The Role of the Estrogen-Related Receptor Alpha (ERRa) in Hypoxia and Its Implications for Cancer Metabolism.

Under low oxygen conditions (hypoxia), cells activate survival mechanisms including metabolic changes and angiogenesis, which are regulated by HIF-1. The estrogen-related receptor alpha (ERRα) is a transcription factor with important roles in the regulation of cellular metabolism that is overexpressed in hypoxia, suggesting that it plays a role in cell survival in this condition. This review enumerates and analyses the recent evidence that points to the role of ERRα as a regulator of hypoxic genes, both in cooperation with HIF-1 and through HIF-1- independent mechanisms, in invertebrate and vertebrate models and in physiological and pathological scenarios. ERRα's functions during hypoxia include two mechanisms: (1) direct ERRα/HIF-1 interaction, which enhances HIF-1's transcriptional activity; and (2) transcriptional activation by ERRα of genes that are classical HIF-1 targets, such as VEGF or glycolytic enzymes. ERRα is thus gaining recognition for its prominent role in the hypoxia response, both in the presence and absence of HIF-1. In some models, ERRα prepares cells for hypoxia, with important clinical/therapeutic implications.

Chronic Comorbidities in Middle Aged Patients Contribute to Ineffective Emergency Hematopoiesis in Covid-19 Fatal Outcomes.

BACKGROUND AND AIMS: Mexico is among the countries with the highest estimated excess mortality rates due to the COVID-19 pandemic, with more than half of reported deaths occurring in adults younger than 65 years old. Although this behavior is presumably influenced by the young demographics and the high prevalence of metabolic diseases, the underlying mechanisms have not been determined. METHODS: The age-stratified case fatality rate (CFR) was estimated in a prospective cohort with 245 hospitalized COVID-19 cases, followed through time, for the period October 2020-September 2021. Cellular and inflammatory parameters were exhaustively investigated in blood samples by laboratory test, multiparametric flow cytometry and multiplex immunoassays. RESULTS: The CFR was 35.51%, with 55.2% of deaths recorded in middle-aged adults. On admission, hematological cell differentiation, physiological stress and inflammation parameters, showed distinctive profiles of potential prognostic value in patients under 65 at 7 days follow-up. Pre-existing metabolic conditions were identified as risk factors of poor outcomes. Chronic kidney disease (CKD), as single comorbidity or in combination with diabetes, had the highest risk for COVID-19 fatality. Of note, fatal outcomes in middle-aged patients were marked from admission by an inflammatory landscape and emergency myeloid hematopoiesis at the expense of functional lymphoid innate cells for antiviral immunosurveillance, including NK and dendritic cell subsets. CONCLUSIONS: Comorbidities increased the development of imbalanced myeloid phenotype, rendering middle-aged individuals unable to effectively control SARS-CoV-2. A predictive signature of high-risk outcomes at day 7 of disease evolution as a tool for their early stratification in vulnerable populations is proposed.

Subclassification of B-acute lymphoblastic leukemia according to age, immunophenotype and microenvironment, predicts MRD risk in Mexican children from vulnerable regions.

Introduction: The decisive key to disease-free survival in B-cell precursor acute lymphoblastic leukemia in children, is the combination of diagnostic timeliness and treatment efficacy, guided by accurate patient risk stratification. Implementation of standardized and high-precision diagnostic/prognostic systems is particularly important in the most marginalized geographic areas in Mexico, where high numbers of the pediatric population resides and the highest relapse and early death rates due to acute leukemias are recorded even in those cases diagnosed as standard risk. Methods: By using a multidimensional and integrated analysis of the immunophenotype of leukemic cells, the immunological context and the tumor microenvironment, this study aim to capture the snapshot of acute leukemia at disease debut of a cohort of Mexican children from vulnerable regions in Puebla, Oaxaca and Tlaxcala and its potential use in risk stratification. Results and discussion: Our findings highlight the existence of a distinct profile of ProB-ALL in children older than 10 years, which is associated with a six-fold increase in the risk of developing measurable residual disease (MRD). Along with the absence of CD34+ seminal cells for normal hematopoiesis, this ProB-ALL subtype exhibited several characteristics related to poor prognosis, including the high expression level of myeloid lineage markers such as MPO and CD33, as well as upregulation of CD19, CD34, CD24, CD20 and nuTdT. In contrast, it showed a trend towards decreased expression of CD9, CD81, CD123, CD13, CD15 and CD21. Of note, the mesenchymal stromal cell compartment constituting their leukemic niche in the bone marrow, displayed characteristics of potential suppressive microenvironment, such as the expression of Gal9 and IDO1, and the absence of the chemokine CXCL11. Accordingly, adaptive immunity components were poorly represented. Taken together, our results suggest, for the first time, that a biologically distinct subtype of ProB-ALL emerges in vulnerable adolescents, with a high risk of developing MRD. Rigorous research on potential enhancing factors, environmental or lifestyle, is crucial for its detection and prevention. The use of the reported profile for early risk stratification is suggested.

Factors and Practices Associated with Self-Medicating Children among Mexican Parents.

BACKGROUND: Pediatric self-medication is based on the subjective interpretation of symptoms in children by the mother or an adult, the decision to self-medicate is made by a third party. The objective of this work is to provide information on the factors and practices associated with the self-medication of children among parents in Mexico. METHODS: A cross-sectional and descriptive study was conducted between June 2020 and December 2021 on Mexican parents with children under 12 years of age. Online questionnaires were completed with sections on sociodemographic characteristics, use of medicines or medicinal plants and their treated symptoms, sources of collection, and their recommendation. RESULTS: A total of 9905 online surveys were completed with representation from the 32 states of Mexico, and the prevalence of self-medication was 49.6% (n = 4908). Associated factors were age, having two or more children, children with chronic illnesses, medium educational level, unemployment or employment unrelated to health, medium and high socioeconomic level, and lack of medical security. Respondents self-medicated their children on the recommendation of a family member or friend (55.8%), and own initiative (28%). The most used medication was VapoRub (61.3%), followed by paracetamol (56.9%) and chamomile (33.1%), and the most prevalent symptoms were flu/flow (47.7%) followed by cough (34.2%). The main reasons were perceiving symptoms as not serious (69.9%) and reusing medications (51.9%). CONCLUSIONS: There is a high prevalence of self-medication in children in Mexico, mainly associated with children with chronic diseases and families with three or more children.

In silico testing of flavonoids as potential inhibitors of protease and helicase domains of dengue and Zika viruses.

Background: Dengue and Zika are two major vector-borne diseases. Dengue causes up to 25,000 deaths and nearly a 100 million cases worldwide per year, while the incidence of Zika has increased in recent years. Although Zika has been associated to fetal microcephaly and Guillain-Barré syndrome both it and dengue have common clinical symptoms such as severe headache, retroocular pain, muscle and join pain, nausea, vomiting, and rash. Currently, vaccines have been designed and antivirals have been identified for these diseases but there still need for more options for treatment. Our group previously obtained some fractions from medicinal plants that blocked dengue virus (DENV) infection in vitro. In the present work, we explored the possible targets by molecular docking a group of molecules contained in the plant fractions against DENV and Zika virus (ZIKV) NS3-helicase (NS3-hel) and NS3-protease (NS3-pro) structures. Finally, the best ligands were evaluated by molecular dynamic simulations. Methods: To establish if these molecules could act as wide spectrum inhibitors, we used structures from four DENV serotypes and from ZIKV. ADFR 1.2 rc1 software was used for docking analysis; subsequently molecular dynamics analysis was carried out using AMBER20. Results: Docking suggested that 3,5-dicaffeoylquinic acid (DCA01), quercetin 3-rutinoside (QNR05) and quercetin 3,7-diglucoside (QND10) can tightly bind to both NS3-hel and NS3-pro. However, after a molecular dynamics analysis, tight binding was not maintained for NS3-hel. In contrast, NS3-pro from two dengue serotypes, DENV3 and DENV4, retained both QNR05 and QND10 which converged near the catalytic site. After the molecular dynamics analysis, both ligands presented a stable trajectory over time, in contrast to DCA01. These findings allowed us to work on the design of a molecule called MOD10, using the QND10 skeleton to improve the interaction in the active site of the NS3-pro domain, which was verified through molecular dynamics simulation, turning out to be better than QNR05 and QND10, both in interaction and in the trajectory. Discussion: Our results suggests that NS3-hel RNA empty binding site is not a good target for drug design as the binding site located through docking is too big. However, our results indicate that QNR05 and QND10 could block NS3-pro activity in DENV and ZIKV. In the interaction with these molecules, the sub-pocket-2 remained unoccupied in NS3-pro, leaving opportunity for improvement and drug design using the quercetin scaffold. The analysis of the NS3-pro in complex with MOD10 show a molecule that exerts contact with sub-pockets S1, S1', S2 and S3, increasing its affinity and apparent stability on NS3-pro.

Anti-inflammatory and antinociceptive effects of an ethanol extract from Senna septemtrionalis.

Senna septemtrionalis (Viv.) H.S. Irwin & Barneby (Fabaceae) is a medicinal plant used as a folk remedy for inflammation and pain. The objective of this study was to evaluate the anti-inflammatory and antinociceptive actions of an ethanol extract of Senna septemtrionalis aerial parts (SSE). The in vitro anti-inflammatory effects of SSE were assessed using LPS-stimulated macrophages and the subsequent quantification of the levels of cytokines (IL-6, IL-1ß, and TNF-α) with ELISA kits, nitric oxide (NO), and hydrogen peroxide (H2O2). The in vivo anti-inflammatory actions of SSE were evaluated with the TPA-induced ear oedema test and the carrageenan-induced paw oedema test. The antinociceptive actions of SSE (10-200 mg/kg p.o.) were assessed using three models: two chemical assays (formalin-induced orofacial pain and acetic acid-induced visceral pain) and one thermal assay (hot plate). SSE showed in vitro anti-inflammatory actions with IC50 values calculated as follows: 163.3 µg/ml (IL-6), 154.7 µg/ml (H2O2) and > 200 µg/ml (IL-1ß, TNF-α, and NO). SSE showed also in vivo anti-inflammatory actions in the TPA test (40% of inhibition of ear oedema) and the carrageenan test (ED50 = 137.8 mg/kg p.o.). SSE induced antinociceptive activity in the formalin orofacial pain test (ED50 = 80.1 mg/kg) and the acetic acid-induced writhing test (ED50 = 110 mg/kg). SSE showed no antinociceptive actions in the hot plate assay. The pre-treatment with glibenclamide abolished the antinociceptive action shown by SSE alone. Overall, SSE exerted in vitro and in vivo anti-inflammatory actions, and in vivo antinociceptive effects by the possible involvement of ATP-sensitive K + channels.

Antiviral and immunomodulatory effects of polyphenols on macrophages infected with dengue virus serotypes 2 and 3 enhanced or not with antibodies.

Background: There is a lack of specific antiviral therapy against dengue virus (DENV) in current use. Therefore, a great proportion of dengue cases progress to severe clinical forms due to a complex interplay between virus and host immune response. It has been hypothesized that heterotypic non-neutralizing antibodies enhance DENV infection in phagocytic cells, and this induces an inflammatory response that is involved in the pathogenesis of severe dengue. Purpose: To identify the antiviral and immunomodulatory effects of polyphenols on dengue virus infection. Methods: Human U937-DC-SIGN macrophages were infected with DENV serotypes 2 or 3 in the presence or not of enhancing antibody 4G2. Viral titers and the secretion of tumor necrosis factor-alpha, IL-6, IL-10 and interferon-alpha were analyzed timely. Results: DENV infection alone induced high production of IL-6 and TNF-α, but in the presence of 4G2 antibody, viral titers and TNF-α secretion were potentiated. Based on anti-inflammatory antecedents, the polyphenols curcumin, fisetin, resveratrol, apigenin, quercetin and rutin were tested for antiviral and immunomodulatory properties. Only quercetin and fisetin inhibited DENV-2 and DENV-3 infection in the absence or presence of enhancing antibody (>90%, p<0.001); they also inhibited TNF-α and IL-6 secretion (p<0.001). Conclusion: Quercetin and fisetin down-regulate the production of proinflammatory cytokines induced by DENV infection enhanced by antibodies a mechanism involved in severe dengue.

Self-medication practice in pregnant women from central Mexico.

Self-medication during pregnancy represents a serious threat for mother and child health. The objective of this study was to evaluate the prevalence and the factors associated with self-medication among Mexican women living in the central region of Mexico. This is a descriptive interview-study of 1798 pregnant women or women who were pregnant no more than 3 years ago, when the interview was carried out. Data analysis was carried out with chi-square analysis and odds ratio. The prevalence of self-medication (allopathic drugs, medicinal plants, and other products, including vitamins, food supplements, among others) was 21.9%. The factors associated (p < 0.05) with self-medication were: higher education (college and postgraduate), smoking, and consumption of alcohol. Smoking was the strongest factor (OR: 2.536; 1.46-4.42) associated to self-medication during pregnancy, followed by consumption of alcohol (OR: 2.06; 1.38-3.08), and higher education (OR: 1.607; 1.18-2.19). Medicinal plant consumption was associated with nausea, constipation, migraine, and cold (p < 0.05), whereas he self-medication of allopathy was associated with gastritis and migraine (p < 0.05). Self-medication was influenced mainly by a relative or friend, who recommended the use of herbal medicine/allopathic medication. Two of the most common medicinal plants (arnica and ruda) here informed are reported to induce abortion or toxicity during pregnancy. The findings showed that self-medication (medicinal plants and allopathic medication) is a common practice among pregnant women from central Mexico. Adequate counselling of pregnant women by healthcare professionals about the potential risks of self-medication with herbal medicine and allopathic drugs during pregnancy is strongly warranted.

Bursera copallifera Extracts Have Cytotoxic and Migration-Inhibitory Effects in Breast Cancer Cell Lines.

Plants from the Bursera genus are widely distributed in the tropical dry forests of Mexico. In traditional medicine, extracts from different species of Bursera have been used for a wide range of biological activities, including the treatment of cancer-related symptoms. Compounds present in the Bursera genus include lignans, flavonoids, steroids, short-chain aliphatic alkanes, acetates, alcohols, ketones, and terpenoids. In some instances, secondary metabolites of these classes of compounds may induce cytotoxicity, and therefore we sought to investigate the effects of B. copallifera leaf extracts in breast cancer cell lines to evaluate their potential therapeutic value for the treatment of breast cancer, one of the most prevalent types of cancer in women worldwide. Two B. copallifera leaf extracts exerted cytotoxic effects on both the MCF7 and MDA-MB-231 breast cancer cell line models. The cytotoxic effect was more evident in the MDA-MB-231 triple negative cell line inhibiting also the migration of these cells. We identified hydroxycinnamic acid and flavonol derivatives as major phenolic components of the extracts. Our results strongly suggest a potential use of the Bursera leaf extracts rich in phenolic compounds, their individual phenolic compounds, or their combinations for the treatment of breast cancer.

Taraxacum officinale and Urtica dioica extracts inhibit dengue virus serotype 2 replication in vitro.

BACKGROUND: Urtica dioica, Taraxacum officinale, Calea integrifolia and Caesalpinia pulcherrima are widely used all over the world for treatment of different illnesses. In Mexico, these plants are traditionally used to alleviate or counteract rheumatism and inflammatory muscle diseases. In the present study we evaluated the activity of aqueous and methanolic extracts of these four plants, on the replication of dengue virus serotype 2 (DENV2). METHODS: Extraction process was carried out in a Soxtherm® system at 60, 85 and 120 °C; a chemical fractionation in silica gel chromatography was performed and compounds present in the active fractions were identified by HPLC-DAD-ESI/MSn. The cytotoxic concentration and the inhibitory effect of extracts or fractions on the DENV2 replication were analyzed in the BHK-21 cell line (plaque forming assay). The half maximal inhibitory concentration (IC50) and the selectivity index (SI) were calculated for the extracts and fractions. RESULTS: The methanolic extracts at 60 °C of T. officinale and U. dioica showed the higher inhibitory effects on DENV2 replication. After the chemical fractionation, the higher activity fraction was found for U. dioica and T. officinale, presenting IC50 values of 165.7 ± 3.85 and 126.1 ± 2.80 µg/ml, respectively; SI values were 5.59 and 6.01 for each fraction. The compounds present in T. officinale, were luteolin and caffeoylquinic acids derivatives and quercertin diclycosides. The compounds in the active fraction of U. dioica, were, chlorogenic acid, quercertin derivatives and flavonol glycosides (quercetin and kaempferol). CONCLUSIONS: Two fractions from U. dioica and T. officinale methanolic extracts with anti-dengue activity were found. The compounds present in both fractions were identified, several recognized molecules have demonstrated activity against other viral species. Subsequent biological analysis of the molecules, alone or in combination, contained in the extracts will be carried out to develop therapeutics against DENV2.

Medicinal Plants from North and Central America and the Caribbean Considered Toxic for Humans: The Other Side of the Coin.

The consumption of medicinal plants has notably increased over the past two decades. People consider herbal products as safe because of their natural origin, without taking into consideration whether these plants contain a toxic principle. This represents a serious health problem. A bibliographic search was carried out using published scientific material on native plants from Mexico, Central America, and the Caribbean, which describe the ethnobotanical and toxicological information of medicinal plants empirically considered to be toxic. A total of 216 medicinal plants belonging to 77 families have been reported as toxic. Of these plants, 76 had been studied, and 140 plants lacked studies regarding their toxicological effects. The toxicity of 16 plants species has been reported in clinical cases, particularly in children. From these plants, deaths have been reported with the consumption of Chenopodium ambrosioides, Argemone mexicana, and Thevetia peruviana. In most of the cases, the principle of the plant responsible for the toxicity is unknown. There is limited information about the toxicity of medicinal plants used in Mexico, Central America, and the Caribbean. More toxicological studies are necessary to contribute information about the safe use of the medicinal plants cited in this review.

Antinociceptive Activity of Ent-Dihydrotucumanoic Acid Isolated from Gymnosperma glutinosum Spreng Less.

Preclinical Research The diterpene ent-dihydrotumanoic acid (DTA) was among the compounds isolated from Gymnosperma glutinosum (Spreng) Less (Asteraceae). There are no reports regarding the pharmacological effects of DTA. Cytotoxicity against cancer cells (1-250 µM), and the antibacterial (50-1400 µM) activity of DTA were evaluated using the MTT assay, and the minimum inhibitory concentration test, respectively. The antidiarrheal (1-100 mg/kg p.o.) and anti-inflammatory (2 mg/ear) effects of DTA were evaluated using castor oil and 12-O-tetradecanoylphorbol-13-acetate, respectively. The antinociceptive and sedative effects of DTA (1-100 mg/kg p.o.) were evaluated using two models of chemically-induced nociception, and the pentobarbital-induced sleeping time test, respectively. The antinociceptive mechanism of DTA was evaluated using the acetic acid writhing test with inhibitors related to pain processing pathways. The effects of DTA (10-100 mg/kg p.o.) on locomotor activity were evaluated using the rotarod test. DTA lacked cytotoxic activity (IC50 > 100 µM) on cancer cells, possessed moderate antibacterial effects against B. subtillis (MIC= 175 µM), moderate antidiarrheal and anti-inflammatory effects, and minimal vasorelaxant effects. In the formalin test, DTA showed antinociceptive effects in both phases. In the acetic acid test, DTA showed antinociceptive activity (ED50 = 50.2 ± 5.6 mg/kg) with potency similar to that of naproxen (NPX; ED50 =33.7 ± 4.5 mg/kg) an effect blocked by naloxone implicating an opioid mechanism. DTA also exerted antidiarrheal activity and showed no sedative effects or changes in locomotor activity in mice. Drug Dev Res 78 : 340-348, 2017. © 2017 Wiley Periodicals, Inc.

The antinociceptive effects of a standardized ethanol extract of the Bidens odorata Cav (Asteraceae) leaves are mediated by ATP-sensitive K+ channels.

ETHNOPHARMACOLOGICAL RELEVANCE: Bidens odorata Cav (Asteraceae) is used for the empirical treatment of inflammation and pain. AIM OF THE STUDY: This work evaluated the in vitro and in vivo toxicity, antioxidant activity, as well as the anti-inflammatory and antinociceptive effects of an ethanol extract from Bidens odorata leaves (BOE). MATERIALS AND METHODS: The in vitro toxicity of BOE (10-1000µg/ml) was evaluated with the comet assay in PBMC. The in vivo acute toxicity of BOE (500-5000mg/kg) and the effect of BOE (10-1000µg/ml) on the level of ROS in PBMC were determined. The in vivo anti-inflammatory activity of BOE was assessed using the TPA-induced ear edema in mice. The antinociceptive activities of BOE (50-200mg/kg p.o.) were assessed using the acetic acid and formalin tests. The antinociceptive mechanism of BOE was determined using naloxone and glibenclamide. RESULTS: BOE lacked DNA damage, and showed low in vivo toxicity (LD50 > 5000mg/kg p.o.). BOE inhibited ROS production (IC50 = 252.13 ± 20.54µg/ml), and decreased inflammation by 36.1 ± 3.66%. In both antinociceptive test, BOE (200mg/kg) exerted activity with similar activity than the reference drugs. CONCLUSION: B. odorata exerts low in vitro and in vivo toxicity, antioxidant effects, moderate in vivo anti-inflammatory activity, and antinociceptive effects mediated by ATP-sensitive K+ channels.

Justicia spicigera Schltdl. and kaempferitrin as potential anticonvulsant natural products.

Justicia spicigera Schltdl. is a vegetal species traditionally used to control epilepsy, but scientific evidence is required to reinforce this activity. The aim of the study was to evaluate the anticonvulsant-like activity of J. spicigera aqueous extract (JsAE) and a bioactive compound. JsAE was assessed in a dose-response manner (30, 100 and 1000mg/kg, i.p.) using the pentylenetetrazol (PTZ)-induced seizures and maximal electroshock seizure (MES) test in mice in comparison to ethosuximide (ETX, reference drug 100mg/kg, i.p.) or phenytoin (25mg/kg, i.p.), respectively. Then a significant dosage (1000mg/kg, i.p.) was chosen to examine electrographic activity (EEG) in rats. Treatment groups were compared to the vehicle and ETX in the convulsive behavior alone or simultaneous to EEG after PTZ-induced seizures (80 or 35mg/kg, i.p., mice or rats). Kaempferitrin (a flavonoid of JsAE) and ETX were administered via intracerebroventricular (i.c.v, 4th ventricle, 1µg/µL) and tested in the presence of PTZ in rats. Results confirmed that JsAE delayed the onset of seizures and reduced frequency of tonic convulsion and mortality in mice. JsAE or kaempferitrin also decreased the EEG spikes frequency and amplitude in a similar manner than EXT in rats. In conclusion, these preliminary data give evidence of the potential of J. spicigera as possible anticonvulsant as recommended in folk medicine for treating epilepsy, where kaempferitrin is suggested as a partial responsible bioactive compound.

Use of medicinal plants by health professionals in Mexico.

ETHNOPHARMACOLOGICAL RELEVANCE: The use of medicinal plants in Mexico has been documented since pre-Hispanic times. Nevertheless, the level of use of medicinal plants by health professionals in Mexico remains to be explored. AIM OF THE STUDY: To evaluate the use, acceptance and prescription of medicinal plants by health professionals in 9 of the states of Mexico. MATERIALS AND METHODS: Direct and indirect interviews, regarding the use and acceptance of medicinal plants, with health professionals (n=1614), including nurses, physicians, pharmacists, and odontologists from nine states in Mexico were performed from January 2015 to July 2016. The interviews were analyzed with the factor the informant consensus (FIC). RESULTS: The information obtained indicated that 46% of those interviewed feel patients should not use medicinal plants as an alternative therapy. Moreover, 54% of health professionals, and 49% of the physicians have used medicinal plants as an alternative therapy for several diseases. Twenty eight percent of health professionals, and 26% of the physicians, have recommended or prescribed medicinal plants to their patients, whereas 73% of health professionals were in agreement with receiving academic information regarding the use and prescription of medicinal plants. A total of 77 plant species used for medicinal purposes, belonging to 40 botanical families were reported by the interviewed. The results of the FIC showed that the categories of diseases of the digestive system (FIC=0.901) and diseases of the respiratory system (FIC=0.898) had the greatest agreement. CONCLUSIONS: This study shows that medicinal plants are used for primary health care in Mexico by health professionals.

Antinociceptive Activity of an Ethanol Extract of Justicia spicigera.

Preclinical Research The aim of the present study was to evaluate the antinociceptive and sedative activity of an ethanol extract of Justicia spicigera an evergreen used in Mexican traditional medicine for the relief of pain, wounds, fever and inflammation. At 200 mg/kg po, the maximum dose examined, the ethanol extract of J. spicigera (JSE) had analgesic activity in mice in the acetic acid writhing test, the second phase of the formalin test and the tail flick test that was similar in efficacy to the NSAID, naproxen (150 mg/kg po). JSE was inactive in the hot plate test and and the ketamine-induced sleeping time test; it had no sedative effects. These results show that the ethanol extract from the leaves of J. spicigera has antinociceptive effects in mice without inducing sedation. Drug Dev Res 77 : 180-186, 2016. © 2016 Wiley Periodicals, Inc.

Plants used in the traditional medicine of Mesoamerica (Mexico and Central America) and the Caribbean for the treatment of obesity.

ETHNOPHARMACOLOGICAL RELEVANCE: Obesity is a worldwide medical concern. New ethnobotanical information regarding the antiobesity effect of medicinal plants has been obtained in the last 30 years in response to socio-demographic changes and high-fat diets became common. AIM OF THE STUDY: This review provides a summary of medicinal plants used in Mexico, Central America and the Caribbean for the empirical treatment of obesity in terms of ethnobotany, toxicity, pharmacology, conservation status, trade and chemistry. MATERIALS AND METHODS: Bibliographic investigation was performed by analyzing recognized books, undergraduate and postgraduate theses and peer-reviewed scientific articles, consulting worldwide accepted scientific databases from the last four decades. Medicinal plants used for the treatment of obesity were classified in two categories: (1) plants with pharmacological evidence and (2) plants without pharmacological evidence. RESULTS: A total of 139 plant species, belonging to 61 families, native to Mexico, Central America and the Caribbean that are used for the empirical treatment of obesity were recorded. From these plants, 33 were investigated in scientific studies, and 106 plants lacked scientific investigation. Medicinal plants were experimentally studied in vitro (21 plants) and in vivo (16 plants). A total of 4 compounds isolated from medicinal plants used for the empirical treatment of obesity have been tested in vitro (2 compounds) and in vivo (4 compounds) studies. No clinical trials on obese subjects (BMI>30 kg/m(2)) have been performed using the medicinal plants cited in this review. There are no herbal-based products approved in Mexico for the treatment of obesity. CONCLUSIONS: There are a limited number of scientific studies published on medicinal plants from Mexico, Central America and the Caribbean used for the treatment of obesity. This review highlights the need to perform pharmacological, phytochemical, toxicological and ethnobotanical studies with medicinal flora to obtain new antiobesity agents.

Magnolia dealbata seeds extract exert cytotoxic and chemopreventive effects on MDA-MB231 breast cancer cells.

CONTEXT: Cancer prevention remains a high priority for the scientific world. Magnolia dealbata Zucc (Magnoliaceae), a Mexican endemic species, is used for the empirical treatment of cancer. OBJECTIVE: To evaluate the cytotoxic and cancer chemopreventive effects of an ethanol extract of Magnolia dealbata seeds (MDE). MATERIALS AND METHODS: The cytotoxic effect of MDE, at concentrations ranging from 1 to 200 µg/ml, on human cancer cells and human nontumorigenic cells was evaluated using the MTT assay for 48 h. The apoptotic activities of MDE 25 µg/ml on MDA-MB231 breast cancer cells were evaluated using the TUNEL assay and the detection of caspase 3 using immunofluorescence analysis for 48 h, each. The chemopreventive effect was evaluated by administrating different doses of MDE, between 1 and 50 mg/kg, injected intraperitoneally daily into athymic mice which were implanted with MDA-MB231 cells during 28 days. The growth and weight of tumors were measured. RESULTS: MDE showed cytotoxic effects on MDA-MB231 cells (IC50 = 25 µg/ml) and exerted pro-apoptotic activities as determined by DNA fragmentation in MDA-MB231 cells. MDE 25 µg/ml also induces the activation of caspase 3 in MDA-MB231 cells. These results suggest that Magnolia dealbata may be an optimal source of the bioactive compounds: honokiol (HK) and magnolol (MG). MDE 50 mg/kg i.p. exerted chemopreventive effects by inhibiting the growth of MDA-MB231 tumor by 75% in athymic mice, compared to the control group. CONCLUSIONS: MDE exerts cytotoxic, apoptotic and chemopreventive activities on MDA-MB231 human cancer cells.

Rutin exerts antitumor effects on nude mice bearing SW480 tumor.

BACKGROUND AND AIMS: We previously showed that extracts from Phoradendron serotinum and Croton lechleri exerted in vitro cytotoxic and in vivo antitumor effects and that their main component was rutin (RTN; 3-rhamnosyl-glucosylquercetin). However, it is unknown whether RTN exerts in vivo antitumoral effects on human colon cancer cells. The aim of this work was to evaluate the antitumor effects of RTN on a murine model. METHODS: Cytotoxic effects of RTN on human cancer and non-tumorigenic cell lines were evaluated using the MTT assay. Different doses of RTN were injected intraperitoneally daily into nu/nu mice bearing tumors of SW480 colon cancer cells during 32 days. The growth and weight of tumors were measured. Serum levels of VEGF, survival time, increase in life span and toxicological effects on body weight and organ weight were also analyzed. RESULTS: RTN showed the highest cytotoxic effects against SW480 cells (IC50 = 125 µM) as compared to the other cancer cells lines and decreased, in a dose dependent manner, the tumor volume and weight of mice bearing SW480 tumor. RTN 20 mg/kg, the highest dose tested, lacked toxic effects on body weight and relative organ weight in mice, increased mean survival time by 50 days, and decreased by 55% the VEGF serum levels compared to untreated mice. CONCLUSIONS: RTN exerts in vitro cytotoxic effects on SW480 cells, induces in vivo antitumor effects, lacks toxic effects on mice bearing SW480 tumor and exerts antiangiogenic properties.

Kaempferitrin induces apoptosis via intrinsic pathway in HeLa cells and exerts antitumor effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Justicia spicigera is used for the empirical treatment of cervical cancer in Mexico. Recently, we showed that Justicia spicigera extracts exerted cytotoxic and antitumoral effects and the major component of this extract was kaempferitrin (KM). MATERIALS AND METHODS: The cytotoxic and apoptotic effect of KM on human cancer cells and human nontumorigenic cells were evaluated using MTT and TUNEL assays, and Annexin V/Propidium iodide detection by flow cytometry. The effect of KM on cell cycle was analyzed by flow cytometry with propidium iodide. The apoptotic and cell cycle effects were also evaluated by western blot analysis. Also, different doses of KM were injected intraperitoneally daily into athymic mice bearing tumors of HeLa cells during 32 days. The growth and weight of tumors were measured. RESULTS: KM induces high cytotoxic effects in vitro and in vivo against HeLa cells. The general mechanisms by which KM induces cytotoxic effects include: cell cycle arrest in G1 phase and apoptosis via intrinsic pathway in a caspase dependent pathway. Also, KM exerts chemopreventive and antitumor effects. CONCLUSION: KM exerts cytotoxic and antitumor effects against HeLa cells.