Antihypertensive Effect of Rice Bran Derived Amino Acids Through Modulation of iNOS Expression and Renal Histopathology in DOCA Salt Induced Hypertensive Rats
DOI:
10.29303/jppipa.v12i1.13491Published:
2026-01-31Downloads
Abstract
Hypertension is a major global health concern and a leading risk factor for cardiovascular mortality. Conventional treatment with ACE inhibitors like captopril is effective but often causes adverse effects including cough, dizziness, and renal impairment. This study evaluated the antihypertensive effects of rice bran in DOCA-salt-induced hypertensive rats. In vitro analysis revealed 45.58% soluble fiber and rich amino acid content, including 2.121 mg L-Arginine, a nitric oxide precursor promoting vasodilation. Male Wistar rats were divided into five groups: negative control, positive control, captopril treatment (5 mg/kg BW), and rice bran supplementation at 1% and 2% of 25 g feed. The 2% rice bran group significantly (p < 0.05) reduced renal iNOS expression by 88.32% compared to hypertensive controls, surpassing captopril's 22.96% reduction. Histopathological examination revealed notable renal protection with complete absence of fatty degeneration and minimal glomerular inflammation in the 2% rice bran group. These findings demonstrate potent antihypertensive activity through ACE inhibition, enhanced nitric oxide bioavailability, and mitigation of oxidative and inflammatory stress, establishing rice bran as a promising natural therapeutic alternative for hypertension management
Keywords:
ACE inhibitor DOCA-salt Histopathology Hypertension iNOSReferences
Altaleb, A., & Rajab, S. H. (2021). The type of interstitial inflammatory cell infiltrate and the severity of glomerular injury; an underestimated morphologic correlation. Journal of Nephropathology, 10(3), e30–e30. https://doi.org/10.34172/jnp.2021.30
Andrabi, S. M., Sharma, N. S., Karan, A., Shahriar, S. M. S., Cordon, B., Ma, B., & Xie, J. (2023). Nitric Oxide: Physiological Functions, Delivery, and Biomedical Applications. Advanced Science, 10(30), 2303259. https://doi.org/10.1002/advs.202303259
Arendshorst, W. J., Vendrov, A. E., Kumar, N., Ganesh, S. K., & Madamanchi, N. R. (2024). Oxidative Stress in Kidney Injury and Hypertension. Antioxidants, 13(12), 1454. https://doi.org/10.3390/antiox13121454
Bryan, N. S. (2022). Nitric oxide deficiency is a primary driver of hypertension. Biochemical Pharmacology, 206, 115325. https://doi.org/10.1016/j.bcp.2022.115325
Burnier, M., & Egan, B. M. (2019). Adherence in Hypertension: A Review of Prevalence, Risk Factors, Impact, and Management. Circulation Research, 124(7), 1124–1140. https://doi.org/10.1161/CIRCRESAHA.118.313220
Carey, R. M., Calhoun, D. A., Bakris, G. L., Brook, R. D., Daugherty, S. L., Dennison-Himmelfarb, C. R., Egan, B. M., Flack, J. M., Gidding, S. S., Judd, E., Lackland, D. T., Laffer, C. L., Newton-Cheh, C., Smith, S. M., Taler, S. J., Textor, S. C., Turan, T. N., White, W. B., & on behalf of the American Heart Association Professional/Public Education and Publications Committee of the Council on Hypertension; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Genomic and Precision Medicine; Council on Peripheral Vascular Disease; Council on Quality of Care and Outcomes Research; and Stroke Council. (2018). Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association. Hypertension, 72(5). https://doi.org/10.1161/HYP.0000000000000084
Cohen, A. H., & Schrier, R. W. (Eds.). (1999). Atlas of diseases of the kidney. 2 / Volume editors: Arthur H. Cohen .̤ with 12 contributors. Current Medicine.
Daehn, I. S., & Duffield, J. S. (2021). The glomerular filtration barrier: A structural target for novel kidney therapies. Nature Reviews Drug Discovery, 20(10), 770–788. https://doi.org/10.1038/s41573-021-00242-0
Dang, T. T., & Vasanthan, T. (2019). Modification of rice bran dietary fiber concentrates using enzyme and extrusion cooking. Food Hydrocolloids, 89, 773–782. https://doi.org/10.1016/j.foodhyd.2018.11.024
Griendling, K. K., Camargo, L. L., Rios, F. J., Alves-Lopes, R., Montezano, A. C., & Touyz, R. M. (2021). Oxidative Stress and Hypertension. Circulation Research, 128(7), 993–1020. https://doi.org/10.1161/CIRCRESAHA.121.318063
Hanif, M. O., Rout, P., & Ramphul, K. (2025). Acute Renal Tubular Necrosis. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK507815/
Haraldsson, B., Nyström, J., & Deen, W. M. (2008). Properties of the Glomerular Barrier and Mechanisms of Proteinuria. Physiological Reviews, 88(2), 451–487. https://doi.org/10.1152/physrev.00055.2006
Henderson, A. J., Ollila, C. A., Kumar, A., Borresen, E. C., Raina, K., Agarwal, R., & Ryan, E. P. (2012). Chemopreventive Properties of Dietary Rice Bran: Current Status and Future Prospects. Advances in Nutrition, 3(5), 643–653. https://doi.org/10.3945/an.112.002303
Husain, M. J., Datta, B. K., Kostova, D., Joseph, K. T., Asma, S., Richter, P., Jaffe, M. G., & Kishore, S. P. (2020). Access to Cardiovascular Disease and Hypertension Medicines in Developing Countries: An Analysis of Essential Medicine Lists, Price, Availability, and Affordability. Journal of the American Heart Association, 9(9), e015302. https://doi.org/10.1161/JAHA.119.015302
Husain, S. (2024). Role of Podocyte in Kidney Disease. Frontiers in Bioscience-Landmark, 29(7), 250. https://doi.org/10.31083/j.fbl2907250
Ivanovska, I. L., Tobin, M. P., Bai, T., Dooling, L. J., & Discher, D. E. (2023). Small lipid droplets are rigid enough to indent a nucleus, dilute the lamina, and cause rupture. Journal of Cell Biology, 222(8), e202208123. https://doi.org/10.1083/jcb.202208123
Joyce, E., Glasner, P., Ranganathan, S., & Swiatecka-Urban, A. (2017). Tubulointerstitial nephritis: Diagnosis, treatment, and monitoring. Pediatric Nephrology, 32(4), 577–587. https://doi.org/10.1007/s00467-016-3394-5
Konstantinidi, M., & Koutelidakis, A. E. (2019). Functional Foods and Bioactive Compounds: A Review of Its Possible Role on Weight Management and Obesity’s Metabolic Consequences. Medicines, 6(3), 94. https://doi.org/10.3390/medicines6030094
Lee, J., Bae, E. H., Ma, S. K., & Kim, S. W. (2016). Altered Nitric Oxide System in Cardiovascular and Renal Diseases. Chonnam Medical Journal, 52(2), 81. https://doi.org/10.4068/cmj.2016.52.2.81
Li, G., Li, Z., & Liu, J. (2024). Amino acids regulating skeletal muscle metabolism: Mechanisms of action, physical training dosage recommendations and adverse effects. Nutrition & Metabolism, 21(1), 41. https://doi.org/10.1186/s12986-024-00820-0
Li, X. C., Zhang, J., & Zhuo, J. L. (2017). The vasoprotective axes of the renin-angiotensin system: Physiological relevance and therapeutic implications in cardiovascular, hypertensive and kidney diseases. Pharmacological Research, 125, 21–38. https://doi.org/10.1016/j.phrs.2017.06.005
Mahalak, K. K., Liu, L., Bobokalonov, J., Narrowe, A. B., Firrman, J., Bittinger, K., Hu, W., Jones, S. M., & Moustafa, A. M. (2024). Supplementation with soluble or insoluble rice-bran fibers increases short-chain fatty acid producing bacteria in the gut microbiota in vitro. Frontiers in Nutrition, 11, 1304045. https://doi.org/10.3389/fnut.2024.1304045
Martinez Valenzuela, L., Draibe, J., Fulladosa, X., & Torras, J. (2020). New Biomarkers in Acute Tubulointerstitial Nephritis: A Novel Approach to a Classic Condition. International Journal of Molecular Sciences, 21(13), 4690. https://doi.org/10.3390/ijms21134690
Messerli, F. H., Bangalore, S., Bavishi, C., & Rimoldi, S. F. (2018). Angiotensin-Converting Enzyme Inhibitors in Hypertension. Journal of the American College of Cardiology, 71(13), 1474–1482. https://doi.org/10.1016/j.jacc.2018.01.058
Norlander, A. E., Madhur, M. S., & Harrison, D. G. (2018). The immunology of hypertension. Journal of Experimental Medicine, 215(1), Article 1. https://doi.org/10.1084/jem.20171773
Nurmahdi, H., Prasetyawan, S., Wenno, M. R., & Aulann’am, A. (2017). Antihypertension Effect from Bakasang’s Peptide Extract Based on MDA Levels in Sera and iNOS Expression in Cardiac Tissue of Rats Hypertensive Model. International Journal of Pharmaceutical and Clinical Research, 9(2), Article 2. https://doi.org/10.25258/ijpcr.v9i2.8295
Pannangpetch, P., Tangsucharit, P., Thanaruksa, R., Proongkhong, T., Srisuwan, S., & Aekthammarat, D. (2022). Antihypertensive effect of Mali-Nil surin rice bran hydrolysate and its mechanisms related to the EDHF-mediated vasorelaxation and L-type Ca2+ channel-mediated vasoconstriction in L-NAME hypertensive rats. Biomedicine & Pharmacotherapy, 150, 113003. https://doi.org/10.1016/j.biopha.2022.113003
Poitou-Verkinder, A.-L., Francois, A., Drieux, F., Lepretre, S., Legallicier, B., Moulin, B., Godin, M., & Guerrot, D. (2015). The Spectrum of Kidney Pathology in B-Cell Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma: A 25-Year Multicenter Experience. PLOS ONE, 10(3), e0119156. https://doi.org/10.1371/journal.pone.0119156
Pollak, M. R., Quaggin, S. E., Hoenig, M. P., & Dworkin, L. D. (2014). The Glomerulus: The Sphere of Influence. Clinical Journal of the American Society of Nephrology, 9(8), 1461–1469. https://doi.org/10.2215/CJN.09400913
Radi, R. (2018). Oxygen radicals, nitric oxide, and peroxynitrite: Redox pathways in molecular medicine. Proceedings of the National Academy of Sciences, 115(23), 5839–5848. https://doi.org/10.1073/pnas.1804932115
Rashid, H., Jali, A., Akhter, M. S., & Abdi, S. A. H. (2023). Molecular Mechanisms of Oxidative Stress in Acute Kidney Injury: Targeting the Loci by Resveratrol. International Journal of Molecular Sciences, 25(1), 3. https://doi.org/10.3390/ijms25010003
Ray, S. C., Mason, J., & O’Connor, P. M. (2019). Ischemic Renal Injury: Can Renal Anatomy and Associated Vascular Congestion Explain Why the Medulla and Not the Cortex Is Where the Trouble Starts? Seminars in Nephrology, 39(6), 520–529. https://doi.org/10.1016/j.semnephrol.2019.10.002
Riyadi, P. H., Tanod, W. A., Sulistiyati, D. T., Aulanni’am, A., & Suprayitno, E. (2020). Effects of Nile Tilapia (Oreochromis niloticus) Viscera Hydrolyzate on Blood Pressure, TNF-α and IL-6 Expression in Rats (Rattus norvegicus) Induced by DOCA-Salt. Indian Journal of Animal Research, Of. https://doi.org/10.18805/ijar.b-1195
Sun, D., Wang, J., Shao, W., Wang, J., Yao, L., Li, Z., & Ohno, S. (2020). Pathogenesis and damage targets of hypertensive kidney injury. Journal of Translational Internal Medicine, 8(4), 205–209. https://doi.org/10.2478/jtim-2020-0033
Valentini, A., Heilmann, R. M., Kühne, A., Biagini, L., De Bellis, D., & Rossi, G. (2025). The Renin–Angiotensin–Aldosterone System (RAAS): Beyond Cardiovascular Regulation. Veterinary Sciences, 12(8), 777. https://doi.org/10.3390/vetsci12080777
Vernier, I. C. S., Neres-Santos, R. S., Andrade-Oliveira, V., & Carneiro-Ramos, M. S. (2023). Immune Cells Are Differentially Modulated in the Heart and the Kidney during the Development of Cardiorenal Syndrome 3. Cells, 12(4), 605. https://doi.org/10.3390/cells12040605
Vn, Dr. V., & Vn, Dr. K. (2021). A study on correlates of chronic kidney disease. International Journal of Advanced Research in Medicine, 3(1), Article 1. https://doi.org/10.22271/27069567.2021.v3.i1d.144
Whelton, P. K., Carey, R. M., Aronow, W. S., Casey, D. E., Collins, K. J., Dennison Himmelfarb, C., DePalma, S. M., Gidding, S., Jamerson, K. A., Jones, D. W., MacLaughlin, E. J., Muntner, P., Ovbiagele, B., Smith, S. C., Spencer, C. C., Stafford, R. S., Taler, S. J., Thomas, R. J., Williams, K. A., … Wright, J. T. (2018). 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. Journal of the American College of Cardiology, 71(19), e127–e248. https://doi.org/10.1016/j.jacc.2017.11.006
Williams, B., Mancia, G., Spiering, W., Agabiti Rosei, E., Azizi, M., Burnier, M., Clement, D. L., Coca, A., De Simone, G., Dominiczak, A., Kahan, T., Mahfoud, F., Redon, J., Ruilope, L., Zanchetti, A., Kerins, M., Kjeldsen, S. E., Kreutz, R., Laurent, S., … Brady, A. (2018). 2018 ESC/ESH Guidelines for the management of arterial hypertension. European Heart Journal, 39(33), 3021–3104. https://doi.org/10.1093/eurheartj/ehy339
Wu, Y., Xu, H., Tu, X., & Gao, Z. (2021). The Role of Short-Chain Fatty Acids of Gut Microbiota Origin in Hypertension. Frontiers in Microbiology, 12, 730809. https://doi.org/10.3389/fmicb.2021.730809
Xu, Z., Yang, S., Tan, Y., Zhang, Q., Wang, H., Tao, J., Liu, Q., Wang, Q., Feng, W., Li, Z., Wang, C., & Cui, L. (2025). Inflammation in cardiovascular-kidney-metabolic syndrome: Key roles and underlying mechanisms–a comprehensive review. Molecular and Cellular Biochemistry, 480(12), 6039–6075. https://doi.org/10.1007/s11010-025-05379-9
Zhang, C., Fang, X., Zhang, H., Gao, W., Hsu, H. J., Roman, R. J., & Fan, F. (2021). Genetic susceptibility of hypertension‐induced kidney disease. Physiological Reports, 9(1). https://doi.org/10.14814/phy2.14688
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