Masters Degrees (Medical Physiology)

Permanent URI for this collection

https://scholar.sun.ac.za/handle/10019.1/3553

Browse

Browsing Masters Degrees (Medical Physiology) by browse.metadata.advisor "Barbara, Huisamen"

Now showing 1 - 1 of 1
  • Thumbnail Image
    Item
    Aspalathus linearis as a possible SGLT2 inhibitor : investigating the antihypertensive effects of green rooibos extracts
    (Stellenbosch : Stellenbosch University, 2023-03) Willemse, Ilze Verona; Barbara, Huisamen; Erna, Marais; Shantal, Windvogel; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Division of Medical Physiology.
    ENGLISH ABSTRACT: Introduction: Obesity-induced non-communicable disease development is a growing epidemic. SGLT2, located in kidneys, reabsorb glucose and sodium from urine. Studies suggest SGLT2 expression and activity are upregulated during chronic hyperglycaemia. SGLT2-inhibitors, a costly class of anti-diabetic treatment, are also cardio-protective and anti-hypertensive. An alternative treatment is Rooibos (Aspalathus linearis), a native South African plant. Afriplex GRT™ and E1CHA, are Rooibos extracts containing high levels of Aspalathin. It is hypothesized that Rooibos may reduce diet-induced hypertension and vascular dysfunction. Aim(s): To (i) verify whether different Rooibos extracts embody SGLT2- inhibitors as a key mechanism of action to counteract diet-induced metabolic changes, (ii) determine the possible expression levels of SGLT2 in aortic tissue and (iii) whether this is modulated by ingestion of Rooibos extracts. Methods: Adult male Wistar rats were randomly allocated into either Controls (rodent chow) or HFD (obesogenic diet)(n=96/group) and further subdivided into eight treatment groups (n=12-36/group). Animals were on diets for 16 weeks, with a 6-week treatment period (last 6 weeks) with 60mg/kg/day of either Afriplex GRT™ or E1CHA (SA Rooibos council) or Empagliflozin (EMPA) (10mg/kg/day) (positive control). Body weight, food and water consumption, blood glucose, blood pressure, IP fat weight, liver weight, and ex vivo vascular reactivity (on aorta’s without PVAT) was determined. Western blot analysis of aortic tissue was conducted to determine activation and expression levels of the proteins implicated in vascular function (AMPK, eNOS, PKB/Akt), SGLT2, ATM, mTOR,S6Kinase and markers of SGLT2 activation and expression (ERK and IĸB). Serum was used to determine aldosterone and endothelin 1 (ET-1) expression levels by means of ELISA kits. Results: HFD animals had amplified food consumption, body weight, glucose levels, IP fat, liver weight, and was hypertensive. Moreover, the aortas of HFD had decreased in the following: phosphorylated AMPK, total IĸB, total and phosphorylated ATM, total and phosphorylated mTOR, phosphorylated ERKp42. While the following were increased: total SGLT2, total ERK p42/p44. Treatment with GRT™ reduced the following: water intake, IP fat weight, fasting and non-fasting glucose levels, systolic and mean arterial blood pressure. Furthermore GRT™ increased total ERK p42/p44 expression and ERK p42 activation vs Untreated control. E1CHA treatment increased vasodilation, fasting blood glucose levels, and body weight. While it reduced vasoconstriction, water intake, IP fat weight, total ATM, phosphorylated ERK p42, total and phosphorylated mTOR and liver weight (compared to the Untreated HFD). Treatment with EMPA increased glucose tolerance, total ERKp42/p44 and total AMPK. The following were reduced: vasodilation, IP fat weight, fasting blood glucose and water consumption. Conclusion: The HFD model had an adverse influence on cardiovascular health. In HFD animals, treatment with E1CHA improved vascular function, while treatment with GRT™ improved glucose metabolism and blood pressure. Furthermore, EMPA treatment improved glucose tolerance in the HFD group. E1CHA and GRT™ also showed characteristics of EMPA. Therefore, E1CHA and GRT™ may be potential alternative therapeutic agents against obesity induced insulin resistance, hypertension and vascular dysfunction. We conclude that SGLT2 is present within the aortic tissue and that they are upregulated during insulin resistance. Furthermore, Rooibos extracts may mimic the mechanism of action of SGLT2-inhibitors.