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RESEARCH PAPER
Hepato-renal protection by ferulic acid in a type 2 diabetic rat model: in vivo and in silico insights into carbohydrate metabolism, REDOX balance, and inflammation modulation
1
Department of Biochemistry, Federal University Oye-Ekiti, Ekiti State, Nigeria
2
Biomembrane, Phytomedicine, and Drug Development Unit, Department of Biochemistry, Federal University Oye-Ekiti, Ekiti State, Nigeria
3
Centre for Quality of Health and Living, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein, South Africa
4
University Medical Centre, Federal University Oye-Ekiti, Ekiti State, Nigeria
Submission date: 2024-11-27
Final revision date: 2025-04-19
Acceptance date: 2025-07-04
Corresponding author
KEYWORDS
TOPICS
Diabetes/CVDPharmaceuticsOther - medical biotechnologyProtein sequence and structure analysis and modeling
ABSTRACT
Background:
Type 2 diabetes (T2D) is a global health concern characterized by pancreatic -cell dysfunction, which disrupts multiple biochemical pathways. Consequently, treatments that target various pathways are essential. This study evaluates the hepato-renal protective effects of ferulic acid (FA) in T2D, focusing on carbohydrate metabolism, oxidative stress, and inflammation using in vivo and in silico approaches.
Material and methods:
T2D was induced in male Wistar rats using fructose and streptozotocin. After 28 days of FA treatment, biochemical analyses were performed to measure glucose, glycosylated hemoglobin, insulin, liver enzymes (ALT, AST, ALP), renal markers (creatinine, uric acid, BUN), and antioxidant status (SOD, CAT, GSH, MDA) in the liver and kidney. Pro-inflammatory markers (NF-κB-p65, IL-1β, IL-6) were evaluated in the liver and kidney. Molecular docking studies were also conducted to assess FA’s interaction with key T2D-related proteins.
Results:
FA treatment improved pancreatic β-cell function, increased insulin levels, and reduced serum glucose and glycosylated hemoglobin. Liver function, renal markers, and hepatic glycogen content improved significantly, and diabetes-induced weight loss was reversed. FA inhibited pancreatic α-amylase, intestinal α-glucosidase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase, while enhancing hexokinase activity. Notably, FA improved antioxidant status and reduced inflammatory mediators in diabetic rats. Molecular docking revealed that FA exhibits stronger binding affinity and greater inhibitory potential against key diabetes-related proteins compared to metformin.
Conclusions:
FA offers hepato-renal protection in T2D by modulating carbohydrate metabolism, oxidative stress, and inflammation, highlighting its potential as a therapeutic agent against T2D.
Type 2 diabetes (T2D) is a global health concern characterized by pancreatic -cell dysfunction, which disrupts multiple biochemical pathways. Consequently, treatments that target various pathways are essential. This study evaluates the hepato-renal protective effects of ferulic acid (FA) in T2D, focusing on carbohydrate metabolism, oxidative stress, and inflammation using in vivo and in silico approaches.
Material and methods:
T2D was induced in male Wistar rats using fructose and streptozotocin. After 28 days of FA treatment, biochemical analyses were performed to measure glucose, glycosylated hemoglobin, insulin, liver enzymes (ALT, AST, ALP), renal markers (creatinine, uric acid, BUN), and antioxidant status (SOD, CAT, GSH, MDA) in the liver and kidney. Pro-inflammatory markers (NF-κB-p65, IL-1β, IL-6) were evaluated in the liver and kidney. Molecular docking studies were also conducted to assess FA’s interaction with key T2D-related proteins.
Results:
FA treatment improved pancreatic β-cell function, increased insulin levels, and reduced serum glucose and glycosylated hemoglobin. Liver function, renal markers, and hepatic glycogen content improved significantly, and diabetes-induced weight loss was reversed. FA inhibited pancreatic α-amylase, intestinal α-glucosidase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase, while enhancing hexokinase activity. Notably, FA improved antioxidant status and reduced inflammatory mediators in diabetic rats. Molecular docking revealed that FA exhibits stronger binding affinity and greater inhibitory potential against key diabetes-related proteins compared to metformin.
Conclusions:
FA offers hepato-renal protection in T2D by modulating carbohydrate metabolism, oxidative stress, and inflammation, highlighting its potential as a therapeutic agent against T2D.
REFERENCES (45)
1.
Adeyi OE, Somade OT, Ajayi BO, James AS, Adeboye TR, Olufemi DA, Oyinlola EV, Sanyaolu ET, Mufutau IO. 2023. The anti-inflammatory effect of ferulic acid is via the modulation of nfb-tnf--il-6 and STAT1-PIAS1 signaling pathways in 2-methoxyethanol-induced testicular inflammation in rats. Phytomed Plus. 3: 100464.
2.
Alqahtani SAM, Awan ZA, Alasmary MY, Al Amoudi SM. 2022. Association between serum uric acid with diabetes and other biochemical markers. J Fam Med Prim Care. 11: 1401-1409.
3.
Baginski ES, Foà PP, Zak B. 1974. Glucose-6-phosphatase. In: Bergmeyer HU (ed.). Methods of Enzymatic Analalysis. Vol. 3. Elsevier. pp. 876–880.
4.
Beers RF, Sizer IW. 1952. A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Biol Chem. 195(1): 133–140.
5.
Braithwaite SS, Palazuk B, Colca JR, Edwards CW III, Hofmann C. 1995. Reduced expression of hexokinase II in insulin-resistant diabetes. Diabetes. 44(1): 43–48.
6.
Brandstrup N, Kirk J, Bruni C. 1957. Determination of hexokinase in tissues. J Gerontol. 1957; 12(2): 166–171.
7.
Ceriello A. 2003. New insights on oxidative stress and diabetic complications may lead to a “causal” antioxidant therapy. Diabetes Care. 26(5): 1589–1596.
8.
Chaachouay N, Zidane L. 2024. Plant-derived natural products: a source for drug discovery and development. Drugs Drug Candidates. 3(1): 184–207.
9.
Chowdhury S, Ghosh S, Das AK, Sil PC. 2019. Ferulic acid protects hyperglycemia-induced kidney damage by regulating oxidative insult, inflammation, and autophagy. Front Pharmacol. 10: 27.
10.
Dab H, Ben Hamed S, Hodroj W, Zourgui L. 2023. Combined diabetes and chronic stress exacerbates cytokine production and oxidative stress in rat liver and kidney. Biotechnol Biotechnol Equip. 37(1): 250–259.
11.
Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, Ostolaza H, Martín C. 2020. Pathophysiology of type 2 diabetes mellitus. Int J Mol Sci. 21(17): 6275.
12.
Gancedo JM, Gancedo C. 1971. Fructose-1,6-diphosphatase, phosphofructokinase and glucose-6-phosphate dehydrogenase from fermenting and non-fermenting yeasts. Arch Mikrobiol. 76: 132–138.
13.
Gong L, Feng D, Wang T, Ren Y, Liu Y, Wang J. 2020. Inhibitors of -amylase and -glucosidase: Potential linkage for whole cereal foods on prevention of hyperglycemia. Food Sci Nutr. 8(12): 6320–6337.
14.
González P, Lozano P, Ros G, Solano F. 2023. Hyperglycemia and oxidative stress: an integral, updated and critical overview of their metabolic interconnections. Int J Mol Sci. 24(11): 9352.
15.
Gornall AG, Bardawill CJ, David MM. 1949. Determination of serum proteins by means of the biuret reaction. J Biol Chem. 177(2): 751–766.
16.
Hano C, Tungmunnithum D. 2020. Plant polyphenols, more than just simple natural antioxidants: Oxidative stress, aging and age-related diseases. Medicines (Basel). 7(5): 26. https://doi.org/ 10.3390/medicines7050026.
17.
Hatting M, Tavares CD, Sharabi K, Rines AK, Puigserver P. 2018. Insulin regulation of gluconeogenesis. Ann N Y Acad Sci. 1411(1): 21–35.
18.
Jiang S, Young JL, Wang K, Qian Y, Cai L. 2020. Diabetic- induced alterations in hepatic glucose and lipid metabolism: the role of type 1 and type 2 diabetes mellitus. Mol Med Rep. 22(2): 603–611.
19.
Kanwal A, Kanwar N, Bharati S, Srivastava P, Singh SP, Amar S. 2022. Exploring new drug targets for type 2 diabetes: Success, challenges and opportunities. Biomedicines. 10(2): 331.
20.
Keane KN, Cruzat VF, Carlessi R, de Bittencourt PIH Jr, Newsholme P. 2015. Molecular events linking oxidative stress and inflammation to insulin resistance and -cell dysfunction. Oxid Med Cell Longev. 2015(1): 181643.
21.
Kumar R, Saha P, Kumar Y, Sahana S, Dubey A, Prakash O. 2020. A review on diabetes mellitus: type 1 & type 2. World J Pharm Pharm Sci. 9(10): 838–850.
22.
Li XY, Chow CK. 1994. An improved method for the measurement of malondialdehyde in biological samples. Lipids. 29(1): 73–75.
23.
Liu Y, Shi L, Qiu W, Shi Y. 2022. Ferulic acid exhibits anti-inflammatory effects by inducing autophagy and blocking NLRP3 inflammasome activation. Mol Cell Toxicol. 18(4): 509–519.
24.
Misra HP, Fridovich I. 1972. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem. 247(10): 3170–3175.
25.
Muhammed MT, Aki-Yalcin E. 2024. Molecular docking: Principles, advances, and its applications in drug discovery. Lett Drug Des Discov. 21(3): 480–495.
26.
Ndrepepa G. 2019. Myeloperoxidase – a bridge linking inflammation and oxidative stress with cardiovascular disease. Clin Chim Acta. 493: 36–51.
27.
Owens C, Belcher R. 1965. A colorimetric micro-method for the determination of glutathione. Biochem J. 94(3): 705.
28.
Pandi A, Raghu MH, Chandrashekar N, Kalappan V.M. 2022. Cardioprotective effects of ferulic acid against various drugs and toxic agents. Beni-Suef Univ J Basic Appl Sci. 11(1): 92.
29.
Park JE, Han JS. 2024. Improving the effect of ferulic acid on inflammation and insulin resistance by regulating the JNK/ERK and NF-B pathways in TNF--treated 3T3-L1 adipocytes. Nutrients. 16(2): 294.
30.
Passonneau J, Lauderdale V. 1974. A comparison of three methods of glycogen measurement in tissues. Anal Biochem. 60(2): 405–412.
31.
Plowman TJ, Shah MH, Fernandez E, Christensen H, Aiges M, Ramana KV. 2023. Role of innate immune and inflammatory responses in the development of secondary diabetic complications. Curr Mol Med. 23(9): 901–920.
32.
Quaile MP, Melich DH, Jordan HL, Nold JB, Chism JP, Polli JW, Smith GA, Rhodes MC. 2010. Toxicity and toxicokinetics of metformin in rats. Toxicol Appl Pharmacol. 243(3): 340–347.
33.
Rasch R, Mogensen C. 1980. Urinary excretion of albumin and total protein in normal and streptozotocin diabetic rats. Eur J Endocrinol. 95(3): 376–381.
34.
Reitman S, Frankel S. 1957. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol. 28(1): 56–63.
35.
Roy S, Metya SK, Sannigrahi S, Rahaman N, 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 cell. Endocrine. 44: 369–379.
36.
Salau VF, Erukainure OL, Olofinsan KO, Bharuth V, Ijomo-ne OM, Islam MS. 2023. Ferulic acid improves glucose homeostasis by modulation of key diabetogenic activities and restoration of pancreatic architecture in diabetic rats. Fundam Clin Pharmacol. 37(2): 324–339.
37.
Serasanambati M, Chilakapati SR. 2016. Function of nuclear factor kappa B (NF-B) in human diseases — a review. South Indian J Biol Sci. 2(4): 368–387.
38.
Sies H, Belousov VV, Chandel NS, Davies MJ, Jones DP, Mann GE, Murphy MP, Yamamoto M, Winterbourn C. 2022. Defining roles of specific reactive oxygen species (ROS) in cell biology and physiology. Nat Rev Mol Cell Biol. 23(7): 499–515.
39.
Stumvoll M, Goldstein BJ, Van Haeften TW. 2005. Type 2 diabetes: Principles of pathogenesis and therapy. Lancet. 365(9467): 1333–1346.
40.
Tanase DM, Gosav EM, Costea CF, Ciocoiu M, Lacatusu CM, Maranduca MA, Ouatu A, Floria M. 2020. The intricate relationship between type 2 diabetes mellitus (T2DM), insulin resistance (IR), and nonalcoholic fatty liver disease (NAFLD). J Diabetes Res. 2020(1): 3920196.
41.
Teli DM, Gajjar AK. 2023. Glycogen synthase kinase-3: A potential target for diabetes. Bioorg Med Chem. 117406.
42.
Vasbinder A, Anderson E, Shadid H, Berlin H, Pan M, Azam TU, Khaleel I, Padalia K, Meloche C, O’Hayer P. 2022. Inflammation, hyperglycemia, and adverse outcomes in individuals with diabetes mellitus hospitalized for COVID-19. Diabetes Care. 45(3): 692–700.
43.
Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, Heer FT, de Beer TAP, Rempfer C, Bor- doli L. 2018. SWISS-MODEL: Homology modelling of protein structures and complexes. Nucleic Acids Res. 46(W1): W296–W303.
44.
Wilson RD, Islam MS. 2012. Fructose-fed streptozotocin- injected rat: An alternative model for type 2 diabetes. Pharmacol Rep. 64(1): 129–139.
45.
Zeng Z, Xiao G, Liu Y, Wu M, Wei X, Xie C, Wu G, Jia D, Li Y, Li S. 2024. Metabolomics and network pharmacology reveal partial insights into the hypolipidemic mechanisms of ferulic acid in a dyslipidemia mouse model. Front Pharmacol. 15: 1466114.
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