Signal transduction of the insulin secretion induced by the chalcone analogue, (E)-3-(phenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one, and its role in glucose and lipid metabolism.

A chalcone analogue, (E)-3-(phenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (DMU 101), was synthesized using classic base catalysis and Claisen-Schmidt condensation, and then screened for its antidiabetic properties. The compound's effects on glucose and lipid metabolism were assayed in rats that were treated acutely and for a short time to elucidate its mechanism of action, evaluating glucose tolerance and lactate dehydrogenase activity in response to chalcone analogue administration. The chalcone's in vitro and ex vivo effects on glycogen, glucose, lipid and lipolysis were also investigated, as well as the mechanism by which it induces 45Ca2+ influx-mediated insulin secretion. The analogue (10 mg/kg) diminished glycemia, without inducing acute cell damage, increased glycogen content in the skeletal muscle and reduced serum triacylglycerol and total cholesterol, but did not alter high-density lipoprotein or low-density lipoprotein. Chalcone (10 µM) stimulated glucose uptake in the soleus muscle and did not modulate in vitro or ex vivo lipolysis. This analogue also increased insulin secretion by triggering calcium influx and blocking ATP-sensitive K+ channels and voltage-dependent calcium channels. However, it also modulated stored calcium via sarco/endoplasmic reticulum calcium ATPase (SERCA) and ryanodine receptor (RYR) activity. These findings indicate that this chalcone may induce cellular repolarization via a mechanism mediated by calcium-dependent potassium channels.

Extract of Calyces from Physalis peruviana Reduces Insulin Resistance and Oxidative Stress in Streptozotocin-Induced Diabetic Mice.

Diabetes mellitus is a metabolic disorder mainly characterized by obesity, hyperglycemia, altered lipid profile, oxidative stress, and vascular compromise. Physalis peruviana is a plant used in traditional Colombian medicine for its known activities of glucose regulation. This study aimed to evaluate the anti-diabetic activity of the butanol fraction from an extract of Physalis peruviana calyces in two doses (50 mg/kg and 100 mg/kg) in induced type 2 diabetic mice. Blood glucose levels were evaluated once a week, demonstrating that a dose of 100 mg/kg resulted in greater regulation of blood glucose levels in mice throughout the experiment. The same overall result was found for the oral glucose tolerance test (OGTT) and the homeostatic model assessment for insulin resistance (HOMA- IR). The lipid profile exhibited improvement compared to the non-treated group, a dose of 100 mg/kg having greater protection against oxidative stress (catalase, superoxide dismutase, and malondialdehyde levels). Histopathological findings in several tissues showed structure preservation in most of the animals treated. The butanol fraction from Physalis peruviana at 100 mg/kg showed beneficial results in improving hyperglycemia, lipidemia, and oxidative stress status, and can therefore be considered a beneficial coadjuvant in the therapy of diabetes mellitus.

Inhibitory effects of an extract of fruits of Physalis peruviana on some intestinal carbohydrases / Evaluación in vitro del efecto de un extracto de frutos de Physalis peruviana sobre algunas carbohidrasas intestinales

Physalis peruviana is an Andean specie whose fruits are eaten as food and also has been reported in Colombian folk medicine for diabetes mellitus treatment. In addition, previous pharmacological studies on diabetic Wistar rats, an extract of P. peruviana fruits has been showed antidiabetic activity. In order to deepen in P. peruviana action mode as antidiabetic, in this investigation were determinate the Inhibitory Concentrations 50 (IC50) of P. peruviana fruits crude extract on alpha glucosidase from S. cerevisiae and from intestinal rat powder, on maltase and alpha amylase enzymes. The kinetic behavior of the extract on each enzyme was also investigated, and the enzyme constant (Km) and maximum rate (Vmax) were determined. Extract of fruits of P. peruviana showed different IC50 for alpha glucosidase from S. cerevisiae and intestinal rat powder, suggesting greater affinity for the enzyme of mammalian source (4114.7 and 3552.7 µg/mL, respectively). For maltase, the IC50 was close to that obtained for alpha glucosidase (4191.0 µg/mL) while for alpha amylase, the extract exhibited the highest inhibition (IC50: 619.9 g/mL). Regarding kinetic behavior, the extract showed competitive inhibition on alpha-glucosidase and maltase, and on the non-competitive type of alpha amylase. These suggest that inhibition of intestinal carbohydrases is one of the modes of action for the antidiabetic activity of fruits of P. peruviana.

Physalis peruviana es una especie andina, cuyos frutos además de ser usados como alimento, son empleados en la medicina tradicional para el tratamiento de la diabetes mellitus. Además, estudios farmacológicos previos en ratas Wistar han demostrado actividad antidiabética de extractos de frutos de P. peruviana. Con el fin de profundizar en el modo de acción de la actividad antidiabética de los frutos de P. peruviana, en la presente investigación se determinó la concentración inhibitoria 50 (CI50) del extracto crudo de frutos de P. peruviana, sobre las enzimas alfa glucosidasa obtenida de S. cerevisiae y de polvo intestinal de rata, maltasa y alfa amilasa. El comportamiento cinético del extracto sobre cada una de las enzimas también fue investigado y la constante enzimática (Km) y la velocidad máxima (Vmax) fueron determinadas. El extracto de frutos de P. peruviana, mostró diferentes valores de CI50 para alfa glucosidasa obtenida de S. cerevisiae y para la obtenida de polvo intestinal de rata, sugiriendo una mayor afinidad por la enzima de origen mamífero (4114,7 and 3552,7 µg/mL, respectivamente). Para maltasa la CI50 fue cercana a la obtenida para alfa glucosidasa (4191,0 µg/mL), mientras para alfa amilasa, el extracto presentó la mayor inhibición (CI50: 619,9 g/mL). Respecto al comportamiento cinético, el extracto mostró inhibición de tipo competitiva sobre alfa glucosidasa y maltasa y no competitiva sobre alfa amilasa. Los resultados sugieren que la inhibición de carbohidrasas intestinales es uno de los modos de acción de los frutos de P. peruviana como agente antidiabético.