Aspalathin-Rich Green Rooibos Extract Lowers LDL-Cholesterol and Oxidative Status in High-Fat Diet-Induced Diabetic Vervet Monkeys.

Patrick Orlando,Elizabeth Joubert,Christo J.F Muller,Nireshni Chellan,Phiwayinkosi Dludla,Ilenia Cirilli,Johan Louw,Luca Tiano

doi:10.3390/molecules24091713

Abstract

Type 2 diabetic patients possess a two to four-fold-increased risk for cardiovascular diseases (CVD). Hyperglycemia, oxidative stress associated with endothelial dysfunction and dyslipidemia are regarded as pro-atherogenic mechanisms of CVD. In this study, high-fat diet-induced diabetic and non-diabetic vervet monkeys were treated with 90 mg/kg of aspalathin-rich green rooibos extract (Afriplex GRT) for 28 days, followed by a 1-month wash-out period. Supplementation showed improvements in both the intravenous glucose tolerance test (IVGTT) glycemic area under curve (AUC) and total cholesterol (due to a decrease of the low-density lipoprotein [LDL]) values in diabetics, while non-diabetic monkeys benefited from an increase in high-density lipoprotein (HDL) levels. No variation of plasma coenzyme Q10 (CoQ10) were found, suggesting that the LDL-lowering effect of Afriplex GRT could be related to its ability to modulate the mevalonate pathway differently from statins. Concerning the plasma oxidative status, a decrease in percentage of oxidized CoQ10 and circulating oxidized LDL (ox-LDL) levels after supplementation was observed in diabetics. Finally, the direct correlation between the amount of oxidized LDL and total LDL concentration, and the inverse correlation between ox-LDL and plasma CoQ10 levels, detected in the diabetic monkeys highlighted the potential cardiovascular protective role of green rooibos extract. Taken together, these findings suggest that Afriplex GRT could counteract hyperglycemia, oxidative stress and dyslipidemia, thereby lowering fundamental cardiovascular risk factors associated with diabetes.

Highlights

Diabetes mellitus is a global pandemic afflicting 425 million adults worldwide, with trends suggesting the rate will continue to rise, reaching 642 million in 2040 [1]
This study aimed to evaluate the biological activity of standardized, pharmaceutical-grade, aspalathin-rich green rooibos extract (Afriplex, GRT) containing 12.8% aspalathin in improving the oxidative status and lipid profile of high-fat diet-fed diabetic and healthy non-human primates (Chlorocebus pygerythrus)
After 4 weeks of treatment, low-density lipoprotein (LDL) levels of diabetic monkeys remained unchanged (Figure 1B), while the total cholesterol significantly increased in comparison following 2 weeks treatment (Figure 1A) (+8%, p = 0.032)

Summary

Introduction

Diabetes mellitus is a global pandemic afflicting 425 million adults worldwide, with trends suggesting the rate will continue to rise, reaching 642 million in 2040 [1]. Almost 90% of diabetic patients are affected by the lifestyle-related sub-type, type 2 diabetes (T2DM) [2], a progressive metabolic disease characterized by insulin resistance and eventual functional failure of pancreatic beta cells [3]. It is known that T2DM is associated with higher cardiovascular morbidity and mortality. Type 2 diabetic patients have a two to four-fold increased risk of incident coronary heart disease, ischemic stroke and a 1.5 to 3.6-fold increase in mortality [4]. Hyperglycemia is a key cardiovascular risk factor for patients with type 2 diabetes [5]. Increased glucose flux through the polyol pathway, intracellular formation of advanced glycation end products (AGE) and increased expression of its receptors [5], as well as activation of protein kinase C (PKC) [6]

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