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Objectives Metabolic syndrome (MetS), a multiplex risk factor for cardiovascular disease and type 2 diabetes, is increasingly prevalent worldwide. Ellagitannin geraniin, a polyphenol found in the rind of rambutan (Nephelium lappaceum), has demonstrated therapeutic effects against metabolism dysfunction. The aim of this study was to characterize the metabolic effects and possible mechanism of geraniin in rats with MetS induced by a high-fat diet (HFD). Methods MetS was induced in Sprague Dawley rats on an HFD, followed by a daily oral gavage of geraniin (25 mg/kg) for 4 wk. The outcomes of geraniin-treated rats were compared with those of untreated rats on either a control diet or an HFD and with rats with MetS treated with metformin on a daily basis (200 mg/kg). Results The supplementation of geraniin ameliorated multiple metabolic abnormalities caused by HFD, including hypertension, impaired glucose and lipid metabolism, ectopic fat deposition in the visceral fat and liver, and disturbed antioxidant mechanism and inflammatory response. The benefits conferred by geraniin were comparable to metformin. Transcriptomic analysis revealed a profound influence of geraniin on the hepatic expression profiles. The lipid and steroid metabolic processes that were aberrantly activated by HFD were suppressed by geraniin. Based on the differential transcriptomes, geraniin also exerted a significant modulatory effect on the expression of mitochondrial genes, potentially influencing the mitochondrial activity and leading to the observed beneficial effects. Conclusion Geraniin supplementation mitigated metabolic anomalies of MetS in rats, making it an attractive drug candidate for further investigation.

Chronic hyperglycemia increases oxidative stress, activates inflammatory pathways and reduces nerve growth factor (NGF) among diabetic patients, which contribute to development of diabetic peripheral neuropathy (DPN). Tocotrienol-Rich Vitamin E (Tocovid) possesses potent antioxidant and anti-inflammatory properties which are postulated to target these pathogeneses in order to ameliorate DPN. This study aims to evaluate the effects of Tocovid on nerve conduction parameters and serum biomarkers among diabetic patients. This multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial was conducted on 80 eligible participants. The intervention group (n = 39) was randomly allocated to receive 200 mg of Tocovid twice a day, and the control group (n = 41) received placebo twice a day. At the end of eight weeks, the nerve conduction parameters, as assessed by nerve conduction study, as well as serum biomarkers (NGF, malondialdehyde, vascular cell adhesion molecule 1, tumor necrosis factor receptor 1 and thromboxane B2) were compared between the two groups. Compared to placebo, Tocovid significantly improves the nerve conduction velocities of all nerves (+1.25 m/s, interquartile range [IQR] 3.35, p &lt, 0.001, median nerve, +1.60 m/s, IQR 1.80, p &lt, 0.001, sural nerve, +0.75 m/s, IQR 2.25, p &lt, 0.001, tibial nerve). Meanwhile, the levels of serum NGF were significantly higher in the Tocovid group as compared to placebo at eight weeks post-intervention. Participants receiving Tocovid illustrated highly significant improvement in terms of nerve conduction velocities for all nerves tested after eight weeks of supplementation. In addition, Tocovid supplementation elevated the levels of serum NGF, in which its increase is postulated to reflect enhanced neuronal functions. This novel finding suggests that Tocovid could be a disease-modifying agent targeting serum NGF to improve nerve conduction velocities.

Objective A preliminary study showed that geraniin extracted from Nephelium lappaceum L. at 50 mg/kg caused reduction in blood glucose and insulin resistance. The present study serves to further investigate the effects of geraniin at increasing doses between 3.125 and 100 mg/kg in high-fat diet-treated rats. Methods Geraniin (95% purity) was extracted and purified from rambutan rind. Two groups of male Sprague-Dawley rats were fed with 60% high-fat diet and standard rat chow, respectively, for 12 weeks. High-fat diet-treated rats were then administered geraniin at different doses. Body weight, blood pressure and blood glucose readings were measured. At the end of treatment, blood was collected for analysis of glycated haemoglobin A1c (HbA1c), insulin, advanced glycation end-product (AGE) levels, renin, aldosterone and electrolytes. Results Within the first week of treatment, even the lowest dose of geraniin caused a significant reduction in blood pressure, which was comparable to control diet-treated rats. There were no changes in serum electrolytes, renin or aldosterone. Similarly, there was a significant reduction in serum insulin, insulin resistance and AGE levels at the lowest dose. However, there was no significant decrease in fasting blood glucose or HbA1c. The effects of decreasing insulin, insulin resistance and AGEs were observed only at the lower doses, unlike the results observed for blood pressure reduction. Conclusion Geraniin at lower doses improved blood pressure and other metabolic parameters. Secondary metabolites of geraniin, associated with antihypertensive activity, are relatively different to those involved in inhibiting AGE formation and increasing insulin sensitivity. The secondary metabolites of geraniin may be individually responsible for the bioactivities demonstrated.

The present study aimed to outline the physiological and metabolic disparity between chow- and purified ingredient-based high-fat diets and their efficacy in the induction of metabolic syndrome (MetS). Male, 3-week-old Sprague Dawley rats were randomly assigned to chow-based control diet, chow-based high-fat diet, purified control diet, and purified high-fat diet for 12 weeks. Physical and biochemical changes were documented. Chow-based diets, irrespective of the lipid content, resulted in significantly lower weight gain and organ weight compared to purified ingredient-based diets. Circulating insulin, total proteins, albumin, and certain lipid components like the triglycerides, total cholesterol, and high-density lipoprotein-cholesterol were also lower in the chow-based diet groups. Both chow- and purified high-fat diets induced central obesity, hypertension, and hyperglycaemia, but the latter was associated with earlier onset of the metabolic aberrations and additionally, dyslipidaemia. In conclusion, purified high-fat diet is a better diet for MetS induction in rats. PRACTICAL APPLICATIONS: Modeling metabolic syndrome is commonly accomplished with the use of chow- or purified ingredient diets enriched with carbohydrates and/or lipids, but the differences and associated drawbacks are unclear. This study highlights that chow- or modified chow-based diets have a tendency to introduce unwanted metabolic changes which are inconsistent with the progression of metabolic syndrome. Thus, the use of these diets in metabolic disease study should be avoided. On the other hand, purified high-fat diet which can effectively induce the features of metabolic syndrome is highly recommended.