CHLOROGENIC ACID FROM SARGASSUM ILICIFOLIUM ATTENUATES CHEMOTHERAPYINDUCED NEPHROTOXICITY THROUGH SIRT1 ACTIVATION
DOI:
https://doi.org/10.22159/ajpcr.2026v19i4.56942Keywords:
sargassum ilicifolium, nephroprotection, SIRT1, Chlorogenic acidAbstract
Objectives: The present study aimed to evaluate the nephroprotective potential of Sargassum ilicifolium extract against cyclophosphamide (CPM) drug-induced kidney injury using integrated in vitro, in silico, and in vivo approaches, with emphasis on sirtuin 1 (SIRT1)-mediated mechanisms.
Methods: The ethanolic extract of S. ilicifolium was characterized using ultraviolet-visible spectroscopy, Fourier transform infrared, nuclear magnetic resonance, and liquid chromatography-mass spectrometry (LC-MS) analyses. Cytotoxicity and SIRT1 expression were assessed by SIRT1 assay in HK-2 cells, supported by molecular docking studies of chlorogenic acid (CGA) with SIRT1. Acute oral toxicity and nephroprotective efficacy were evaluated in cyclophosphamide-induced renal injury in rats through biochemical and histopathological analyses.
Results: LC-MS analysis revealed diverse phytochemicals, with CGA identified as the major constituent (m/z 354.31, retention time 4.5 min). CGA exhibited low cytotoxicity (IC50=237.6 μg/mL) and significantly restored SIRT1 expression in HK-2 cells. Docking studies showed favorable binding with SIRT1 (–5.85 kcal/mol). In vivo, cyclophosphamide markedly elevated serum creatinine (1.57±0.085 mg/dL), uric acid (5.95±0.267 mg/dL), and urea (98.23±3.549 mg/dL), whereas treatment with S. ilicifolium (400 mg/kg) normalized these biomarkers (~0.56 mg/dL creatinine, ~2.0 mg/dL uric acid, ~28–29 mg/dL urea) and preserved renal histoarchitecture. Cyclophosphamide induced electrolyte imbalance and renal tubular dysfunction in rats, whereas treatment with S. ilicifolium extract restored sodium (144.57±3.459 mmol/L) and chloride (101.22±0.465 mmol/L) levels and shifted potassium and calcium closer to the normal range, indicating renoprotective activity. All data were tested for statistical significance at **p<0.01 and ***p<0.001 versus the negative control.
Conclusion: S. ilicifolium extract exhibited significant nephroprotective activity through SIRT1 upregulation, biochemical normalization, and renal tissue preservation, supporting its potential as a natural therapeutic candidate for drug-induced kidney damage.
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References
1. Lewington AJ, Cerdá J, Mehta RL. Raising awareness of acute kidney injury: A global perspective of a silent killer. Kidney Int. 2013;84(3):457-67. doi: 10.1038/ki.2013.153, PMID 23636171
2. Mehta RL, Cerdá J, Burdmann EA, Tonelli M, García-García G, Jha V. International Society of Nephrology’s 0by25 initiative for acute kidney injury (zero preventable deaths by 2025): A human rights case for nephrology. Lancet. 2015;385(9987):2616-43. doi: 10.1016/s0140- 6736(15)60126-x, PMID 25777661
3. Chawla LS, Bellomo R, Bihorac A, Goldstein SL, Siew ED, Bagshaw SM. Acute kidney disease and renal recovery: Consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup. Nat Rev Nephrol. 2017;13(4):241-57. doi: 10.1038/nrneph.2017.2, PMID 28239173
4. Levey AS. Defining AKD: The spectrum of AKI, AKD, and CKD. Nephron. 2022;146(3):302-5. doi: 10.1159/000516647, PMID 34167119
5. He W, Wang Y, Zhang MZ, You L, Davis LS, Fan H. Sirt1 activation protects the mouse renal medulla from oxidative injury. J Clin Invest. 2010 Apr 01;120(4):1056-68. doi: 10.1172/jci41563
6. Kitada M, Kume S, Takeda-Watanabe A, Kanasaki K, Koya D. Sirtuins and renal diseases: Relationship with aging and diabetic nephropathy. Clin Sci (Lond). 2013 Feb 01;124(3):153-64. doi: 10.1042/cs20120190
7. Chen HH, Zhang YX, Lv JL, Liu YY, Guo JY, Zhao L. Role of sirtuins in metabolic disease-related renal injury. Biomed Pharmacother. 2023 May 1;161:114417. doi: 10.1016/j.biopha.2023.114417
8. Kume S, Haneda M, Koya D. SIRT1 in renal disease: Mechanisms and therapeutic potential. J Mol Med. 2012;90(8):907-15.
9. Hasegawa K, Wakino S, Yoshioka K, Tatematsu S, Hara Y, Minakuchi H. Kidney-specific overexpression of Sirt1 protects against acute kidney injury by retaining peroxisome function. J Biol Chem. 2010;285(17):13045-56. doi: 10.1074/jbc.M109.067728, PMID 20139070
10. Morigi M, Perico L, Benigni A. Sirtuins in renal health and disease. J Am Soc Nephrol. 2018;29(7):1799-809. doi: 10.1681/asn.2017111218, PMID 29712732
11. Gao LI, Zhong X, Jin J, Li J, Meng XM. Potential targeted therapy and diagnosis based on novel insight into growth factors, receptors, and downstream effectors in acute kidney injury and acute kidney injury-chronic kidney disease progression. Signal Transduct Target Ther. 2020 Feb 14;5(1):9. doi: 10.1038/s41392-020-0106-1, PMID 32296020
12. Lameire N, Kellum JA, KDIGO AK Guideline Work Group. Contrast-induced acute kidney injury and renal support for acute kidney injury: A KDIGO summary (Part 2). Crit Care. 2013 Feb 04;17(1):205. doi: 10.1186/cc11455, PMID 23394215
13. Rushdi MI, Abdel-Rahman IA, Saber H, Attia EZ, Abdelraheem WM, Madkour HA. Pharmacological and natural products diversity of the brown algae genus Sargassum. RSC Adv. 2020;10(42):24951-72. doi: 10.1039/d0ra03576a, PMID 35517468
14. Hima RV, Harikrishnan S, Parivallal M, Rahman MS, Basha SM, Sreedhar K. Analysis of the chemical, nutrient and physicochemical properties of brown macroalgae, Sargassum ilicifolium collected from Mandapam coast, Rameshwaram. Biochem Cell Arch. 2023 Sep 15;23(2):1029-36. doi: 10.51470/bca.2023.23.2.1029
15. Torres-Narváez A, Olvera-Ramírez AM, Castaño-Sánchez K, Chávez-Servín JL, Reis De Souza TC, McEwan NR. Therapeutic and nutraceutical potential of Sargassum species: A narrative review. Mar Drugs. 2025;23(9):343. doi: 10.3390/md23090343, PMID 41003312
16. Saraswati, Giriwono PE, Iskandriati D, Andarwulan N. Screening of in-vitro anti-inflammatory and antioxidant activity of Sargassum ilicifolium crude lipid extracts from different coastal areas in Indonesia. Mar Drugs. 2021 Apr 28;19(5):252. doi: 10.3390/md19050252, PMID 33925071
17. Purohit P, Kataria MK. Phytochemicals screening, antioxidant and antimicrobial activity of Carica papaya leaf extracts. Int J Curr Pharm Res. 2024;16(3):95-8. doi: 10.22159/ijcpr.2024v16i3.4087
18. Avalappa HE, Padiyappa SD, Pathappa NI, Bettadatunga PT, Pramod SN. Legume Indian bean (Phaseolus vulgaris) partially purified anti-nutritional protein factor exhibit anti-oxidant, immunomodulatory and anti-cancer properties. Int J Pharm Pharm Sci. 2023;15(2):8-17. doi: 10.22159/ijpps.2023v15i2.46831
19. Saeed NA, Rasool AM, Zeebaree AY. Anti-cancer possibility of zingier officiale nanoparticles: Mechanisms and therapeutic understanding. Int J Appl Pharm. 2025;17(6):417-22. doi: 10.22159/ijap.2025v17i6.55836
20. Xu S, Gao Y, Zhang Q, Wei S, Chen Z, Dai X. SIRT1/3 activation by resveratrol attenuates acute kidney injury in a septic rat model. Oxid Med Cell Long. 2016;2016:7296092. doi: 10.1155/2016/7296092
21. Vishwanadham Rao V, Narayanappa Shanti K, Manjegowda DS. Molecular docking and graphical trajectory analysis of Cinnamomum zeylanicum compounds for targeting human maltase-glucoamylase in diabetes management. Int J Appl Pharm. 2025 Nov 7;17(6):367-80.
22. Vijayabaskaran M, Sivakumar P, Sambathkuamr R, Perumal P, Sivakumar T, Jayakar B. Anti-inflammatory and toxicity evaluation of ethyl-ethyl-propyl-valerate (EEPV) in albino rats: Application of OECD guidelines for testing of chemicals (Test No. 423). Int J Chem Res. 2011;2(4):4-7.
23. Rehman MU, Tahir M, Ali F, Qamar W, Lateef A, Khan R. Cyclophosphamide-induced nephrotoxicity, genotoxicity, and damage in kidney genomic DNA of Swiss albino mice: The protective effect of ellagic acid. Mol Cell Biochem. 2012 Jun;365(1-2):119-27. doi: 10.1007/s11010-012-1250-x, PMID 22286819
24. Ajiboye BO, Famusiwa CD, Nifemi DM, Ayodele BM, Akinlolu OS, Fatoki TH. Nephroprotective effect of Hibiscus sabdariffa leaf flavonoid extracts via KIM-1 and TGF-1β signaling pathways in streptozotocin-induced rats. ACS Omega. 2024 Apr 19;9(17): 19334-44. doi: 10.1021/acsomega.4c00254, PMID 38708257
25. Khalil AM, Kasem NR, Ali AS, Salman MM. Brown seaweed Sargassum cinereum extract ameliorates the hepato and nephrotoxicity induced by cyclophosphamide in male albino rats: Hematological Biochemical and histobiochemical examinations. Saudi J Pathol Microbiol. 2020 Feb 29;5(2):86-94. doi: 10.36348/sjpm.2020. v05i02.009
26. Yang J, Kwon YS, Kim MJ. Isolation and characterization of bioactive compounds from Lepisorus thunbergianus (Kaulf.). Arab J Chem. 2015 May 01;8(3):407-13. doi: 10.1016/j.arabjc.2014.11.056
27. Abdel-Daim MM, Abushouk AI, Abdeen A, Halawa SM, Khalifa HA. Antioxidant and nephroprotective effects of polyphenol-rich plant extracts in drug-induced kidney injury. Biomed Pharmacother. 2018;97:1681-9.
28. Wang J, Guo HM. Astragaloside IV ameliorates high glucose-induced HK-2 cell apoptosis and oxidative stress by regulating the Nrf2/ARE signaling pathway. Exp Ther Med. 2019;17(6):4409-16. doi: 10.3892/ etm.2019.7495, PMID 31086575
29. Bao L, Li J, Zha D, Zhang L, Gao P, Yao T. Chlorogenic acid prevents diabetic nephropathy by inhibiting oxidative stress and inflammation through modulation of the Nrf2/HO-1 and NF-κB pathways. Int Immunopharmacol. 2018;54:245-53. doi: 10.1016/j. intimp.2017.11.021, PMID 29161661
30. Zhang Y, Li Y, Zhang J, Wang L, Chen X, Liu Q. Chlorogenic acid prevents diabetic nephropathy by inhibiting oxidative stress and inflammation through modulation of the Nrf2/HO-1 and NF-κB pathways. J Diabetes Res. 2017;2017:9645238. doi: 10.1155/2017/9645238
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