Characteristics of soybean (Glycine max) protein hydrolysate by bromelain and its effect on inflammation and kidney disorders in gentamicin-induced male Wistar rats

Document Type : Original Article

Authors

1 Faculty of Medicine, Universitas Kristen Maranatha Jalan Prof.Drg. Suria Sumantri 65 Bandung 40163, Indonesia

2 Faculty of Pharmacy, Universitas Padjadjaran Jl. Ir. Soekarno, KM 21 Jatinangor – Sumedang, 45363, Indonesia

3 Faculty of Medicine, Universitas Jenderal Achmad Yani, Jalan Terusan Jenderal Sudirman, Cimahi 40531 PO Box 148, Indonesia

10.22038/ijbms.2024.78131.16885

Abstract

Objective(s): Soybeans have various positive effects on health, including anti-inflammatory and preventing kidney damage. There is concern regarding the phytoestrogen content due to the high isoflavone content in soybeans. Various forms of soybean processing have been tried; in this study, the hydrolysis method will be used to obtain the active substance Arginine-Glycine-Aspartate (RGD) tripeptide in soybean protein hydrolyzed by bromelain (SPHB). The research aimed to determine the characteristics and influence of SPHB on kidney function, inflammation, body weight, and estrogen in male Wistar rats induced by gentamicin.
Materials and Methods: Soybeans (Glycine max) are hydrolyzed using the proteolytic enzyme Bromelain from pineapples. The proteomics was investigated using Liquid-Chromatography Mass Spectroscopy Tandem (LC-MS/MS). SPHB in three doses would be tested for 28 days on male Wistar rats induced by gentamicin. The parameters measured were body weight, high-sensitive cell reactive protein (hs-CRP) levels, urea, creatinine, and estrogen levels.
Results: SPHB has a low molecular weight (LMW) of 10 kDa and contains RGD in the lunasin sequence. SPHB showed no effect on body weight (P>0.05). The impact of SPHB on hs-CRP, urea, and creatinine showed differences significantly from the positive control, especially SPHB at a dose of 112 mg/day (P<0.01). Meanwhile, SPHB has almost no effect on estrogen levels.
Conclusion: The administration of SPHB with LMW and contains lunasin showed decreased inflammation and kidney function parameters but did not affect body weight and estrogen levels in induced gentamicin Wistar rats.

Keywords

Main Subjects

References

1. Messina M, Duncan A, Messina V, Lynch H, Kiel J, Erdman JW Jr. The health effects of soy: A reference guide for health professionals. Front Nutr 2022; 9: 970364-970396. 
2. Kim IS, Kim CH, Yang WS. Physiologically active molecules and functional properties of soybeans in human health-a current perspective. Int J Mol Sci 2021; 22: 4054-4079. 
3. Ramasamy A, Jothivel N, Das S, Swapna A, Albert AP, Barnwal P, et al. Evaluation of the protective role of Glycine max seed extract (soybean oil) in drug-induced nephrotoxicity in experimental rats. J Diet Suppl. 2018; 15: 583-595. 
4. Ashaolu TJ. Health applications of soy protein hydrolysates. Int J Pept Res Ther 2020; 26: 2333–2343 
5. Messina M, Rogero MM, Fisberg M, Waitzberg D. Health impact of childhood and adolescent soy consumption. Nutr Rev 2017; 75: 500-515. 
6. Kim IS, Yang WS, Kim CH. Beneficial effects of soybean-derived bioactive peptides. Int J Mol Sci 2021; 22: 8570-8582. 
7. Chen ST, Yang HY, Huang HY, Peng SJ, Chen JR. Effects of various soya protein hydrolysates on lipid profile, blood pressure, and renal function in five-sixths nephrectomized rats. British J Nutr 2006; 96: 435-441. 
8. Yang J, Zhu B, Dou J, Li X, Tian T, Tong X, et al. Structural characterization of soy protein hydrolysates and their transglutaminase-induced gelation properties. Lwt Food Sci Technol 2023;179:114668-1146677. 
9. Rafieian-Kopaei M, Beigrezaei S, Nasri H, Kafeshani M. Soy protein and chronic kidney disease: An updated review. Int J Prev Med 2017; 8:105-110. 
10. Chatterjee C, Gleddie S, Xiao CW. Soybean bioactive peptides and their functional properties. Nutrients 2018;10:1211-1226. 
11. Kusmardi K, Nessa N, Estuningtyas A, Tedjo A. The effect of lunasin from Indonesian soybean extract on histopatologic examination and COX-2 expression in dextran sodium sulfate-induced rats colon. Int J Physiol Pathophysiol Pharmacol 2018; 10: 154-162. 
12. Jones G, Srivastava A. Understanding Lunasin’s biology and potential as a cancer therapeutic by utilizing Drosophila genetics. Exp Biol Med 2014; 239: 519-528. 
13. Alves de Souza SM, Hernández-Ledesma B, de Souza TLF. Lunasin as a promising plant-derived peptide for cancer therapy. Int J Mol Sci 2022; 23: 9548-9567.
14. Randjelovic P, Veljkovic S, Stojiljkovic N, Sokolovic D, Ilic I. Gentamicin nephrotoxicity in animals: Current knowledge and future perspectives. EXCLI J 2017; 16: 388-399
15. Udupa V, Prakash V. Gentamicin induced acute renal damage and its evaluation using urinary biomarkers in rats. Toxicol Rep 2019; 6: 91-99. 
16. Hidayat M, Prahastuti S, Yusuf M, Hasan K. Nutrition profile and potency of RGD motif in protein hydrolysate of green peas as an antifibrosis in chronic kidney disease. Iran J Basic Med Sci 2021; 24: 734-743
17. Carrero JJ, Hecking M, Chesnaye NC, Jager KJ. Sex and gender disparities in the epidemiology and outcomes of chronic kidney disease. Nat Rev Nephrol 2018; 14: 151-164.
18. Sproston NR, Ashworth JJ. Role of C-reactive protein at sites of inflammation and infection. Front Immunol 2018; 9: 754-764. 
19. Tsai YW, Chan YL, Chen YC, Cheng YH, Chang SS. Association of elevated blood serum high-sensitivity C-reactive protein levels and body composition with chronic kidney disease: A population-based study in Taiwan. Medicine (Baltimore) 2018; 97: e11896-11903. 
20. Universitas Kristen Maranatha. Measurement and producing green peas protein hydrolysate (Pisum sativum) as an antifibrotic for chronic kidney disease therapy. Universitas Kristen Maranatha. Ministry of Law and Human Rights of the Republic of Indonesia. Patents. 2019. Registration number: P00201907647
21. Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227:680-685.
22. Kielkopf CL, Bauer W, Urbatsch IL. Bradford assay for determining protein concentration. Cold Spring Harb Protoc 2020; 2020: 102269.
23. Li J, Zhu HJ. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics of drug-metabolizing enzymes and transporters. Molecules 2020; 25: 2718-2726. 
24. Faccio L, Da Silva AS, Tonin AA, França RT, Gressler LT, Copetti MM, et al. Serum levels of LH, FSH, estradiol and progesterone in female rats experimentally infected by Trypanosoma evansi. Exp Parasitol 2013;135: 110-115. 
25. Kandemir FM, Ozkaraca M, Yildirim BA, Hanedan B, Kirbas A, Kilic K, et al. Rutin attenuates gentamicin-induced renal damage by reducing oxidative stress, inflammation, apoptosis, and autophagy in rats. Ren Fail 2015; 37: 518-525. 
26. Akchurin OM, Kaskel F. Update on inflammation in chronic kidney disease. Blood Purif 2015; 39: 84-92. 
27. de Medeiros AF, de Queiroz J, Maciel B, de Araújo Morais AH. Hydrolysed proteins and vegetable peptides: anti-inflammatory mechanisms in obesity and potential therapeutic targets. Nutrients 2022; 14: 690-703. 
28. Yi G, Li H, Liu M, Ying Z, Zhang J, Liu X. Soybean protein-derived peptides inhibit inflammation in LPS induced RAW264.7 macrophages via the suppression of TLR4-mediated MAPK-JNK and NF-kappa B activation. J Food Biochem 2020; 44: e13289. 
29. Kucuk M, Gulcin I. Purification, and characterization of the carbonic anhydrase enzyme from Black Sea trout (Salmo trutta Labrax Coruhensis) kidney and inhibition effects of some metal ions on enzyme activity. Environ Toxicol Pharmacol 2016; 44: 134-139.
30. Liu J, Jia SH, Kirberger M, Chen N. Lunasin as a promising health-beneficial peptide. Eur Rev Med Pharmacol Sci 2014; 18: 2070-2075. 
31. He L, Peng X, Zhu J, Liu G, Chen X, Tang C, et al. Protective effects of curcumin on acute gentamicin-induced nephrotoxicity in rats. Can J Physiol Pharmacol 2015; 93: 275-282. 
32. Zhang C, Shang Y, Chen X, Midgley AC, Wang Z, Zhu D, et al. Supramolecular Nanofibers containing arginine-glycine-aspartate (RGD) peptides boost therapeutic efficacy of extracellular vesicles in kidney repair. ACS Nano 2020; 14: 12133-12147.
33. Lule VK, Garg S, Pophaly SD, Hitesh, Tomar SK. Potential health benefits of lunasin: a multifaceted soy-derived bioactive peptide. J Food Sci 2015; 80: R485-494.  
34. Cheung WW, Paik KH, Mak RH. Inflammation and cachexia in chronic kidney disease. Pediatr Nephrol 2010; 25: 711-724. 
35. Harris RBS. Direct and indirect effects of leptin on adipocyte metabolism. Biochim Biophys Acta Mol Basis Dis 2014; 1842: 414- 423. 
36. Akhlaghi M, Zare M, Nouripour F. Effect of soy, and soy isoflavones on obesity-related anthropometric measures: A systematic review and meta-analysis of randomized controlled clinical trials. Adv Nutr 2017; 8: 705-717. 
37. Reed KE, Camargo J, Hamilton-Reeves J, Kurzer M, Messina M. Neither soy nor isoflavone intake affects male reproductive hormones: An expanded and updated meta-analysis of clinical studies. Reprod Toxicol 2021; 100: 60-67. 
38. Messina M. Soybean isoflavone exposure does not have feminizing effects on men: A critical examination of the clinical evidence. Fertil Steril 2010; 93: 2095-2104. 
39. Messina M, Mejia SB, Cassidy A, Duncan A, Kurzer M, Nagato C, et al. Neither soy foods nor isoflavones warrant classification as endocrine disruptors: A technical review of the observational and clinical data. Crit Rev Food Sci Nutr 2022; 62: 5824-5588.
Iranian Journal of Basic Medical Sciences
Volume 28, Issue 1
January 2025
Pages 56-62

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