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Inhibition of dipeptidyl peptidase-4 (DPP4), antioxidant, antiglycation and anti-inflammatory effect of Ferulic acid against streptozotocin toxicity mediate nephropathy in diabetic rats

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Abstract

The protein glycation due to high blood glucose mediate release of inflammatory intermediate contributes in the development of diabetic nephropathy. Ferulic acid (FA) is a phenolic compound distributed in different foods as whole grains. Inhibitors of DPP4 improve GLP-1-mediated insulin secretion and inhibit liver gluconeogenesis. This study investigated the impact of FA as anti-inflammatory, antioxidant and antiglycation against streptozotocin-induced diabetic nephropathy in rats. This study was carried out on total ninety male rats allocated into six (each 15 rats); group I (control). All other animals (groups II–VI) were receiving 65 mg/kg STZ for induction of diabetes. Rats in group II (untreated diabetic). Rats in groups III–V were treated with FA (10, 20, 30 mg/kg bw) respectively, i.p. for 8 weeks. Group VI received 10 units insulin daily, sc. Fasting blood samples were subjected for assay of glycated hemoglobin (HA1c), serum MDA, aldose reductase, total antioxidant, DPP4 while kidney tissue subjected for assay of malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), IL-1β and AGEs. Data obtained showed that, FA showed antioxidant activity by reducing MDA and enhancement antioxidant activity compared with untreated rats (p < 0.001) with dose dependence. In addition, FA reduced the activities of aldose reductase, DPP4 (p < 0.001), decreased IL-6, TNF-α and AGEs versus untreated rats (p < 0.001). Histological investigation revealed an improvement in the nephron structure in diabetic rat treated with FA versus untreated group. It was concluded that, FA possesses a potent antioxidant and anti-inflammatory and DPP4 inhibitor. For that, it was considered as a protective agent against the risk of diabetic nephropathy and can be used as alternative or complementary supplement.

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References

  • Acosta-Estrada BA, Lazo-Vélez MA, Nava-Valdez Y, Gutiérrez-Uribe JA, Serna-Saldívar SO (2014) Improvement of dietary fiber, ferulic acid and calcium contents in pan bread enriched with nejayote food additive from white maize (Zea mays). J Cereal Sci 60:264–269

    Article  CAS  Google Scholar 

  • Ahmed N, Babaei-Jadidi R, Howell SK, Thornalley PJ, Beisswenger PJ (2005) Glycated and oxidized protein degradation products are indicators of fasting and postprandial hyperglycemia in diabetes. Diabetes Care 28:2465–2471

    Article  CAS  Google Scholar 

  • Bezerra G, Pereira M, Ostrosky E, Barbosa E, Moura M, Ferrari M, Aragão C, Gomes A (2017) Compatibility study between ferulic acid and excipients used in cosmetic formulations by TG/DTG, DSC and FTIR. J Therm Anal Calorim 127:1683–1691

    Article  CAS  Google Scholar 

  • Biemesderfer D, Nagy T, DeGray B, Aronson PS (1999) Specific association of megalin and the Naþ/Hþexchanger isoform NHE3 in the proximal tubule. J Biol Chem 274:17518–17524

    Article  CAS  Google Scholar 

  • Brouwers O, Niessen PM, Haenen G, Miyata T, Brownlee M, Stehouwer CD, De Mey JG, Schalkwijk CG (2010) Hyperglycaemia-induced impairment of endothelium-dependent vasorelaxation in rat mesenteric arteries is mediated by intracellular methylglyoxal levels in a pathway dependent on oxidative stress. Diabetologia 53:989–1000

    Article  CAS  Google Scholar 

  • D’Agati V, Yan SF, Ramasamy R, Schmidt AM (2010) RAGE, glomerulosclerosis and proteinuria: roles in podocytes and endothelial cells. Trends Endocrinol Metab 21:50–56

    Article  Google Scholar 

  • Fazary AE, Ju YH (2007) Feruloyl esterases as biotechnological tools: current and future perspectives. Acta Biochim Biophys Sin 39:811–828

    Article  CAS  Google Scholar 

  • Girardi ACC, Degray BC, Nagy T, Biemesderfer D, Aronson PS (2001) Association of Naþ-Hþexchanger isoform NHE3 and dipeptidylpeptidase IV in the renal proximal tubule. J Biol Chem 276:46671–46677

    Article  CAS  Google Scholar 

  • Ha H, Lee HB (2000) Reactive oxygen species as glucose signaling molecules in mesangial cells cultured under high glucose. Kidney Int Suppl 77:S19-25

    Article  CAS  Google Scholar 

  • Itagaki S, Kurokawa T, Nakata C, Saito Y, Oikawa S, Kobayashi M, Hirano T, Iseki K (2009) In vitro and in vivo antioxidant properties of ferulic acid: a comparative study with other natural oxidation inhibitors. Food Chem 114:466–471

    Article  CAS  Google Scholar 

  • Jung EH, Kim SR, Hwang IK, Ha TY (2007) Hypoglycemic effects of a phenolic acid fraction of rice bran and ferulic acid in c57bl/ksj-db/db mice. J Agric Food Chem 55:9800–9804

  • Kang ES, Lee GT, Kim BS, Kim CH, Seo GH, Han SJ, Hur KY, Ahn CW, Ha H, Jung M, Ahn YS, Cha BS, Lee HC (2008) Lithospermic acid B ameliorates the development of diabetic nephropathy in OLETF rats. Eur J Pharmacol 579:418–425

    Article  CAS  Google Scholar 

  • Kuenzig W, Chau J, Norkus E, Holowaschenko H, Mergens W, Conney AH (1984) Caffeic and ferulic acid as blockers of nitrosamine formation. Carcinogenesis 5:309–313

  • Lambeir AM, Durinx C, Scharp_e S, De Meester I (2003) Dipeptidyl-peptidase IV from bench to bedside: an update on structural properties, functions, and clinical aspects of the enzyme DPP IV. Crit Rev Clin Lab Sci 40: 209–294

  • Lee EY, Chung CH (2007) The role of glomerular podocytes in diabetic nephropathy. Korean Diabetes J 31:451–454

  • Lin FH, Lin JY, Gupta RD, Tournas JA, Burch JA, Selim MA, Monteiro-Riviere NA, Grichnik JM, Zielinski J, Pinnell SR (2005) Ferulic acid stabilizes a solution of vitamins C and E and doubles its photoprotection of skin. J Invest Dermatol 125:826–832

  • Marguet D, Baggio L, Kobayashi T, Bernard AM, Pierres M, Nielsen PF, Ribel U, Watanabe T, Drucker DJ, Wagtmann N (2000) Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26. Proc Natl Acad Sci USA 97:6874–6879

    Article  CAS  Google Scholar 

  • Martins FL, Bailey MA, Girardi ACC (2020) Endogenous activation of glu-cagon-like peptide-1 receptor contributes to blood pressure control:role of proximal tubule Na. Hypertension 76:839–848

    Article  CAS  Google Scholar 

  • Matsui T, Higashimoto Y, Nishino Y, Nakamura N, Fukami K, Yamagishi SI (2017) RAGE-Aptamer blocks the development and progression of experimental diabetic nephropathy. Diabetes 66:1683–1695

    Article  CAS  Google Scholar 

  • McLellan AC, Thornalley PJ, Benn J, Sonksen PH (1994) Glyoxalase system in clinical diabetes mellitus and correlation with diabetic complications. Clin Sci (lond) 87:21–29

    Article  CAS  Google Scholar 

  • Moldovan M, Lahmar A, Bogdan C, Părăuan S, Tomuţă I, Crişan M (2017) Formulation and evaluation of a water-in-oil cream containing herbal active ingredients and ferulic acid. Clujul Med 90:212–219

    Google Scholar 

  • Mori H, Kawabata K, Yoshimi N, Tanaka T, Murakami T, Okada T, Murai H (1999) Chemopreventive effects of ferulic acid on oral and rice germ on large bowel carcinogenesis. Anticancer Res 19:3775–3778

  • Ou S, Kwok KC (2004) Ferulic acid: pharmaceutical functions, preparation and applications in foods. J Sci Food Agric 84:1261–1269

  • Pacheco BPM, Crajoinas RO, Couto GK, Davel APC, Lessa LM, Rossoni LV, Girardi ACC (2011) Dipeptidyl peptidase IV inhibition attenuates blood pressure rising in young spontaneously hypertensive rats. J Hypertens 29:520–528

    Article  CAS  Google Scholar 

  • Papadopoulou-Marketou N, Chrousos GP, Kanaka-Gantenbein C (2017) Diabetic nephropathy in type 1 diabetes: a review of early natural history, pathogenesis, and diagnosis. Diabetes Metab Res Rev 33:e2841

    Article  Google Scholar 

  • Pinheiro LS, de Melo AD, Andreazzi AE, de Caires Júnior LC, Costa MB, Garcia RMG (2011) Protocol of insulin therapy for streptozotocin-diabetic rats based on a study of food ingestion and glycemic variation. Scand J Lab Anim Sci 38(2):117–127

    CAS  Google Scholar 

  • Pospisilik JA, Stafford SG, Demuth HU, Brownsey R, Parkhouse W, Finegood DT, McIntosh CH, Pederson RA (2002) Long-term treatment with the dipeptidyl peptidase IV inhibitor P32/98 causes sustained improvements in glucose tolerance, insulin sensitivity, hyperinsulinemia, and beta-cell glucose responsiveness in VDF (fa/fa) Zucker rats. Diabetes 51:943–950

    Article  CAS  Google Scholar 

  • Price RK, Welch RW, Lee-Manion AM, Bradbury I, Strain JJ (2008) Total phenolics and antioxidant potential in plasma and urine of humans after consumption of wheat bran. Cereal Chem 85:152–157

    Article  CAS  Google Scholar 

  • Ramasamy R, Yan SF, Schmidt AM (2011) Receptor for AGE (RAGE): signaling mechanisms in the pathogenesis of diabetes and its complications. Ann N Y Acad Sci 1243:88–102

    Article  CAS  Google Scholar 

  • Roy S, Metya SK, Sannigrahi S, Rahaman N (2013) Ahmed F (2013) Treatment with ferulic acid to rats with streptozotocin-induced diabetes: effects on oxidative stress, pro-inflammatory cytokines, and apoptosis in the pancreatic β cell. Endocrine 44(2):369–379

    Article  CAS  Google Scholar 

  • Souris KC, Forbes JM (2009) Interactions between advanced glycation end-products (AGE) and their receptors in the development and progression of diabetic nephropathy are these receptors valid therapeutic targets. Curr Drug Targets 10:42–50

    Article  Google Scholar 

  • Sri Balasubashini M, Rukkumani R, Menon VP (2003) Protective effects of ferulic acid on hyperlipidemic diabetic rats. Acta Diabetol 40:118–122

  • Srinivasan M, Sudheer AR, Menon VP (2007) Ferulic acid: therapeutic potential through its antioxidant property. J Clin Biochem Nutr 40:92–100

    Article  CAS  Google Scholar 

  • Yagi K, Ohishi N (1979) Action of ferulic acid and its derivatives as antioxidants. J Nutr Sci Vitaminol (Tokyo) 25:127–130

  • Zhang ZE, Yao SD, Lin WZ, Wang WF, Jin YZ, Lin NY (1998) Mechanism of reaction of nitrogen dioxide radical with hydroxycinnamic acid derivatives: a pulse radiolysis study. Free Radic Res 29:13–16

  • Ziyadeh FN (2004) Mediators of diabetic renal disease: the case for TGF-Beta as the major mediator. J Am Soc Nephrol 15:S55–S57

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This project was funded by the Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah, under grant no (G-264-247-1443). The authors, therefore, acknowledge with thanks DSR for technical and financial support.

Funding

This project was funded by the Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah, under grant no (G-264–247-1443).

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Science, King Abdulaziz University (KAU), Jeddah, Saudi Arabia

    Maryam A. AL-Ghamdi

  2. Vitamin D Pharmacogenomics Research Group, King Abdulaziz University (KAU), Jeddah, 23623, Saudi Arabia

    Maryam A. AL-Ghamdi

  3. Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University (KAU), Jeddah, 23623, Saudi Arabia

    Maryam A. AL-Ghamdi

  4. Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt

    Said S. Moselhy

Authors
  1. Maryam A. AL-Ghamdi
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  2. Said S. Moselhy
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Contributions

RMM, SSM design protocol, RMM and SSY running experiments, All authors analyzed data, interpretations, revise manuscript and approve it for publication.

Corresponding author

Correspondence to Said S. Moselhy.

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Ethics approval

The study protocol was approved by the Ethics Committee of King Abdulaziz University Hospital, Jeddah, Saudi Arabia. The protocol was done according to the ethical guidelines of the 1975 Declaration of Helsinki.

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All authors share equally in preparation of this manuscript.

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All authors approve to publish the manuscript.

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The authors declare no competing interests.

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AL-Ghamdi, M.A., Moselhy, S.S. Inhibition of dipeptidyl peptidase-4 (DPP4), antioxidant, antiglycation and anti-inflammatory effect of Ferulic acid against streptozotocin toxicity mediate nephropathy in diabetic rats. Environ Sci Pollut Res 30, 33942–33948 (2023). https://doi.org/10.1007/s11356-022-24568-3

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