DOI: 10.25381/cput.25912987.v1
title: Modulatory role of rooibos on exercise-induced oxidative stress and performance while exploring influences on the human metabolome and effect of genetic variations

description: Ethics reference number: CPUT/HWS-REC 2018/H2The present study is based on the fact that, despite the widely acknowledged impacts of OS on human health, this phenomenon is not yet well enough understood to allow for effective clinical manipulation and potential development of therapeutic interventions and/or modulators(Sharifi-Rad et al., 2020; Ji & Yeo, 2021). After many years of research studies, there is little therapeutic interventions directly attributed to the research into oxidative stress mainly due to the lack of standardised human models. Despite, many developed <i>in vitro</i> and animal models of oxidative stress-based research to date there is no reliable human intervention model. Even though the <i>in vitro</i> and animal models are helpful, they do not generally translate well to humans in the field of oxidative stress (Oteiza et al., 2021). Furthermore, it is challenging to induce oxidative stress in a predictable and controllable manner in a human without undue risk of further harm (Alberto De La Riva et al., 2023). Nonetheless, this phenomenon must be further studied to understand the role of radicals and AOXs in physiology, but also for possible development of modulatory and/or therapeutic interventions.<br>Generally, if OS is not effectively and properly managed, it may lead to damage of important cellular macromolecules including DNA, lipid and protein (Kurutas, 2015; Luna & Estévez, 2018)and eventually cellular dysfunctions, impairments and/or ultimate development of several diseases (Pingitore et al., 2015). However, genes encoding for the endogenous AOX enzymes that help to mitigate potential oxidative stress damage, unfortunately, might possess genetic variations that may affect/ impact the effectiveness of these AOX enzymes and subsequently influence the extent of OS damage or other exercise-induced ailments in individuals. To date, there is a lack of therapeutic/ interventional approaches for mitigating exercise-induced cell stress. The synthetic drugs that are commonly used to counteract the harmful effects of exercise-induced cell stress are expensive and often have serious side effects as most of them are stimulants (Nieman et al., 2006). Therefore, novel, safer and relatively inexpensive approaches are needed to supplement, substitute and/or support current existing approaches. It has been observed that consumption of polyphenolic-rich plant phytochemical may offer some help. For centuries, people have consumed plants and their products for food, nutritional support and/or as a source of medicines (Che & Zhang, 2019). However, current literature or knowledge on metabolite shift and molecular mechanisms that occur upon consumption of phytochemical flavonoid compounds is very limited (Oteiza et al., 2021). Hence, the application of metabolomics to analyse metabolites are sensitive to both external and internal stimuli and possess the ability to reflect what is going on within the organism's metabolome in response to perturbations or interventions (Duft et al., 2017; Wishart, 2019). Furthermore, metabolomic provides a platform to understand the cellular mechanisms from a metabolite point of view, which may also help in the design and/or development of a potential modulator or interventional therapy to mitigate exercise-induced oxidative stress ailments (Miao et al., 2018). In the past two to three decades, the identification of plant products and their ingestion by individuals and sports professionals in an attempt to minimise the effects of OS experienced during certain physical activities has significantly increased. Furthermore, there is an increasing trend worldwide by consumers including natural products in their daily diet to serve as health boosting, disease prevention strategies and to maintain their health (Calixto, 2019). It has been well reported that various plants and natural products have long been used to treat almost all kinds of ill-health conditions(Che & Zhang, 2019). Hence, it is not surprising that athletes use of natural plant products as a means to modulate exercise-induced ailments or pathologies emerging to have several advantages over synthetic drugs. Rooibos, an indigenous South African herbal tea and a dietary source of unique bioactive including AOXs,<b> </b>may complement and assist in alleviating and/or mitigate exercise-induced ailments or deleterious effects caused by excessive RONS. The research into the health benefits of bioactive appears to have started in the 1980’s driven by the<b> </b>importance of antioxidants to human health, but more recently research has highlighted, additional health benefits associated with fruit and vegetable consumption (Oteiza et al., 2021). A detailed explanation on exercise and OS, the antioxidant defence systems, exercise-induced alterations of the human metabolome, genetic variations, phytochemical polyphenols, and lastly the promising Rooibos as a potential polyphenolic-rich phytochemical source, and the role(s) it may play to alleviate and mitigate exercise-induced OS and related ailments are reviewed in chapter 2.<br>The study aim was motivated by the identification of gaps in the current body of knowledge (Chapter 3) related to exercise-induced oxidative stress in humans, effect on the metabolome, the role of genetic variability and exercise performance outcomes and potential dietary interventions, with focus on using the indigenous herbal tea, Rooibos. These gaps are addressed in the <b>four phases </b>of our study, with <b>phase I</b>, establishing an exercise-induced oxidative stress human model suitable for testing any herbal intervention, <b>Phase II</b>, using the proposed model (phase I) to assess the modulatory role and potential of a standardised fermented Rooibos beverage to serve as an ergogenic aid using a dietary intervention design, <b>Phase III</b>, evaluating the effect of a standardised fermented Rooibos beverage on the study participants’ plasma metabolome with emphasis on possible metabolite(s) shift and/or metabolic pathways and lastly <b>phase IV</b>,<b> </b>evaluating the influence of genetic variability in the human antioxidant system on exercise-induced oxidative stress and muscle damage biomarkers.<b> </b>A description of the study participant cohort and methods used in the various study phases is detailed in Chapter 4 while the findings obtained for each of the study phases are presented in the results and discussion section (Chapter 5). The study summary and<b> </b>conclusion reached based on the new knowledge and results of this study is presented in Chapter 6. The references is provided in Chapter 7, followed by additional results pertaining to each of the study phases, while the thesis is concluded with Chapter 8, appendices of relevant study support documents such as consent forms, questionnaires and the ethical clearance certificate issued before commencement of this research study.