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Marine Drugs
Volume 23
Issue 8
10.3390/md23080331
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Article

Screening and Assessment of Hypoglycemic Active Peptide from Natural Edible Pigment Phycobiliprotein Based on Molecular Docking, Network Pharmacology, Enzyme Inhibition Assay Analyses, and Cell Experiments

by
Zhimin Zhu
1,2,
Yan Zhang
1,2,
Bingbing He
1,
Limin He
1,
Guihong Fang
1,
Yi Ning
1,
Pengcheng Fu
2,* and
Jing Liu
1,*
1
International Collaborative Research Center for the Development and Utilization of Tropical Food for Special Medical Purpose, School of Public Health, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou 571199, China
2
State Key Laboratory of Marine Resource Utilization in South China Sea, Hainan University, Haikou 570228, China
*
Authors to whom correspondence should be addressed.
Mar. Drugs 2025, 23(8), 331; https://doi.org/10.3390/md23080331
Submission received: 16 July 2025 / Revised: 4 August 2025 / Accepted: 12 August 2025 / Published: 17 August 2025
(This article belongs to the Special Issue Marine Nutraceuticals and Functional Foods: 2nd Edition)
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Abstract

Phycobiliproteins have gained increasing attention for their antidiabetic potential, yet the specific bioactive peptides and their targets and molecular mechanisms have remained unclear. In this study, four peptides with potential hypoglycemic activity were identified through virtual screening. Network pharmacology was employed to elucidate their hypoglycemic mechanism in the treatment of T2DM. A subsequent in vitro assay confirmed that the synthesized peptides, GR-5, SA-6, VF-6, and IR-7, exhibited significant inhibitory activity against α-glucosidase and DPP-IV. In insulin-resistant HepG2 models, all four peptides exhibited no cytotoxicity. Among them, GR-5 demonstrated the most promising therapeutic potential by remarkably enhancing cellular glucose consumption capacity. Furthermore, GR-5 administration substantially increased glycogen synthesis and enzymatic activities of hexokinase and pyruvate kinase with statistically significant improvements compared to the control groups. This study provides novel peptide candidates for T2DM treatment and validates an integrative strategy for targeted bioactive peptide discovery, advancing the development of algal protein-based therapeutics.
Keywords: phycobiliprotein; hypoglycemic peptide; molecular docking; network pharmacology; α-glucosidase; DPP-IV; IR-HepG2 phycobiliprotein; hypoglycemic peptide; molecular docking; network pharmacology; α-glucosidase; DPP-IV; IR-HepG2
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MDPI and ACS Style

Zhu, Z.; Zhang, Y.; He, B.; He, L.; Fang, G.; Ning, Y.; Fu, P.; Liu, J. Screening and Assessment of Hypoglycemic Active Peptide from Natural Edible Pigment Phycobiliprotein Based on Molecular Docking, Network Pharmacology, Enzyme Inhibition Assay Analyses, and Cell Experiments. Mar. Drugs 2025, 23, 331. https://doi.org/10.3390/md23080331

AMA Style

Zhu Z, Zhang Y, He B, He L, Fang G, Ning Y, Fu P, Liu J. Screening and Assessment of Hypoglycemic Active Peptide from Natural Edible Pigment Phycobiliprotein Based on Molecular Docking, Network Pharmacology, Enzyme Inhibition Assay Analyses, and Cell Experiments. Marine Drugs. 2025; 23(8):331. https://doi.org/10.3390/md23080331

Chicago/Turabian Style

Zhu, Zhimin, Yan Zhang, Bingbing He, Limin He, Guihong Fang, Yi Ning, Pengcheng Fu, and Jing Liu. 2025. "Screening and Assessment of Hypoglycemic Active Peptide from Natural Edible Pigment Phycobiliprotein Based on Molecular Docking, Network Pharmacology, Enzyme Inhibition Assay Analyses, and Cell Experiments" Marine Drugs 23, no. 8: 331. https://doi.org/10.3390/md23080331

APA Style

Zhu, Z., Zhang, Y., He, B., He, L., Fang, G., Ning, Y., Fu, P., & Liu, J. (2025). Screening and Assessment of Hypoglycemic Active Peptide from Natural Edible Pigment Phycobiliprotein Based on Molecular Docking, Network Pharmacology, Enzyme Inhibition Assay Analyses, and Cell Experiments. Marine Drugs, 23(8), 331. https://doi.org/10.3390/md23080331

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