. Agric. Food Chem. 2014, 62, 9211−9222
