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Investigating the modulating effects of Afriplex GRT Extract on vascular function and antioxidant status in obese Wistar rat

Maqeda, Zimvo (2018-03)

Thesis (MSc)--Stellenbosch University, 2018.

Thesis

Introduction Obesity is associated with the development of metabolic syndrome, a conglomerate of cardiometabolic risk factors, which synergistically result in cardiovascular diseases (CVDs), the major leading cause of death worldwide. The indigenous South African plant Rooibos (Aspalathus linearis), contains polyphenolic phytochemicals such as aspalathin, which is unique to Rooibos and has been associated with its health promoting properties. These include antidiabetic, anti-inflammatory, antioxidant, anti-obesity and cardiovascular benefits. Not much is known about the health promoting properties of Afriplex GRTTM, an aspalathin-rich Rooibos extract. It is hypothesised that Afriplex GRT™ may ameliorate the development of hypertension, vascular dysfunction and oxidative stress in a model of obese Wistar rats. Aim To investigate the ameliorative effect of Afriplex GRT™ extract on blood pressure, vascular function and oxidative stress in diet-induced obese Wistar rats. Methods Adult male Wistar rats were randomly divided into 5 experimental groups (n=10/group) and fed a Control or high-fat-diet (HFD), to induce obesity over a period of 16 weeks. Rats in the HFD and Control groups received the aspalathin-rich extract supplemented at 60 mg/kg/day from week 10 to 16. A Captopril (50 mg/kg/day) group was included as a positive control. Food and water intake, body weight, blood glucose, blood pressure, intraperitoneal (IP) fat mass, liver weight, leptin levels and vascular reactivity was measured. Western blotting of proteins involved in vascular function such as eNOS, AMPK and PKB were performed in aortic tissue. Antioxidant status and oxidative stress were determined in the liver tissue of experimental groups. This was done by measuring the activities of the primary antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and performing the thiobarbituric reactive substances (TBARS) assay which measures malondialdehyde as an indicator of lipid peroxidation. Results and Discussion HFD animals presented with increased food intake, leptin levels, body weight, glucose levels, IP fat and liver mass compared to Control animals. Furthermore, HFD animals had decreased fluid intake and increased blood pressure vs the Control animals. Additionally, they presented with a downregulation in total and phosphorylated PKB and AMPK expression. HFD rats also had reduced SOD, CAT and GPx activity, increased malondialdehyde (MDA) levels and phosphorylated eNOS levels vs Control animals. Supplementation with GRT extract significantly decreased body weight, leptin levels, IP fat, liver mass and improved glucose metabolism. Furthermore, it increased vasodilation, total eNOS expression, AMPK phosphorylation according to the AMPK ratio, whereas it decreased blood pressure. Additionally, it upregulated SOD, CAT and GPx activity and decreased MDA levels in the liver. Captopril decreased blood pressure, increased vasodilation and upregulated PKB, AMPK and eNOS expression. Therefore, supplementation with GRT extract alleviated the plethora of cardiovascular risk factors presented by the HFD animals. Conclusion The HFD model demonstrated detrimental effects on cardiovascular health. Treatment with the Afriplex GRTTM extract improved glucose metabolism, vascular function and antioxidant status in the HFD animals. Therefore, Afriplex GRT™ extract may be a potential therapeutic agent against obesity-related vascular dysfunction, impaired glucose homeostasis, elevated blood pressure and oxidative stress.

Inleiding Vetsug word geassosieer met die ontwikkeling van metaboliese sindroom, 'n konglomeraat van kardiometaboliese risikofaktore, wat sinergisties lei tot kardiovaskulêre siektes (CVD's), die grootste oorsaak van die dood wêreldwyd. Die inheemse Suid-Afrikaanse plant, Rooibos (Aspalathus linearis), bevat polifenoliese fitochemikalieë soos aspalatien, wat uniek is aan Rooibos en geassosieer word met sy gesondheidsbevorderende eienskappe. Dit sluit in antidiabetiese, anti-inflammatoriese, antioksidant, anti-vetsug en kardiovaskulêre voordele. Nie veel is bekend oor die gesondheidsbevorderende eienskappe van Afriplex GRTTM, 'n aspalatienryke Rooibos-ekstrak, nie. Daar word gepostuleer dat Afriplex GRTTM die ontwikkeling van hipertensie, vaskulêre disfunksie en oksidatiewe stres kan verbeter in 'n model van vetsugtige Wistar-rotte. Doelstelling Om die verbeterende effekte van Afriplex GRT™ ekstrak op bloeddruk, vaskulêre funksie en oksidatiewe stres in dieet-geïnduseerde vetsugtige Wistar-rotte te ondersoek. Metodes Volwasse manlike Wistar-rotte is lukraak verdeel in 5 eksperimentele groepe (n = 10 / groep) en is ‘n Kontrole of hoëvet-dieet (HFD) gevoer om vetsug oor 'n tydperk van 16 weke te veroorsaak. Rotte in die HFD- en Kontrole groepe het die aspalatien-ryke ekstrak as aanvulling ontvang vanaf week 10 tot 16 teen 60 mg / kg / dag. 'n Captopril (50 mg / kg / dag) groep is as 'n positiewe kontrole ingesluit. Voedsel- en waterinname, liggaamsgewig, bloedglukose, bloeddruk, intraperitoneaal (IP) vetmassa, lewergewig, leptienvlakke en vaskulêre reaktiwiteit is gemeet. Westerse klad tegnieke is uitgevoer om die uitdrukking van proteïene betrokke by vaskulêre funksie, soos eNOS, AMPK en PKB, in aortiese weefsel te bepaal. Antioksidant status en oksidatiewe stres is bepaal in die lewerweefsel van eksperimentele groepe. Dit is gedoen deur die aktiwiteite van die primêre anti-oksidant ensieme- superoksied dismutase (SOD), katalase (CAT), glutatioonperoksidase (GPx) te meet, en die tiobarbituursuur reaktiewe stowwe (TBARS) te toets wat malondialdehied meet as 'n aanduiding van lipiedperoksidasie. Resultate en Gevolgtrekking HFD-diere het verhoogde voedselinname, leptienvlakke, liggaamsgewig, basale glukosevlakke, IP-vet en lewermassa in vergelyking met Kontrole-diere getoon. Verder het HFD-diere verminderde vloeistofinname, en verhoogde bloeddruk teenoor die Kontrole diere gehad. Daarbenewens het hulle 'n onderdrukking in totale en gefosforileerde PKB en AMPK uitdrukking getoon. HFD rotte het ook verlaagde SOD, CAT en GPx aktiwiteit, sowel as verhoogde malonaldialdehied (MDA) en gefosforileerde eNOS vlakke teenoor Kontrole diere getoon. Aanvulling met GRT ekstrak het tot beduidend verminderde liggaamsgewig, leptienvlakke, IP-vet, lewermassa en verbeterde glukose metabolisme gelei. Verder het dit vasodilatasie, totale eNOS-uitdrukking, sowel as AMPK-fosforilering volgens die AMPK-verhouding verhoog, terwyl dit bloeddruk verlaag het. Daarbenewens het dit SOD, CAT en GPx aktiwiteit opreguleer en MDA-vlakke in die lewer verminder. Captopril het bloeddruk verminder, vasodilatasie bevorder en PKB-, AMPK- en eNOS-uitdrukking verhoog. Aanvulling met die GRT ekstrak het dus die oorvloed van kardiovaskulêre risikofaktore waarmee die HFD-diere gepresenteer het, verlig. Afsluiting Die HFD-model het nadelige uitwerking op kardiovaskulêre gesondheid getoon. Behandeling met die Afriplex GRT™ ekstrak het glukose metabolisme, vaskulêre funksie en antioksidante status in die HFD diere verbeter. Die Afriplex GRT™ ekstrak mag dus ʼn potensiële terapeutiese middel wees teen die behandeling van vetsugverwante vaskulêre disfunksie, verswakte glukose homeostase, verhoogde bloeddruk en oksidatiewe stres.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/103585
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