Phytochemical analysis and antihyperglycemic activity of Castilleja arvensis.

Castilleja genus comprises approximately 211 species, some of them exhibiting potential in treating various diseases. Remarkably, despite its abundance, there is a significant lack of scientific studies that explore the chemical composition and/or therapeutic activity of this genus. In this work, the chemical composition of Castilleja arvensis was determined, and its antihyperglycemic activity was evaluated in vivo, in vitro, and ex vivo. Hydroalcoholic extract of C. arvensis (HECa) was obtained from the maceration of aerial parts. HECa was fractionated by liquid-liquid extractions to obtain the CH2Cl2 fraction (DF), EtOAc fraction (EF), n-BuOH fraction (BF) and aqueous residue (AR). The antihyperglycemic activity was determined in vivo through oral glucose and sucrose tolerance tests in normoglycemic CD-1 mice. Ex vivo assays were performed to determine intestinal glucose absorption, muscular glucose uptake and hepatic glucose production. α-glucosidase inhibitory activity was evaluated in vitro. Phytochemical screening was carried out through conventional chromatography techniques. Structure elucidation of the isolated compounds was performed by GC-MS and NMR experiments. HECa, its fractions and AR showed significant antihyperglycemic activity in vivo. According to the in vitro and ex vivo assays, this effect can be attributed to different mechanisms of action, including a delay in intestinal glucose absorption, an improvement in insulin sensitivity, and the regulation of hepatic glucose production. These effects may be due to different metabolites identified in fractions from the HECa, including genkwanin, acacetin, verbascoside and ipolamiide. Thus, current research shows that C. arvensis is an important source of bioactive compounds for the management of glycemia.

Ramon Flour (Brosimum alicastrum Swartz) Ameliorates Hepatic Lipid Accumulation, Induction of AMPK Phosphorylation, and Expression of the Hepatic Antioxidant System in a High-Fat-Diet-Induced Obesity Mouse Model.

Excessive consumption of fat and carbohydrates, together with a decrease in traditional food intake, has been related to obesity and the development of metabolic alterations. Ramon seed is a traditional Mayan food used to obtain Ramon flour (RF) with high biological value in terms of protein, fiber, micronutrients, and bioactive compounds such as polyphenols. However, few studies have evaluated the beneficial effects of RF. Thus, we aimed to determine the metabolic effects of RF consumption on a high-fat-diet-induced obesity mouse model. We divided male BALB/c mice into four groups (n = 5 each group) and fed them for 90 days with the following diets: Control (C): control diet (AIN-93), C + RF: control diet adjusted with 25% RF, HFD: high-fat diet + 5% sugar in water, and HFD + RF: high-fat diet adjusted with 25% RF + 5% sugar in water. The RF prevented the increase in serum total cholesterol (TC) and alanine transaminase (ALT) that occurred in the C and HFD groups. Notably, RF together with HFD increased serum polyphenols and antioxidant activity, and it promoted a decrease in the adipocyte size in white adipose tissue, along with lower hepatic lipid accumulation than in the HFD group. In the liver, the HFD + RF group showed an increase in the expression of ß-oxidation-related genes, and downregulation of the fatty acid synthase (Fas) gene compared with the HFD group. Moreover, the HFD + RF group had increased hepatic phosphorylation of AMP-activated protein kinase (AMPK), along with increased nuclear factor erythroid 2-related factor 2 (NRF2) and superoxide dismutase 2 (SOD2) protein expression compared with the HFD group. Thus, RF may be used as a nutritional strategy to decrease metabolic alterations during obesity.

In Vivo Anti-Inflammatory Effect, Antioxidant Activity, and Polyphenolic Content of Extracts from Capsicum chinense By-Products.

By-products of Capsicum chinense Jacq., var Jaguar could be a source of bioactive compounds. Therefore, we evaluated the anti-inflammatory effect, antioxidant activity, and their relationship with the polyphenol content of extracts of habanero pepper by-products obtained from plants grown on black or red soils of Yucatán, Mexico. Moreover, the impact of the type of extraction on their activities was evaluated. The dry by-product extracts were obtained by maceration (ME), Soxhlet (SOX), and supercritical fluid extraction (SFE). Afterward, the in vivo anti-inflammatory effect (TPA-induced ear inflammation) and the in vitro antioxidant activity (ABTS) were evaluated. Finally, the polyphenolic content was quantified by Ultra-Performance Liquid Chromatography (UPLC), and its correlation with both bioactivities was analyzed. The results showed that the SFE extract of stems of plants grown on red soil yielded the highest anti-inflammatory effect (66.1 ± 3.1%), while the extracts obtained by ME and SOX had the highest antioxidant activity (2.80 ± 0.0052 mM Trolox equivalent) and polyphenol content (3280 ± 15.59 mg·100 g-1 dry basis), respectively. A negative correlation between the anti-inflammatory effect, the antioxidant activity, and the polyphenolic content was found. Overall, the present study proposed C. chinense by-products as a valuable source of compounds with anti-inflammatory effect and antioxidant activity.

Evaluación del efecto hipoglucemiante de una fracción peptídica de las semillas de chía (Salvia hispanica L) en ratas macho Wistar inducidas con aloxano / Evaluation of the hypoglycemic effect of a peptide fraction of chia seeds (Salvia hispánica L) in male Wistar rats induced with alloxan

Introducción: se han realizado investigaciones sobre la diabetes con péptidos de diferentes fuentes alimentarias en animales experimentales para aplicarse después en los seres humanos. Objetivo: la finalidad de este trabajo fue evaluar en ratas el efecto hipoglucemiante de una fracción peptídica de chía obtenida por hidrólisis enzimática. Materiales y métodos: de la harina de chía se obtuvo una fracción rica en proteína que fue hidrolizada con pepsina-pancreatina, generándose una fracción peptídica (> 10 kDa) por ultrafiltración. Se utilizaron cinco grupos de ratas (uno de normoglucémicas y cuatro de diabetizadas con aloxano). Se realizó una curva de tolerancia a la sacarosa, proporcionándoles el disacárido antes de la medición. La sangre se tomó de la punta de la cola a los 0, 30, 60, 90 y 120 minutos. Resultados: el contenido proteico de la harina fue del 49,51 %. La fracción peptídica (> 10 kDa) presentó un 91 % de proteína; de esta se suministró una dosis de 50 mg/kg que demostró una tendencia a la disminución de la glucosa sanguínea en la primera hora, aunque no se encontró significancia entre el blanco y las dosis evaluadas. No hubo disminución de la absorción de glucosa frente al fármaco de referencia. A los 120 min del periodo postprandial no se encontraron diferencias entre las dosis, el blanco y la acarbosa, lo que denota un retorno al estado basal. Los valores en las ratas diabetizadas fueron opuestos a los de la acarbosa, por lo que no existió relación entre el mecanismo de acción del fármaco con el efecto analizado. Conclusión: las fracciones peptídicas de chía de > 10 kDa no presentaron efecto hipoglucemiante con la dosis única suministrada. (AU)

Introduction: diabetes research with peptides from foods has been conducted in animal experiments to be later applied to humans. Objective: the main purpose of this work was to evaluate in rats the hypoglycemic effect of a peptide fraction of chia seeds derived by enzymatic hydrolysis. Materials and methods: from chia flour a protein-rich fraction was obtained, which was hydrolyzed with pepsin-pancreatin system enzymes to yield a peptide fraction (> 10 kDa) by ultrafiltration. Five rat groups (one normoglycemic and four diabetized with alloxan) were used. A sucrose tolerance curve was performed, providing the disaccharide before measurement. Blood was taken from the tip of the tail at 0 (before sugar), 30, 60, 90, and 120 minutes. Results: the protein content of chia flour was 49.51 %. The peptide fraction (> 10 kDa) had 91 % of protein. A dose of 50 mg/kg showed in rats a tendency to decrease blood glucose within the first hour, but no significance was found between the target and the doses evaluated. There was no decrease in glucose absorption vs. the reference drug. At 120 min postprandial, no differences were found between doses, water, and acarbose, showing a return to the baseline status. The tolerance curve in diabetic rats was opposite to that of acarbose, so there was no relationship between the drug's mechanism of action and this analyzed effect. Conclusion: the peptide fraction of chia of > 10 kDa showed no hypoglycemic effect at the single dose that was administered. (AU)

Evaluation of antihyperglycemic activity of plants in northeast mexico.

iabetes mellitus is one of the most common non-contagious diseases. In 2017, The International Diabetes Federation reported that around 425 million people suffer from diabetes worldwide. Medications used for the treatment of diabetes lead to unwanted side effects, and thus, new safe drugs are necessary. Some natural plant-based products exhibit anti hyperglycemic activity and low toxicity. The aim of this study was to evaluate the antihyperglycemic activity (using both in vitro and in vivo models) as well as cytotoxicity of the extracts obtained from various plants. Nine extracts from a total of eight plant species were subjected to in vitro α-amylase and α-glucosidase inhibition assays. Subsequently, they were assessed through the ex vivo everted sac assay, and finally, the in vivo antihyperglycemic activity was evaluated. The extracts obtained from Ceanothus coeruleus, Chrysactinia mexicana and Zanthoxylum fagara inhibited the activities of α-amylase and α-glucosidase in the in vitro assays. Ethyl acetate and hydroalcoholic extracts from Jatropha dioica, hydroalcoholic extract from Salvia ballotaeflora and Chrysactinia mexicana, as well as methanolic extract from Ricinus communis and Zanthoxylum fagara significantly reduced the glucose uptake in the ex vivo everted intestinal sac test. All the eight extracts showed antihyperglycemic effect through the in vivo model of the Glucose Tolerance Test, using starch as the carbohydrate source.  The antihyperglycemic effect of the extracts could be mediated through the inhibition of digestive enzymes and/or the absorption of glucose through the intestine. However, the mechanism of action for the hydroalcoholic extract of Salvia texana and the methanolic extract of Turnera diffusa, which showed a strong in vivo antihyperglycemic effect, is unclear.

[Evaluation of the hypoglycemic effect of a peptide fraction of chia seeds (Salvia hispánica L.) in male Wistar rats induced with alloxan]. / Evaluación del efecto hipoglucemiante de una fracción peptídica de las semillas de chía (Salvia hispanica L.) en ratas macho Wistar inducidas con aloxano.

INTRODUCTION: Introduction: diabetes research with peptides from foods has been conducted in animal experiments to be later applied to humans. Objective: the main purpose of this work was to evaluate in rats the hypoglycemic effect of a peptide fraction of chia seeds derived by enzymatic hydrolysis. Materials and methods: from chia flour a protein-rich fraction was obtained, which was hydrolyzed with pepsin-pancreatin system enzymes to yield a peptide fraction (> 10 kDa) by ultrafiltration. Five rat groups (one normoglycemic and four diabetized with alloxan) were used. A sucrose tolerance curve was performed, providing the disaccharide before measurement. Blood was taken from the tip of the tail at 0 (before sugar), 30, 60, 90, and 120 minutes. Results: the protein content of chia flour was 49.51 %. The peptide fraction (> 10 kDa) had 91 % of protein. A dose of 50 mg/kg showed in rats a tendency to decrease blood glucose within the first hour, but no significance was found between the target and the doses evaluated. There was no decrease in glucose absorption vs. the reference drug. At 120 min postprandial, no differences were found between doses, water, and acarbose, showing a return to the baseline status. The tolerance curve in diabetic rats was opposite to that of acarbose, so there was no relationship between the drug's mechanism of action and this analyzed effect. Conclusion: the peptide fraction of chia of > 10 kDa showed no hypoglycemic effect at the single dose that was administered.

INTRODUCCIÓN: Introducción: se han realizado investigaciones sobre la diabetes con péptidos de diferentes fuentes alimentarias en animales experimentales para aplicarse después en los seres humanos. Objetivo: la finalidad de este trabajo fue evaluar en ratas el efecto hipoglucemiante de una fracción peptídica de chía obtenida por hidrólisis enzimática. Materiales y métodos: de la harina de chía se obtuvo una fracción rica en proteína que fue hidrolizada con pepsina-pancreatina, generándose una fracción peptídica (> 10 kDa) por ultrafiltración. Se utilizaron cinco grupos de ratas (uno de normoglucémicas y cuatro de diabetizadas con aloxano). Se realizó una curva de tolerancia a la sacarosa, proporcionándoles el disacárido antes de la medición. La sangre se tomó de la punta de la cola a los 0, 30, 60, 90 y 120 minutos. Resultados: el contenido proteico de la harina fue del 49,51 %. La fracción peptídica (> 10 kDa) presentó un 91 % de proteína; de esta se suministró una dosis de 50 mg/kg que demostró una tendencia a la disminución de la glucosa sanguínea en la primera hora, aunque no se encontró significancia entre el blanco y las dosis evaluadas. No hubo disminución de la absorción de glucosa frente al fármaco de referencia. A los 120 min del periodo postprandial no se encontraron diferencias entre las dosis, el blanco y la acarbosa, lo que denota un retorno al estado basal. Los valores en las ratas diabetizadas fueron opuestos a los de la acarbosa, por lo que no existió relación entre el mecanismo de acción del fármaco con el efecto analizado. Conclusión: las fracciones peptídicas de chía de > 10 kDa no presentaron efecto hipoglucemiante con la dosis única suministrada.

Antihyperglycemic and hypoglycemic activity of Mayan plant foods in rodent models.

BACKGROUND: Postprandial hyperglycemia and decreased insulin secretion are relevant to risk factors in the development of type 2 diabetes and its complications. Plant foods with antidiabetic properties could be an affordable alternative in the prevention and treatment of this disease. In the present study, the antihyperglycemic and hypoglycemic activity of Bixa orellana, Psidium guajava L., Cucurbita moschata, Raphanus sativus L. and Brassica oleracea var. capitata - Mayan plant foods - were evaluated at doses of 5 and 10 mg kg-1 . Antihyperglycemic activity was measured in healthy Wistar rats and those with obesity induced by high-sucrose diet (group HSD) (20%). The hypoglycemic activity was measure in healthy CD1 mice. RESULTS: Fasting glucose, Lee index and the body weight of HSD rats increased significantly (P ≤ 0.05) after 12 weeks of induction compared to healthy rats. In healthy rats, P. guajava and Bixa orellana (10 mg kg-1 ) demonstrated higher and statistically different (P ≤ 0.05) antihyperglycemic activity compared to control acarbose (0.5 mg kg-1 ). In the HSD rat group, all Mayan plant foods (10 mg kg-1 ) demonstrated antihyperglycemic activity statistically equal (P ≤ 0.05) to control acarbose. However, Brassica oleracea and R. sativus registered the highest antihyperglycemic activity. Bixa orellana and P. guajava (5 mg kg-1 ) showed similar hypoglycemic activity (P ≤ 0.05) to glibenclamide (0.5 mg kg-1 ) but was not significant (P ≤ 0.05) compared to insulin (5 UI kg-1 ). CONCLUSION: The present study provides valuable evidence on the possible health benefits of Mayan plant foods. These foods could contribute to the development of therapeutic diet strategies for the prevention and treatment of diabetes. © 2021 Society of Chemical Industry.

Human Keratinocytes Adopt Neuronal Fates After In Utero Transplantation in the Developing Rat Brain.

Human skin contains keratinocytes in the epidermis. Such cells share their ectodermal origin with the central nervous system (CNS). Recent studies have demonstrated that terminally differentiated somatic cells can adopt a pluripotent state, or can directly convert its phenotype to neurons, after ectopic expression of transcription factors. In this article we tested the hypothesis that human keratinocytes can adopt neural fates after culturing them in suspension with a neural medium. Initially, keratinocytes expressed Keratins and Vimentin. After neural induction, transcriptional upregulation of NESTIN, SOX2, VIMENTIN, SOX1, and MUSASHI1 was observed, concomitant with significant increases in NESTIN detected by immunostaining. However, in vitro differentiation did not yield the expression of neuronal or astrocytic markers. We tested the differentiation potential of control and neural-induced keratinocytes by grafting them in the developing CNS of rats, through ultrasound-guided injection. For this purpose, keratinocytes were transduced with lentivirus that contained the coding sequence of green fluorescent protein. Cell sorting was employed to select cells with high fluorescence. Unexpectedly, 4 days after grafting these cells in the ventricles, both control and neural-induced cells expressed green fluorescent protein together with the neuronal proteins ßIII-Tubulin and Microtubule-Associated Protein 2. These results support the notion that in vivo environment provides appropriate signals to evaluate the neuronal differentiation potential of keratinocytes or other non-neural cell populations.

[Antihypertensive, antihyperglycemic, and antioxidant effects of Stevia rebaudiana Bertoni (creole variety INIFAP C01) extracts on Wistar rats with induced metabolic syndrome]. / Efecto antihipertensivo, antihiperglucemiante y antioxidante de los extractos de Stevia rebaudiana Bertoni (variedad criolla INIFAP C01) en ratas Wistar con síndrome metabólico inducido.

INTRODUCTION: Introduction: medicinal plants have demonstrated therapeutic applications for treating different diseases, including chronic and degenerative diseases associated with metabolic syndrome. Objectives: to assess the weight control and the antihypertensive, antihyperglycemic and antioxidant effects of aqueous and ethanolic extracts of Stevia rebaudiana (creole variety INIFAP C01) leaves and stems cultivated in the Muna and Mocochá municipalities (Yucatán, México). Methods: aqueous and ethanolic extracts of leaves (HAMU and HEMU, respectively) and stems (TAMU and TEMU, respectively) from Muna, and aqueous and ethanolic extracts of leaves (HAMO and HEMO, respectively) and stems (TAMO and TEMO, respectively) from Mocochá were orally administered to Wistar male rats induced to metabolic syndrome. Weight, blood pressure, blood sugar levels, malondialdehyde (MDA) levels, and superoxide dismutase (SOD) levels in blood plasma were measured. Results: TAMU and HAMO samples reduced weight by 1.91 % and 1.57 %, respectively. On the other hand, HEMU and HAMU samples reduced systolic (PAS) and diastolic (PAD) blood pressure levels by 29.31-30.47 % and 36.69-36.98 %. In the glucose tolerance test (GTT) HEMU showed a reduction in blood sugar levels of 10.94 % on the first day, and of 14.83 % on day 30. TEMO and TAMO samples showed lower malondialdehyde (MDA) concentrations of 7.0 and 7.3 µM, respectively. HEMU and TEMU showed a higher superoxide dismutase (SOD) concentration of 1.29 and 1.12 U/mL, respectively. Conclusions: extracts of S. rebaudiana can help to control weight gain, to decrease blood pressure and the incidence of diabetes, and to reduce oxidative damage.

INTRODUCCIÓN: Introducción: las plantas medicinales han mostrado tener aplicaciones terapéuticas en el tratamiento de diferentes enfermedades, entre ellas las enfermedades crónicas degenerativas presentes en el síndrome metabólico (SM). Objetivos: evaluar el efecto en el control del peso, así como el efecto antihipertensivo, antihiperglucémico y antioxidante, de extractos acuosos y etanólicos de hojas y tallos de Stevia rebaudiana, variedad criolla INIFAP C01, producidas en los municipios de Muna y Mocochá (Yucatán, México). Métodos: se administraron por vía oral extractos acuosos y etanólicos de hojas (HAMU y HEMU, respectivamente) y tallos procedentes de Muna (TAMU y TEMU, respectivamente), así como extractos acuosos y etanólicos de hojas (HAMO y HEMO, respectivamente) y tallos de Mocochá (TAMO y TEMO, respectivamente), a ratas Wistar macho en las que se indujo un SM. Se registraron los pesos y se midieron los niveles de presión arterial (PA) y glucosa en sangre, así como los niveles de malondialdehído (MDA) y superóxido-dismutasa (SOD) en plasma sanguíneo. Resultados: TAMU y HAMO mostraron porcentajes de reducción del peso del 1,91 % y 1,57 %, respectivamente. HEMU y HAMU mostraron porcentajes de reducción de la presión arterial sistólica (PAS) y diastólica (PAD) del 30,47-29,31 % y 36,98-36,69 %, respectivamente. En el test de tolerancia oral a la glucosa (TTOG), HEMU mostró porcentajes de reducción de la glucosa sanguínea del 10,94 % en el día uno y del 14,83 % en el día 30. TEMO y TAMO mostraron una menor concentración de MDA, de 7,0 y 7,3 µM, respectivamente, y HEMU y TEMU mostraron una mayor concentración de SOD, de 1,29 y 1,12 U/mL, respectivamente. Conclusiones: los extractos de S. rebaudiana pueden ayudar a controlar el aumento de peso, disminuir las cifras de presión arterial y la incidencia de diabetes, y reducir el daño oxidativo.

A Cecropia peltata ethanolic extract reduces insulin resistance and hepatic steatosis in rats fed a high-fat diet.

ETHNOPHARMACOLOGICAL RELEVANCE: Cecropia peltata L. (CP) leaves have been used in Latin American traditional medicine by its purported hypoglycemic, anti-inflammatory and antioxidant properties. PURPOSE: The aim of this study was to evaluate the metabolic effects of an ethanolic extract of CP leaves in rats fed a high-fat diet and 10% of sugar in water (HFD). METHODS: Male Wistar rats were randomly divided into four groups: group 1 was fed a control diet; groups 2, 3 and 4 were fed a HFD. In addition, group 3 was co-administered with 10 mg/kg/day of CP extract (HFD + CP) and group 4 with a solution of 5 mg/kg/day metformin (HFD + M) for 90 days. RESULTS: Body weight gain and serum triglycerides were significantly decreased in the HFD + CP group compared with the HFD and HFD + M groups. Glucose tolerance increased in the HFD + CP compared with the HFD group. Administration with CP extract reduced adipose tissue lipolysis and lipid accumulation in liver of HFD + CP rats with respect to HFD and HFD + M groups. Histological examinations showed that the area of the adipocytes in WAT and the area of lipid vesicles in BAT were significantly smaller in the HFD + CP group than in the HFD and HFD + M groups. CONCLUSION: Administration of a CP extract prevented glucose intolerance and hepatic lipid accumulation in rats fed a HFD in association with reduced adipocyte hypertrophy, demonstrating potential antidiabetic properties.

Efecto anticancerígeno del almidón modificado de banano (Musa cavendish AAA) en ratas con 1.2-dimetilhidrazina / Anticancer effect of modified banana (Musa cavendish AAA) starch in rats with 1.2-dimethylhydrazine

Introducción: el almidón resistente (AR) no se digiere completamente en el intestino humano sino que se fermenta en colon; disminuye el pH intestinal, ya que se producen ácidos grasos de cadena corta, interviniendo de manera benéfica en el tratamiento preventivo y curativo del cáncer de colon rectal. La pirodextrinización y la hidrólisis enzimática son modificaciones al almidón nativo (AN) que pueden incrementar la cantidad de AR. Objetivo: el objetivo de este proyecto fue evaluar los efectos del almidón nativo de M. cavendish AAA y de los almidones modificados química y enzimáticamente sobre diversos marcadores tumorales en ratas. Métodos: se realizaron modificaciones (química y enzimática) del AN del banano M. cavendish AAA y se evaluaron en ratas tratadas con 1,2-DMH. Se utilizaron 25 ratas Sprague Dawley machos divididas en cinco grupos experimentales: CP, CN, AN, PI y MER. Durante 4 semanas recibieron la dieta experimental asignada a cada grupo. Los grupos CP, AN, PI y MER recibieron 2 inyecciones s.c. (subcutáneas) semanales de 1,2-DMH (40 mg/kg) (semanas 3 y 4). En las heces se evaluaron el pH, la enzima ß-glucuronidasa y los ácidos grasos de cadena corta, y se realizó un estudio histopatológico del ciego y el colon para detectar lesiones microscópicas. Resultados: la actividad de ß-glucuronidasa disminuyó (p < 0,05) para los grupos AN, PI y MER en comparación con el CP. La mayor proporción de ácido butírico se observó en el AN (p < 0,05) frente al CN. El 60 % de las enteritis fueron de grado severo en el CP, mientras que en los grupos experimentales fueron de 40 %. Conclusiones: los gránulos de almidón nativo resistieron la pirodextrinización pero el tratamiento con a-amilasa rompió la estructura del gránulo de pirodextrina. De acuerdo a los tratamientos suministrados a las ratas, conforme mayor es la cantidad de AR presente en la dieta (AN), las células neoplásicas no avanzan más allá de la membrana basal, sugiriendo un posible efecto protector o anticancerígeno celular

Introduction: resistant starch (RS) is not completely digested in the human intestine but is fermented in the colon; intestinal pH decreases as short-chain fatty acids are produced. This is beneficial for health, and for preventing and treating rectal colon cancer. Pyrodextrinization and enzymatic hydrolysis are modifications to native starch (NS) that may increase the amount of RS. Objective: the objective of this project was to evaluate the effects of M. cavendish AAA native and both chemically and enzymatically modified starches on tumor markers in rats. Methods: modifications (chemical and enzymatic) were made to M. cavendish AAA NS, and were evaluated in rats with 1,2-DMH. Male Sprague Dawley rats (25) were used, divided into five experimental groups: PC, NC, NS, PI, and ERM. During 4 weeks they received the experimental diet assigned to each group. The PC, NS, PI and ERM groups received 2 weekly s.c. (subcutaneous) injections of 1,2-DMH (40 mg/kg) (third and fourth week). In feces, pH, ß-glucuronidase enzyme, and short-chain fatty acids were evaluated, and a histopathological study was performed of the intestine to detect microscopic lesions. Results: the activity of ß-glucuronidase decreased (p < 0.05) for NS, PI and ERM vs. PC. The highest proportion of butyric acid was observed in the NS (p < 0.05) vs. NC group. Sixty percent of enteritides were severe in grade in the PC group, and 40 % in the experimental groups. Conclusions: native starch granules resisted pyrodextrinization, but treatment with a-amylase broke the structure of the pyrodextrin granule. According to the treatments given to the rats, as the amount of RS present in the diet increases (NS), the neoplastic cells do not advance beyond the basement membrane, suggesting a possible cell-protective or anticancer effect

Characterization of Mechanical Allodynia and Skin Innervation in a Mouse Model of Type-2 Diabetes Induced by Cafeteria-Style Diet and Low-Doses of Streptozotocin.

Background: Painful distal symmetrical polyneuropathy (DPN) is a frequent complication of type-2 diabetes mellitus (T2DM) that commonly presents as neuropathic pain and loss of skin nerve fibers. However, there are limited therapies to effectively treat DPN and many of the current animal models of T2DM-induced DPN do not appear to mirror the human disease. Thus, we validated a DPN mouse model induced by a cafeteria-style diet plus low-doses of streptozotocin (STZ). Methods: Female C57BL/6J mice were fed either standard (STD) diet or obesogenic cafeteria (CAF) diet for 32 weeks, starting at 8 weeks old. Eight weeks after starting diets, CAF or STD mice received either four low-doses of STZ or vehicle. Changes in body weight, blood glucose and insulin levels, as well as oral glucose- and insulin-tolerance tests (OGTT and ITT) were determined. The development of mechanical hypersensitivity of the hindpaws was determined using von Frey filaments. Moreover, the effect of the most common neuropathic pain drugs was evaluated on T2DM-induced mechanical allodynia. Finally, the density of PGP -9.5+ (a pan-neuronal marker) axons in the epidermis from the hindpaw glabrous skin was quantified. Results: At 22-24 weeks after STZ injections, CAF + STZ mice had significantly higher glucose and insulin levels compared to CAF + VEH, STD + STZ, and STD + VEH mice, and developed glucose tolerance and insulin resistance. Skin mechanical sensitivity was detected as early as 12 weeks post-STZ injections and it was significantly attenuated by intraperitoneal acute treatment with amitriptyline, gabapentin, tramadol, duloxetine, or carbamazepine but not by diclofenac. The density of PGP-9.5+ nerve fibers was reduced in CAF + STZ mice compared to other groups. Conclusion: This reverse translational study provides a painful DPN mouse model which may help in developing a better understanding of the factors that generate and maintain neuropathic pain and denervation of skin under T2DM and to identify mechanism-based new treatments.

[Anticancer effect of modified banana (Musa cavendish AAA) starch in rats with 1.2-dimethylhydrazine]. / Efecto anticancerígeno del almidón modificado de banano (Musa cavendish AAA) en ratas con 1,2-dimetilhidrazina.

INTRODUCTION: Introduction: resistant starch (RS) is not completely digested in the human intestine but is fermented in the colon; intestinal pH decreases as short-chain fatty acids are produced. This is beneficial for health, and for preventing and treating rectal colon cancer. Pyrodextrinization and enzymatic hydrolysis are modifications to native starch (NS) that may increase the amount of RS. Objective: the objective of this project was to evaluate the effects of M. cavendish AAA native and both chemically and enzymatically modified starches on tumor markers in rats. Methods: modifications (chemical and enzymatic) were made to M. cavendish AAA NS, and were evaluated in rats with 1,2-DMH. Male Sprague Dawley rats (25) were used, divided into five experimental groups: PC, NC, NS, PI, and ERM. During 4 weeks they received the experimental diet assigned to each group. The PC, NS, PI and ERM groups received 2 weekly s.c. (subcutaneous) injections of 1,2-DMH (40 mg/kg) (third and fourth week). In feces, pH, ß-glucuronidase enzyme, and short-chain fatty acids were evaluated, and a histopathological study was performed of the intestine to detect microscopic lesions. Results: the activity of ß-glucuronidase decreased (p < 0.05) for NS, PI and ERM vs. PC. The highest proportion of butyric acid was observed in the NS (p < 0.05) vs. NC group. Sixty percent of enteritides were severe in grade in the PC group, and 40 % in the experimental groups. Conclusions: native starch granules resisted pyrodextrinization, but treatment with α-amylase broke the structure of the pyrodextrin granule. According to the treatments given to the rats, as the amount of RS present in the diet increases (NS), the neoplastic cells do not advance beyond the basement membrane, suggesting a possible cell-protective or anticancer effect.

INTRODUCCIÓN: Introducción: el almidón resistente (AR) no se digiere completamente en el intestino humano sino que se fermenta en colon; disminuye el pH intestinal, ya que se producen ácidos grasos de cadena corta, interviniendo de manera benéfica en el tratamiento preventivo y curativo del cáncer de colon rectal. La pirodextrinización y la hidrólisis enzimática son modificaciones al almidón nativo (AN) que pueden incrementar la cantidad de AR. Objetivo: el objetivo de este proyecto fue evaluar los efectos del almidón nativo de M. cavendish AAA y de los almidones modificados química y enzimáticamente sobre diversos marcadores tumorales en ratas. Métodos: se realizaron modificaciones (química y enzimática) del AN del banano M. cavendish AAA y se evaluaron en ratas tratadas con 1,2-DMH. Se utilizaron 25 ratas Sprague Dawley machos divididas en cinco grupos experimentales: CP, CN, AN, PI y MER. Durante 4 semanas recibieron la dieta experimental asignada a cada grupo. Los grupos CP, AN, PI y MER recibieron 2 inyecciones s.c. (subcutáneas) semanales de 1,2-DMH (40 mg/kg) (semanas 3 y 4). En las heces se evaluaron el pH, la enzima ß-glucuronidasa y los ácidos grasos de cadena corta, y se realizó un estudio histopatológico del ciego y el colon para detectar lesiones microscópicas. Resultados: la actividad de ß-glucuronidasa disminuyó (p < 0,05) para los grupos AN, PI y MER en comparación con el CP. La mayor proporción de ácido butírico se observó en el AN (p < 0,05) frente al CN. El 60 % de las enteritis fueron de grado severo en el CP, mientras que en los grupos experimentales fueron de 40 %. Conclusiones: los gránulos de almidón nativo resistieron la pirodextrinización pero el tratamiento con α-amilasa rompió la estructura del gránulo de pirodextrina. De acuerdo a los tratamientos suministrados a las ratas, conforme mayor es la cantidad de AR presente en la dieta (AN), las células neoplásicas no avanzan más allá de la membrana basal, sugiriendo un posible efecto protector o anticancerígeno celular.

α-Glucosidase inhibitory activity and in vivo antihyperglycemic effect of secondary metabolites from the leaf infusion of Ocimum campechianum mill.

ETHNOPHARMACOLOGICAL RELEVANCE: Wild basil (Ocimum campechianum Mill.), an aromatic herb of the Lamiaceae family known as "albahaca de monte" (Spanish) or "x'kakaltun" (Mayan) in Yucatan, is used in Mayan traditional medicine to treat diabetes, as well as to alleviate fever symtoms, stomach pain, conjunctivitis, and various skin affections. AIM OF THE STUDY: To isolate and identify the bioactive metabolites responsible for the α-glucosidase inhibitory activity previously detected in the leaf infusion O. campechianum. MATERIALS AND METHODS: The bioassay-guided fractionation and purification of the lyophilized infusion was carried out using a liquid-liquid partition procedure, followed by successive chromatographic purifications of the semipurified fractions. The isolated metabolites were identified by comparing their spectroscopic data with those reported in the literature. The liophylized infusion, together with the semipurified fractions, and the pure metabolites were tested for their antioxidant and α-glucosidase inhibitory activities, as well as their antihyperglycemic effect. RESULTS: Chromatographic purification of the semipurified fractions led to the isolation of the polymethoxylated flavones 5-demethyl nobiletin (1) and 5-demethyl sinensetin (2), together with luteolin (3), methyl rosmarinate (4) and rosmarinic acid (5). Metabolites 4 and 5 appear to be responsible for the α-glucosidase inhibitory activity and the antihyperglycemic effect detected in the lyophilized infusion. A Lineweaver-Burk double reciprocal plot confirmed that the higher α-glucosidase inhibitory activity of 4 is of non-competitive nature. Both 4 and 5 caused a decrease in blood glucose higher than that caused by acarbose, a result that appears to be related to their strong α-glucosidase inhibitory activity. Even though flavonoids 1-3 did not show a good inhibition of α-glucosidase, these products decreased blood glucose in the in vivo model, suggesting a different antihyperglycemic mechanism. CONCLUSIONS: The results confirm both the traditional use of O. campechianum and the importance of the leaf infusion as a potential source of antihyperglycemic agents. The isolation of 5-demethyl nobiletin (1) and 5-demethyl sinensetin (2) from O. campechianum and other Ocimum spp. suggests that polymethoxyflavones can be considered chemotaxonomical markers for the genus.

[Wound healing effect of peptide fractions from Phaseolus lunatus proteins by enzymatic hydrolysis]. / Efecto cicatrizante de fracciones peptídicas derivadas de la hidrólisis enzimática de proteínas de Phaseolus lunatus.

INTRODUCTION: Introduction: protein hydrolysates from plant seeds are a source of bioactive peptides. However, no studies on wound healing activity have been published. Objective: to evaluate the healing effect in vivo (in mice) of enzymatic hydrolysates of Phaseolus lunatus using pepsin, pancreatin, the pepsin-pancreatin sequential system and the peptide fractions of each hydrolysate, greater and less than 10 kDa. Methods: the wound healing tests were performed on mice divided in groups of five mice per treatment. The wounds were monitored with a stereomicroscope (Stemi™ DV4), measuring the area with photographs on days 0, 1, 3, 6, 8 and 10. The time elapsed from the formation of each wound to 80% reduction of its area was calculated. Finally, the fraction or hydrolysate amino acid residues that showed greater wound healing activity were identified by HPLC chromatography (Agilent 1100 series). Results: the wounds treated with pancreatin hydrolysate (PanH) and with its fraction greater than 10 kDa (PanF1) showed 80% of healing at 2.86 and 3.03 days, respectively, while this occurred using the control at 5.04 days. These represented the greatest wound healing activity of all the treatments. The analysis of the amino acids determined an important presence of hydrophobic and basic residues that contributed significantly to wound healing. Conclusion: the PanH hydrolysate, obtained from the protein concentrate of Phaseolus lunatus, and its fraction greater than 10 kDa could be used to encourage wound healing.

INTRODUCCIÓN: Introducción: los hidrolizados de proteína de semillas de plantas son una fuente de péptidos bioactivos. Sin embargo, no se han publicado estudios sobre la actividad cicatrizante de heridas. Objetivo: evaluar el efecto cicatrizante in vivo (en ratones) de hidrolizados enzimáticos de Phaseolus lunatus empleando pepsina, pancreatina, el sistema secuencial pepsina-pancreatina y las fracciones peptídicas de cada hidrolizado, mayores y menores de 10 kDa. Métodos: las pruebas de cicatrización se realizaron en ratones divididos en grupos de cinco ratones por tratamiento. Las heridas se observaron en un estereomicroscopio (Stemi™ DV4), midiendo el área con fotografías los días 0, 1, 3, 6, 8 y 10. Se calculó el tiempo transcurrido desde la formación de cada herida hasta el 80% de reducción de su área. Por último, los residuos aminoacídicos de la fracción o hidrolizado que mostró mayor actividad cicatrizante fueron identificados por cromatografía HPLC (Agilent 1100 series). Resultados: las heridas tratadas con hidrolizado de pancreatina (PanH) y su fracción mayor de 10 kDa (PanF1) mostraron un avance del 80% de cicatrización a los 2,86 y 3,03 días, respectivamente, mientras que con el control fueron 5,04 días. Estos representaron la mayor actividad cicatrizante de todos los tratamientos. El análisis de aminoácidos determinó una presencia importante de residuos hidrofóbicos y básicos que contribuyeron de manera notable a la cicatrización de heridas. Conclusión: el hidrolizado PanH, obtenido del concentrado proteico de Phaseolus lunatus, y su fracción mayor de 10 kDa podrían ser usados para favorecer la cicatrización de heridas.

Efecto cicatrizante de fracciones peptídicas derivadas de la hidrólisis enzimática de proteínas de Phaseolus lunatus / Wound healing effect of peptide fractions from Phaseolus lunatus proteins by enzymatic hydrolysis

Introducción: los hidrolizados de proteína de semillas de plantas son una fuente de péptidos bioactivos. Sin embargo, no se han publicado estudios sobre la actividad cicatrizante de heridas. Objetivo: evaluar el efecto cicatrizante in vivo (en ratones) de hidrolizados enzimáticos de Phaseolus lunatus empleando pepsina, pancreatina, el sistema secuencial pepsina-pancreatina y las fracciones peptídicas de cada hidrolizado, mayores y menores de 10 kDa. Métodos: las pruebas de cicatrización se realizaron en ratones divididos en grupos de cinco ratones por tratamiento. Las heridas se observaron en un estereomicroscopio (Stemi(TM) DV4), midiendo el área con fotografías los días 0, 1, 3, 6, 8 y 10. Se calculó el tiempo transcurrido desde la formación de cada herida hasta el 80% de reducción de su área. Por último, los residuos aminoacídicos de la fracción o hidrolizado que mostró mayor actividad cicatrizante fueron identifi cados por cromatografía HPLC (Agilent 1100 series). Resultados: las heridas tratadas con hidrolizado de pancreatina (PanH) y su fracción mayor de 10 kDa (PanF1) mostraron un avance del 80% de cicatrización a los 2,86 y 3,03 días, respectivamente, mientras que con el control fueron 5,04 días. Estos representaron la mayor actividad cicatrizante de todos los tratamientos. El análisis de aminoácidos determinó una presencia importante de residuos hidrofóbicos y básicos que contribuyeron de manera notable a la cicatrización de heridas. Conclusión: el hidrolizado PanH, obtenido del concentrado proteico de Phaseolus lunatus, y su fracción mayor de 10 kDa podrían ser usados para favorecer la cicatrización de heridas

Introduction: protein hydrolysates from plant seeds are a source of bioactive peptides. However, no studies on wound healing activity have been published. Objective: to evaluate the healing effect in vivo (in mice) of enzymatic hydrolysates of Phaseolus lunatus using pepsin, pancreatin, the pepsin-pancreatin sequential system and the peptide fractions of each hydrolysate, greater and less than 10 kDa. Methods: the wound healing tests were performed on mice divided in groups of fi ve mice per treatment. The wounds were monitored with a stereomicroscope (Stemi(TM) DV4), measuring the area with photographs on days 0, 1, 3, 6, 8 and 10. The time elapsed from the formation of each wound to 80% reduction of its area was calculated. Finally, the fraction or hydrolysate amino acid residues that showed greater wound healing activity were identifi ed by HPLC chromatography (Agilent 1100 series). Results: the wounds treated with pancreatin hydrolysate (PanH) and with its fraction greater than 10 kDa (PanF1) showed 80% of healing at 2.86 and 3.03 days, respectively, while this occurred using the control at 5.04 days. These represented the greatest wound healing activity of all the treatments. The analysis of the amino acids determined an important presence of hydrophobic and basic residues that contributed significantly to wound healing. Conclusion: the PanH hydrolysate, obtained from the protein concentrate of Phaseolus lunatus, and its fraction greater than 10 kDa could be used to encourage wound healing

Effects of modified banana (Musa cavendish)starch on glycemic control and blood pressure in rats with high sucrose diet.

INTRODUCTION: insulin resistance (IR) is the preliminary stage of diseases such as diabetes and hypertension. These diseases can be controlled through medication, yet the consumption of functional foods (FF) may be one complementary treatment option. Ingredients for these FF could be the pyrodextrin and enzymatically resistant maltodextrin (ERM) obtained from the native starch (NS) of M. cavendishin this study. OBJECTIVE: to evaluate the effects of modified banana starch on glycemic control and blood pressure in rats with high sucrose diet (HSD). METHODS: we utilized 25 male Wistar rats 20 of which received a HSD and five were fed a normal diet and purified water (PW) for 12 weeks. At the end of week 8, the rats fed a HSD were divided into four groups: positive control (PC), native starch (NS), pyrodextrin (PI), and enzymatically resistant maltodextrin (ERM). The negative control (NC) comprised the five rats fed PW. We evaluated the glucose tolerance test, blood pressure (BP), insulin levels, total cholesterol (TC), high-density lipoproteins (HDL), and triglycerides. RESULTS: differential scanning calorimetry and scanning electron microscopy of the modified starches demonstrated that the pyroconversion treatment did not visibly affect the NS granules, while ERM was modified by the action of α-amylase. Starch treatments reduced glucose, insulin, HOMA-IR, and BP in comparison with PC (p < 0.05). Glucose AUC (0-120 min) was also decreased after starch treatments with respect to PC (p < 0.05). CONCLUSION: NS and its modified products exerted beneficial effects on glycemic control, lipid metabolism, and BP in obese rats fed a HSD. Although the modified starches presented lower resistance to digestion than NS, their expected properties were maintained.

Effects of modified banana (musa cavendish)starch on glycemic control and blood pressure in rats with high sucrose diet / Efectos del almidón modificado de banano (Musa cavendish AAA) sobre el control glucémico y la presión arterial en ratas con dieta alta en sacarosa

Objective: to evaluate the adequacy of dietary intake and the anthropometric nutritional status of pregnant adolescents in the city of Niterói, Rio de Janeiro, Brazil. Materials and methods: forty-two adolescents (13-19 years of age), with single-fetus gestation, assisted in the public prenatal health care units between 2008-2014, participated in the study. Body mass index (BMI) was used to assess the nutritional status. Dietary intake was assessed by 24h dietary recalls on two days during a week and one during weekend. Basal metabolic rate was measured by indirect calorimetry and used to determine the energy requirements. Mixed effects models were used to assess dietary intake over the gestational weeks (random effect) and BMI. Results: mean age (SD) of the pregnant women was 16.5 (1.5) years and the majority received allowance from a cash transfer federal program. Overall, 30.3% were overweight/obese pre-pregnancy and 16.7%, during pregnancy. Energy and protein intake adequacies decreased with increasing BMI and gestational week. There was adequate dietary intake of energy, protein, vitamin A and zinc and insufficient intakes of iron and calcium. There was excessive intake of sodium. Conclusions: pregnant adolescents living in underprivileged socio-economic environments assisted for prenatal care in primary health care units have adequate intakes of energy, protein, vitamin A and zinc. Pre-pregnancy overweight and high sodium intake are causes of concern due to the future implications for their health. The official Brazilian recommended criterion for anthropometric assessment in pregnancy of adolescents proved to be inadequate

Objetivo: evaluar la adecuación de la ingesta dietética y el estado nutricional antropométrico de adolescentes embarazadas en Niterói, Río de Janeiro, Brasil. Materiales y métodos: participaron en el estudio 42 adolescentes de 13-19 años, con gestación de feto único, asistidas en las unidades públicas de atención prenatal entre 2008 y 2014. El índice de masa corporal (IMC) se utilizó para evaluar el estado nutricional. La ingesta dietética fue evaluada por recuerdos diarios de 24h dos días durante una semana y uno durante el fin de semana. La tasa metabólica basal se midió mediante calorimetría indirecta y se utilizó para determinar los requerimientos energéticos. Se emplearon modelos de efectos mixtos para evaluar la ingesta alimentaria durante las semanas de gestación (SG, efecto aleatorio) y el IMC. Resultados: la mayoría de las mujeres embarazadas recibían subsidios de un programa federal de Transferencia de efectivo. En general, el 30,3% tenía sobrepeso/obesidad antes del embarazo y el 16,7%, durante el embarazo. La cantidad de energía y la ingesta de proteínas disminuyeron con el aumento del IMC y la SG. Había una ingesta dietética adecuada de energía, proteínas, vitamina A y una ingesta insuficiente de hierro y calcio. Conclusiones: las adolescentes embarazadas tienen un consumo adecuado de energía, proteínas y vitamina A. El sobrepeso previo y el alto consumo de sodio son causas de preocupación debido a las implicaciones futuras para su salud. El criterio oficial brasileño recomendado para la evaluación antropométrica en el embarazo de los adolescentes demostró ser inadecuado

Establishment and Phytochemical Analysis of a Callus Culture from Ageratina pichinchensis (Asteraceae) and Its Anti-Inflammatory Activity.

A protocol was established to produce bioactive compounds in a callus culture of Ageratina pichinchensis by using 1 mg L-1 NAA with 0.1 mg L-1 KIN. The phytochemical study of the EtOAc extract obtained from the callus biomass, allowed the isolation and characterization of eleven secondary metabolites, of which dihydrobenzofuran (5) and 3-epilupeol (7), showed important anti-inflammatory activity. Compound 5 inhibits in vitro the secretion of NO (IC50 = 36.96 ± 1.06 µM), IL-6 (IC50 = 73.71 ± 3.21 µM), and TNF-α (IC50 = 73.20 ± 5.99 µM) in RAW (Murine macrophage cells) 264.7 macrophages, as well as the activation of NF-κB (40% at 150 µM) in RAW-blue macrophages, while compound 7 has been described that inhibit the in vivo TPA-induced ear edema, and the in vitro production of NO, and the PLA2 enzyme activity. In addition, quantitative GC-MS analysis showed that the anti-inflammatory metabolites 5 and 7 were not detected in the wild plant. Overall, our results indicated that A. pichinchensis can be used as an alternative biotechnological resource for obtaining anti-inflammatory compounds. This is the first report of the anti-inflammatory activity of compound 5 and its production in a callus culture of A. pichinchensis.

Acute Hypoglycemic and Antidiabetic Effect of Teuhetenone A Isolated from Turnera diffusa.

Diabetes mellitus is a chronic degenerative disease that causes long-term complications and represents a serious public health problem. Turnera diffusa (damiana) is a shrub that grows throughout Mexico and is traditionally used for many illnesses including diabetes. Although a large number of plant metabolites are known, there are no reports indicating which of these are responsible for this activity, and this identification was the objective of the present work. Through bioassay-guided fractionation of a methanolic extract obtained from the aerial part of T. diffusa, teuhetenone A was isolated and identified as the main metabolite responsible for the plant's hypoglycemic activity. Alpha-glucosidase inhibitory activity and cytotoxicity of this metabolite were determined. Hypoglycemic and antidiabetic activities were evaluated in a murine model of diabetes in vivo, by monitoring glucose levels for six hours and comparing them with levels after administering various controls. Teuhetenone A was not cytotoxic at the tested concentrations, and did not show inhibitory activity in the glucosidase test, and the in vivo assays showed a gradual reduction in glucose levels in normoglycemic and diabetic mice. Considering these results, we suggest that teuhetenone A has potential as an antidiabetic compound, which could be further submitted to preclinical assays.