Antioxidant and Hepatoprotective Effects of Eucheuma denticulatum (N. L. Burman) F. S. Collins & Hervey in Carbon Tetrachloride-Induced Liver Injury

Hepatoprotection by Eucheuma denticulatum

Authors

  • Mohammad Amil Zulhilmi BENJAMIN Institute for Tropical Biology and Conservation, Universiti Malaysia Sabah, Jalan UMS, 88400 Kota Kinabalu, Sabah, Malaysia. https://orcid.org/0000-0001-6483-1362
  • Jeyanthi PALANISAMY Faculty of Science and Technology, Universiti Malaysia Sabah, Jalan UMS, 88400 Kota Kinabalu, Sabah, Malaysia.
  • Wilson Thau Lym YONG Biotechnology Research Institute, Universiti Malaysia Sabah, Jalan UMS, 88400 Kota Kinabalu, Sabah, Malaysia. https://orcid.org/0000-0001-8431-8486
  • Mohammad IQBAL Biotechnology Research Institute, Universiti Malaysia Sabah, Jalan UMS, 88400 Kota Kinabalu, Sabah, Malaysia.

DOI:

https://doi.org/10.51200/jtbc.v23i.6864

Keywords:

oxidative stress, hepatoprotection, ethanolic extract, Eucheuma denticulatum, antioxidants, carbon tetrachloride

Abstract

Oxidative stress-related liver injury is a major global health concern and highlights the need for safe and effective hepatoprotective agents from natural sources. Eucheuma denticulatum (N. L. Burman) F. S. Collins & Hervey, a red seaweed of economic importance, is a primary source of ι-carrageenan with potential medicinal and therapeutic value. This study evaluated the antioxidant and hepatoprotective effects of the ethanolic extract of E. denticulatum (EEED). Antioxidant activity was assessed using total phenolic content (TPC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays, while hepatoprotective effects were investigated in Sprague-Dawley rats (n = 4 per group) with carbon tetrachloride (CCl4)-induced liver injury. Biochemical analyses measured serum liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and hepatic antioxidants including glutathione (GSH), malondialdehyde (MDA), catalase (CAT), and glutathione S-transferase (GST). EEED showed low TPC (9.93 ± 0.10 mg GAE/g) and weak DPPH scavenging activity (40.77 ± 0.01%) compared with ascorbic acid (98.24 ± 0.01%) at 5,000 µg/mL. In CCl4-treated rats, ALT and AST were significantly elevated, while GSH, CAT, and GST were depleted with an increase in MDA. EEED pretreatment reduced ALT by 18–28% and AST by 8–13%, increased GSH by 65–82%, reduced MDA by 53–89%, and improved antioxidant status with increases in CAT of 15–30% and GST of 55–64%. Overall, EEED demonstrated hepatoprotective effects despite low radical scavenging activity, which indicates potential as a natural therapeutic candidate for oxidative liver injury.

References

Ahmad M, Tahir M, Hong Z, Zia MA, Rafeeq H, Ahmad MS, Rehman S ur, Sun J (2025) Plant and marine-derived natural products: sustainable pathways for future drug discovery and therapeutic development. Frontiers in Pharmacology 15: 1497668. https://doi.org/10.3389/fphar.2024.1497668.

Athar M, Iqbal M (1998) Ferric nitrilotriacetate promotes N-diethylnitrosamine-induced renal tumorigenesis in the rat: implications for the involvement of oxidative stress. Carcinogenesis 19: 1133–1139. https://doi.org/10.1093/carcin/19.6.1133.

Awang MA, Benjamin MAZ, Anuar A, Ismail MF, Ramaiya SD, Mohd Hashim SNA (2023) Dataset of gallic acid quantification and their antioxidant and anti-inflammatory activities of different solvent extractions from kacip fatimah (Labisia pumila Benth. & Hook. f.) leaves. Data in Brief 51: 109644. https://doi.org/10.1016/j.dib.2023.109644.

Aware CB, Patil DN, Suryawanshi SS, Mali PR, Rane MR, Gurav RG, Jadhav JP (2022) Natural bioactive products as promising therapeutics: a review of natural product-based drug development. South African Journal of Botany 151: 512–528. https://doi.org/10.1016/j.sajb.2022.05.028.

Balasubramaniam V, June Chelyn L, Vimala S, Mohd Fairulnizal MN, Brownlee IA, Amin I (2020) Carotenoid composition and antioxidant potential of Eucheuma denticulatum, Sargassum polycystum and Caulerpa lentillifera. Heliyon 6: e04654. https://doi.org/10.1016/j.heliyon.2020.e04654.

Balasubramaniam V, Lee JC, Noh MFM, Ahmad S, Brownlee IA, Ismail A (2016) Alpha-amylase, antioxidant, and anti-inflammatory activities of Eucheuma denticulatum (N.L. Burman) F.S. Collins and Hervey. Journal of Applied Phycology 28: 1965–1974. https://doi.org/10.1007/s10811-015-0690-6.

Bitwell C, Indra S Sen, Luke C, Kakoma MK (2023) A review of modern and conventional extraction techniques and their applications for extracting phytochemicals from plants. Scientific African 19: e01585. https://doi.org/10.1016/j.sciaf.2023.e01585.

Buege JA, Aust SD (1978) [30] Microsomal lipid peroxidation. In: Methods in Enzymology, Fleischer S, Packer L (eds.). Academic Press: Cambridge, MA, USA: 302–310. DOI: https://doi.org/10.1016/S0076-6879(78)52032-6.

Chaudhary P, Janmeda P, Docea AO, Yeskaliyeva B, Abdull Razis AF, Modu B, Calina D, Sharifi-Rad J (2023) Oxidative stress, free radicals and antioxidants: potential crosstalk in the pathophysiology of human diseases. Frontiers in Chemistry 11: 1158198. 10.3389/fchem.2023.1158198.

Claiborne A (1985) Catalase activity. In: Handbook Methods for Oxygen Radical Research. Greenwald RA (ed.). CRC Press: Boca Raton, FL, USA: 283–284.

Cordiano R, Gioacchino M Di, Mangifesta R, Panzera C, Gangemi S, Minciullo PL (2023) Malondialdehyde as a potential oxidative stress marker for allergy-oriented diseases: an update. Molecules 28: 5979. https://doi.org/10.3390/molecules28165979.

FAO (2020) The State of World Fisheries and Aquaculture: Sustainability in Action. Food and Agriculture Organization of the United Nations: Rome, Italy; 1–206. https://doi.org/10.4060/ca9229en.

Gabrielli F, Bernasconi E, Toscano A, Avossa A, Cavicchioli A, Andreone P, Gitto S (2025) Side effects of immunosuppressant drugs after liver transplant. Pharmaceuticals 18: 342. https://doi.org/10.3390/ph18030342.

Gins MS, Gins VK, Kononkov PF, Baikov AA, Pivovarov VF, Fotev Y V., Gins EM (2019) The effect of low positive temperature on the content of low-molecular weight antioxidants in the organs of a vegetable Chrysanthemum. Russian Agricultural Sciences 45: 434–438. https://doi.org/10.3103/s1068367419050070.

Gulcin İ (2020) Antioxidants and antioxidant methods: an updated overview. Archives of Toxicology 94: 651–715. https://doi.org/10.1007/s00204-020-02689-3.

Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S-transferase: the first enzymatic step in mercapturic acid formation. Journal of Biological Chemistry 249: 7130–7139. https://doi.org/10.1016/s0021-9258(19)42083-8.

Hakim MM, Patel IC (2020) A review on phytoconstituents of marine brown algae. Future Journal of Pharmaceutical Sciences 6: 129. https://doi.org/10.1186/s43094-020-00147-6.

Hung LD, Hirayama M, Ly BM, Hori K (2015) Purification, primary structure, and biological activity of the high-mannose N-glycan-specific lectin from cultivated Eucheuma denticulatum. Journal of Applied Phycology 27: 1657–1669. https://doi.org/10.1007/s10811-014-0441-0.

Iqbal M, Benjamin MAZ, Lee P-C (2025) Modulation of oxidative stress by Centella asiatica (L.) Urb. leaves against carbon tetrachloride-induced hepatic damage in rats. Journal of Tropical Biology and Conservation 22: 76–87. https://doi.org/10.51200/jtbc.v22i.6289.

Iqbal M, Giri U, Giri DK, Alam MS, Athar M (1999) Age-dependent renal accumulation of 4-hydroxy-2-nonenal (HNE)-modified proteins following parenteral administration of ferric nitrilotriacetate commensurate with its differential toxicity: implications for the involvement of HNE-protein adducts in oxidative stress and carcinogenesis. Archives of Biochemistry and Biophysics 365: 101–112. https://doi.org/10.1006/abbi.1999.1135.

Jinoni DA, Benjamin MAZ, Mus AA, Goh LPW, Rusdi NA, Awang MA (2024) Phaleria macrocarpa (Scheff.) Boerl. (Mahkota Dewa) seed essential oils: extraction yield, volatile components, antibacterial, and antioxidant activities based on different solvents using Soxhlet extraction. Kuwait Journal of Science 51: 100173. https://doi.org/10.1016/j.kjs.2023.100173.

Jollow DJ, Mitchell JR, Zampaglione N, Gillette JR (1974) Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology 11: 151–169. https://doi.org/10.1159/000136485.

Li S, Tan H-Y, Wang N, Zhang Z-J, Lao L, Wong C-W, Feng Y (2015) The role of oxidative stress and antioxidants in liver diseases. International Journal of Molecular Sciences 16: 26087–26124. https://doi.org/10.3390/ijms161125942.

Lin D, Xiao M, Zhao J, Li Z, Xing B, Li X, Kong M, Li L, Zhang Q, Liu Y, Chen H, Qin W, Wu H, Chen S (2016) An overview of plant phenolic compounds and their importance in human nutrition and management of type 2 diabetes. Molecules 21: 1374. https://doi.org/10.3390/molecules21101374.

Mayore S, Damongilala LJ, Mewengkang HW, Salindeho N, Makapedua DM, Sanger G (2018) Analisis fitokimia dan uji total kapang pada rumput laut kering. Media Teknologi Hasil Perikanan 6: 77–81. https://doi.org/10.35800/mthp.6.3.2018.21256.

Mohd Rosdan MDE, Awang MA, Benjamin MAZ, Mohd Amin SF, Julmohammad N (2024) Effect of ultrasound-assisted osmotic dehydration (UAOD) pretreatment on Mangifera pajang Kosterm. fruit pulp: drying kinetics, chemical qualities, and color measurement. Journal of Food Process Engineering 47: e14721. https://doi.org/10.1111/jfpe.14721.

Nandi A, Yan L-J, Jana CK, Das N (2019) Role of catalase in oxidative stress- and age-associated degenerative diseases. Oxidative Medicine and Cellular Longevity 2019: 9613090. https://doi.org/10.1155/2019/9613090.

Necas J, Bartosikova L (2013) Carrageenan: a review. Veterinární Medicína 58: 187–205. https://doi.org/10.17221/6758-VETMED.

Pérez M, Dominguez-López I, Lamuela-Raventós RM (2023) The chemistry behind the Folin–Ciocalteu method for the estimation of (poly)phenol content in food: total phenolic intake in a mediterranean dietary pattern. Journal of Agricultural and Food Chemistry 71: 17543–17553. https://doi.org/10.1021/acs.jafc.3c04022.

Qadri SS, Javaid D, Reyaz A, Ganie SY, Reshi MS (2025) Liver disorders and phytotherapy. Toxicology Reports 14: 102047. https://doi.org/10.1016/j.toxrep.2025.102047.

Singhal SS, Singh SP, Singhal P, Horne D, Singhal J, Awasthi S (2015) Antioxidant role of glutathione S-transferases: 4-hydroxynonenal, a key molecule in stress-mediated signaling. Toxicology and Applied Pharmacology 289: 361–370. https://doi.org/10.1016/j.taap.2015.10.006.

Sultana F, Wahab MA, Nahiduzzaman M, Mohiuddin M, Iqbal MZ, Shakil A, Mamun A-A, Khan MSR, Wong L, Asaduzzaman M (2023) Seaweed farming for food and nutritional security, climate change mitigation and adaptation, and women empowerment: a review. Aquaculture and Fisheries 8: 463–480. https://doi.org/10.1016/j.aaf.2022.09.001.

Tanna B, Mishra A (2018) Metabolites unravel nutraceutical potential of edible seaweeds: an emerging source of functional food. Comprehensive Reviews in Food Science and Food Safety 17: 1613–1624. https://doi.org/10.1111/1541-4337.12396.

Thanebal SAP, Vun-Sang S, Iqbal M (2021) Hepatoprotective effects of Pandanus amaryllifolius against carbon tetrachloride (CCl4) induced toxicity: a biochemical and histopathological study. Arabian Journal of Chemistry 14: 103390. https://doi.org/10.1016/j.arabjc.2021.103390.

Unsal V, Cicek M, Sabancilar İ (2021) Toxicity of carbon tetrachloride, free radicals and role of antioxidants. Reviews on Environmental Health 36: 279–295. https://doi.org/10.1515/reveh-2020-0048.

Vairetti M, Di Pasqua LG, Cagna M, Richelmi P, Ferrigno A, Berardo C (2021) Changes in glutathione content in liver diseases: an update. Antioxidants, 10: 364. https://doi.org/10.3390/antiox10030364.

Wu JY, Tso R, Teo HS, Haldar S (2023) The utility of algae as sources of high value nutritional ingredients, particularly for alternative/complementary proteins to improve human health. Frontiers in Nutrition 10: 1277343. https://doi.org/10.3389/fnut.2023.1277343.

Zakaria ZA, Kamisan FH, Kek TL, Salleh MZ (2020) Hepatoprotective and antioxidant activities of Dicranopteris linearis leaf extract against paracetamol-induced liver intoxication in rats. Pharmaceutical Biology 58: 478–489. https://doi.org/10.1080/13880209.2020.1764058.

Published

2026-05-08

How to Cite

BENJAMIN, M. A. Z. ., PALANISAMY, J. ., YONG, W. T. L. ., & IQBAL, M. . (2026). Antioxidant and Hepatoprotective Effects of Eucheuma denticulatum (N. L. Burman) F. S. Collins & Hervey in Carbon Tetrachloride-Induced Liver Injury: Hepatoprotection by Eucheuma denticulatum. Journal of Tropical Biology & Conservation (JTBC), 23, 51–64. https://doi.org/10.51200/jtbc.v23i.6864
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