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.

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.

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.

[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.

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.

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.

Evaluation of Hypotensive and Antihypertensive Effects of Velvet Bean (Mucuna pruriens L.) Hydrolysates.

Hypertension could cause significant worldwide health problems that affect 15-20% of all adults; according to National Health and Nutrition Examination Survey, about 29% of the adult population in the United States are hypertensive. Recent research has shown that peptides derived from the hydrolysis of food proteins can decrease blood pressure. This study was carried out to evaluate the hypotensive and antihypertensive potential of Mucuna pruriens protein hydrolysates in in vitro and in vivo models. M. pruriens protein concentrate was prepared by wet fractionation and enzymatically hydrolyzed using Alcalase®, Flavourzyme®, and the sequential system Alcalase-Flavourzyme at different times (5-120 min). The biological potential was measured in vitro based on the IC50 value as well as in vivo effect, measuring the systolic (SBP) and diastolic (DBP) blood pressure in normotensive and antihypertensive Wistar-Kyoto rats by the tail-cuff method. Hydrolysis of M. pruriens protein concentrates with commercial enzymes generated extensive hydrolysates with angiotensin-converting enzyme (ACE-I) inhibitory activity (IC50: 0.589-0.993 mg/mL) and hypotensive (SBP: 0.6-47.43%, DBP: 1.94-43.47%) and antihypertensive (SBP: 8.84-27.29% DBP: 16.1-29.37%) effect. These results indicate that Mucuna pruriens protein hydrolysate (MPPH) could be used as a functional ingredient to prevent blood pressure increase.