Sara García-Jiménez

Antidiabetic and toxicological evaluations of naringenin in normoglycaemic and NIDDM rat models and its implications on extra-pancreatic glucose regulation

Aim:  The present investigation was designed to determine the in vivo antidiabetic effect of naringenin (NG) in normoglycaemic and diabetic rat models through blood glucose (GLU) measurements following acute and subchronic time periods. Possible modes of action of NG were investigated and its acute toxicity determined.

Dose-dependent antihypertensive determination and toxicological studies of tilianin isolated from Agastache mexicana.

ETHNOPHARMACOLOGICAL RELEVANCE Agastache mexicana is used in Mexican traditional medicine for the treatment of hypertension, anxiety and related diseases. AIM OF THE STUDY Current work was developed to establish pharmacological/toxicological parameters of tilianin, a flavone extracted from Agastache mexicana in order to propose it for clinical trials. MATERIALS AND METHODS Acute and sub-acute toxicology studies in Imprinting Control Region (ICR) mice and median effective dose (ED50) determination in conscious spontaneously hypertensive rats (SHR) were done. RESULTS A median lethal dose (LD50) of 6624 mg/kg (6201, 7076) in mice and significant antihypertensive effect (ED50=53.51 mg/kg) in SHR were determined. Moreover, sub-acute oral administration of tilianin did not alter body weight, clinical chemistry parameters (alanine amino-transferase, aspartate amino-transferase, total cholesterol, high density lipoprotein, low density lipoprotein, triglycerides, glucose and insulin), and also did not induce any toxic or adverse effects on kidney, heart, liver, and lung functions. CONCLUSIONS We have shown that tilianin, isolated from Agastache mexicana, was not toxic for rodents. Also, its antihypertensive effect was dose-dependent and ED50 (53.51 mg/kg) calculated was lesser than LD50 determined (6624 mg/kg), which suggest a wide range of pharmacology-toxicology patterns. Results support the hypothesis that tilianin must be investigated and developed for clinical trials as antihypertensive drug.

Serum Leptin is Associated With Metabolic Syndrome in Obese Mexican Subjects

The metabolic syndrome (MetS) is a cluster of metabolic abnormalities including insulin resistance, dyslipidemia, high blood pressure, and abdominal adiposity. Obese patients develop leptin resistance, and an increased waist circumference (WC) due to deposition of abdominal fat. The aim of this study was to evaluate the association between circulating leptin levels and MetS among sample adult Mexican workers.

Antihyperglycemic and sub-chronic antidiabetic actions of morolic and moronic acids, in vitro and in silico inhibition of 11β-HSD 1

Morolic (1) and moronic (2) acids are the main constituents of acetonic extract from Phoradendron reichenbachianum (Loranthaceae), a medicinal plant used in Mexico for the treatment of diabetes. The aim of the current study was to establish the sub-acute antidiabetic and antihyperlipidemic effects of compounds 1 and 2 over non insulin-dependent diabetic rat model. Also, to determine the antihyperglycemic action on normoglycemic rats by oral glucose tolerance test. Daily-administered morolic (1) and moronic (2) acids (50 mg/kg) significantly lowered the blood glucose levels at 60% since first day until tenth day after treatment than untreated group (p<0.05). Moreover, analyzed blood samples obtained from diabetic rats indicated that both compounds diminished plasmatic concentration of cholesterol (CHO) and triglycerides (TG), returning them to normal levels (p<0.05). Also, pretreatment with 50 mg/kg of each compound induced significant antihyperglycemic effect after glucose and sucrose loading (2 g/kg) compared with control group (p<0.05). In vitro studies showed that compounds 1 and 2 induced inhibition of 11β-HSD 1 activity at 10 μM. However, in silico analysis of the pentaclyclic triterpenic acids on 11β-HSD 1 revealed that all compounds had high docking scores and important interactions with the catalytic site allowing them to inhibit 11β-HSD 1 enzyme. In conclusion, morolic and moronic acids have shown sustained antidiabetic and antihyperglycemic action possibly mediated by an insulin sensitization with consequent changes of glucose, cholesterol and triglycerides, in part mediated by inhibition of 11β-HSD 1 as indicated by in vitro and in silico studies.

Antidiabetic, antihyperlipidemic and anti-inflammatory effects of tilianin in streptozotocin-nicotinamide diabetic rats.

Flavonoids from medicinal plants have been used in traditional medicine to treat a variety of prevalent diseases. Flavones activate the signaling pathways promoting fuel metabolism and insulin sensitizing in hepatocytes and adipocytes, which suggests that flavones may have the potential to exert in vivo antidiabetic and antihyperlipidemic effects. Thus, the aim of the current study was to determine the antidiabetic, antihyperlipidemic and anti-inflammatory effects of tilianin in diabetic rats. Also, to understand the mechanism involved using in vitro 3T3-L1 cells and tissues from experimental animals treated with test samples through molecular profile studies. Non insulin-dependent diabetic mellitus (NIDDM) rats were treated over a short period (for 10 days) with 60mg/Kg/day of tilianin. After treatment, a biochemical blood profile was determined. Also, adipose and thoracic aortic tissues were used to determine pro-inflammatory profile, adiponectin and adhesion molecules by real-time PCR. In 3T3-L1 cells pretreated with tilianin (10μM), PPARα, PPARγ, GLUT4, FATP-1 and ACSL-1 mRNA expression were measured. In order to explain the potential PPARα interaction with tilianin, a docking study with PPARα was carried out. Thus, intragastric administration of tilianin and metformin induced a decrease in plasma glucose (GLU) in diabetic rats on day 6, and remained significantly lower until the end of the treatment; also blood triacylglycerides (TAG) and cholesterol (CHOL) (p<0.05) were diminished. Moreover, IL-1β and IL-18 expression was significantly decreased in adipose tissue (p<0.05); meanwhile adiponectin was significantly overexpressed (p<0.05). Besides, ICAM-1 expression was significantly reduced in aortic tissue (p<0.05). In 3T3-L1 cells it was found that tilianin increased PPARα and ACSL1 mRNA levels (p<0.05). Finally, tilianin docking studies with PPARα showed polar interactions with Glu269, Tyr314, His 440 and Tyr464 residues. In conclusion, short-term tilianin treatment might exert its antidiabetic and antihyperlipidemic effect by modulating a pro-inflammatory profile, and increasing adiponectin expression. In addition, our results suggest the possible interaction of tilianin with PPARα.

Screening for marijuana and cocaine abuse by immunoanalysis and gas chromatography.

Drug abuse among college students is characterized by lower academic performance and long‐term negative consequences. Screening to detect students at high risk of consuming drugs is of primary importance to insure early identification and appropriate levels of care. As a result, this study aimed to determine the current or past use of drug abuse through a questionnaire applied to a student population at the Universidad Autónoma del Estado de Morelos. The results were confirmed by immunoanalysis and gas chromatography of urine. We interviewed 181 students aged 15 to 21 (gender was not considered in this study), and urine samples were collected for analytical analysis. For detection of metabolites Delta9‐THCA‐A and benzoylecgonine from marijuana and cocaine, respectively, a homogenous enzymatic inmmunoanalysis was used; subsequent samples were analyzed by a mass spectrometer with quadrupole detector. Seven samples of the total (181) did not completely fit the inclusion criteria and were eliminated. The results showed 0.50% and 1.16% positive samples for benzoylecgonine and Delta9‐THCA‐A, respectively. These results are not different from those of the National Questionnaire on Addiction. We can establish a program for detecting drug consumption in our students. This kind of study is important in order to implement programs that can help us to decrease the abuse of drugs in our college population.

Chrysin Induces Antidiabetic, Antidyslipidemic and Anti-Inflammatory Effects in Athymic Nude Diabetic Mice

Extensive knowledge of diabetes and its complications is helpful to find new drugs for proper treatment to stop degenerative changes derived from this disease. In this context, chrysin (5,7-dihydroxyflavone) is a natural product that occurs in a variety of flowers and fruits with anti-inflammatory and antidiabetic effects, among others. Thus, a diabetic model in athymic nude mice was developed and used to establish the ability of chrysin to decrease the secretion of pro-inflammatory cytokines. Also, it was determined the acute (50 mg/kg) and sub-acute (50 mg/kg/day/10 days) antidiabetic and antihyperlipidemic activities after the period of time treatment. Results indicate that chrysin has significant acute antihyperglycemic and antidiabetic effects in nude diabetic mice (p < 0.05). Moreover, triglyceride blood levels were reduced and IL-1β and TNF-α were diminished after 10 days’ treatment compared with control group (p < 0.05). In conclusion, it was found that chrysin could produce similar effects as metformin, a drug used for the treatment of diabetes, since both test samples decreased glucose and triglycerides levels, they impaired the generation of pro-inflammatory cytokines involved in the development of diabetes and its consequences, such as atherosclerosis and other cardiovascular diseases.

Acute and subacute antidiabetic studies of ENP‐9, a new 1,5‐diarylpyrazole derivative

To explore the antihyperglycaemic and antidiabetic effects and to determine the acute toxicity of 5‐(4‐chlorophenyl)‐1‐(2,4‐dichloro‐phenyl)‐4‐methyl‐N‐(piperidin‐1‐yl)‐1H‐pyrazole‐3‐carboxamide (ENP‐9).

Analysis of self-reported adverse reactions to efavirenz and drug interactions in a population with HIV in Mexico

Objective To analyse the most frequent self-reported adverse reactions (ARs), the durability and the causes of antiretrovirals (ARVs) regimens change, concomitant treatments and drug interactions related to the use of ARVs in a group of people living with HIV in Cuernavaca, Morelos, Mexico. Materials and methods Cross-sectional study conducted in a clinic specialising in HIV ‘CAPASITS-Cuernavaca’ in Mexico from February to June 2015. People who wanted to participate were given a questionnaire on demographic characteristics, adherence, concomitant treatments and ARs. To understand the clinical variables, the clinical records were reviewed. Quantitative variables were compared using Student’s t-test for normal data and the Mann-Whitney U test for non-normal data. For comparisons between categorical variables, the χ2 test was used. All tests used a significance level of 0.05. Results A total of 96 people participated, and 218 ARs (mean= 2.3±1.9) were found. The most frequently encountered ARs were dizziness (53.1%), insomnia (21.9%) and lucid dreams (17.7%). Twenty-three people (24%) were polymedicated, and 18 potential interactions were detected in 12 people. Conclusions The results suggest that a thorough analysis of the possible drug interactions should be performed for polymedicated people on ARV treatment and that a protocol should be designed for the monitoring and management of AR to ensure a good adherence to ARV treatment.

Anxiolytic-like effects and toxicological studies of Brickellia cavanillesii (Cass.) A. Gray in experimental mice models.

ETHNOPHARMACOLOGICAL RELEVANCE Brickellia cavanillesii (Asteraceae) (Cass.) A. Gray is one of the popular plants consumed in Central America and Mexico for the treatment of several diseases such as hypertension, diabetes and anxiety, among others. AIM OF THE STUDY To determine the anxiolytic-like effect of B. Cavanillesii and the safety of its use through toxicological studies. MATERIAL AND METHODS Anxiolytic-like effects of soluble-methanol extract of B. cavanillesii (MEBc) were evaluated in ambulatory activity (open-field test), hole-board test, cylinder of exploration, the elevated plus-maze and the potentiation of the sodium pentobarbital-induced hypnosis mice models. On the other hand, in vivo toxicological studies were conducted on acute and sub-acute mice models recommended by OECD. Active MEBc was subjected to phytochemical studies through conventional chromatographic techniques to isolate bioactive compounds. RESULTS MEBc (100mg/Kg) showed significant anxiolytic-like effect on animal model used (p<0.05). The phytochemical analysis of MEBc allowed the isolation of two major compounds nicotiflorin and acacetin, among others. Both compounds were found to be partially responsible for the anxiolytic-like effects. Moreover, a median lethal dose (LD50) higher than 2000mg/Kg was determined in mice and sub-acute oral administration of MEBc (100mg/Kg) did not alter body weight, clinical chemistry parameters (ALT and AST) and it did not induce any toxic nor alteration in the liver, kidney and heart functions. CONCLUSIONS In current investigation, we have shown that MEBc has a wide range of pharmacology-toxicology patterns. The results support further investigation of MEBc as a potential anxiolytic phytomedicinal agent.