Pharmacological and Chemical Analysis of Bauhinia divaricata L. Using an In Vitro Antiadipogenic Model.

Obesity is characterized by an excessive and abnormal accumulation of fat. According to the 2022 National Health and Nutrition Survey, in Mexico, the prevalence of overweight and obesity-diagnosed if one's body mass index (BMI) was ≥25 kg/m2-in adults was 75.2%. A strong association between the amount of visceral fat and diseases such as diabetes mellitus type II has been recognized. Species of the Bauhinia genus have lipid-lowering and antidiabetic properties. The aim of this work was to evaluate the lipolytic and antiadipogenic activity of Bauhinia divaricata L. in 3T3-L1 cells and to identify the major compounds in the bioactive treatments. The extraction of aerial parts allowed us to obtain hexanic (BdHex), ethyl acetate (BdEAc), and hydroalcoholic (BdHA) extracts. Lipid levels were measured in 3T3-L1 cells differentiated into adipocytes. Our evaluation of cell viability identified an IC50 > 1000 µg/mL in all the extracts, and our evaluation of the antiadipogenic activity indicated that there was a significant reduction (p < 0.001) in the accumulation of lipids with hydroalcoholic (60%) and ethyl acetate (75%) extracts of B. divaricate compared with metformin at 30 mM (65%). The major compounds identified in these extracts were as follows: triacetin (1), 2,3-dihydroxypropyl acetate (2), (3E)-2-methyl-4-(1,3,3-trimethyl-7-oxabicyclo[4.1.0]hept-2-yl)-3-buten-2-ol (3), 2,5-dihydroxyphenylacetic acid (4), (3R)-3-hydroxydodecanoic acid (5), kaempferol-3-O-rhamnoside (6), and quercetin 3-O-rhamnoside (7). Some of these naturally occurring compounds have been related to the anti-obesity effects of other medicinal plants; therefore, these compounds isolated from B. divaricata could be responsible for inhibiting the differentiation process from preadipocytes to mature adipocytes.

Antidiabetic Activity of Xoconostle Fruit from Opuntia matudae Scheivar in Mice.

In Mexico, Cactaceae plants are widely used in folk medicine for the treatment of diabetes. The genus Opuntia spp. Opuntia matudae Sheinvar prickly pears are known as xoconostle and are used in Mexican cuisine for their acidic flavor. Currently there are few reports of pharmacological properties of this plant, which include antioxidant and antimicrobial activities. This study focuses on the chemical characterization of the methanolic (OmMe) and aqueous (OmAq) extracts and the evaluation of the antidiabetic activity of O. matudae fruits in two biological models. For the in vivo model, streptozotocin (STZ)-induced diabetic mice were used, and for the in vitro model, liver sections isolated from healthy mice were used. The OmAq (100 mg/kg, oral pathway [p.o.]) extract decreased postprandial glucose peak at 0.5 h after glucose uptake by 43.1%, similarly, OmMe (100 mg/kg, p.o.) extract reduced postprandial glucose peak at 0.5 h by 34.1% in healthy mice. The effect of the two extracts and the fraction of the mixture of unidentified betalains (OmB) of O. matudae evaluated in the isolated mouse liver slice model showed a concentration-dependent decrease in hepatic glucose output (HGO) with and without insulin administration with the OmMe extract. The OmAq extract, however, showed concentration-dependent increases of HGO with and without insulin, and the OmB fraction generally exhibited an insulin mimetic effect. Moreover, both OmAq and OmMe extracts were tested in mice with STZ-induced diabetes (160 mg/kg, intraperitoneal route), using a semichronic daily administration (2-28 days after diabetes onset) of OmAq extract was able to reduce blood glucose by 34.3%, meanwhile OmMe extract reduced blood glucose by 22.9%, 28 days after diabetes onset. We identified five compounds (1-5) in the two extracts, consisting of two phenolic acids (1, 2), three flavanols (3-5), as well as two unidentified betalains. Therefore, we conclude that the aqueous extract of the xoconostle fruit where betalains are present may be useful for the treatment of diabetes mellitus.

Antidepressant and anxiolytic compounds isolated from Salvia elegans interact with serotonergic drugs.

Salvia elegans belongs to a genus plants with biological activities in central nervous system. In this work, the purpose was to evaluate the anxiolytic and antidepressant effects of fractions and compounds isolated from S. elegans and its interaction with serotoninergic drugs by using behavioral tests in mice. Fractions from aerial parts of S. elegans were obtained by column chromatography, SeF1, SeF2, SeF3, and SeF4. Each of them was administered to 25 mg/k in ICR mice subject to forced swimming test (FST), or elevated plus maze test (EPM), or open field test (OFT). The most active fractions were chemically separated until compounds, which were analyzed as anxiolytic or antidepressant and the coadministration of these treatments with 5-HT1A and 5-HT2 drugs was measured in the different biological tests. All fractions were anxiolytic and antidepressant, oleanolic acid (OA) was found in SeF2, and from SeF3, a mixture of terpenes was found; a GC-MS analysis confirmed the presence of two main compounds: rosifoliol and agaraspirol (TM, mixture of terpenes). TM (doses-response curve, 0.01, 0.1, 0.5, 1.0, and 2.0 mg/kg) and OA (5 mg/kg) were also evaluated demonstrating an antidepressant and anxiolytic effect, respectively. The combination of TM (0.5 mg/kg) with 8-OH (selective 5-HT1A receptor agonist) induced an increment of antidepressant activity, while with the antagonist WAY-100635, the effect diminished. But with DOI (5-HT1c/5-HT2 receptor agonist), there was no change, and with KET (5-HT2 receptor antagonist), the activity was increased. When OA is co-administered with 8-OH or with DOI, the anxiolytic activity of this terpene, diminished; but with the combination with antagonists, the effect of OA shows no change. TM and OA were antidepressant and anxiolytic, respectively, on mice exposed to different tests, and these are able to interact with serotoninergic drugs.

Anti-neuroinflammatory effect of agaves and cantalasaponin-1 in a model of LPS-induced damage.

Chronic neuroinflammation is a key component of many neurodegenerative disorders. Chronic activation of this process produces pro-inflammatory cytokines, prostaglandins and reactive oxygen species that induce brain injury and neuronal dysfunction. Agave species contain saponins, compounds with anti-inflammatory activity. Extracts from A. tequilana (At), A. angustifolia (Aan), A. Americana (Aam) (125 mg/kg) and cantalasaponin-1 (5 and 10 mg/kg, isolated from Aam) were administered to male ICR mice with lipopolysaccharide (LPS)-induced neuroinflammation, after which inflammatory cytokines were measured in brain homogenates by using an enzyme-linked immunoassay (ELISA) test. All agave extracts and cantalasaponin-1, reduced brain concentration of LPS-induced pro-inflammatory cytokines IL-6 and TNF-α. Moreover, Cantalasaponin-1 increased the brain concentration of the anti-inflammatory cytokine IL-10. Agave extracts and derived compounds show promising results in the development of novel drugs for neuroinflammatory disease therapy.

Effectiveness of an encecalin standardized extract of Ageratina pichinchensis on the treatment of onychomycosis in patients with diabetes mellitus.

Ageratina pichinchensis is utilized in traditional medicine for the treatment of dermatomycosis and inflammation. The aim of this study was to evaluate the clinical and mycological effectiveness of the topical administration of an enecalin standardized extract of A. pichinchensis for treating onychomycosis in patients with type 2 diabetes mellitus (DM2). A double blind, randomized, and controlled clinical trial was carried out that included patients with DM2 and who had mild or moderate onychomycosis. Participants were administered topically, for 6 months, a lacquer containing the encecalin standardized extract of A. pichinchensis (experimental group) or 8% ciclopirox (control group). In a large percentage of both, the control group (77.2%) and the experimental group (78.5%), clinical efficacy was detected as a decrease in the number of affected nails and a reduction in the severity of nail involvement. Without exhibiting statistically significant differences between groups, the encecalin standardized extract of A. pichinchensis was clinically and mycologically effective in the treatment of mild and moderate onychomycosis in patients with DM2. The treatment of onychomycosis in patients with DM2 implies a greater challenge, while control of blood glucose levels in these patients, played a very important role in the response of patients to treatment.

Extraction of Galphimines from Galphimia glauca with Supercritical Carbon Dioxide.

The anti-depressive and anxiolytic effect of galphimine B (isolated from Galphimia glauca) has been demonstrated by researchers. Therefore, it is necessary to explore extraction techniques that produce materials with adequate quality for pharmaceutical applications. In this work, supercritical extractions of galphimines from Galphimia glauca were performed in the presence of carbon dioxide. Pressure, temperature, particle diameter, and flow rate effects were examined to explore the conditions with the highest yield and the concentration profile of galphimines in the studied interval. The identification of the nor-seco triterpenoids and galphimine B and E was carried out by HPLC analyses. The mathematical modeling of the extraction curves was attained by the approaches proposed by Sovová and Papamichail et al. According to results, the highest yield 2.22% was obtained at 323.15 K, 326 µm, 3 L/min, and 33.75 MPa. Meanwhile, the content of galphimine B in the extract was, on average, 19.5 mg·g-1.

Antidepressant-Like Effect of Bauhinia blakeana Dunn in a Neuroinflammation Model in Mice.

OBJECTIVE: To evaluate the antidepressant effect of Bauhinia blakeana and a standardized fraction in the forced swimming test (FST) on mice with neuroinflammation induced with lipopolysaccharides (LPS). MATERIALS AND METHODS: Evaluation of the antidepressant effect of Bauhinia blakeana hydroalcoholic extract (BbHA) and its fractions was carried out in behavioral tests on mice with LPS-induced neuroinflammation. RESULTS: BbHA had a significant antidepressant effect, measured on healthy mice in the FST. Bio-guided chemical separation of the extract produced a methanolic fraction (BbMe), which decreased the immobility time in FST. In this test, the intraperitoneal administration of LPS induced depression in mice, and BbHA and BbMe counteracted this effect, significantly decreasing the induced depression. Quantification of inflammatory mediators (IL-10, IL-4, IL-6, IL-1ß, and TNF-α) in the brain demonstrated that BbHA and BbMe effectively decreased the effect of LPS on the brain concentration of all measured cytokines. CONCLUSIONS: Bauhinia blakeana produced an antidepressant effect, while BbMe also exerted a modulating effect, on the damage induced by LPS. Rutin, a glycosylated flavonoid, was identified as the main compound in the active fraction, which could mediate in the antidepressant and immunomodulatory effect.

Aislamiento e identificación de compuestos con actividad antiobesidad y antiadipogénica de Thevetia peruviana / Isolation and identification of anti-obesity and anti-adipogenic compounds from Thevetia peruviana

Thevetia peruviana ha sido utilizada en la medicina tradicional mexicana por sus efectos adelgazantes. Para la identificación de las fracciones y los compuestos activos de T. peruviana se utilizó cromatografía en columna abierta y las fracciones obtenidas se evaluaron en ratones con obesidad inducida con glutamato monosódico. Como control positivo se utilizó Orlistat y los tratamientos se administraron oralmente una vez al día durante 8 semanas. La fracción con mayor actividad fue sub-fraccionada y, con la intención de evitar el uso de más ratones, los productos fueron seleccionados por su capacidad para inhibir la adipogénesis en la línea celular 3T3-L1. Los animales tratados con la fracción F-B mostraron un aumento de peso significativamente menor y mantuvieron la sensibilidad a la insulina, así como, niveles significativamente más bajos de colesterol y triglicéridos. El análisis de GC-MS indicó que esta fracción activa está compuesta principalmente por los ácidos palmítico (1), oleico (2) y octadacanoico (3), 2-palmitoil glicerol (4), 2-oleoil glicerol (5) así como la estigmastenona (6).

Thevetia peruviana has been used in Mexican traditional medicine for its slimming effects. Active fractions and compounds from T. peruviana were isolated and identified by means of gravitational open-column chromatography, and the fractions were evaluated on mice with MonoSodium Glutamate-induced obesity. Orlistat was used as positive control, and treatments were administered, orally, once a day for 8 weeks. The fraction with higher activity was sub-fractioned and, with the intention of avoiding using more mice, the fractions were analyzed by evaluating their capability to inhibit adipogenesis in the 3T3-L1 cell line. Animals treated with the F-B fraction revealed a significantly smaller weight increase and maintained adequate insulin sensitivity, and significantly lower blood levels of cholesterol and triglycerides. The active compounds that demonstrated greatest adipogenesis inhibition were palmitic acid (1), oleic acid (2), octadecanoic acid (3), 2-palmitoyl glycerol (4), 2-oleoyl glycerol (5) and stigmastenone (6).

A Malva parviflora´s fraction prevents the deleterious effects resulting from neuroinflammation.

Neuroinflammation, a centralized immune response, is a physiological process by which the organism attempts to remove an injurious stimulus in the central nervous system. Nonetheless, it is known that chronic inflammatory processes play an important role in the onset and progression of neurodegenerative disorders, such as Alzheimer´s disease (AD). Based on this, new strategies to treat AD have been proposed. Among them, the use of non-steroidal anti-inflammatory drugs (NSAIDs) decreases the incidence of this disease. Unfortunately, the prolonged use of NSAIDs results in adverse secondary effects. In this context, plants secondary metabolites have become of great interest. Particularly, our group has demonstrated that the hydroalcoholic extract of Malva parviflora (MpHA) has anti-inflammatory effect and is capable of improving the cognitive deficit present in an AD model. To further characterize the Malva parviflora compounds with anti-inflammatory properties, here we generated a fraction from a dichloromethane extract, which constitutes a less complex mix of compounds than the MpHA. This approach allowed us to isolate a fraction (MpF10) with anti-inflammatory activity, able to ameliorate the spatial learning and memory impairment, and to reduce both astrogliosis as well as IL-1ß and TNF production in a murine model of LPS-mediated neuroinflammation. Among the identified compounds in the MpF10, we found daucosterol (MpDau), which prevented LPS-induced neuroinflammation. Interestingly, MpF10 and MpDau inhibit NFκB activity in macrophages exposed to LPS. Therefore, we propose that the compounds present in the MpF10 represent an alternative to treat neuroinflammation, an important process developed during neurodegenerative diseases such as AD.

Galphimia glauca and Natural Galphimines Block Schizophrenia-Like Symptoms Induced with Apomorphine and MK-801 in Mice.

BACKGROUND: Galphimia glauca has been used for many years in Mexican Traditional Medicine to calm "insane people." Triterpenes, known as galphimines, were identified in this species. One of them, Galphimine-B (G-B), acts selectively on dopaminergic neurons by antagonizing the effect of glutamate on NMDA receptors. The objective of this study was to evaluate the effect of G. glauca methanolic extract (GgMeOH), a Galphimine-Rich Fraction (GRF), as well as the galphimines G-A, G-B, and G-E, on the acute psychosis induced by Apomorphine (APO) in mice and on schizophrenia-like symptoms induced by subchronic administration of MK-801. METHOD: On the first day, ICR male mice were given GgMeOH, GRF, or one of the galphimines. On day two, animals were treated with APO, and on day 3, they were subjected to behavioral tests. In a second test, MK-801 was administered daily for 28 days. In this case, animals were treated daily with G. glauca products from day 9 to day 28 and then subjected to behavioral tests (passive avoidance test, open field test, forced swimming test, and social interaction test). RESULTS: The increased number of stereotyped behaviors and grooming behaviors induced with APO were counteracted by all of the experimental treatments. MK-801 induced an increase in immobility time, which was blocked with G-B; GRF counteracted the decreased social interaction, and GgMeOH and GRF prevented the memory loss induced by MK-801. CONCLUSION: G. glauca and their derivatives products (GRF and galphimines) were able to interact with the dopaminergic and glutamatergic drugs and to block different behaviors associated with some of the positive, negative, and cognitive symptoms of induced schizophrenia in mice. It is necessary to continue with this research, in order to identify their mechanism of action.

Malva parviflora extract ameliorates the deleterious effects of a high fat diet on the cognitive deficit in a mouse model of Alzheimer's disease by restoring microglial function via a PPAR-γ-dependent mechanism.

BACKGROUND: Alzheimer's disease (AD) is a neuropathology strongly associated with the activation of inflammatory pathways. Accordingly, inflammation resulting from obesity exacerbates learning and memory deficits in humans and in animal models of AD. Consequently, the long-term use of non-steroidal anti-inflammatory agents diminishes the risk for developing AD, but the side effects produced by these drugs limit their prophylactic use. Thus, plants natural products have become an excellent option for modern therapeutics. Malva parviflora is a plant well known for its anti-inflammatory properties. METHODS: The present study was aimed to determine the anti-inflammatory potential of M. parviflora leaf hydroalcoholic extract (MpHE) on AD pathology in lean and obese transgenic 5XFAD mice, a model of familial AD. The inflammatory response and Amyloid ß (Aß) plaque load in lean and obese 5XFAD mice untreated or treated with MpHE was evaluated by immunolocalization (Iba-1 and GFAP) and RT-qPCR (TNF) assays and thioflavin-S staining, respectively. Spatial learning memory was assessed by the Morris Water Maze behavioral test. Microglia phagocytosis capacity was analyzed in vivo and by ex vivo and in vitro assays, and its activation by morphological changes (phalloidin staining) and expression of CD86, Mgl1, and TREM-2 by RT-qPCR. The mechanism triggered by the MpHE was characterized in microglia primary cultures and ex vivo assays by immunoblot (PPAR-γ) and RT-qPCR (CD36) and in vivo by flow cytometry, using GW9662 (PPAR-γ inhibitor) and pioglitazone (PPAR-γ agonist). The presence of bioactive compounds in the MpHE was determined by HPLC. RESULTS: MpHE efficiently reduced astrogliosis, the presence of insoluble Aß peptides in the hippocampus and spatial learning impairments, of both, lean, and obese 5XFAD mice. This was accompanied by microglial cells accumulation around Aß plaques in the cortex and the hippocampus and decreased expression of M1 inflammatory markers. Consistent with the fact that the MpHE rescued microglia phagocytic capacity via a PPAR-γ/CD36-dependent mechanism, the MpHE possess oleanolic acid and scopoletin as active phytochemicals. CONCLUSIONS: M. parviflora suppresses neuroinflammation by inhibiting microglia pro-inflammatory M1 phenotype and promoting microglia phagocytosis. Therefore, M. parviflora phytochemicals represent an alternative to prevent cognitive impairment associated with a metabolic disorder as well as an effective prophylactic candidate for AD progression.

Galphimine-B Standardized Extract versus Alprazolam in Patients with Generalized Anxiety Disorder: A Ten-Week, Double-Blind, Randomized Clinical Trial.

Galphimine-B (G-B), a compound isolated from Galphimia glauca, has been shown to possess important anxiolytic activity. In this study, we evaluated the effectiveness and tolerability of a G-B standardized extract (experimental treatment) that was administered daily for 10 weeks in patients with moderate or severe Generalized Anxiety Disorder (GAD). Alprazolam was used as control treatment and administered under the same conditions. A total of 167 patients were included. At the start of the study, the severe anxiety condition prevailed, with an average on the Hamilton Anxiety Scale of 35.1 ± 8.8 and 35.8 ± 8.1 points in the control and experimental groups, respectively. After the 10 weeks of administration, the average was reduced in the control group to 4.6 ± 6.5 points and in the experimental group to 3.5 ± 5.5 points. Therapeutic success in the control group was 85.7% and in the experimental group, 92.0%. A high proportion of patients (22.2%) treated with Alprazolam manifested daytime sleepiness, while in the group treated with the G-B standardized extract, daytime sleepiness was found in 4.7%. In conclusion, a G-B standardized extract demonstrated therapeutic effectiveness in patients with GAD, without exhibiting significant difference with Alprazolam, but showing fewer cases of daytime sleepiness. The trial was registered at http://clinicaltrials.gov by identifier: NCT03702803.

Acute and Chronic Antihypertensive Effect of Fractions, Tiliroside and Scopoletin from Malva parviflora.

Hypertension is a disease of high prevalence and morbidity where vascular inflammation and associated oxidative stress (endothelial dysfunction) is the underlying cause of this pathology. We are reporting the antihypertensive activity of extracts and fractions of Malva parviflora in mice with chronic and acute hypertension. Also, the treatments of this plant were able to counteract the kidney inflammation and associated oxidative stress. The chronic hypertension model consisted of administration of angiotensin II (AGII) during 12 weeks, causing a sustained increase in systolic (SBP) or diastolic (DBP) pressure, with values of pharmacological constants of: ED50 = 0.038 mg/kg y Emax = 135 mmHg for SBP and ED50 = 0.046 mg/kg y Emax = 98 mmHg for DBP. The chronic hypertension caused the inflammation and lipid peroxidation in kidneys, measured by of tissue level of cytokines such as interleukin-1ß (IL-1ß), IL-6, Tumor Necrosis Factor-α (TNF-α), IL-10 and malondialdehyde, and treatments for M. parviflora were able to modulate these parameters. The chemical fractionation allowed to identify three compounds: oleanolic acid, tiliroside and scopoletin, which were tested in a model of acute hypertension. The pharmacodynamic parameters for SBP were ED50 = 0.01 and 0.12 mg/kg while Emax = 33.22 and 37.74 mmHg for scopoletin and tiliroside, respectively; whereas that for DBP data were ED50 = 0.01 and 0.02 mg/kg; with an Emax = 7.00 and 6.24 mmHg, in the same order. M. parviflora, is able to counteract the effect of chronic and acute administration of AGII, on hypertension, but also the inflammatory and oxidative damage in the kidney. The oleanolic acid, scopoletin and tiliroside are the compounds responsible for such activities.

Effect of Standardized Fractions and Tiliroside from Leaves of Tilia americana on Depression Tests in Mice.

Depression affects more than 300 million people worldwide, represents one of the leading causes of disability worldwide. Depression treatment is based on the use of tricyclic antidepressants, selective serotonin reuptake inhibitors. These drugs, although clinically effective, have also been shown to have delayed onset activity and produce significant adverse side effects. Medicinal plants are presented as a source of study in the search for therapies. This study was aimed to assess the antidepressant effect (on forced swimming test -FST- and tail suspension test -TST-) of different fractions and tiliroside from Tilia americana. The organic fractions (FAC1-1, FAC1-2) and aqueous fractions (FAqC2-1, FAqC2-3) were obtained by column chromatography and the HPLC analysis allowed the standardization based on the concentration (mg/g) of several compounds: FAqC2-1 with tiliroside 20, quercitrin 41.7, and quercetin glucoside 73.8; FAqC2-3 with tiliroside 2.4, quercitrin 16.6 and 7-O-luteolin glucoside 35.9; FAC1-1 caffeic acid was quantified with 7.87 ; FAC1-2 with tiliroside 24.7 and quercitrin 19.8. Each fraction was tested in ICR mice at different dose in the FST and TST, as well as in the open field test (OFT); tiliroside was isolated and tested in such assays (at 0.05, 0.1, 0.5, and 1.0 mg/kg). All fractions were active, the better was FAC1-2, and induced a dose-dependent effect on FST with an ED50= 2.59 mg/kg and Emax = 175.4 sec; with a sedative effect in OFT. Tiliroside with like-antidepressant activity, showed a dose-response behavior (ED50= 0.04 mg/kg and Emax = 121.42 sec for FST; ED50= 0.014 mg/kg and Emax = 78.28 sec for TST).

Therapeutic Effectiveness of Galphimia glauca in Young People with Social Anxiety Disorder: A Pilot Study.

Social anxiety is one of the most common disorders found in the population attending the first level of health care. Galphimia glauca has been used for many years in Mexican traditional medicine to treat "nervous disorders". A standardized extract of this species has been evaluated in clinical studies that have proven its efficacy and safety in patients with generalized anxiety disorder. In this work, a double-blind clinical trial was carried out, using sertraline as a control. Patients from both sexes (18 to 35 years old) with moderate or severe social anxiety were included. Experimental group was treated daily (orally), for 10 weeks, with an extract from G. glauca containing 0.374 mg/dose of Galphimine-B (G-B, active compound). Patients in the control group were given sertraline (50 mg) in the same conditions. All patients were evaluated every two weeks. Another assessment was done one month after the end of the administration period. A total of 34 patients was included, 17 in each group. Women were predominant, and the mean age was 25 ± 4.7 years. In patients who received the G. glauca standardized extract, a significant reduction in anxiety was observed, with a value (in the Brief Social Phobia Scale) of 41.1±10.3 points at the start and 11.2±5.6 points at the end of treatment, while patients treated with sertraline had a value of 37.7±7.3 points at the beginning and 11.1±5.2 points at the end. No significant difference was observed between the treated groups. In a similar way, the health scale showed a gradual and continuous improvement in each of the five evaluations. In conclusion, the 10-week oral administration of G. glauca standardized extract showed efficacy and safety in patients with social anxiety disorder, without showing a significant difference from patients treated with sertraline.

Identification of Digestive Enzyme Inhibitors from Ludwigia octovalvis (Jacq.) P.H.Raven.

Current antiobesity and antidiabetic tools have been insufficient to curb these diseases and frequently cause side effects; therefore, new pancreatic lipase and α-glucosidase inhibitors could be excellent aids for the prevention and treatment of these diseases. The aim of this study was to identify, quantify, and characterize the chemical compounds with the highest degree of inhibitory activity of these enzymes, contained in a Ludwigia octovalvis hydroalcoholic extract. Chemical purification was performed by liquid-liquid separation and column chromatography. Inhibitory activities were measured in vitro, employing acarbose, orlistat, and a Camellia sinensis hydroalcoholic extract as references. For structural elucidation, Nuclear Magnetic Resonance was carried out, and High Performance Liquid Chromatography was used to quantify the compounds. For α-glucosidases, L. octovalvis hydroalcoholic extract and its ethyl acetate fraction showed half-maximal Inhibitory Concentration (IC50) values of 700 and 250 µg/mL, for lipase, 480 and 718 µg/mL, while C. sinensis showed 260 and 587 µg/mL. The most active compounds were identified as ethyl gallate (1, IC50 832 µM) and gallic acid (2, IC50 969 µM); both displayed competitive inhibition of α-glucosidases and isoorientin (3, IC50 201 µM), which displayed uncompetitive inhibition of lipase. These data could be useful in the development of a novel phytopharmaceutical drug.

Pharmacological interaction of Galphimia glauca extract and natural galphimines with Ketamine and Haloperidol on different behavioral tests.

Due to the high prevalence of psychiatric disorders and the prevalent side effects produced by the antipsychotic drugs available, it is necessary to search for new therapeutic options. Galphimia glauca has been used for many years in Mexican traditional medicine for treating mental diseases. From this plant, some compounds, denominated galphimines, have been discovered and have shown to possess the ability of modifying the frequency of discharge of dopaminergic neurons in the Ventral tegmental area. The objective of the present work was to evaluate the effect produced by the G. glauca extract, a Galphimine rich fraction (GRF), as well as the pure galphimines (G-A, G-B, and G-E) on behavioral models in mice. Products obtained from G. glauca were evaluated in the Haloperidol-induced catalepsy test and in the acute schizophrenia-like symptoms-induced with Ketamine (KET) in mice. Catalepsy was evaluated through the bar test, and schizophrenia-like symptoms, by means of the Open Field Test (OFT), Passive Avoidance Test (PAT), and the Forced Swimming Test (FST). The methanolic extract from G. glauca, GRF, and the pure galphimines were able to interact with the dopaminergic pathway and modify the behavioral response such as to potentiate the cataleptic effect induced with Haloperidol and to inhibit the behavior induced by KET in mice exposed to OFT, and FST. Moreover, the G. glauca extract and GRF were capable of blocking the cognitive decline that was induced with KET in mice (evaluated by PAT). Based on these results, it is possible to assume that part of the effect of G. glauca is due to the interaction of Galphimines with the dopaminergic and glutamatergic systems in vivo. It can be concluded that the products obtained from G. glauca potentiate the cataleptic effect induced with Haloperidol and show a protector effect on some of the symptoms generated by KET in mice (KET is capable of provoking halucinations in humans and psychosis-like behaviour in mice). With this basis, the metanolic extract from G. glauca, and the GRF are capable of blocking positive and cognitive symptoms associated with psychosis induced by KET. In addition, it could be suggested that the galphimines are responsible for the inhibition of the positive symptoms observed.

Anxiolytic effect of fatty acids and terpenes fraction from Aloysia triphylla: Serotoninergic, GABAergic and glutamatergic implications.

Aloysia triphylla (Verbenaceae) is an aromatic medicinal plant, and it is used for the treatment of "nervous" problems as, "sadness" and "nervousness". While, there are no reports about its pharmacological activity in animal models. The objective of this work was to evaluate the anxiolytic effect of the extracts and fractions of this species and to measure the interaction of the most active fraction with serotonergic, glutamatergic and GABAergic drugs. An elevated plus maze test was carried ought where the methanol (AtM), dicloromethane (AtD) and hexanic (AtH) extracts presented anxiolytic activity in mice when exposed to the test. Also, different fractions obtained from the AtD were evaluated (AtF1, AtF2 and AtF3, 15mg/kg), and showed that fraction AtF1 possessed the anxiolytic activity, in the same model. Then, AtF1 was co-administered with different drugs, which act on GABAergic (bicuculline, picrotoxin, pentylenetetrazol, baclofen and phaclofen), or serotononinergic (DOI, 8-OH-DPAT, WAY 100635 and ketanserine) or glutamatergic (NMDA, MPEP and MK-801) systems. The anxiolytic activity of AtF1 was modified by GABAergic and serotoninergic drugs. Chemical analysis of this fraction by using GC-MS, showed that it contains hexadecanoic acid, hexadecanoic acid methyl ester, octadecanoic acid methyl ester, eicosanoic acid methyl ester, vitamin E, α-amiryn, campesterol, sitosterol, stigmastan-2,22, dien-3-ol (4) and stigmasta 5, 24 (28) dien-3-ol.

Homoisoflavonoids and Chalcones Isolated from Haematoxylum campechianum L., with Spasmolytic Activity.

Haematoxylum campechianum is a medicinal plant employed as an astringent to purify the blood and to treat stomach problems such as diarrhea and dysentery. A bio-guided chemical fractionation of the methanolic extract obtained from this plant allowed for the isolation of five compounds: two chalcones known as sappanchalcone (1); 3-deoxysappanchalcone (2); three homoisoflavonoids known as hematoxylol A (3); 4-O-methylhematoxylol (4); and, hematoxin (5). The spasmolytic activity was determined in an in vitro model (electrically induced contractions of guinea pig ileum), and allowed to demonstrate that the methanolic extract (EC50 = 62.11 ± 3.23) fractions HcF7 (EC50 = 61.75 ± 3.55) and HcF9 (EC50 = 125.5 ± 10.65) and compounds 1 (EC50 = 16.06 ± 2.15) and 2 (EC50 = 25.37 ± 3.47) of Haematoxylum campechianum present significant relaxing activity as compared to papaverine (EC50 = 20.08 ± 2.0) as a positive control.

Pharmacokinetic Study of Biotransformation Products from an Anxiolytic Fraction of Tilia americana.

An anxiolytic fraction of Tilia americana standardized in tiliroside, rutin, quercitrin, quercetin glucoside, and kaempferol was obtained. After oral administration of the fraction, the above-mentioned flavonoids were not detected in plasma over 24 h. However, meta and para hydroxyphenylacetic acid and dihydroxyphenylacetic acid (m-HPAA, p-HPAA and DOPAC) were monitored. These are the biotransformation compounds of the aglycones of kaempferol and quercetin; these aglycones are products of the other flavonoids present in the anxiolytic fraction. The analytical methods (HPLC) for flavonoids and the related compounds (m-HPAA, p-HPAA and DOPAC) were validated, determining the parameters of accuracy, precision, specificity or selectivity, limit of detection, quantification range, and robustness. The pharmacokinetic assay was performed with ICR mice strains, which were given 200 mg/kg of the standardized active fraction. The results of validation of the analytical methods were obtained, allowing it to be established in a validated way that no flavonoids present in the anxiolytic fraction of T. americana were detected in plasma. However, detection and follow up was possible for the serum levels of m-HPAA, p-HPAA, and DOPAC. The three compounds follow a two-compartment model with very similar parameters between m-HPAA and p-HPAA, some being different from the ones characterized in the pharmacokinetics of DOPAC.