Polyphenol harmony: Ferulic acid and protocatechuic acid combination attenuates diabetic nephropathy in Sprague-Dawley rats
Abstract
Diabetic nephropathy (DN) is an alarming consequence of diabetes mellitus, characterized by progressive kidney dysfunction and damage. Despite advancements in diabetes management, the prevalence of DN remains a significant concern. Natural compounds such as ferulic acid (FA) and protocatechuic acid (PCA) have shown potential in ameliorating diabetic complications. This research paper investigates the individual and combined effects of FA and PCA in an experimental model of DN in rats. Male rats were assigned into five groups: Control, Diabetic control, FA-treated (100 mg/kg, p.o.), PCA-treated (100 mg/kg, p.o.), and FA + PCA-treated groups. Diabetes was induced by streptozotocin injection (55 mg/kg, i.p.), and the treatment groups received oral administration of FA, PCA, or their combination for eight weeks. Renal function, oxidative stress markers, and histopathological changes were assessed at the end of the study. The diabetic control group exhibited impaired renal function, increased oxidative stress, and histological abnormalities in the kidney tissues. Treatment with FA, PCA, and FA + PCA significantly improved renal function, as evidenced by reduced serum creatinine, cystatin C, blood urea nitrogen, and urine albumin levels. Moreover, these treatments led to a decline in oxidative stress markers and restoration of antioxidant enzyme activities. The combination of FA and PCA showed a synergistic effect, demonstrating a more pronounced improvement in renal parameters and histological changes compared to individual treatments. These findings highlight the potential renoprotective effects of FA and PCA in diabetic nephropathy.
Keywords
Diabetic nephropathy ferulic acid protocatechuic acid streptozotocin renal function oxidative stress
References
- [1] Mahajan M., Upaganlawar A, Upasani C. Nephroprotective Effect of coenzyme Q10 alone and in combination with N-acetylcysteine in diabetic nephropathy. Eur Pharm J. 2021; 68(1): 30-39. https://doi.org/10.2478/afpuc-2020-0020.
- [2] Gembillo G, Ingrasciotta Y, Crisafulli S, Luxi N, Siligato R, Santoro D, Trifirò G. Kidney Disease in diabetic patients: From pathophysiology to pharmacological aspects with a focus on therapeutic ınertia. Int J Mol Sci. 2021; 22(9): 4824. https://doi.org/10.3390/ijms22094824
- [3] Gheith O, Farouk N, Nampoory N, Halim MA, Al-Otaibi T. Diabetic kidney disease: world wide difference of prevalence and risk factors. J Nephropharmacol. 2015;5(1):49-56.
- [4] Wang G, Ouyang J, Li S, Wang H, Lian B, Liu Z, Xie L. The analysis of risk factors for diabetic nephropathy progression and the construction of a prognostic database for chronic kidney diseases. J Transl Med. 2019; 17(1): 264. https://doi.org/10.1186/s12967-019-2016-y
- [5] Mahajan M, Gulecha V, Upaganlawar A, Upasani C. Antioxidant Defense in Diabetic Nephropathy In: Uddin S, Upaganlawar A. (Eds). Oxidative Stress and Antioxidant Defense: Biomedical value in Health and Diseases, Nova Science Publishers, Inc., New York, 2019, pp. 427-463.
- [6] Arora MK, Singh UK. Molecular mechanisms in the pathogenesis of diabetic nephropathy: An update. Vasc Pharmacol. 2013; 58(4):259-271. https://doi.org/10.1016/j.vph.2013.01.001
- [7] Rossing P, Persson F, Frimodt-Møller M. Prognosis and treatment of diabetic nephropathy: Recent advances and perspectives. Nephrol Ther. 2018; 14: S31-37. https://doi.org/10.1016/j.nephro.2018.02.007
- [8] Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001; 414(6865): 813-820. https://doi.org/10.1038/414813a
- [9] Srinivasan M, Sudheer AR, Menon VP. Ferulic acid: therapeutic potential through its antioxidant property. J Clin Biochem Nutr. 2007; 40(2): 92-100. https://doi.org/10.3164/jcbn.40.92
- [10] Harini R, Pugalendi KV. Antioxidant and antihyperlipidaemic activity of protocatechuic acid on streptozotocin diabetic rats. Redox Report. 2010; 15(2): 71-80. https://doi.org/10.1179/174329210X12650506623285
- [11] Ling W, Huang Y, Huang YM, Fan RR, Sui Y, Zhao HL. Global trend of diabetes mortality attributed to vascular complications, 2000–2016. Cardiovasc Diabetol. 2020;19(1):182. https://doi.org/10.1186/s12933-020-01159-5
- [12] Agrawal N, Sadhukhan P, Saha S, Sil PC. Therapeutic insights against oxidative stress induced diabetic nephropathy: A review. J Autoimmun Disod. 2015;1:1. https://doi.org/10.21767/2471-8513.100002.
- [13] Tesch GH, Allen TJ. Rodent models of streptozotocin-induced diabetic nephropathy. Nephrology (Carlton). 2007;12(3):261-266. https://doi.org/10.1111/j.1440-1797.2007.00796.x
- [14] Kelly DJ, Zhang Y, Hepper C, Gow RM, Jaworski K, Kemp BE, Wilkinson-Berka JL, Gilbert RE. Protein kinase C β inhibition attenuates the progression of experimental diabetic nephropathy in the presence of continued hypertension. Diabetes. 2003;52(2):512-518. https://doi.org/10.2337/diabetes.52.2.512
- [15] Chowdhury S, Ghosh S, Das AK, Sil PC. Ferulic acid protects hyperglycemia-induced kidney damage by regulating oxidative insult, inflammation and autophagy. Front Pharmacol. 2019; 10:27. https://doi.org/10.3389/fphar.2019.00027
- [16] Chowdhury S, Ghosh S, Rashid K, Sil PC. Deciphering the role of ferulic acid against streptozotocin-induced cellular stress in the cardiac tissue of diabetic rats. Food Chem Toxicol. 2016;97:187-198. https://doi.org/10.1016/j.fct.2016.09.011
- [17] Zhang S, Gai Z, Gui T, Chen J, Chen Q, Li Y. Antioxidant Effects of protocatechuic acid and protocatechuic aldehyde: Old wine in a new bottle. Evid Based Complement Alternat Med. 2021; 8:6139308. https://doi.org/10.1155/2021/6139308.
- [18] Kakkar S, Bais S. A review on protocatechuic Acid and its pharmacological potential. ISRN Pharmacol. 2014;2014:952943. https://doi.org/10.1155/2014/952943
- [19] Kim BH, Lee ES, Choi R, Nawaboot J, Lee MY, Lee EY, Kim HS, Chung CH. Protective effects of curcumin on renal oxidative stress and lipid metabolism in a rat model of type 2 diabetic nephropathy. Yonsei Med J. 2016; 57(3):664-673. http://dx.doi.org/10.3349/ymj.2016.57.3.664
- [20] Serina JJ, Castilho PC. Using polyphenols as a relevant therapy to diabetes and its complications, a review. Crit Rev Food Sci Nutr. 2022 ;62(30):8355-8387. https://10.1080/10408398.2021.1927977
- [21] Sun C, Zhao C, Guven EC, Paoli P, Simal‐Gandara J, Ramkumar KM, Wang S, Buleu F, Pah A, Turi V, Damian G. Dietary polyphenols as antidiabetic agents: Advances and opportunities. Food Front. 2020; 1(1):18-44. https://doi.org/10.1002/fft2.15
- [22] Qi MY, Wang XT, Xu HL, Yang ZL, Cheng Y, Zhou B. Protective effect of ferulic acid on STZ-induced diabetic nephropathy in rats. Food & Function. 2020;11(4):3706-3718. https://doi.org/10.1039/C9FO02398D
- [23] Bhattacharjee N, Dua TK, Khanra R, Joardar S, Nandy A, Saha A, De Feo V, Dewanjee S. Protocatechuic acid, a phenolic from Sansevieria roxburghiana leaves, suppresses diabetic cardiomyopathy via stimulating glucose metabolism, ameliorating oxidative stress, and inhibiting inflammation. Front Pharmacol. 2017; 8(8):251. https://doi.org/10.3389/fphar.2017.00251
Details
| Primary Language | English |
|---|---|
| Subjects | Medical Pharmacology |
| Journal Section | Articles |
| Authors | |
| Publication Date | June 28, 2025 |
| Published in Issue | Year 2024 Volume: 28 Issue: 5 |