ACE inhibitory and DPP-IV inhibitory activity of collagen peptides derived from the snapper salmon (Otolithes ruber) skin collagen via papain and pepsin-trypsin hydrolysis

Cherise Elisha , Prashant Bhagwat , Ayodeji Amobonye , Santhosh Pillai

Collagen and Leather ›› 2026, Vol. 8 ›› Issue (1) : 16

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Collagen and Leather ›› 2026, Vol. 8 ›› Issue (1) :16 DOI: 10.1186/s42825-026-00248-7
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ACE inhibitory and DPP-IV inhibitory activity of collagen peptides derived from the snapper salmon (Otolithes ruber) skin collagen via papain and pepsin-trypsin hydrolysis
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Abstract

Fish-based collagen supplements have potential health benefits, including antioxidant, ACE inhibitory, and DPP-IV inhibitory properties, which are expressed upon their digestion in the gastrointestinal system, thus releasing bioactive peptides (BPs). This study evaluated the pre-digestion of fish collagen using papain as a pre-digestive enzyme, which has broad specificity to enhance collagen breakdown and BPs release. Fish skin collagen was extracted via acid solubilisation, confirmed as type-I, and subsequently hydrolysed using two methods: pepsin-trypsin digestion (PTD) and pre-digestion with papain followed by PTD (PDPTD). The PDPTD–fish collagen hydrolysates (FCH) exhibited IC50 values (mg/mL) of 0.088 for ACE, 1.67 for DPP-IV, as well as 2.38 and 0.026 for antioxidant activities including DPPH and ABTS radicals scavenging, respectively, which were significantly lower than that of PTD-FCH. The FCH (PTD and PDPTD) were identified using LC-MS/MS analysis, and molecular docking studies showed lower binding energies for PDPTD–FCH peptides, particularly IGFPGFPG, against ACE (-11.2 kcal/mol) and DPP-IV (-9.1 kcal/mol), suggesting better inhibitory ability exhibited by BPs. This study highlighted fish collagen as a valuable source of BPs with enhanced bioactivity when pre-digested with papain, indicating its potential for functional foods and nutraceutical industries.

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Keywords

Fish collagen / Antioxidant peptides / Antihypertensive and antidiabetic potential / Functional foods / Nutraceuticals

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Cherise Elisha, Prashant Bhagwat, Ayodeji Amobonye, Santhosh Pillai. ACE inhibitory and DPP-IV inhibitory activity of collagen peptides derived from the snapper salmon (Otolithes ruber) skin collagen via papain and pepsin-trypsin hydrolysis. Collagen and Leather, 2026, 8(1): 16 DOI:10.1186/s42825-026-00248-7

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Funding

National Research Foundation of South Africa (MND 210510600423)

Innovation Builder Funding, Durban University of Technology, South Africa(Innovation Builder Funding, Durban University of Technology, South Africa)

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