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Ecklonia maxima: a potential NRF2 antioxidant modulator in Glucotoxicity-induced oxidative stress

Thesis (MSc)--Stellenbosch University, 2025.

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Main Author: Bekko, Adam
Other Authors: Abdul, Naeem Sheik
Format: Thesis
Language:English
Published: Stellenbosch : Stellenbosch University 2025
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access_status_str Open Access
author Bekko, Adam
author2 Abdul, Naeem Sheik
author_browse Abdul, Naeem Sheik
Bekko, Adam
author_facet Abdul, Naeem Sheik
Bekko, Adam
author_sort Bekko, Adam
collection Thesis
dc_rights_str_mv Stellenbosch University
description Thesis (MSc)--Stellenbosch University, 2025.
format Thesis
id oai:scholar.sun.ac.za:10019.1/134515
institution Stellenbosch University (South Africa)
language English
last_indexed 2026-06-10T12:41:24.431Z
license_str Other — see source repository
provenance_str_mv Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository
publishDate 2025
publishDateRange 2025
publishDateSort 2025
publisher Stellenbosch : Stellenbosch University
publisherStr Stellenbosch : Stellenbosch University
record_format dspace
source_str SUNScholar — Stellenbosch University Repository
spelling oai:scholar.sun.ac.za:10019.1/134515 Ecklonia maxima: a potential NRF2 antioxidant modulator in Glucotoxicity-induced oxidative stress Bekko, Adam Abdul, Naeem Sheik Le Roes-Hill, Marilize Stellenbosch University. Faculty of Science. Dept. of Biochemistry. Type 2 diabetes Oxidative stress Antioxidants -- Mechanism of action Type 2 diabetes mellitus -- Complications -- Alternative treatment Marine natural products -- Therapeutic use Kelps -- Therapeutic use Cells -- Effect of stress on UCTD Thesis (MSc)--Stellenbosch University, 2025. Bekko, A. 2025. Ecklonia maxima: A potential NRF2 antioxidant modulator in Glucotoxicity-induced oxidative stress. Unpublished masters thesis. Stellenbosch: Stellenbosch University [online]. Available: https://scholar.sun.ac.za/items/1949a560-afad-4c42-8663-7029b1b17acd ENGLISH ABSTRACT: With a lack of access to proper medical infrastructure, low- and middle-income countries remain predisposed to many non-communicable diseases like diabetes. The rise of type 2 diabetes mellitus (T2DM) is reaching epidemic levels worldwide; however, in the global South, this rise in prevalence is far surpassing what the global North is facing. This results in not only an increased level of prevalence but also means that many people who are diagnosed with these disorders remain untreated. One of the most commonly overlooked complications of T2DM is the detrimental effect that chronic hyperglycaemia has on oxidative stress. This chronic hyperglycaemic state has been linked to an increase in reactive oxygen species, which has further been associated with an increase in mitochondrial dysfunction and oxidative damage to cell macromolecules. This has been observed as a common causal agent for many of the micro- and macro-vascular complications present within diabetic patients. Targeting oxidative stress and mitochondrial dysfunction is therefore seen as a plausible therapeutic opportunity to prevent diabetic complications. Natural products have long provided a foundation for therapeutic discovery, yet the potential of marine resources remains largely untapped. Among these, the indigenous brown kelp Ecklonia maxima has been particularly overlooked despite its richness in bioactive sulphated polysaccharides, known as fucoidan. This research sought not only to extract these compounds via hot water extraction but also to utilise an enzymatic modification technique using a novel multi-copper oxidase, an approach de-signed to improve their bioactivity. In a model mimicking diabetic stress, both native and enzyme-modified fucoidans demonstrated bioactivity. At low concentrations, they robustly quenched intracellular ROS, rebalanced redox homeostasis, and activated cytoprotective pathways. Notably, a pronounced NRF2 upregulation was observed at 25 µg/mL, while PGC-1α expression was consistently and significantly enhanced across all treatments, underscoring improved mitochondrial resilience. Beyond antioxidant defence, the fucoidans exhibited remarkable hepatoprotective capacity, restoring metabolic efficiency and supporting anti-apoptotic mechanisms. Although our data revealed variations in the effectiveness of native and modified treatments, 25 µg/mL showed the most consistent and positive outcomes across all pathways tested. Notably, enzyme-modified fucoidans generally produced stronger responses, supporting enzymatic modification as a relevant strategy to enhancing bio-activity. By integrating indigenous knowledge with modern scientific approaches, this study attempted to advance the use of Ecklonia maxima’s fucoidan as culturally relevant, affordable, and effective co-treatments for type 2 diabetes and potentially other metabolic disorders where oxidative stress plays a central role. AFRIKAANSE OPSOMMING: Geen opsomming beskikbaar. Masters 2025-12-11T13:52:17Z 2025-12-11T13:52:17Z 2025-12 Thesis https://scholar.sun.ac.za/handle/10019.1/134515 en Stellenbosch University xiii, 105 pages : illustrations, maps application/pdf Stellenbosch : Stellenbosch University
spellingShingle Type 2 diabetes
Oxidative stress
Antioxidants -- Mechanism of action
Type 2 diabetes mellitus -- Complications -- Alternative treatment
Marine natural products -- Therapeutic use
Kelps -- Therapeutic use
Cells -- Effect of stress on
UCTD
Bekko, Adam
Ecklonia maxima: a potential NRF2 antioxidant modulator in Glucotoxicity-induced oxidative stress
title Ecklonia maxima: a potential NRF2 antioxidant modulator in Glucotoxicity-induced oxidative stress
title_full Ecklonia maxima: a potential NRF2 antioxidant modulator in Glucotoxicity-induced oxidative stress
title_fullStr Ecklonia maxima: a potential NRF2 antioxidant modulator in Glucotoxicity-induced oxidative stress
title_full_unstemmed Ecklonia maxima: a potential NRF2 antioxidant modulator in Glucotoxicity-induced oxidative stress
title_short Ecklonia maxima: a potential NRF2 antioxidant modulator in Glucotoxicity-induced oxidative stress
title_sort ecklonia maxima a potential nrf2 antioxidant modulator in glucotoxicity induced oxidative stress
topic Type 2 diabetes
Oxidative stress
Antioxidants -- Mechanism of action
Type 2 diabetes mellitus -- Complications -- Alternative treatment
Marine natural products -- Therapeutic use
Kelps -- Therapeutic use
Cells -- Effect of stress on
UCTD
url https://scholar.sun.ac.za/handle/10019.1/134515
work_keys_str_mv AT bekkoadam eckloniamaximaapotentialnrf2antioxidantmodulatoringlucotoxicityinducedoxidativestress