The effects of a watery extract of Agathosma on the development of hypertension

Lombard, Jurie Wynand (2014-04)

Thesis (MScMedSc)--Stellenbosch University, 2014.

Thesis

ENGLISH ABSTRACT: Introduction: Obesity is a major risk factor for non-communicable diseases (NCD), a collective term given to type 2 diabetes (T2D), hypertension (HTN) and cardiovascular disease (CVD). Globally, NCDs are the leading cause of death. In recognition of this, untested remedies are flooding the market. Buchu water is one of these herbal remedies advertised as having antihypertensive properties. This water is a by-product of the extraction of the oil from the leaves of Agathosma. Buchu water is already freely available to the public. Aim: The aims of the present study were to test the effect of ingestion of Buchu water on i) the blood pressure (BP) of diet induced hypertensive as well as normotensive rats when given as pre-treatment; ii) HTN in rats when used as treatment; iii) endothelial function using aortic rings from control and hypertensive rats; iv) the expression and/or activation of signalling proteins involved in NO production in the endothelium (PKB/Akt, AMPK, eNOS); v) insulin sensitizing effects in cardiomyocytes prepared from insulin resistant rats to determine possible cardiovascular effects. Methodology: We utilized rat models of obesity induced HTN and diet-induced obesity (DIO). Male Wistar rats were rendered i) hypertensive by feeding a high fat diet (HFD) and ii) insulin resistant after being placed on a high caloric diet for 16 weeks. Half the animals were placed on Buchu water treatment (26% (v/v) Buchu water) for a period of 16 weeks. Blood pressure, urine output, water and food consumption were measured. The animals on the HFD were sacrificed and intraperitoneal fat weight determined, aortas used in aortic ring studies and blood collected for biochemical analyses. Animals in the DIO model were sacrificed after 16 weeks and cardiomyocytes prepared to determine insulin sensitivity. Results: The HFD caused increases in body weight, visceral adiposity and blood pressure. Chronic Buchu water treatment i) reduced body weight gain and visceral adiposity in the HFD animals; ii) affected leptin levels and components of the renin-angiotensin-aldosterone system (RAAS); iii) it both prevented the development of HTN when given in conjunction with the HFD and restored BP when used as treatment while having no effect on the BP of the control animals; iv) it had no effect on endothelial function nor did it activate any signalling proteins involved in the synthesis of NO in the endothelium that may be responsible for vasodilation in the arteries; v) it elevated basal myocardial glucose uptake which can be cardioprotective. Conclusion: Our present study was novel and demonstrated that Buchu water treatment exhibits similar properties to that of antihypertensive medication known as angiotensin-converting enzyme inhibitors. It acts on the whole body RAAS in a similar manner reducing both BP and weight gain. It also reduced metabolic aberrations (HTN, leptin, aldosterone) seen in animals on a HFD, partly through visceral fat remodelling. In addition Buchu water also elicits some cardioprotective properties. Thus we conclude that Buchu water is an alternative, cost effective and ready available means to treat HTN and is beneficial to one’s health.

AFRIKAANSE OPSOMMING: Inleiding: Vetsug is een van die hoof risikofaktore vir nie-oordraagbare siektes (NCD), 'n kollektiewe term vir tipe 2-diabetes (T2D), hoë bloeddruk (HTN) en kardiovaskulêre siektes (CVD). Wêreldwyd neem NCD toe en is die hoofoorsaak van sterftes. Na aanleiding hiervan, is daar tans ʼn oorstroming van natuurlike produkte wat geadverteer word as antihipertensiewe middels maar met geen wetenskaplike bewyse hiervan nie. Boegoewater is een van hierdie kruiemiddels wat bestaan uit die waterige byproduk van ekstraksie van boegoe-olie uit die blare van Agathosma. Boegoewater is reeds vrylik beskikbaar aan die publiek. Doelstellings: Die doelwitte van hierdie studie was om die effek van Boegoewater op i) die bloeddruk van hipertensiewe en kontrole rotte, beide voorkomend en as ii) behandeling; iii) endoteelfunksie van aortaringe; iv) die uitdrukking van proteiene betrokke by NO seintransduksie (PKB/Akt, AMPK, eNOS); v) insulien sensitisering van kardiomiosiete, te toets. Metodes: Ons het gebruik gemaak van twee rot modelle; i) wat vetsug veroorsaak met gepaardgaande hoë bloeddruk en ’n ander wat gepaardgaan met ii) dieet-geïnduseerde vetsugtig (DIO) met insulienweerstandigheid. Manlike Wistar rotte was geklassifieer as i) hipertensief na inname 'n hoë vet dieet (HFD) en as ii) insulien weerstandig na inname van 'n hoë kalorie dieet (DIO) vir 16 weke. Die helfte van die diere is met Boegoewater behandel (26% (v / v) Boegoewater) vir 'n tydperk van 16 weke. Gedurende die 16 weke van behandeling is die bloeddruk, urine, water- en voedselverbruik gemeet. Die diere op die HFD is na 16 weke opgeoffer en die liggaamsgewig en intraperitoneale vet gewig bepaal, die aorta ringe is geisoleer vir kontraksie/ontspannings studies en die bloed gekollekteer vir biochemiese analises. Die diere in die DIO model is ook na 16 weke geslag en kardiomiosiete is voorberei om die insuliensensitiwiteit te bepaal. Resultate: Die HFD het 'n toename in liggaamsgewig, viserale vet en bloeddruk teweeggebring. Kroniese Boegoewater behandeling het i) die liggaamsgewigtoename en viserale vet verlaag in die HFD diere; ii) leptienvlakke en komponente van die RAAS verlaag; iii) die ontwikkelling van hoë bloeddruk voorkom asook alreeds verhoogde bloeddruk effektief verlaag; iv) geen effek op endoteelfunksie of die uitdrukking van proteiene geassoseerd met NO produksie, getoon nie; v) basale glukose opname van kardiomiosiete verbeter. Gevolgtrekkings: Ons huidige studie, die eerste van sy soort, het getoon dat Boegoewater behandeling die aanvang van HTN kan voorkom, asook hipertensie kan behandel . Die studie het aangetoon dat Boegoewater soortgelyke eienskappe as die angiotensien-omskakelingsensiem (ACE) inhibeerders besit aangesien dit komponente van die RAAS beïnvloed het, gewigstoename beperk het en bloeddruk verlaag het. Metaboliese veranderinge soos leptienverlaging word aan hermodelering van die vetdepots toegeskryf. Verder lei Boegoewater behandeling tot miokardiale beskerming. Dit het ook metaboliese afwykings (soos HTN en glukose onverdraagsaamheid) in individue op 'n HFD verminder deur deels viserale vet hermodellering. Bykomend aan al die einskappe het Boegoewater beskerming ontlok teen iskemie deur verbeterde glukose opname tydens basale vlakke in kardiomiosiete. Ons het daarin geslaag om te bewys dat Boegoewater 'n alternatiewe, koste-effektiewe en beskikbare middel is om HTN meer te behandel en dat dit voordelig is vir jou gesondheid.

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