Pharmacological Characterization Of Solanum Cernuum Vell.: 31-norcycloartanones With Analgesic And Anti-inflammatory Properties

Cycloeucalenone (1) and 24-oxo-31-norcycloartanone (2) obtained from Solanum cernuum Vell. were assayed to explore their pharmacologic roles. Previous studies showed that (2) has selective activity against lung tumor cell line (NCIH460) which expresses high levels of COX-2, suggesting its role in inflammatory process, and also a link between chronic inflammation and cancer-associated process. Dichloromethane crude extract (DCE) significantly reduced writhing and stretching induced by 0.8 % acetic acid at a dose of 100, 300, and 600 mg/kg, po; oral administration of different doses of (1) and (2) also displayed significant analgesic and anti-inflammatory effects in the writhing acetic acid test (p < 0.0001). Selected oral doses of both compounds (100 and 50 mg/kg) were assayed in the carrageenan-induced paw edema model. Compound (2) showed significant activity during the early phase (1.5-6 h) and also in the late phase (48 h) (p < 0.01). The anti-nociceptive activity observed for the compounds (1) and (2) and DCE was found to be related to the inhibition of different mediators involved in inflammation and nociceptive process. Both compounds decrease COX-2 protein expression, although only compound (2) reached a significant response (p < 0.05 vs control). However, in vitro Sirtuin 1 activity and TNF-α production in THP-1 macrophages were not affected. © 2013 Springer.223179185Bjorkman, S., Akeson, J., Helfer, M., Fyge, A., Gustafsson, L.L., Cerebral uptake of morphine in the Pig calculated from arteriovenous plasma-concentration gradients - an alternative to tissue microdialysis (1995) Life Sci, 57, pp. 2335-2345Corrêa, M.P., (1984) Dicionário de Plantas Úteis Do Brasil e Das Exóticas Cultivadas, , Imprensa Nacional, Rio de JaneiroCragg, G., Grothaus, P., Newman, D., Impact of natural products on developing new anti-cancer agents (2009) Chem Rev, 109, pp. 3012-3043Dao, T., Le, T., Nguyen, P., Thuong, P., Pham, T., Woo, E., Lee, K., Oh, W., SIRT1 inhibitory diterpenoids from the Vietnamese medicinal plant Croton tonkinensis (2010) Panta Medica, 76, pp. 1011-1074Ghosh, S., Hayden, M.S., New regulators of NF-kappa B in inflammation (2008) Nat Rev Immunol, 8, pp. 837-848Grando, R., Antonio, M., Araujo, C., Soares, C., Medeiros, M., De Carvalho, J., Lourenco, A., Lopes, L., Antineoplastic 31-norcycloartanones from Solanum cernuum Vell (2008) Zeitschrif fur Naturforschung Sect C-A J Biosci, 63, pp. 507-514Jain, R., Sharma, A., Gupta, S., Sarethy, I.P., Gabrani, R., Solanum nigrum: Current perspectives on therapeutic properties (2011) Altern Med Rev, 16, pp. 78-85Kang, N., Zhang, J., Qiu, F., Tashiro, S., Onodera, S., Ikejima, T., Inhibition of EGFR signaling augments oridonin-induced apoptosis in human laryngeal cancer cells via enhancing oxidative stress coincident with activation of both the intrinsic and extrinsic apoptotic pathways (2010) Cancer Lett, 294, pp. 147-158Kongkathip, N., Dhumma-upakorn, P., Kongkathip, B., Chawananoraset, K., Sangchomkaeo, P., Hatthakitpanichakul, S., Study on cardiac contractility of cycloeucalenol and cycloeucalenone isolated from Tinospora crispa (2002) Journal of Ethnopharmacology, 83 (1-2), pp. 95-99. , DOI 10.1016/S0378-8741(02)00210-6, PII S0378874102002106Lorenzi, H., Matos, F.J.A., (2000) Plantas Medicinais No Brasil, Nativas e Exóticas, , Instituto Plantarum de Estudos da flora Ltda, São PauloNunes, F.P.B., Sampaio, S.C., Santoro, M.L., Sousa-e-Silva, M.C.C., Long-lasting anti-inflammatory properties of Crotalus durissus terrificus snake venom in mice (2007) Toxicon, 49 (8), pp. 1090-1098. , DOI 10.1016/j.toxicon.2007.01.017, PII S0041010107000475Pedernera, M.A., Guardia, T., Calderón, C., Rotelli, A.E., De La Rocha, N.E., Saad, J.R., Verrilli, M.A.L., Pelzer, L.E., Anti-inflammatory effect of Acacia visco extracts in animal models (2010) Inflammopharmacology, 18, pp. 253-260Penissi, A., Vera, M., Mariani, M., Rudolph, M., Cenal, J., De Rosas, J., Fogal, T., Piezzi, R., Novel antiulcer alpha, beta-unsaturated lactones inhibit compound 48/80-induced mast cell degranulation (2009) Eur J Pharmacol, 612, pp. 122-130Posadas, I., Bucci, M., Roviezzo, F., Rossi, A., Parente, L., Sautebin, L., Cirino, G., Carrageenan-induced mouse paw oedema is biphasic, age-weight dependent and displays differential nitric oxide cyclooxygenase-2 expression (2004) British Journal of Pharmacology, 142 (2), pp. 331-338. , DOI 10.1038/sj.bjp.0705650Praman, S., Mulvany, M.J., Allenbach, Y., Marston, A., Hostettmann, K., Sirirugsa, P., Jansakul, C., Effects of an n-butanol extract from the stem of Tinospora crispa on blood pressure and heart rate in anesthetized rats (2011) J Ethnopharmacol, 133, pp. 675-686Rajic, A., Akihisa, T., Ukiya, M., Yasukawa, K., Sandeman, R.M., Chandler, D.S., Polya, G.M., Inhibition of trypsin and chymotrypsin by anti-inflammatory triterpenoids from Compositae flowers (2001) Planta Medica, 67 (7), pp. 599-604. , DOI 10.1055/s-2001-17350Ramírez-Cisneros, M., Rios, M., Déciga-Campos, M., Aguilar-Guadarrama, A., Phytochemical study and anti-inflammatory, antidiabetic and free radical scavenger evaluations of Krameria pauciflora methanol extract (2012) Molecules, 17, pp. 861-872Rodrigues, V.E.G., Carvalho, D.A., Etnobotanical survey of medicinal plants in the dominion of meadows in the region of the Alto Rio Grande, Minas Gerais (2001) Revista Ciência e Agrotecnologia, 25, pp. 102-123Shafiee, A., Bagheri, M., Shekarchi, M., Abdollahi, M., The antinociceptive activities of 1-(4-aryl-2-thiazolyl)-3,5- disubstituted-2 pyrazolines in mouse writhing test (2003) Journal of Pharmacy and Pharmaceutical Sciences, 6 (3), pp. 359-361. , http://www.ualberta.ca/~csps/JPPS6(3)/M.Abdollahi/pyrazoline.htmSouza-Brito, A., (1994) Manual de Ensaios Toxicológicos in Vivo, , Editora UNICAMP, CampinasSpindola, H.M., Servat, L., Denny, C., Rodrigues, R.A.F., Eberlin, M.N., Cabral, E., Sousa, I.M.O., Foglio, M.A., Antinociceptive effect of geranylgeraniol and 6a,7b-dihydroxyvouacapan- 17b-oate methyl ester isolated from Pterodon pubescens Benth (2010) BMC Pharmacol, 10, pp. 1-10Takahashi, T., Kozaki, K.-I., Yatabe, Y., Achiwa, H., Hida, T., Increased expression of COX-2 in the development of human lung cancers (2002) Journal of Environmental Pathology, Toxicology and Oncology, 21 (2), pp. 177-181Vendramini-Costa, D., De Castro, I., Ruiz, A., Marquissolo, C., Pilli, R., De Carvalho, J., Effect of goniothalamin on the development of Ehrlich solid tumor in mice (2010) Bioorg Med Chem, 18, pp. 6742-6747Vlachojannis, J.E., Cameron, M., Chrubasik, S., Medicinal use of potato-Derived products: A systematic review (2010) Phytother Res, 24, pp. 159-162Yang, X.W., Li, S.M., Wu, L., Li, Y.L., Feng, L., Shen, Y.H., Tian, J.M., Zhang, W.D., Abiesatrines A-J: Anti-inflammatory and antitumor triterpenoids from Abies georgei Orr (2010) Org Biomol Chem, 8, pp. 2609-2616Yeung, F., Hoberg, J.E., Ramsey, C.S., Keller, M.D., Jones, D.R., Frye, R.A., Mayo, M.W., Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase (2004) EMBO Journal, 23 (12), pp. 2369-2380. , DOI 10.1038/sj.emboj.7600244Yoshizaki, T., Milne, J., Imamura, T., Schenk, S., Sonoda, N., Babendure, J., Lu, J., Olefsky, J., SIRT1 exerts anti-inflammatory effects and improves insulin sensitivity in adipocytes (2009) Mol Cell Biol, 29, pp. 1363-1374Yoshizaki, T., Schenk, S., Imamura, T., Babendure, J., Sonoda, N., Bae, E., Oh, D., Olefsky, J., SIRT1 inhibits inflammatory pathways in macrophages and modulates insulin sensitivity (2010) Am J Physiol Endocrinol Metab, 298, pp. E419-E42

Diuretic And Potassium-sparing Effect Of Isoquercitrin - An Active Flavonoid Of Tropaeolum Majus L.

Aim of the study: Previous studies have shown that the extracts obtained from Tropaeolum majus L. exhibit pronounced diuretic effects supporting the ethnopharmacological use of this plant as diuretic. In the present work, phytochemical investigation, guided by bio-assay in spontaneously hypertensive rats (SHR), was carried out in order to identify the compounds responsible for diuretic action. Material and methods: Chromatographic fractionation of the hydroethanolic extract yielded an active fraction (TMLR) rich in isoquercitrin. TMLR (25-100 mg/kg) and isoquercitrin (5-10 mg/kg), as well the reference drug hydrochlorothiazide (10 mg/kg) were orally administered in a single dose or daily for 7 days to SHR. The urine excretion rate, pH, density, conductivity and content of sodium (Na+) and potassium (K+) electrolytes were measured in the urine of saline-loaded animals. Results: The urinary excretion rate was dose-dependently increased in both TMLR and isoquercitrin groups, as well as Na+. Despite the changes in urinary excretion of electrolytes, the plasmatic levels of Na+ and K+ had not been changed. In addition, we did not find any evidence of renal toxicity or other adverse effects in these animals, even after prolonged treatment with TMLR or isoquercitrin. Conclusion: This research supports and extends the ethnomedicinal use of T. majus as diuretic. This activity seems to be associated to the presence of the flavonol isoquercitrin. © 2010 Elsevier Ireland Ltd.1342210215Benjumea, D., Abdala, S., Hernandez-Luis, F., Perez-Paz, P., Martin-Herrera, D., Diuretic activity of Artemisia thuscula, an endemic canary species (2005) Journal of Ethnopharmacology, 100 (1-2), pp. 205-209. , DOI 10.1016/j.jep.2005.03.005, PII S0378874105002096, Perspectives of EthnopharmacologyBinet, L., A biologist physician in the country (1964) Biology and Medicine Journal, 53, pp. 5-28Correa, M.P., (1978) Dicionário Das Plantas Úteis Do Brasil e Das Exóticas Cultivadas, , Imprensa Nacional, Rio de JaneiroDe-la-Cruz, H., Vilcapoma, G., Zevallos, P.A., Ethnobotanical study of medicinal plants used by the Andean people of Canta, Lima, Peru (2007) Journal of Ethnopharmacology, 111 (2), pp. 284-294. , DOI 10.1016/j.jep.2006.11.018, PII S0378874106006210De Medeiros, J.M., Macedo, M., Contancia, J.P., Nguyen, C., Cunningham, G., Miles, D.H., Antithrombin activity of medicinal plants of the Azores (2000) Journal of Ethnopharmacology, 72, pp. 157-165Emura, K., Yokomizo, A., Toyoshi, T., Moriwaki, M., Effect of enzymatically modified isoquercitrin in spontaneously hypertensive rats (2007) Journal of Nutritional Science and Vitaminology, 53 (1), pp. 68-74. , DOI 10.3177/jnsv.53.68Ferreira, R.B.G., Vieira, M.C., Zárete, N.A.H., Análise de crescimento de Tropaeolum majus 'jewel' em função de espaçamentos entre plantas (2004) Revista Brasileira de Plantas Medicinais, 7, pp. 57-66Ferro, D., (2006) Fitoterapia: Conceitos Clínicos, , Atheneu, São PauloGaskell, S.J., Electrospray: Principles and practice (1997) Journal of Mass Spectrometry, 32 (7), pp. 677-688. , DOI 10.1002/(SICI)1096-9888(199707)32:7<677::AID-JMS536>3.0.CO;2-GGasparotto Jr., A., Boffo, M.A., Lourenco, E.L., Stefanello, M.E., Kassuya, C.A.L., Marques, M.C., Natriuretic and diuretic effects of Tropaeolum majus (Tropaeolaceae) in rats (2009) Journal of Ethnopharmacology, 122, pp. 517-522Goos, K.H., Albrecht, U., Schneider, B., Efficacy and safety profile of a herbal drug containing nasturtium herb and horseradish root in acute sinusitis, acute bronchitis and acute urinary tract infection in comparison with other treatments in the daily practice/results of a prospective cohort study (2006) Arzneimittelforschung, 56, pp. 249-257Griffiths, D.W., Deighton, N., Birch, A.E., Patrian, B., Baur, R., Stadler, E., Identification of glucosinolates on the leaf surface of plants from the Cruciferae and other closely related species (2001) Phytochemistry, 57 (5), pp. 693-700. , DOI 10.1016/S0031-9422(01)00138-8, PII S0031942201001388Jackson, E.K., Drugs affecting renal and cardiovascular function (1996) Goodman and Gilman's the Pharmacological Basis of Therapeutics, pp. 685-713. , Hardman, J.C., Gilman, A.G., Limbird, L.E. (Eds.), Pergamon Press, New YorkJohns, T., Kitts, W.D., Newsome, F., Towers, G.H.N., Anti-reproductive and other medicinal effects of Tropaeolum tuberosum (1982) Journal of Ethnopharmacology, 5 (2), pp. 149-161. , DOI 10.1016/0378-8741(82)90040-XKau, S.T., Keddie, J.R., Andrews, D., A method for screening diuretic agents in the rat (1984) Journal of Pharmacological Methods, 11 (1), pp. 67-75. , DOI 10.1016/0160-5402(84)90054-8Lacaille-Dubois, M.A., Franck, U., Wagner, H., Search for potential angiotensin converting enzyme (ACE)-inhibitors from plants (2001) Phytomedicine, 8 (1), pp. 47-52Li, J., Wang, Z.-W., Zhang, L., Liu, X., Chen, X.-H., Bi, K.-S., HPLC analysis and pharmacokinetic study of quercitrin and isoquercitrin in rat plasma after administration of Hypericum japonicum thunb. extract (2008) Biomedical Chromatography, 22 (4), pp. 374-378. , DOI 10.1002/bmc.942Lykkesfeldt, J., Moller, B.L., Synthesis of benzylglucosinolate in Tropaeolum majus L. (isothiocyanates as potent enzyme inhibitors) (1993) Plant Physiology, 102, pp. 609-613Maghrani, M., Zeggwagh, N.-A., Haloui, M., Eddouks, M., Acute diuretic effect of aqueous extract of Retama raetam in normal rats (2005) Journal of Ethnopharmacology, 99 (1), pp. 31-35. , DOI 10.1016/j.jep.2005.01.045Mietkiewska, E., Giblin, E.M., Wang, S., Barton, D.L., Dirpaul, J., Brost, J.M., Katavic, V., Taylor, D.C., Seed-specific heterologous expression of a nasturtium FAE gene in Arabidopsis results in a dramatic increase in the proportion of erucic acid (2004) Plant Physiology, 136 (1), pp. 2665-2675. , DOI 10.1104/pp.104.046839Pantoja, C.V., Chiang, L.C., Norris, B.C., Concha, J.B., Diuretic, natriuretic and hypotensive effects produced by Allium sativum (garlic) in anaesthetized dogs (1991) Journal of Ethnopharmacology, 31, pp. 325-331Roesler, R., Catharino, R.R., Malta, L.G., Eberlin, M.N., Pastore, G., Antioxidant activity of Caryocar brasiliense (pequi) and characterisation of components by electrospray ionization mass spectrometry (2008) Food Chemistry, 110, pp. 711-717Sarikonda, V.K., Watson, R.E., Opara, O.C., DiPette, D.J., Experimental animal models of hypertension (2009) Journal of the American Society of Hypertension, 3, pp. 158-165Schramm, D.D., German, J.B., Potential effects of flavonoids on the etiology of vascular disease (1998) Journal of Nutritional Biochemistry, 9 (10), pp. 560-566. , DOI 10.1016/S0955-2863(98)00051-5, PII S0955286398000515Schramm, D.D., Wang, J.F., Holt, R.R., Ensunsa, J.L., Gonsalves, J.L., Lazarus, S.A., Schmitz, H.H., Keen, C.L., Chocolate procyanidins decrease the leukotriene-prostacyclin ratio in humans and human aortic endothelial cells (2001) American Journal of Clinical Nutrition, 73 (1), pp. 36-40Stanic, G., Samarzija, I., Diuretic activity of Satureja montana subsp. Montana extracts and oil in rats (1993) Phytotherapy Research, 7, pp. 363-366Trippodo, N.C., Frohlich, E.D., Similarities of genetic (spontaneous) hypertension. Man and rat (1981) Circulation Research, 48, pp. 309-319Wu, J., Muir, A.D., Isoflavone content and its potential contribution to the antihypertensive activity in soybean angiotensin I converting enzyme inhibitory peptides (2008) Journal of Agricultural and Food Chemistry, 56, pp. 9899-9904Zanetti, G.D., Manfron, M.P., Hoelzel, S.C.S., Análise morfo-anatômica de Tropaeolum majus L. (Tropaeolaceae) (2004) IHERINGIA Série Botânica, 59, pp. 173-17

Prevalence and predictors of poor outcome in children with febrile neutropaenia presenting to the emergency department

First published: 13 April 2022Objective: Children with acquired neutropaenia due to cancer chemotherapy are at high risk of severe infection. The present study aims to describe the prevalence and predictors of poor outcomes in children with febrile neutropaenia (FN). Methods: This is a multicentre, prospective observational study in tertiary Australian EDs. Cancer patients with FN were included. Fever was defined as a single temperature ≥38°C, and neutropaenia was defined as an absolute neutrophil count <1000/mm3. The primary outcome was the ICU admission for organ support therapy (inotropic support, mechanical ventilation, renal replacement therapy, extracorporeal life support). Secondary outcomes were: ICU admission, ICU length of stay (LOS) ≥3 days, proven or probable bacterial infection, hospital LOS ≥7 days and 28-day mortality. Initial vital signs, biomarkers (including lactate) and clinical sepsis scores, including Systemic Inflammatory Response Syndrome, quick Sequential Organ Failure Assessment and quick Paediatric Logistic Organ Dysfunction-2 were evaluated as predictors of poor outcomes. Results: Between December 2016 and January 2018, 2124 episodes of fever in children with cancer were screened, 547 episodes in 334 children met inclusion criteria. Four episodes resulted in ICU admission for organ support therapy, nine episodes required ICU admission, ICU LOS was ≥3 days in four, hospital LOS was ≥7 days in 153 and two patients died within 28 days. Vital signs, blood tests and clinical sepsis scores, including Systemic Inflammatory Response Syndrome, quick Sequential Organ Failure Assessment and quick Paediatric Logistic Organ Dysfunction-2, performed poorly as predictors of these outcomes (area under the receiver operating characteristic curve <0.6). Conclusions: Very few patients with FN required ICU-level care. Vital signs, biomarkers and clinical sepsis scores for the prediction of poor outcomes are of limited utility in children with FN.Elliot Long, Franz E Babl, Natalie Phillips, Simon Craig, Michael Zhang, Amit Kochar, Mary McCaskill, Meredith L Borland, Monica A Slavin, Robert Phillips, Richard De A Lourenco, Francoise Michinaud, Karin A Thursky, Gabrielle Haeusler, Australian PICNICC Study Group and the PREDICT Networ

GloPID-R report on chikungunya, o'nyong-nyong and Mayaro virus, part 5: entomological aspects

The GloPID-R (Global Research Collaboration for Infectious Disease Preparedness) chikungunya (CHIKV), o’nyong-nyong (ONNV) and Mayaro virus (MAYV) Working Group has been established to investigate natural history, epidemiology and clinical aspects of infection by these viruses. Here, we present a report dedicated to entomological aspects of CHIKV, ONNV and MAYV. Recent global expansion of chikungunya virus has been possible because CHIKV established a transmission cycle in urban settings using anthropophilic vectors such as Aedes albopictus and Aedes aegypti. MAYV and ONNV have a more limited geographic distribution, being confined to Africa (ONNV) and central-southern America (MAYV). ONNV is probably maintained through an enzootic cycle that has not been characterized yet, with Anopheles species as main vectors and humans as amplification hosts during epidemics. MAYV is transmitted by Haemagogus species in an enzootic cycle using non-human primates as the main amplification and maintenance hosts, and humans becoming sporadically infected when venturing in or nearby forest habitats. Here, we focused on the transmission cycle and natural vectors that sustain circulation of these viruses in their respective locations. The knowledge of the natural ecology of transmission and the capacity of different vectors to transmit these viruses is crucial to understand CHIKV emergence, and to assess the risk that MAYV and ONNV will expand on wide scale using anthropophilic mosquito species not normally considered primary vectors. Finally, the experts identified knowledge gaps and provided adapted recommendations, in order to address future entomological investigations in the right direction

Building the glycolisis and Krebs cycle as a puzzle: a strategy to learning metabolic pathways.

First year physical  education  students must  understand metabolic  pathways to know how our body produces  energy  during  exercise  of different intensities and  rest.   However,  in a  first contact they usually complain about the difficulty to understand and visualize all the process such as the sequence of reactions,  the structure of the molecules and mainly what is changing in the molecule.  In an attempt to make easier the comprehension  of the metabolic  pathways we make a puzzle in a classroom where the  students have to build  the  glicolysis and  Krebs cycle through some clues given to guide them  to organize  the  sequence  of reactions.   For  this,  the  students were divided  in groups  of four and  each one received figures with  the  structural formula  of the  molecules and  their  names.  The  groups  that were changing  in the  structure were colored.  The  clues included  information such as the  compound that begins the pathway and its final product, number  and kind of enzymes involved, number  of ATPs produced,  reactions  with negative energy variation and number of compounds rich in energy produced. The students have no difficulty to visualize the structures or building these pathways. After that, they have some questions  to answer to see if they understand and learned the pathway. They reported that is easier  to  understand what  is changing  and  why,  making  the  comprehension  of what  is occurring during  exercise easier and have no difficulties to discuss and answer the questionnaire

<em>PNPLA6</em> mutations cause Boucher-Neuhauser and Gordon Holmes syndromes as part of a broad neurodegenerative spectrum.

Boucher-Neuh&auml;user and Gordon Holmes syndromes are clinical syndromes defined by early-onset ataxia and hypogonadism plus chorioretinal dystrophy (Boucher-Neuh&auml;user syndrome) or brisk reflexes (Gordon Holmes syndrome). Here we uncover the genetic basis of these two syndromes, demonstrating that both clinically distinct entities are allelic for recessive mutations in the gene PNPLA6. In five of seven Boucher-Neuh&auml;user syndrome/Gordon Holmes syndrome families, we identified nine rare conserved and damaging mutations by applying whole exome sequencing. Further, by dissecting the complex clinical presentation of Boucher-Neuh&auml;user syndrome and Gordon Holmes syndrome into its neurological system components, we set out to analyse an additional 538 exomes from families with ataxia (with and without hypogonadism), pure and complex hereditary spastic paraplegia, and Charcot-Marie-Tooth disease type 2. We identified four additional PNPLA6 mutations in spastic ataxia and hereditary spastic paraplegia families, revealing that Boucher-Neuh&auml;user and Gordon Holmes syndromes in fact represent phenotypic clusters on a spectrum of neurodegenerative diseases caused by mutations in PNPLA6. Structural analysis indicates that the majority of mutations falls in the C-terminal phospholipid esterase domain and likely inhibits the catalytic activity of PNPLA6, which provides the precursor for biosynthesis of the neurotransmitter acetylcholine. Our findings show that PNPLA6 influences a manifold of neuronal systems, from the retina to the cerebellum, upper and lower motor neurons and the neuroendocrine system, with damage of this protein causing an extraordinarily broad continuous spectrum of associated neurodegenerative disease