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Aspalathus linearis as a possible SGLT2 inhibitor : investigating the antihypertensive effects of green rooibos extracts
Thesis (MSc)--Stellenbosch University, 2023.
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| Language: | en_ZA |
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Stellenbosch : Stellenbosch University
2023
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| _version_ | 1867614000008658944 |
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| access_status_str | Open Access |
| author | Willemse, Ilze Verona |
| author2 | Huisamen, Barbara |
| author_browse | Huisamen, Barbara Willemse, Ilze Verona |
| author_facet | Huisamen, Barbara Willemse, Ilze Verona |
| author_sort | Willemse, Ilze Verona |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (MSc)--Stellenbosch University, 2023. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/128452 |
| institution | Stellenbosch University (South Africa) |
| language | en_ZA |
| last_indexed | 2026-06-10T12:45:04.096Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2023 |
| publishDateRange | 2023 |
| publishDateSort | 2023 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/128452 Aspalathus linearis as a possible SGLT2 inhibitor : investigating the antihypertensive effects of green rooibos extracts Willemse, Ilze Verona Huisamen, Barbara Marais, Erna Windvogel, Shantal Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Division of Medical Physiology. Metabolic syndrome Hypotensive agents Rooibos tea Chronic diseases -- Treatment Obesity -- Animal models Epidemiology UCTD Thesis (MSc)--Stellenbosch University, 2023. 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. AFRIKAANSE OPSOMMING: Inleiding: Vetsug-geïnduseerde nie-oordraagbare siekte-ontwikkeling is 'n groeiende epidemie. SGLT2, geleë in die niere, herabsorbeer glukose en natrium uit urine. Studies dui daarop dat SGLT2 uitdrukking en aktiwiteit opgereguleer word tydens chroniese hiperglukemie. SGLT2-inhibeerders, 'n duur klas antidiabetiese behandeling, is ook kardiobeskermend en anti- hipertensief. 'n Alternatiewe behandeling is Rooibos (Aspalathus linearis), 'n inheemse SuidA frikaanse plant. Afriplex GRT™ en E1CHA, is rooibos-ekstrakte wat hoë vlakke van aspalathin bevat. Daar word veronderstel dat Rooibos dieetgeïnduseerde hipertensie en vaskulêre disfunksie kan verminder. Doelwitte: Om (i) te verifieer of verskillende Rooibos ekstrakte SGLT2-inhibeerders verteenwoordig, as ‘n sleutelmeganisme van aksie om dieet-geïnduseerde metaboliese veranderinge teen te werk, en (ii) die moontlike uitdrukkingsvlakke van SGLT2 in aortaweefsel te bepaal en (iii) of dit gemoduleer word deur inname van Rooibos ekstrakte. Metode(s): Volwasse manlike Wistar-rotte is ewekansig verdeel in Kontroles (knaagdier voedsel) of HFD (obesogeniese dieet) (n=96/groep) en verder onderverdeel in agt behandelingsgroepe (n=12-36//groep). Diere was vir 16 weke op dieet, met 'n 6-week behandelingsperiode (laaste 6 weke) met 60mg/kg/dag van óf Afriplex GRT™ óf E1CHA (SA Rooibos Raad) en Empagliflozin (EMPA) (10mg/kg/dag) (positiewe kontrole). Liggaamsgewig, voedsel- en water inname, bloedglukose, bloeddruk, intraperitoneale vet (IP), lewer gewig en vaskulêre reaktiwiteit (op aortas sonder PVAT) is bepaal. Western klad analise is uitgevoer om aktivering en uitdrukking vlakke van die proteïene betrokke by vaskulêre funksie (eNOS, AMPK, PKB/Akt), SGLT2, ATM, mTOR,S6Kinase en merkers van SGLT2 aktivering en uitdrukking (ERK en IĸB) te bepaal. Serum is gebruik om aldosteroon en Endothelin 1 (ET-1) uitdrukkingsvlakke te bepaal deur middel van ELISA kits. Resultate: HFD-diere het verhoogde voedselinname, liggaamsgewig, glukosevlakke, IP-vet, lewer gewig en bloeddruk gehad. Verder het die aortas van HFD afgeneem in die volgende: gefosforileerde AMPK, totale IĸB, totale en gefosforileerde ATM, totale en gefosforileerde mTOR, gefosforileerde ERKp42. Terwyl die volgende verhoog is: totaal SGLT2, totaal ERK p42/p44. Behandeling met GRT™ het die volgende verminder: waterinname, IP-vet gewig, vastende en nie-vastende glukosevlakke, sistoliese en gemiddelde arteriële bloeddruk. Verder het GRT™ totale ERK p42/p44 uitdrukking en ERK p42 aktivering verhoog in vergelyking met onbehandelde kontrole. E1CHA-behandeling het vasodilatasie, vastende bloedglukose vlakke en liggaamsgewig verhoog. Terwyl dit vasokonstriksie, waterinname, IP-vet gewig, totale OTM, gefosforileerde ERK p42, totale en gefosforileerde mTOR en lewer gewig verminder het (in vergelyking met die onbehandelde HFD). Behandeling met EMPA verhoogde glukosetoleransie, totale ERKp42/p44 en totale AMPK. Die volgende is verminder: vasodilatasie, IP-vet gewig, vastende bloedglukose en waterverbruik. Gevolgtrekking: Die HFD-model het nadelige effekte op kardiovaskulêre gesondheid gehad. In HFD-diere het behandeling met E1CHA vaskulêre funksie verbeter, terwyl behandeling met GRT™ glukose metabolisme en bloeddruk verbeter het. Verder het EMPA-behandeling glukosetoleransie verbeter in die HFD groep. E1CHA en GRT™ het ook kenmerke van EMPA getoon. Daarom kan E1CHA en GRT™ potensiële alternatiewe terapeutiese middels wees teen vetsug-geïnduseerde insulienweerstandigheid, hipertensie en vaskulêre disfunksie. Ons kom tot die gevolgtrekking dat SGLT2 in die aorta weefsel teenwoordig is en dat dit opgereguleer word tydens insulien verstandigheid. Verder kan Rooibos-ekstrakte die werkingsmeganisme van SGLT2-inhibitore naboot 2023-03-03T08:12:11Z 2023-08-30T13:11:39Z 2023-03-03 2023-03-03T08:12:11Z 2023-08-31T09:18:45Z 2023-03-03T08:12:11Z 2023-08-31T09:18:45Z 2023-03 Thesis https://scholar.sun.ac.za/handle/10019.1/128452 en_ZA Stellenbosch University application/pdf xxi, 180 pages : illustrations application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Metabolic syndrome Hypotensive agents Rooibos tea Chronic diseases -- Treatment Obesity -- Animal models Epidemiology UCTD Willemse, Ilze Verona Aspalathus linearis as a possible SGLT2 inhibitor : investigating the antihypertensive effects of green rooibos extracts |
| title | Aspalathus linearis as a possible SGLT2 inhibitor : investigating the antihypertensive effects of green rooibos extracts |
| title_full | Aspalathus linearis as a possible SGLT2 inhibitor : investigating the antihypertensive effects of green rooibos extracts |
| title_fullStr | Aspalathus linearis as a possible SGLT2 inhibitor : investigating the antihypertensive effects of green rooibos extracts |
| title_full_unstemmed | Aspalathus linearis as a possible SGLT2 inhibitor : investigating the antihypertensive effects of green rooibos extracts |
| title_short | Aspalathus linearis as a possible SGLT2 inhibitor : investigating the antihypertensive effects of green rooibos extracts |
| title_sort | aspalathus linearis as a possible sglt2 inhibitor investigating the antihypertensive effects of green rooibos extracts |
| topic | Metabolic syndrome Hypotensive agents Rooibos tea Chronic diseases -- Treatment Obesity -- Animal models Epidemiology UCTD |
| url | https://scholar.sun.ac.za/handle/10019.1/128452 |
| work_keys_str_mv | AT willemseilzeverona aspalathuslinearisasapossiblesglt2inhibitorinvestigatingtheantihypertensiveeffectsofgreenrooibosextracts |