Polymatin A from Smallanthus macroscyphus leaves: A safe and promising antidiabetic compound.

Smallanthus macroscyphus is an herb native to South America whose leaves are a source of antidiabetic compounds, although complete information about their safe use is not available yet. This study was developed to evaluate the toxicity profile of both 10% decoction and the sesquiterpene lactone polymatin A from S. macroscyphus leaves through in vitro cytotoxicity assays and in vivo subchronic oral toxicity. Cell viability of Hep-G2, COS1, CHO-K1 and Vero cell lines decreased in a concentration-dependent manner when cells were incubated with 0.4-200 µg ml(-1) of dry extract or 0.12-60 µg ml(-1) of polymatin A. In subchronic studies, decoction was orally administered to Wistar rats for 90 days at daily doses of 70, 140 and 280 mg kg(-1) of dry extract, whereas polymatin A was administered in the same way at doses of 7, 14 and 28 mg kg(-1) . No toxicity signs or deaths were observed. There were no changes in the behavior, body or organ weights, hematological, biochemical or urine parameters of the rats. No histopathological lesions were observed in the examined organs. The results indicate that the 10% decoction and polymatin A from S. macroscyphus leaves may be considered as non-toxic substances at a wide range of doses, including the effective hypoglycemic dose. Copyright © 2016 John Wiley & Sons, Ltd.

Yacon roots (Smallanthus sonchifolius) improve oxidative stress in diabetic rats.

CONTEXT: Smallanthus sonchifolius (Poepp. and Endl.) H. Robinson, Asteraceae (yacon) roots are a natural product recognized by the traditional medicine to treat diabetes-related problems. There are no reports concerning the potential of yacon roots to reduce oxidative stress and ameliorate diabetes complications in diabetic animals. OBJECTIVE: This work analyzes the in vivo antioxidant activity and beneficial effects of yacon roots, using a model of streptozotocin-induced diabetes in rats. MATERIALS AND METHODS: Lipid peroxidation and other indicators of oxidative stress were determined in liver and kidney homogenates from non-diabetic rats, untreated diabetic rats, and diabetic rats treated orally with yacon flour (340 mg fructooligosaccharide/kg/d) as a diet supplement for 90 d. Biochemical parameters were determined in liver, kidney, and blood at the end of the experimental period. RESULTS: Yacon supplementation to diabetic rats produced a significant decrease in malondialdehyde levels in both liver (-30.97%) and kidney (-19.15%). Hepatic superoxide dismutase and catalase activities were significantly lower in diabetic-treated rats (-13.46 and -64.33%, respectively) compared with diabetic controls. Similar results were observed in kidney. The treatment of diabetic rats produced an increase of glutathione peroxidase and glutathione levels in liver (172.50 and 35.91%, respectively) and kidney (177.78 and 57.76%, respectively). Plasma cholesterol and triacylglycerol levels and liver fatty acid composition, which were altered in diabetic rats, reverted back to nearly normal with yacon treatment. CONCLUSIONS: These results indicate that yacon root flour is a potential diet supplement with high in vivo antioxidant activity.

Smallanthus macroscyphus: a new source of antidiabetic compounds.

The aim of the present study was to analyze the in vivo hypoglycaemic effects of both decoction of Smallanthus macroscyphus leaves and pure crystalline polymatin A isolated from its leaves. Phytochemical analysis of the leaf decoction showed that its major constituents were caffeic, chlorogenic and three dicaffeoilquinic acids, together with the sesquiterpene lactone polymatin A. Oral glucose tolerance test in normal rats was performed to evaluate the hypoglycemic activity and to choose the minimum effective dose of the decoction and polymatin A. They have effective hypoglycemic activity at the minimum dose of 140 mg dry extract and 14 mg crystalline powder/kg body weight, respectively, and were selected for the following experiments. Oral administration of a single-dose of decoction produced a moderate lowering effect in fasting glycemia of normal rats, whereas polymatin A had no significant effect. We also assessed the effect of a single-dose on post-prandial blood glucose, resulting in an inhibition of the hyperglycemic peak after sucrose overload. Daily administration of decoction or polymatin A for 4 weeks produced an effective glycemic control in diabetic animals, with a decrease in urinary glucose excretion and a significant reduction in the HbA1c levels. Although there were no significant increases in plasma insulin levels, both treatments improved the fasting blood glucose/insulin ratio. In vivo acute toxicity studies were performed in adult Wistar rats. There were no deaths or signs of toxicity observed after oral administration of decoction or polymatin A at any dose level up to the highest dose tested (14.0 and 2.8 g/kg, respectively). The results presented here strongly support the notion that S. macroscyphus represents a new source of antidiabetic compounds that could help to manage diabetes more efficiently and safely.

Protective effect of yacon leaves decoction against early nephropathy in experimental diabetic rats.

Nephropathy is the most common cause of morbidity and mortality in diabetic patients. Prevention of this complication has a major relevance. Smallanthus sonchifolius (yacon) leaves have been shown to ameliorate hyperglycemia in streptozotocin-induced diabetic rats. We examined the beneficial effects of yacon leaves decoction on diabetic nephropathy and explored the possible underlying action mechanism. Streptozotocin-diabetic rats were orally administered 10% yacon leaves water decoction (70mg dry extract/kg body weight) once a day for 4weeks. Biochemical parameters in blood and urine were analyzed and immunohistochemistry staining, western immunoblotting and qRT-PCR were assessed. Yacon decoction significantly decreased high blood glucose level in diabetic rats and improved insulin production. Diabetic-dependent alterations in urinary albumin excretion, creatinine clearance, kidney hypertrophy and basement membrane thickening were attenuated by yacon decoction. These findings were associated with a marked decrease in TGF-ß1/Smad2/3 signaling. The expression of molecular markers of diabetic nephropathy such as collagen IV, laminin-1, fibronectin and collagen III were also diminished in the yacon-treated group compared to control diabetic group. These results suggest that yacon leaves decoction is a protective agent against renal damage in diabetic nephropathy, whose action can be mediated by TGF-ß/Smads signals.

Hypoglycemic activity of leaf organic extracts from Smallanthus sonchifolius: Constituents of the most active fractions.

The aim of the present study was to determine the in vivo hypoglycemic activity of five organic extracts and enhydrin obtained from yacon leaves. The main constituents of the most active fraction were identified. Five organic extracts and pure crystalline enhydrin were administered to normoglycemic, transiently hyperglycemic and streptozotocin (STZ)-diabetic rats. The fasting and post-prandial blood glucose, and serum insulin levels were estimated and an oral glucose tolerance test (OGTT) was performed for the evaluation of hypoglycemic activity and dose optimization of each extract. We found that the methanol, butanol and chloroform extracts showed effective hypoglycemic activity at minimum doses of 50, 10 and 20mg/kg body weight, respectively, and were selected for further experiments. Oral administration of a single-dose of each extract produced a slight lowering effect in the fasting blood glucose level of normal healthy rats, whereas each extract tempered significantly the hyperglycemic peak after food ingestion. Daily administration of each extract for 8 weeks produced an effective glycemic control in diabetic animals with an increase in the plasma insulin level. Phytochemical analysis of the most active fraction, the butanol extract, showed that caffeic, chlorogenic and three dicaffeoilquinic acids were significant components. Additionally, enhydrin, the major sesquiterpene lactone of yacon leaves, was also effective to reduce post-prandial glucose and useful in the treatment of diabetic animals (minimum dose: 0.8mg/kg body weight). The results presented here strongly support the notion that the phenolic compounds above as well as enhydrin are important hypoglycemic principles of yacon leaves that could ameliorate the diabetic state.

Subchronic 4-month oral toxicity study of dried Smallanthus sonchifolius (yacon) roots as a diet supplement in rats.

Yacon roots are a rich source of fructooligosaccharides (FOS) and have a long use tradition as food in the Andean region. However, there are no published reports regarding their toxicology and use safety. The aim of this study was to analyze the effects of subchronic (4-months) oral consumption of dried yacon root flour as a diet supplement using normal Wistar rats. Two daily intake levels were used, equivalent to 340 mg and 6800 mgFOS/body weight, respectively. Yacon administered as a diet supplement was well tolerated and did not produce any negative response, toxicity or adverse nutritional effect at both intake levels used. Yacon root consumption showed no hypoglycemic activity in normal rats and resulted in significantly reduced post-prandial serum triacylglycerol levels in both doses assayed. Conversely, serum cholesterol reduction was not statistically significant. Cecal hypertrophy was observed in rats fed only the high dose. Our results indicating lack of toxicity and a certain beneficial metabolic activity in normal rats warrant further experiments with normal subjects and patients suffering metabolic disorders. They should also be considered when establishing the regulatory framework of this natural product by national health authorities and international trade agencies.