PHYTO-PHARMACOLOGICAL EVALUATIONS OF NELUMBO NUCIFERA (GAERTN) IN CYCLOPHOSPHAMIDE-INDUCED NEPHROTOXITY IN RATS
DOI:
https://doi.org/10.22159/ajpcr.2026v19i2.56946Keywords:
Nelumbo nucifera, Methanolic extract, Phytochemical screening, 2,2-diphenyl-1-picrylhydrazyl assay, Antioxidant activity, Histopathology, Wild and knockout yeast strains, cyclophosphamide, Nephroprotective, Oxidative stress, Cytokines, Glutathione, Catalase, MalondialdehydeAbstract
Objectives: Nelumbo nucifera (Gaertn) (Sacred Lotus) is a medicinally important plant conventionally used for the treatment of inflammatory and oxidative stress-related disorders. The present study aimed to evaluate the phytochemical profile, antioxidant potential, and protective effects of methanolic and aqueous extracts of N. nucifera against cyclophosphamide (CP)-induced toxicity.
Methods: Extractive values of methanolic and aqueous extracts were determined, followed by preliminary phytochemical screening and quantification of total phenolic and flavonoid contents. Antioxidant activity was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Cytotoxicity and growth curve studies were performed using wild-type and Δtrx2 yeast strains to assess biocompatibility and stress response. In vivo nephroprotective effect was evaluated in CP-induced nephrotoxicity models by measuring serum creatinine, urea, uric acid, protein, globulin, alanine aminotransferase, aspartate aminotransferase, glutathione, catalase, and malondialdehyde levels, along with pro-inflammatory cytokines tumor necrosis factor-alpha and interleukin-1 beta.
Results: The aqueous extract yielded higher extractive value (13.0% w/w), whereas the methanolic extract exhibited higher phenolic (1.50 mg/100 mg) and flavonoid (2.33 mg/100 mg) content. DPPH assay revealed potent free-radical scavenging activity for methanolic extract (IC50=42.32 μg/mL), closer to ascorbic acid. Yeast cytotoxicity studies confirmed the safety of the extracts and demonstrated their membrane-protective effects. In vivo studies showed that both extracts significantly (p<0.05–p<0.001) attenuated CP-induced alterations in renal and oxidative stress biomarkers, with methanolic extract (200 mg/kg) showing maximal protective effects.
Conclusion: N. nucifera extracts, particularly the methanolic fraction, possess strong antioxidant, nephroprotective, hepatoprotective, and anti-inflammatory activities. These findings support its potential therapeutic application in managing CP-induced nephrotoxity and oxidative stress-related disorders.
Downloads
References
1. Sharifi-Rad M, Anil Kumar NV, Zucca P, Varoni EM, Dini L, Panzarini E, et al. Lifestyle, oxidative stress, and antioxidants: Back and forth in the pathophysiology of chronic diseases. Front Physiol. 2020 Jul 2;11:694. doi: 10.3389/fphys.2020.00694, PMID 32714204
2. Nathan C, Cunningham-Bussel A. Beyond oxidative stress: An immunologist’s guide to reactive oxygen species. Nat Rev Immunol. 2013 May;13(5):349-61. doi: 10.1038/nri3423, PMID 23618831
3. Ahlmann M, Hempel G. The effect of cyclophosphamide on the immune system: Implications for clinical cancer therapy. Cancer Chemother Pharmacol. 2016 Oct;78(4):661-71. doi: 10.1007/s00280-016-3152-1, PMID 27646791
4. Shahidi F, Ambigaipalan P. Phenolics and polyphenolics in foods, beverages and spices: Antioxidant activity and health effects-a review. J Funct Foods. 2015;18:820-97. doi: 10.1016/j.jff.2015.06.018
5. Thakur M, Vasudeva N, Sharma S, Datusalia AK. Plants and their bioactive compounds as a possible treatment for traumatic brain injury-induced multi-organ dysfunction syndrome. CNS Neurol Disord Drug Targets. 2023 Nov 1;22(9):1313-34. doi: 10.2174/18715273216662208 30164432, PMID 36045522
6. Kirtikar KR, Basu BD. Indian Medicinal Plants. 2nd ed. India, New Delhi: International Book Distributors; 1975. p. 116-20.
7. Sheikh SA, Ethno-medicinal uses and pharmacological activities of lotus (Nelumbo nucifera). J Med Plants Stud. 2014;2(6):42-6. doi: 10.22271/plants
8. Kokate CK, editor. Practical Pharmacognosy. 4th ed. New Delhi: Vallabh Prakashan; 1994. p. 112-20.
9. Lin Z, Zhang C, Cao D, Damaris RN, Yang P. The latest studies on lotus (Nelumbo nucifera)-an emerging horticultural model plant. Int J Mol Sci. 2019;20(15):3680. doi: 10.3390/ijms20153680, PMID 31357582
10. Mukherjee PK. Quality assurance of herbal drugs and stability testing. In: Quality Control and Evaluation of Herbal Drugs. Netherlands: Elsevier; 2019. p. 685-705. doi: 10.1016/b978-0-12-813374-3.00019-3
11. Inchan A, Chootip K, Kongthong K, Bualeong T, Sumsakul W, Apaikawee P, et al. Lotus seed (Nelumbo nucifera Gaertn.) extract at low dose ameliorates reproductive dysfunction in L-NAME-induced hypertension and oxidative stress in male rats. J Tradit Complement Med. 2025;15(4):404-13. doi: 10.1016/j.jtcme.2024.05.001, PMID 40677545
12. Mehta NR, Patel EP, Patani PV, Shah B. Nelumbo nucifera (Lotus): A review on ethanobotany, phytochemistry and pharmacology. Indian J Pharm Biol Res. 2013 Jun;1(4):152-67. doi: 10.30750/ijpbr.1.4.26
13. Yamini R, Kannan M, Thamaraisevi SP, Uma D, Santhi R. Phytochemical screening and nutritional analysis of Nelumbo nucifera (Pink lotus) flower petals and seeds. Int J Chem Stud. 2019;7(3):3540- 5. doi: 10.22271/chemi
14. Tungmunnithum D, Pinthong D, Hano C. Flavonoids from Nelumbo nucifera Gaertn., a medicinal plant: Uses in traditional medicine, phytochemistry and pharmacological activities. Medicines (Basel). 2018;5(4):127. doi: 10.3390/medicines5040127, PMID 30477094
15. Preethika K, Arul Pamila U, Karpagam S. Comparative phytochemical analysis of white and pink flower of Nelumbo nucifera. Int J Sci Eng Res (IJSR). 2018;7(8):1073-5. doi: 10.21275/art2019663
16. Sahu R, Sahu B. Insights into the chemical composition, nutritional value, and pharmacological activities of Nelumbo nucifera Gaertn. J Biomed Res. 2024;5(1):26-8. doi: 10.46439/biomedres.5.040
17. Chen G, Zhu M, Guo M. Research advances in traditional and modern use of Nelumbo nucifera: Phytochemicals, health promoting activities and beyond. Crit Rev Food Sci Nutr. 2019;59 (Suppl 1):S189-209. doi: 10.1080/10408398.2018.1553846, PMID 30633540
18. Sruthi DR, Indira G. A comparative evaluation of maceration, soxhlation and ultra sound assisted extraction for the phytochemical screening of the leaves of Nephelium lappaceum. L. (Sapindaceae). J Pharmacogn Phytochem. 2016;5(5):386-9. doi: 10.22271/phyto
19. Parkhe G, Bharti D. Phytochemical investigation and determination of total phenols and flavonoid concentration in leaves extract of Vitex trifolia Linn. J Drug Deliv Ther. 2019;9(4-A):705-7. doi: 10.22270/ jddt.v9i4-a.3554
20. Alara OR, Abdurahman NH, Ukaegbu CI. Soxhlet extraction of phenolic compounds from Vernonia cinerea leaves and its antioxidant activity. J Appl Res Med Aromat Plants. 2018 Dec 1;11:12-7. doi: 10.1016/j.jarmap.2018.07.003
21. Lakshmi PK, Pawar RS. Hygrophila auriculata improves insulin resistance by reducing oxidative stress, membrane stabilization and increasing hepatic heat shock protein 70 (Hsp70) expression. Rev Bras Farmacogn. 2024;34(2):428-39. doi: 10.1007/s43450-023-00485-5
22. Singh P, Sahota PP, Singh RK. Evaluation and characterization of new α-L-rhamnosidase-producing yeast strains. J Gen Appl Microbiol. 2015;61(5):149-56. doi: 10.2323/jgam.61.149, PMID 26582283
23. Ayza MA, Zewdie KA, Yigzaw EF, Ayele SG, Tesfaye BA, Tafere GG, et al. Potential protective effects of antioxidants against cyclophosphamide-induced nephrotoxicity. Int J Nephrol. 2022;2022:5096825. doi: 10.1155/2022/5096825, PMID 35469319
24. Sharma S, Baboota S, Amin S, Mir SR. Ameliorative effect of a standardized polyherbal combination in methotrexate-induced nephrotoxicity in the rat. Pharm Biol. 2020;58(1):184-99. doi: 10.1080/13880209.2020.1717549, PMID 32083987
25. Temel Y, Kucukler S, Yıldırım S, Caglayan C, Kandemir FM. Protective effect of chrysin on cyclophosphamide-induced hepatotoxicity and nephrotoxicity via the inhibition of oxidative stress, inflammation, and apoptosis. Naunyn Schmiedebergs Arch Pharmacol. 2020;393(3):325- 37. doi: 10.1007/s00210-019-01741-z, PMID 31620822
26. Li C, He Y, Yang Y, Gou Y, Li S, Wang R, et al. Antioxidant and inflammatory effects of Nelumbo nucifera Gaertn. Leaves. Oxid Med Cell Longev. 2021;2021:8375961. doi: 10.1155/2021/8375961, PMID 34992717
27. Ayza MA, Rajkapoor B, Wondafrash DZ, Berhe AH. Protective effect of Croton macrostachyus (Euphorbiaceae) stem bark on cyclophosphamide-induced nephrotoxicity in rats. J Exp Pharmacol. 2020;12:275-83. doi: 10.2147/jep.s260731, PMID 32943947
Published
How to Cite
Issue
Section
Copyright (c) 2026 Sulakshana Pawar, RAGHUVEER IRCHHIAYA
This work is licensed under a Creative Commons Attribution 4.0 International License.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.