María Eva González-Trujano’s research while affiliated with National Institute of Psychiatry Ramón de la Fuente Muñiz and other places

Background Recently, the antinociceptive effect of LMH-2, a σ1 receptor antagonist, has been reported in diabetic mice with neuropathic pain. However, the mechanism by which this effect is produced is not completely clear. In this study, we explored the involvement of TRPV1 and the MOR-NMDAR complex in the antiallodynic effect of LMH-2 in hyperglycemic mice with neuropathic pain. Methods Hyperglycemia was induced in mice by administering streptozotocin-nicotinamide. Four weeks later, once neuropathic pain was established, the antiallodynic effect of LMH-2 (56.2 mg/kg) was evaluated using the up-down method with the von Frey filaments, both in the absence and the presence of capsazepine (8 mg/kg, ip), naloxone (NLX, 1 mg/kg, ip), NMDA (0.4 nM/10 µL, it), or their co-administration (NLX-NMDA). Gabapentin was used as positive control. Results Pretreatment with NLX did not alter the antiallodynic effect of LMH-2 in the up-down method with the von Frey filaments in hyperglycemic mice, whereas NMDA significantly reduced it. The addition of NLX to NMDA (NLX-NMDA) did not modify the effect of NMDA alone on the antiallodynic activity of LMH-2. Additionally, capsazepine completely blocked the antinociceptive effect of LMH-2 in hyperglycemic mice. Molecular docking analysis suggested a potential interaction between LMH-2 and TRPV1. Moreover, a higher dose of LMH-2 did not cause mortality or damage in healthy mice. Conclusion These results suggest the potential utility of LMH-2 in the treatment of diabetic neuropathy and highlight a key role for TRPV1 in LMH-2’s antiallodynic mechanism, along with a possible, albeit limited, interaction with the MOR/NMDA complex.

Bocconia arborea S. Watson (B. arborea) belongs to the Papaveraceae family and is used in folk medicine because of its depressant effect on the central nervous system. However, its benefits on cerebral paroxysmal activity as an anticonvulsant treatment remain unknown. This study aimed to evaluate the anticonvulsant effect of B. arborea and one of its abundant isolated metabolites dihydrosanguinarine (DHS) by means of experimental models of seizures in mice simultaneously to an electrocorticographic (ECoG) analysis. B. arborea was prepared as extracts with different polarity using hexane (HEX), dichloromethane (DCM), and methanol (MeOH) solvents to choose the most active one and to identify and isolate a bioactive metabolite. DHS was purified from the HEX extract. The anticonvulsant activity was evaluated with each extract giving an intraperitoneal (i.p.) administration of 100 mg/kg, and 30 min after, seizure behavior was induced by the pentylenetetrazole (PTZ, 85 mg/kg, i.p.) or maximal electroshock stimulation (MES) tests in mice. Molecular docking analysis was performance to reinforce the possible mechanism of action. Our results of seizure behavior and ECoG analysis showed that the HEX extract significantly (p < 0.0001) delayed the onset of seizures and decreased the incidence (p < 0.005) with lower mortality rate (p < 0.05), where DHS was partially responsible for this activity with a possible GABAergic mechanism of action involving the BDZ allosteric site. The MeOH extract also produced a significant effect (p < 0.05) but with less intensity than the HEX extract in the PTZ-induced seizures. A similar anticonvulsant response was observed in the MES test in the presence of DHS (p < 0.005) and the HEX extract (p < 0.05), but not in the case of the MeOH extract. In conclusion, our study provides evidence that non-polar and polar constituents of B. arborea participate in its anticonvulsant property, where DHS might play an important role in the therapy of convulsions mediated by GABAA/BDZ receptor modulation.

Objectives: The patient's family history of type 2 diabetes (FH-DM2) has been negatively associated with the functionality of endothelial cells (ECs). Our objectives in this work were to use human umbilical vein endothelial cells (HUVECs) as a model, to substantiate whether FH-DM2 influences endothelial phenotype and impairs NO and ROS synthesis, cell metabolism, and mitochondrial activity of ECs from individuals with FH-DM2. Methods: In this study were evaluated the synthesis of reactive oxygen species (ROS) and nitric oxide (NO), mitochondrial membrane potential (MMP), mRNA of eNOS, glucose consumption, and lactate synthesis in HUVECs from newborns with FH-DM2. Furthermore, we also evaluated EC complexity and cell size through flow cytometry. Results: Our results showed significant differences in HUVECs with FH-DM2, regarding their complexity and cell size, in the synthesis of ROS (p<0.01), and NO (p<0.05); they also reflected diminished glucose consumption and slight changes in the lactate levels. Conclusion: In conclusion, our results showed that HUVECs from children with FH-DM2 have a reduced capability of synthesizing ROS and NO, which might be linked to the metabolism of endothelial cells. These results are relevant since early endothelial dysfunction has been reported in individuals with FH-DM2, and could be used to establish preventive measures to reduce the risk of developing atherosclerosis or cardiovascular diseases in healthy individuals, but with this family background.

The genus Salvia (Lamiaceae) is widely distributed in Mexico with approximately 300 species. Aerial parts, leaves, and branches of sages are prepared as infusions or decoctions in traditional Mexican medicine to treat conditions such as dysentery, diarrhea, gastritis, stomach-ache, headache, sore throat, cough, bronchitis, fever, diabetes, epilepsy, nerves, insomnia, anxiety, among other ailments. The aim of this review was to compile and resume relevant information from literature regarding the chemical constituents of the pimarane and labdane type isolated from Mexican salvias and their biological activities covering the period from 1986 to 2022. A total of 31 compounds of these types were registered with 24 pimaranes and 7 labdanes. It was noticed that scientific evidence of the participation in the medicinal effects of Salvia species has not yet been reported for most of these diterpenoids. However, those described as bioactive have shown antibacterial, anticancer, anti-inflammatory, antihypotensive, antimutagenic, and antidiabetic properties. The present review provides information on the chemical and biological properties of pimaranes and labdanes from Mexican Salvia species suggesting their potential to become an option of treatment for diabetes and cancer, among other common diseases of Mexican population and of all the world. Nevertheless, further research is encouraged to demonstrate the benefits of these chemical constituents for health. 25 26 Ortiz-Mendoza, N., et al. RESUMEN El género Salvia (Lamiaceae) está ampliamente distribuido en México con aproxima-damente 300 especies. Las partes aéreas, hojas y ramas de salvias son preparadas como infusiones o decocciones y se utilizan en la medicina tradicional mexicana para tratar padecimientos como disentería, diarrea, gastritis, dolor de estómago, dolor de cabeza, dolor de garganta, tos, bronquitis, fiebre, diabetes, epilepsia, ner-vios, insomnio, ansiedad, entre otras enfermedades. El objetivo de esta revisión fue compilar y resumir información de la literatura acerca de los constituyentes químicos de tipo pimarano y labdano aislados de salvias mexicanas cubriendo el periodo de 1986 a 2022, incluyendo aquellas con actividad biológica. Un total de 31 compuestos de este tipo fueron registrados como 24 pimaranos y 7 labdanos. La evidencia de la participación de estos diterpenoides en los efectos medicinales de las especies de Salvia aún no ha sido reportada para la mayoría de estos metabolitos. Sin embargo, los que se han descrito como bioactivos demostraron presentar pro-piedades antibacterianas, anticancerígenas, antiinflamatorias, antihipotensivas, antimutagénicas y antidiabéticas. La presente revisión proporciona información sobre la importancia química y biológica de los pimaranos y labdanos de salvias mexicanas sugiriendo a estos constituyentes como posibles alternativas para el tratamiento de la diabetes y el cáncer, entre otras enfermedades que son comunes en México y en todo el mundo. No obstante, más investigación es requerida para demostrar los beneficios de estos componentes químicos para la salud.

The pharmacological effects of pomegranates have been described considering metabolic aspects such as hypoglycemic and hypolipidemic activities. The pomegranate extract has activity on the central nervous system (CNS) as a natural antidepressant and anxiolytic. The chemical composition of pomegranates is complex since the bioactive compounds are multiple secondary metabolites that have been identified in the extracts derived from the peel, seed, flowers, leaves, or in their combination; so, it has not been easy to identify an individual compound as responsible for its observed pharmacological properties. From this point of view, the present review analyzes the effects of crude extracts or fractions of pomegranates and their possible mechanisms of action concerning antidepressant- and anxiolytic-like effects in animal models. Serotonin receptors, estrogen receptors, the peroxisome proliferator-activated receptor gamma (PPARγ), or monoamine oxidase enzymes, as well as potent antioxidant and neuroplasticity properties, have been described as possible mediators involved in the antidepressant- and anxiolytic-like behaviors after pomegranate treatment. The pharmacological effects observed on the CNS in experimental models associated with a specific stress level suggest that pomegranates could simultaneously modulate the stress response by activating several targets. For the present review, scientific evidence was gathered to integrate it and suggest a possible pathway for mediators to be involved in the mechanisms of action of the pomegranate’s antidepressant- and anxiolytic-like effects. Furthermore, the potential benefits are discussed on comorbid conditions with anxiety and depression, such as perimenopause transition and pain.

Raphanus sativus L. cv. Sango, commonly known as red radish, is widely consumed around the world as a vegetable, but its benefit in pain relief is not sufficiently investigated. This study aimed to evaluate the antinociceptive effects of R. sativus and a possible mechanism of action. An aqueous extract of R. sativus sprouts (AERSS) was investigated by parenteral (10, 30, and 100 mg kg-1, i.p.) and enteral (500 mg kg-1, p.o.) administration in the neurogenic and inflammatory phases of the formalin test, where gastric damage was also evaluated as a possible adverse effect. Ketorolac (5 mg kg-1, i.p.) was used as the reference drug. Endogenous opioid and 5-HT1A serotonin receptors, as well as the cAMP/NO-cGMP pathways, were explored in the study of a possible mechanism of action by using their corresponding antagonists: naloxone, 1 mg kg-1, i.p., WAY100635, 1 mg kg-1, i.p., and enzymatic activators or inhibitors, respectively. Sulforaphane (SFN), a known bioactive metabolite, was analyzed using electroencephalography (EEG) to evidence its central involvement. A significant and dose-dependent antinociceptive activity was observed with the AERSS resembling the antinociceptive effect of the reference drug, with an equivalent significant response with a dose of 500 mg kg-1, p.o. without causing gastric damage. The participation of the endogenous opioid and 5-HT1A serotonin receptors at central and peripheral levels was also observed, with a differential participation of cAMP/NO-cGMP. SFN as one metabolite produced significant changes in the EEG analysis, reinforcing its effects on the CNS. Our preclinical evidence supports the benefits of consuming Raphanus sativus cv. Sango sprouts for pain relief.