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Role of lysophosphatidic acid and its receptors in health and disease:novel therapeutic strategies

Signal Transduction and Targeted Therapy 2021年第3期6卷 630-647页

作者： Luiz Henrique Medeiros Geraldo tania cristina leite de sampaio spohr Rackele Ferreira do Amaral Anna Carolina Carvalho da Fonseca Celina Garcia Fabio de Almeida Mendes Catarina Freitas Marcos Fabio dosSantos Flavia Regina Souza Lima Institute de Ciencias BiomedicasUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil Universite de Paris PARCCINSERMF-75015 ParisFrance Institute Estadual do Cerebro Paulo Niemeyer-Secretaria de Estado de Saude Rio de JaneiroBrazil Instituto de Saiide de Nova Friburgo Universidade Federal Fluminense28625-650 Nova FriburgoBrazil

Lysophosphatidic acid(LPA)is an abundant,bioactive phospholipid,with multiple functions both in development and in pathological ***,we review the literature about the differential signaling of LPA through its specific receptors,which makes this lipid a versatile signaling *** differential signaling is important for understanding how this molecule can have such diverse effects during central nervous system development and angiogenesis;and also,how it can act as a powerful mediator of pathological conditions,such as neuropathic pain,neurodegenerative diseases,and cancer ***,we review the preclinical and clinical uses of Autotaxin,LPA,and its receptors as therapeutic targets,approaching the most recent data of promising molecules modulating both LPA production and *** review aims to summarize the most update knowledge about the mechanisms of LPA production and signaling in order to understand its biological functions in the central nervous system both in health and disease.

关键词： therapeutic clinical diseases

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Taxifolin stability: In silico prediction and in vitro degradation with HPLC-UV/UPLCe ESI-MS monitoring

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Journal of Pharmaceutical Analysis 2021年第2期11卷 232-240页

作者： Fernanda cristina Stenger Moura Carmem Lúciados Santos Machado Favero Reisdorfer Paula Angelica Garcia Couto Maurizio Ricci Valdir Cechinel-Filho Tiago J.Bonomini Louis P.Sandjo tania Mari Belle Bresolin Pharmaceutical Sciences Graduate Program School of Health SciencesCourse of PharmacyUniversidade do Vale do ItajaíItajaíSC88302-202Brazil Laboratory of Research and development of Drugs Pharmaceutical Sciences Graduate ProgramSchool of Health SciencesCourse of PharmacyUniversidade Federal do PampaUruguaianaRS97500-970Brazil department of Pharmaceutical Science Universita degli Studi di PerugiaPerugiaPG06123Italy Chemistry department Universidade Federal de Santa CatarinaTrindadeFlorian opolisSC88040-900Brazil

Taxifolin has a plethora of therapeutic activities and is currently isolated from the stem bark of the tree Larix gmelinni(Dahurian larch). It is a flavonoid of high commercial interest for its use in supplements or in antioxidant-rich functional foods. However, its poor stability and low bioavailability hinder the use of flavonoid in nutritional or pharmaceutical formulations. In this work, taxifolin isolated from the seeds of Mimusops balata, was evaluated by in silico stability prediction studies and in vitro forced degradation studies(acid and alkaline hydrolysis, oxidation, visible/UV radiation, dry/humid heating) monitored by high performance liquid chromatography with ultraviolet detection(HPLC-UV) and ultrahigh performance liquid chromatography-electrospray ionization-mass spectrometry(UPLC-ESI-MS). The in silico stability prediction studies indicated the most susceptible regions in the molecule to nucleophilic and electrophilic attacks, as well as the sites susceptible to oxidation. The in vitro forced degradation tests were in agreement with the in silico stability prediction, indicating that taxifolin is extremely unstable(class 1) under alkaline hydrolysis. In addition, taxifolin thermal degradation was increased by *** the other hand, with respect to photosensitivity, taxifolin can be classified as class 4(stable).Moreover, the alkaline degradation products were characterized by UPLC-ESI-MS/MS as dimers of taxifolin. These results enabled an understanding of the intrinsic lability of taxifolin, contributing to the development of stability-indicating methods, and of appropriate drug release systems, with the aims of preserving its stability and improving its bioavailability.

关键词： Dihydroquercetin In silico stability prediction Forced degradation

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A Nucleotide-based Drug Protects Against Glutamate-and MPP^(+)-Induced Neurotoxicity

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Neuroscience & Medicine 2011年第2期2卷 154-160页

作者： Alejandro Gella tania Martianez Aloa Lamarca cristina Gutierrez Nuria Durany Nuria Casals Basic Sciences department Faculty of Medicine and Health SciencesUniversitat Internacional de CatalunyaBarcelonaSpain Neuroscience Institute Universitat Autònoma de BarcelonaBarcelonaSpain Centro de Investigación Biomédica en Red de la Fisiopatologia de la Obesidad y Nutrición(CIBER-OBN) BarcelonaSpain

Nucleo CMP Forte? is a nucleotide-based drug consisting of cytidinemonophosphate, uridinemonophosphate, uridin-ediphosphate and uridinetriphosphate. It has been prescribed for peripheral nervous system disorders, such as lum-bosciatalgia, diabetic or alcoholic polyneuropathy, or trigeminal neuralgia. Its effects on brain pathologies has re-ceived little attention. We examined its neuroprotective effects on cell toxicity induced by glutamate excitotoxicity or by 1-methyl-4-phenyl-pyridinium (MPP+), an in vitro cell model of Parkinson’s disease. We used the human dopaminergic cell line SH-SY5Y and a primary culture of rat cortical cells pre-treated with the drug for 24 hours and then exposed to MPP+ or glutamate at a range of concentrations. Cell viability was measured at different times. Nucleo CMP Forte? pre-treatment significantly increased the rate of cell division in SH-SY5Y cells, as well as the synthesis of triglycerides and phospholipids. More interestingly, drug pre-treatment significantly reduced MPP+- and glutamate-induced cell death in SH-SY5Y cells and in rat cortical cells. These results indicate that the nucleotides included in Nucleo CMP Forte? are promising therapeutic molecules for the prevention of neuronal death in brain caused by focal ischemia, Parkinson’s disease or other neurodegenerative pathologies.

关键词： Cortical Cell Culture Nucleotides Excitotoxicity Glutamate Neuroprotection Parkinson’s Disease SH-SY5Y Cells

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