Purification of novel anti-inflammatory peptides from enzymatic hydrolysate of the edible microalgal Spirulina maxima
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Abstract Natural bioactive peptides have been known as ingredients in nutraceuticals and pharmaceuticals. In this study, the potential anti-inflammatory peptides were purified from enzymatic hydrolysate of the edible microalgae Spirulina maxima using gastrointestinal endopeptidases (trypsin, α-chymotrypsin, and pepsin). Purification of the hydrolysate resulted in two peptides with amino acid sequences of LDAVNR (P1, 686 Da) and MMLDF (P2, 655 Da). It was found that peptides P1 and P2 exhibited significant inhibition on the release and production of histamine from antigen-stimulated RBL-2H3 mast cells. Moreover, the suppressive effect of P1 and P2 on production as well as expression of interleukin-8 in histamine-stimulated EA.hy926 endothelial cells was determined. Notably, the production of intracellular reactive oxygen species from mast cells and endothelial cells was decreased in the presence of P1 or P2. Collectively, the peptides P1 and P2 from S. maxima could be used as functional ingredients with potent anti-inflammatory benefits.
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Both P1 and P2 exhibited a suppressive effect on production of intracellular ROS in mast and endothelial cells.
“Both P1 and P2 exhibited a suppressive effect on IL-8 expression in histamine-stimulated EA.hy926 endothelial cells, and on the production of intracellular reactive oxygen species (ROS) in the mast and endothelial cells [33].”
From Beneficial Effects of Spirulina Consumption on Brain Health (2022) · cites this paper as [33]
Two novel anti-inflammatory peptides with amino acid sequences LDAVNR (P1) and MMLDF (P2) were purified from the enzymatic hydrolysate of Spirulina maxima.
“Two novel anti-inflammatory peptides with amino acid sequences of LDAVNR (P1, 686 Da) and MMLDF (P2, 655 Da) were purified from the enzymatic hydrolysate of Spirulina maxima.”
From Beneficial Effects of Spirulina Consumption on Brain Health (2022) · cites this paper as [33]
Both P1 and P2 exhibited a suppressive effect on IL-8 expression in histamine-stimulated EA.hy926 endothelial cells.
“Both P1 and P2 exhibited a suppressive effect on IL-8 expression in histamine-stimulated EA.hy926 endothelial cells, and on the production of intracellular reactive oxygen species (ROS) in the mast and endothelial cells [33].”
From Beneficial Effects of Spirulina Consumption on Brain Health (2022) · cites this paper as [33]
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Pepsin: An Excellent Proteolytic Enzyme for the Production of Bioactive Peptides
Ashaolu, T. J., Lee, C., Ashaolu, J. O., Tarhan, Ö., Pourjafar, H., & Jafari, S. M. (2023) · Food Reviews International · doi:10.1080/87559129.2023.2238814 · Cited by 58 · see citing works
“[ 102 ] A m a r a n t h ( A m a r a n t h u s h y p o c h o n d r i a c u s ) ● M e a s u r e m e n t o f N O a n d P r o s t a g l a n d i n”
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“As a result, researchers are interested in obtaining effective bioactive peptides from marine microalgae (Oh et al. 2015; Qian et al. 2013; Suetsuna and Chen 2001; Vo, Ryu, and Kim 2013).”
BackgroundHannan, J. M. A., Ansari, P., Azam, S., Flatt, P. R., & Abdel‐Wahab, Y. H. A. (2020) · British Journal Of Nutrition · doi:10.1017/s0007114520002111 · Cited by 56 · see citing works
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GPETAFLR: A new anti-inflammatory peptide from Lupinus angustifolius L. protein hydrolysate
Millán-Linares, M. C., Millán, F., Pedroche, J., & Yust, M. D. M. (2015) · Journal of Functional Foods · doi:10.1016/j.jff.2015.07.016 · Cited by 52 · see citing works
“…peptides in the range 1-5 kDa have been detected in casein hydrolysates (Mukhopadhya et al., 2014), and anti-inflammatory peptides with molecular weight lower than 1 kDa have been isolated from microalgae and aquatic organisms (Lee et al., 2012; Vo et al., 2013; Ahn, Cho, & Je, 2015).”
BackgroundMartínez-Ruiz, F., Andrade-Bustamante, G., Holguín-Peña, R., Renganathan, P., Gaysina, L., Sukhanova, N., & Puente, E. (2025) · Biomass · doi:10.3390/biomass5020025 · Cited by 51 · see citing works
Ashaolu, T. J., Zarei, M., Agrawal, H., Kharazmi, M. S., & Jafari, S. M. (2023) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2023.2183380 · Cited by 54 · see citing works
“Peptides like Leu-Asp-Ala-Val-Asn-Arg and MetMet-Leu-Asp-Phe among all other plant-based IPs usually have low MW and hydrophobic properties (Kong et al. 2008; Vo, Ryu, and Kim 2013).”
Najafian, L. (2023) · Food & Function · doi:10.1039/d3fo00362k · Cited by 49 · see citing works
A Systemic Review on Microalgal Peptides: Bioprocess and Sustainable Applications
Sathya, R., MubarakAli, D., MohamedSaalis, J., & Kim, J.-W. (2021) · Sustainability · doi:10.3390/su13063262 · Cited by 48 · see citing works
“Additionally, these anti-inflammatory peptides reduce reactive oxygen species production, which releases the inhibition of histamine and IL-8 expression [73].”
BackgroundInkanuwat, A., Sukaboon, R., Reamtong, O., Asawanonda, P., Pattaratanakun, A., Saisavoey, T., Sangtanoo, P., & Karnchanatat, A. (2019) · Food Technology and Biotechnology · doi:10.17113/ftb.57.02.19.5964 · Cited by 43 · see citing works
“Anti-inflammatory Leu-Asp-Ala-Val-Asn-Arg (683 Da) and Met-Met-Leu-Asp-Phe (655 Da) from Spirulina maxima (11), Gln-Cys-Gln-Gln-Ala-Val-Gln-Ser-Ala-Val (1061 Da) from Ruditapes philippinarum (5) and Gln-Cys-Gln-Cys-Ala-Val-GluGly-Gly-Leu (1007 Da) from Crassostrea gigas were also isolated from marine organisms (36), w…”
BackgroundVelayutham, M., Guru, A., Arasu, M. V., Al-Dhabi, N. A., Choi, K. C., Elumalai, P., Harikrishnan, R., Arshad, A., & Arockiaraj, J. (2021) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2021.10.010 · Cited by 43 · see citing works
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Advanced Insights into Walnut Protein: Structure, Physiochemical Properties and Applications
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“Furthermore,anti-inflammatory peptides have been purified from enzymatic hydrolysate of Spirulina maxima (Vo et al., 2013), andS. platensis peptides have been reported to possess anti-hypertensive, antiallergic, anti-inflammatory, anti-atherosclerotic, anti-tumor and antiaging activities (Ovando et…”
BackgroundImmunomodulating peptides for food allergy prevention and treatment
Lozano‐Ojalvo, D., & López‐Fandiño, R. (2017) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2016.1275519 · Cited by 41 · see citing works
“…microalgae Spirulina maxima and, particularly, the pentapeptides DAVNR and MMLDF, inhibit histamine release form RBL-2H3 mast cells sensitized with dinitrophenyl (DNP)-specific IgE and stimulated with DNP-BSA, in parallel with a suppressive effect on intracellular ROS production (Vo et al., 2013).”
BackgroundLeo, E. E. M., Acevedo‐Fernández, J. J., & Campos, M. R. S. (2016) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2016.07.051 · Cited by 38 · see citing works
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Reconsidering the potential of direct microalgal biomass utilization as end-products: A review
Choi, H. I., Sung, Y. J., Hong, M. E., Han, J., Min, B. K., & Sim, S. J. (2022) · Renewable and Sustainable Energy Reviews · doi:10.1016/j.rser.2021.111930 · Cited by 37 · see citing works
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“The chemical methods listed use enzymes for cell wall degradation, as well as a buffer, surfactants, ionic liquids, a strong base, or acid [56].”
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“Recently, some anti-inflammatory properties have also been reported in certain bioresource proteins, including microalgae, salmon pectoral fin and mussel [40-42].”
BackgroundVo, T., Ngo, D., Kang, K., Park, S., & Kim, S. (2014) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201400329 · Cited by 35 · see citing works
Self-citationHa, Y., Lee, W.-H., Jeong, J., Park, M., Ko, J.-Y., Kwon, O. W., Lee, J., & Kim, Y. (2020) · Nutrients · doi:10.3390/nu12051238 · Cited by 35 · see citing works
Liu, H., & Лі, Б. (2022) · Journal of Food Biochemistry · doi:10.1111/jfbc.14122 · Cited by 34 · see citing works
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“Moreover, the results of this study included highly negative”
ResultUnveiling the rise of microalgae-based foods in the global market: Perspective views and way forward
Ang, W. S., Kee, P. E., Lan, J. C.-W., Chen, W.-H., Chang, J.-S., & Khoo, K. S. (2025) · Food Bioscience · doi:10.1016/j.fbio.2024.105390 · Cited by 32 · see citing works
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Food-derived bio-functional peptides for the management of hyperuricemia and associated mechanism
Wang, Y., Ma, M., Huang, Y., Fan, S., Peng, J., Li, S., Su, X., Wang, Y., & Lu, C. (2023) · Food Science and Human Wellness · doi:10.26599/fshw.2022.9250149 · Cited by 30 · see citing works
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Microalgal proteins: Unveiling sustainable alternatives to address the protein challenge
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Xu, Y., Feng, Y., Yang, Y., Cheng, L., Zhou, M., Guo, Y. Y., & Ren, D. (2023) · Food & Function · doi:10.1039/d3fo00768e · Cited by 28 · see citing works
Food Peptides for the Nutricosmetic Industry
Dini, I., & Mancusi, A. (2023) · Antioxidants · doi:10.3390/antiox12040788 · Cited by 28 · see citing works
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“Vo et al. (2013) purified two peptides (LDAVNR and MMLDF) from an enzymatic hydrolysate of Spirulina maxima , which were able to suppress pro-inflammatory cytokine production from endothelial cells and inhibit ROS production and interleukin (IL)-8 expression, two of the main inflammatory process…”
InfluentialUdaypal, U., Goswami, R. K., & Verma, P. (2024) · Algal Research · doi:10.1016/j.algal.2024.103664 · Cited by 28 · see citing works
Huang, R., Zhu, Z., Wu, Q., Bekhit, A. E.-D. A., Wu, S., Chen, M., Wang, J., & Ding, Y. (2023) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1975093 · Cited by 23 · see citing works
“For example, peptides of 3 kDa from Spirulina maxima have been found to exhibit the most superior anti-inflammatory activity than those of >10, 5–10, and 3–5 kDa (Vo, Ryu, and Kim 2013).”
BackgroundResultAn, J., Feng, Y., Zheng, J., Addy, M., Zhang, L., & Ren, D. (2020) · Journal of Food Biochemistry · doi:10.1111/jfbc.13245 · Cited by 23 · see citing works
Antioxidant and angiotensin-I converting enzyme inhibitory peptides from Hippocampus abdominalis
Kim, H., Je, J.-G., Ryu, B., Kang, N., Fernando, I. P. S., Jayawardena, T. U., Sanjeewa, K. K. A., Oh, J.-Y., Lee, T.-G., & Jeon, Y. (2018) · European Food Research and Technology · doi:10.1007/s00217-018-3179-0 · Cited by 23 · see citing works
“The protease hydrolysis is believed to increase the bioavailability of the active peptides and avoid the additional digestion in the gastrointestinal tract [20].”
Self-citationAlgae-derived compounds: Bioactivity, allergenicity and technologies enhancing their values
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“The tripeptide was composed of three hydrophobic amino acids, high hydrophobicity benefited for the peptide to cross the cellular membrane (Vo et al., 2013).”
Vo, T., Kim, Y.-S., Ngo, D., Le, P. U., Kim, S., & Kim, S. (2018) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2018.07.096 · Cited by 21 · see citing works
Self-citationPaterson, S., Alonso-Pintre, L., Morato-López, E., González de la Fuente, S., Gómez-Cortés, P., & Hernández-Ledesma, B. (2025) · Foods · doi:10.3390/foods14020252 · Cited by 20 · see citing works
“Similarly, N. oculata has been reported to generate protein hydrolyzates and peptides with angiotensin-converting enzyme (ACE)-1-inhibitory, antithrombotic, and calcium/calmodulin-dependent kinase II (CAMKII)-inhibitory activities [17,18].”
Advantageous Preparation of Digested Proteic Extracts from Spirulina platensis Biomass
Verdasco-Martín, C. M., Echevarrieta, L., & Otero, C. (2019) · Catalysts · doi:10.3390/catal9020145 · Cited by 22 · see citing works
Application research and progress of microalgae as a novel protein resource in the future
Ma, S. L., Sun, S., Li, T. Z., Yan, Y. J., & Wang, Z. (2024) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2024.2431208 · Cited by 20 · see citing works
“Inflammation is a normal part of the immune system’s response, but it can also cause discomfort and lead to inflammatory diseases due to symptoms such as redness, swelling, fever, and pain (Romay, Ledón, and González 1998; Suttisuwan et al. 2019; Vo, Ryu, and Kim 2013).”
Influential
- Authors
- Vo, T.-S., Ryu, B., & Kim, S.-K.
- Affiliations
- Pukyong National University (KR)
- The University of Queensland (AU)
- Corresponding author
- Kim, Se-Kwon
- Venue
- Journal of Functional Foods
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 5
- Issue
- 3
- Pages
- 1336-1346
- ISSN
- 1756-4646 (ISSN-L)
- OpenAlex
- W2083421143
- Semantic Scholar
- 08ed729b45ce31cef2ca7b019a57bb5d305e4885
- Cited by
- 209
- References
- 43
- Citations by year
- 2026: 16 · 2025: 29 · 2024: 25 · 2023: 22 · 2022: 27 · 2021: 21 · 2020: 13 · 2019: 14 · 2018: 13 · 2017: 7 · 2016: 9 · 2015: 4 · 2014: 7 · 2013: 2
- FWCI
- 3.28
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Journal of Functional Foods (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Hydrolysis and Bioactive Peptides
- Life Sciences › Agricultural and Biological Sciences › Aquatic Science › Seaweed-derived Bioactive Compounds
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Keywords
- anti-inflammatory peptides, Spirulina maxima, enzymatic hydrolysate, peptide purification, histamine release, mast cells, RBL-2H3 cells, interleukin-8, endothelial cells, reactive oxygen species, microalgae, nutraceuticals
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