Fast Skeletal Muscle Troponin and Tropomyosin as a Dietary Source of Antidiabetic and Antihypertensive Bioactive Peptides: An In Silico Study


  • Jorge Andrés Barrero Universidad Nacional de Colombia
  • María Alejandra Barrero Universidad de La Sabana
  • Angélica María González Clavijo Universidad Nacional de Colombia
  • Claudia Marcela Cruz Gimnasio Vermont



Bioactive peptides, Angiotensin-converting enzyme inhibitors, Dipeptidyl-peptidase IV inhibitors, Tropomyosin, Troponin


Background: The nutraceutical properties of food hydrolysates rely on multiple biochemical interactions involving the modulation of enzymes and cellular receptors. Numerous bioactive peptides released from troponin and tropomyosin digestion have been identified. Their characterization has mostly been performed by hydrolysis catalyzed by proteases unrelated to the human digestive system.

Objective: This study aimed to determine the bioactive profile of beef, pork, and chicken meat by analyzing the frequency and pharmacokinetics of biopeptides released from troponin and tropomyosin.

Methods: In silico digestion and biopeptide release frequency were studied by three parameters; bioactive fragments release frequency (AE), frequency percentage (W), and mean occurrence (AS), all stated on the BIOPEP-UWM platform. Further on, hydrolysis end-products were screened based on gastrointestinal-absorption probability and pharmacokinetic profiling performed on SwissADME, SwissTargetPrediction, and ADME/Tlab bioinformatics web tools. Statistical analyses were performed using a one-way ANOVA test.

Results: Dipeptidyl peptidase-IV (DPP-IV) and angiotensin-converting enzyme (ACE) inhibiting biopeptides exhibited the highest release frequency. Moreover, W and AS parameters showed no significant difference (p>0.05) between the myofibrillar isoforms assessed. Seven biopeptides were classified as highly absorbable and reported optimal drug-likeness compliance. Although biopeptides hold good pharmacokinetic properties, the therapeutic potency of biopeptides has been shown to be lower than those of DPP-IV and ACE-inhibiting drugs.

Conclusions: Troponin and tropomyosin are rich dietary sources of bioactive peptides, mainly DPP-IV and ACE inhibitors. Digestion end-products are mainly dipeptides with optimal pharmacokinetic and drug-like properties, suggesting a potential therapeutic application in hypertensive and hyperglycemic disorders.

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Ahmad RS, Imran A, Hussain MB. Nutritional Composition of Meat. In: Arshad MS, editor. Meat Science and Nutrition [Internet]. InTech; 2018 [cited 2021 Jun 16]. Available from:

Badui S. Química De Los Alimentos. [Internet]. Pearson Educación de México, SA de CV; 2006 [cited 2021 Jun 16]. Available from:

Premi, M., Bansal, V. Nutraceuticals for Management of Metabolic Disorders. In: Treating endocrine and metabolic disorders with herbal medicines. 2021. p. 298–320.

Xing L, Liu R, Cao S, Zhang W, Guanghong Z. Meat protein based bioactive peptides and their potential functional activity: a review. Int J Food Sci Technol. 2019;54(6):1956–66. DOI:

Iwaniak A, Minkiewicz P, Pliszka M, Mogut D, Darewicz M. Characteristics of Biopeptides Released In Silico from Collagens Using Quantitative Parameters. Foods. 2020;9(7):965. DOI:

Wang TY, Hsieh CH, Hung CC, Jao CL, Lin PY, Hsieh YL, et al. A study to evaluate the potential of an in silico approach for predicting dipeptidyl peptidase-IV inhibitory activity in vitro of protein hydrolysates. Food Chem. 2017;234:431–8. DOI:

Jao C-L, Hung C-C, Tung Y-S, Lin P-Y, Chen M-C, Hsu K-C. The development of bioactive peptides from dietary proteins as a dipeptidyl peptidase IV inhibitor for the management of type 2 diabetes. BioMedicine. 2015;5(3):14. DOI:

Acquah C, Dzuvor CKO, Tosh S, Agyei D. Anti-diabetic effects of bioactive peptides: recent advances and clinical implications. Crit Rev Food Sci Nutr. 2020;1–14. DOI:

Tu M, Cheng S, Lu W, Du M. Advancement and prospects of bioinformatics analysis for studying bioactive peptides from food-derived protein: Sequence, structure, and functions. TrAC Trends Anal Chem. 2018;105:7–17. DOI:

Dong J, Wang N-N, Yao Z-J, Zhang L, Cheng Y, Ouyang D, et al. ADMETlab: a platform for systematic ADMET evaluation based on a comprehensively collected ADMET database. J Cheminformatics. 2018;10(1):29. DOI:

Daina A, Michielin O, Zoete V. SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res. 2019;47(W1):W357–64. DOI:

The UniProt Consortium. UniProt: a worldwide hub of protein knowledge. Nucleic Acids Res. 2019;47(D1):D506–15. DOI:

Minkiewicz, Iwaniak, Darewicz. BIOPEP-UWM Database of Bioactive Peptides: Current Opportunities. Int J Mol Sci. 2019;20(23):5978. DOI:

Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017;7(1):42717. DOI:

Lee Y-S, Jun H-S. Anti-diabetic actions of glucagon-like peptide-1 on pancreatic beta-cells. Metabolism. 2014;63(1):9–19. DOI:

Casanova-Martí À, Bravo FI, Serrano J, Ardévol A, Pinent M, Muguerza B. Antihyperglycemic effect of a chicken feet hydrolysate via the incretin system: DPP-IV-inhibitory activity and GLP-1 release stimulation. Food Funct. 2019;10(7):4062–70. DOI:

Soler MJ, Batlle D. Revisiting the renin-angiotensin system. Mol Cell Endocrinol. 2021;529:111268. DOI:

Martin M, Deussen A. Effects of natural peptides from food proteins on angiotensin converting enzyme activity and hypertension. Crit Rev Food Sci Nutr. 2019;59(8):1264–83. DOI:

Suetsuna K, Ukeda H, Ochi H. Isolation and characterization of free radical scavenging activities peptides derived from casein. J Nutr Biochem. 2000;11(3):128–31. DOI:

Liu C, Ren D, Li J, Fang L, Wang J, Liu J, et al. Cytoprotective effect and purification of novel antioxidant peptides from hazelnut (C. heterophylla Fisch) protein hydrolysates. J Funct Foods. 2018;42:203–15. DOI:

Deniau B, Rehfeld L, Santos K, Dienelt A, Azibani F, Sadoune M, et al. Circulating dipeptidyl peptidase 3 is a myocardial depressant factor: dipeptidyl peptidase 3 inhibition rapidly and sustainably improves haemodynamics. Eur J Heart Fail. 2020;22(2):290–9. DOI:

Morifuji M, Koga J, Kawanaka K, Higuchi M. Branched-Chain Amino Acid-Containing Dipeptides, Identified from Whey Protein Hydrolysates, Stimulate Glucose Uptake Rate in L6 Myotubes and Isolated Skeletal Muscles. J Nutr Sci Vitaminol (Tokyo). 2009;55(1):81–6. DOI:

Goraya TA, Cooper DMF. Ca2+-calmodulin-dependent phosphodiesterase (PDE1): Current perspectives. Cell Signal. 2005;17(7):789–97. DOI:

O’Brien JJ, O’Callaghan JP, Miller DB, Chalgeri S, Wennogle LP, Davis RE, et al. Inhibition of calcium-calmodulin-dependent phosphodiesterase (PDE1) suppresses inflammatory responses. Mol Cell Neurosci. 2020;102:103449. DOI:

Ramya K, Suresh R, Kumar HY, Kumar BRP, Murthy NBS. Decades-old renin inhibitors are still struggling to find a niche in antihypertensive therapy. A fleeting look at the old and the promising new molecules. Bioorg Med Chem. 2020;28(10):115466. DOI:

Ignat’ev DA, Vorob’ev VV, Ziganshin RKh. Effects of a number of short peptides isolated from the brain of the hibernating ground squirrel on the eeg and behavior in rats. Neurosci Behav Physiol. 1998;28(2):158–66. DOI:

Martini S, Conte A, Tagliazucchi D. Comparative peptidomic profile and bioactivities of cooked beef, pork, chicken and turkey meat after in vitro gastro-intestinal digestion. J Proteomics. 2019;208:103500. DOI:

Mora L, Gallego M, Toldrá F. ACEI-Inhibitory Peptides Naturally Generated in Meat and Meat Products and Their Health Relevance. Nutrients. 2018;10(9):1259. DOI:

Lan VTT, Ito K, Ohno M, Motoyama T, Ito S, Kawarasaki Y. Analyzing a dipeptide library to identify human dipeptidyl peptidase IV inhibitor. Food Chem. 2015;175:66–73. DOI:

Nongonierma AB, Mooney C, Shields DC, FitzGerald RJ. Inhibition of dipeptidyl peptidase IV and xanthine oxidase by amino acids and dipeptides. Food Chem. 2013;141(1):644–53. DOI:

Byun H-G, Kim S-K. Structure and Activity of Angiotensin I Converting Enzyme Inhibitory Peptides Derived from Alaskan Pollack Skin. BMB Rep. 2002;35(2):239–43. DOI:

Cheung, H. S., Wang, F. L., Ondetti, M. A., Sabo, E. F., Cushman, D. W. Binding of peptide substrates and inhibitors of angiotensin-converting enzyme. Importance of the COOH-terminal dipeptide sequence. J Biol Chem [Internet]. 1980;255(2). Available from:

Wu H, He H-L, Chen X-L, Sun C-Y, Zhang Y-Z, Zhou B-C. Purification and identification of novel angiotensin-I-converting enzyme inhibitory peptides from shark meat hydrolysate. Process Biochem. 2008;43(4):457–61. DOI:

Ryan JT, Ross RP, Bolton D, Fitzgerald GF, Stanton C. Bioactive Peptides from Muscle Sources: Meat and Fish. Nutrients. 2011;3(9):765–91. DOI:

Keller F, Hartmann B, Czock D. Time of effect duration and administration interval for sitagliptin in patients with kidney failure. Eur J Drug Metab Pharmacokinet. 2014;39(2):77–85. DOI:

Lin Y, Feng M, Lu C-W, Lei Y-P, He Z-M, Xiong Y. Preservation of vascular DDAH activity contributes to the protection of captopril against endothelial dysfunction in hyperlipidemic rabbits. Eur J Pharmacol. 2017;798:43–8. DOI:

Doroschuk VO, Makukha OG. The peculiarities of the interphase distribution of amino acids in the cloud point extraction systems. Colloids Surf Physicochem Eng Asp. 2017;520:757–63. DOI:

Das T, Mehta CH, Nayak UY. Multiple approaches for achieving drug solubility: an in silico perspective. Drug Discov Today. 2020;25(7):1206–12. DOI:

Acquah C, Stefano ED, Udenigwe CC. Role of hydrophobicity in food peptide functionality and bioactivity. J Food Bioact. 2018;4(1):88–98. DOI:

Yosipof A, Guedes RC, García-Sosa AT. Data Mining and Machine Learning Models for Predicting Drug Likeness and Their Disease or Organ Category. Front Chem. 2018;6:162. DOI:

Tian S, Li Y, Wang J, Zhang J, Hou T. ADME Evaluation in Drug Discovery. 9. Prediction of Oral Bioavailability in Humans Based on Molecular Properties and Structural Fingerprints. Mol Pharm. 2011;8(3):841–51. DOI:

Isvoran A, Louet M, Vladoiu DL, Craciun D, Loriot M-A, Villoutreix BO, et al. Pharmacogenomics of the cytochrome P450 2C family: impacts of amino acid variations on drug metabolism. Drug Discov Today. 2017;22(2):366–76. DOI:

Smith DA, Beaumont K, Maurer TS, Di L. Relevance of Half-Life in Drug Design. J Med Chem. 2018;61(10):4273–82. DOI:

Iwaniak A, Minkiewicz P, Darewicz M, Hrynkiewicz M. Food protein-originating peptides as tastants - Physiological, technological, sensory, and bioinformatic approaches. Food Res Int. 2016;89:27–38. DOI:

Bayes-Genis A, Barallat J, Richards AM. A Test in Context: Neprilysin. J Am Coll Cardiol. 2016;68(6):639–53. DOI:

Salazar J, Rojas-Quintero J, Cano C, Pérez JL, Ramírez P, Carrasquero R, et al. Neprilysin: A Potential Therapeutic Target of Arterial Hypertension? Curr Cardiol Rev. 2020;16(1):25–35. DOI:

Cui J, Jia J. Natural COX-2 Inhibitors as Promising Anti-inflammatory Agents: An Update. Curr Med Chem. 2021;28(18):3622–46. DOI:

Reyes-Díaz A, Del-Toro-Sánchez CL, Rodríguez-Figueroa JC, Valdéz-Hurtado S, Wong-Corral FJ, Borboa-Flores J, et al. Legume Proteins as a Promising Source of Anti-Inflammatory Peptides. Curr Protein Pept Sci. 2019;20(12):1204–17. DOI:

Lim WC, Khan AM. Mapping HLA-A2, -A3 and -B7 supertype-restricted T-cell epitopes in the ebolavirus proteome. BMC Genomics. 2018;19(S1):42. DOI:

Herrera‐Ruiz D, Knipp GT. Current Perspectives on Established and Putative Mammalian Oligopeptide Transporters. J Pharm Sci. 2003;92(4):691–714. DOI:

Wan T, Li X, Sun Y-M, Li Y-B, Su Y. Role of the calpain on the development of diabetes mellitus and its chronic complications. Biomed Pharmacother. 2015;74:187–90. DOI:

Yang. Increased expression of calpain and elevated activity of calcineurin in the myocardium of patients with congestive heart failure. Int J Mol Med [Internet]. 2010 May 25 [cited 2021 Jun 11];26(1). Available from:

Covington MD, Schnellmann RG. Chronic high glucose downregulates mitochondrial calpain 10 and contributes to renal cell death and diabetes-induced renal injury. Kidney Int. 2012;81(4):391–400. DOI:

Dókus LE, Yousef M, Bánóczi Z. Modulators of calpain activity: inhibitors and activators as potential drugs. Expert Opin Drug Discov. 2020;15(4):471–86. DOI:

Donkor IO. An update on the therapeutic potential of calpain inhibitors: a patent review. Expert Opin Ther Pat. 2020;30(9):659–75. DOI:

Mean frequency of occurrence of bioactive peptides in troponin and tropomyosin from beef (B. taurus), chicken (G. gallus) and pork (S. scrofa) fast skeletal muscle.




How to Cite

Barrero, J. A., Barrero, M. A., González Clavijo, A. M., & Cruz, C. M. (2023). Fast Skeletal Muscle Troponin and Tropomyosin as a Dietary Source of Antidiabetic and Antihypertensive Bioactive Peptides: An In Silico Study. Vitae, 30(1).



Foods: Science, Engineering and Technology