Therapeutic effects of an aspalathin-rich green rooibos extract, pioglitazone and atorvastatin combination therapy in diabetic db/db mice

Oral therapeutics used to treat type 2 diabetes and cardiovascular disease often fail to prevent the progression of disease and their comorbidities. Rooibos (Aspalathus linearis), an endemic South African plant used as an herbal tea, has demonstrated positive effects on glycemia and hypercholesterolemia. However, the treatment efficacy of rooibos extract in combination with conventional hypoglycemic and hypolipidemic medications on blood glucose and lipid profiles has not been established. This study aimed to investigate the effects of combining an aspalathin-rich green rooibos extract (Afriplex GRT™) with pioglitazone and atorvastatin, on blood glucose and lipid levels in obese diabetic (db/db) mice. Six-week-old male db/db mice and their nondiabetic lean littermate controls (db+) were divided into 8 experimental groups (n = 6/group). Db/db mice were treated daily either with pioglitazone (25 mg/kg), atorvastatin (80 mg/kg) and GRT (100 mg/kg), a combination of either drug with GRT or a combination of GRT-pioglitazone and atorvastatin for 5 weeks. Untreated vehicle controls were given dimethyl sulfoxide (0.1%) and phosphate buffered saline solution. At termination, serum and liver tissue were collected for lipid and gene expression analysis. Treatment with GRT, pioglitazone and atorvastatin combination effectively lowered fasting plasma glucose (FPG) levels in db/db mice (p = 0.02), whilst increasing body weight, liver weight, and reducing retroperitoneal fat weight. Atorvastatin monotherapy was effective at reducing cholesterol (from 4.00 ± 0.12 to 2.93 ± 0.13, p = 0.0003), LDL-C (from 0.58 ± 0.04 to 0.50 ± 0.00, p = 0.04), HDL-C (from 2.86 ± 0.05 to 2.50 ± 0.04, p = 0.0003) and TG (from 2.77 ± 0.50 to 1.48 ± 0.23, p = 0.04), compared to the untreated diabetic control. The hypotriglyceridemic effect of atorvastatin was enhanced when used in combination with both GRT and pioglitazone. The addition of pioglitazone to GRT significantly lowered FPG and TG. In db/db mice, Apoa1 was significantly downregulated in the liver, whilst Pparγ was significantly upregulated compared to their db+ counterparts. GRT monotherapy downregulated Apoa1 expression (p = 0.02). Atorvastatin combined with GRT significantly downregulated mRNA expression of Apoa1 (p = 0.03), whilst upregulating the expression of Pparγ (p = 0.03), Pparα (p = 0.002), Srebp1 (p = 0.002), and Fasn (p = 0.04). The GRT-pioglitazone-atorvastatin combination therapy downregulated Apoa1 (p = 0.006), whilst upregulating Fasn (p = 0.005), Pparα (p = 0.041), and Srebp1 (p = 0.03). Natural products can improve the efficacy of current drugs to prevent diabetes-associated complications. GRT in combination with pioglitazone enhanced the reduction of FPG, whilst the addition of atorvastatin to the combination, significantly lowered triglyceride levels. However, when GRT was used in combination with atorvastatin only cholesterol levels were affected. Although these results confirm both glucose- and lipoprotein-lowering biological effects of GRT in combination with pioglitazone and atorvastatin, increased expression of genes involved in lipogenesis, cholesterol, and fatty acid transport, β-oxidation, and synthesis and storage of fatty acids, may exacerbate the hepatotoxic effects of atorvastatin.

Positive Effects of Different Drug Forms of Silybin in the Treatment of Metabolic Syndrome

Silymarin and silybin are widely used for their hepatoprotective properties. Our previous studies confirm positive effect of silymarin on lipoprotein profile and lipid homeostasis. Advanced drug forms may improve the bioavailability of these compounds. In this study, we investigate the effects of silybin in different drug forms (standardized silybin, micronized silybin, and silybin in form of phytosomes) on dyslipidemia and glucose metabolism in hereditary hypertriglyceridemic (HHTg) rats. Male HHTg rats were divided into four groups of seven animals and were fed by experimental diets. Silybin significantly decreased serum level of triglycerides in groups of rats fed by standardized silybin and silybin in form of phytosomes compared to control group. Results show that silybin did not affect the total cholesterol level, but significantly increased the levels of HDL cholesterol in all groups of animals. Silybin in a standardized form had the highest hypotriglyceridemic effect. On the other hand, the micronized form has caused the highest increase of protective HDL and most significantly decreased glucose and insulin levels. Our results suggest that silybin is probably responsible for some positive properties of silymarin. Subsequent dose-dependent studies of silybin action may reveal the intensity of its positive effects on lipid and glucose parameters.

The effect of EPA and DHA on metabolic syndrome patients: a systematic review of randomised controlled trials

Metabolic syndrome (MS) is characterised by accumulation of CVD risk factors. The use of very long chain n-3 polyunsaturated fatty acids (VLC n3 PUFA) could potentially benefit MS by reducing risk factors. To better understand the possible VLC n3 PUFA benefits, the literature was systematically reviewed for randomised controlled trials (RCT) that published effects of VLC n3 PUFA on MS patients. 17 RCT fulfilled the inclusion criteria and were analysed for relevance to the research question. The available RCT convincingly show that the administration of VLC n3 PUFA doses > 1 g for at least 3 months produces a significant reduction of triglycerides ranging from 7 % to 25 %. These results confirm the hypotriglyceridemic effect of VLC n3 PUFA in MS patients. The triglyceride lowering may produce further benefits by reducing the % of pro-atherogenic small dense LDL particles (sdLDL) and also perhaps by ameliorating the inflammatory process associated with MS. High doses of VLC n3 PUFA ( ≥ 3 g/day) may produce further TAG reductions but could raise other risk factors such as LDL-C. No clear effects were found on other MS markers. The combination of VLC n3 PUFA plus a statin may be useful to prevent the occurrence of coronary events. More studies are needed using different amounts of VLC n3 PUFA, time lengths, dietary backgrounds and different profiles of MS patients before clear recommendations can be made.

Blood lipids profile in lactating cows fed with supplement of OVOCAP®

This study was conducted to test the effects of feeding supplemental Bulgarian nutritive additive OVOCAP? administrated per os, on blood lipid profile in lactating cows. Twelve lactating American Brown cows (BW = 695 ? 28 kg; at the beginning of the lactation) were separated to two treatments for 1,5 year. Cows were fed typical diets during the winter (corn silage, meadow hay, straw, wheat bran, potatoes and compound feed) and summer (pasture and compound feed). Experimental cows received in addition to concentrate part of their daily ration 2x23 ml OVOCAP? each every 28th day in the month, first doses being on the 3rd and 4th day post partum. Blood samples were collected after every giving doses of OVOCAP?, morning before feeding and sera were analyzed for triglycerides, HDL, LDL, VLDL and total lipids concentration. Feed intake was similar in the two groups. Observed levels of the HDL cholesterol were significant lowered (P?0,05) under the influence of OVOCAP?. Observed levels of LDL and VLDL cholesterol as well as triglycerides and total lipids were significant lowered (P ?0,001) under the influence of OVOCAP?. This results suggest that OVOCAP? may posses hypocholesterolemia and hypotriglyceridemic effect in lactating cows. This experiment demonstrated that OVOCAP? is adjusted to use in lactating cows with sure definite benefit on blood lipoprotein profile.