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Gut-brain connection: The neuroprotective effects of the anti-diabetic drug liraglutide

World Journal of Diabetes 2015年第6期6卷 807-827页

作者： Emanuel Monteiro Candeias Inês Carolina Sebastio Susana Maria Cardoso Sónia Catarina Correia Cristina Isabel carvalho ana Isabel Plácido Maria Sancha Santos Catarina Resende Oliveira paula Isabel Moreira ana Isabel Duarte CNC-Center for Neuroscience and Cell Biology Rua Larga Faculty of Medicine (1st Floor) University of Coimbra Institute for Interdisciplinary Research (IIIUC) University of Coimbra Casa Costa Alem?o-Pólo II Rua D Francisco de Lemos 3030-789 Coimbra Portugal Faculty of Medicine University of Coimbra Life Sciences department University of Coimbra Largo Marquês de Pombal 3004-517 Coimbra Portugal Institute of Biochemistry Faculty of Medicine University of Coimbra Institute of Physiology Faculty of Medicine University of Coimbra

Long-acting glucagon-like peptide-1(GLP-1) analogues marketed for type 2 diabetes(T2D) treatment have been showing positive and protective effects in several different tissues, including pancreas, heart or even brain. This gut secreted hormone plays a potent insulinotropic activity and an important role in maintaining glucose homeostasis. Furthermore, growing evidences suggest the occurrence of several commonalities between T2 D and neurodegenerative diseases, insulin resistance being pointed as a main cause for cognitive decline and increased risk to develop dementia. In this regard, it has also been suggested that stimulation of brain insulin signaling may have a protective role against cognitive deficits. As GLP-1 receptors(GLP-1R) are expressed throughout the central nervous system and GLP-1 may cross the blood-brain-barrier, an emerging hypothesis suggests that they may be promising therapeutic targets against brain dysfunctional insulin signaling-related pathologies. Importantly, GLP-1 actions depend not only on the direct effect mediated by its receptor activation, but also on the gut-brain axis involving an exchange of signals between both tissues via the vagal nerve, thereby regulating numerous physiological functions(e.g., energy homeostasis, glucose-dependent insulin secretion, as well as appetite and weight control). Amongst the incretin/GLP-1 mimetics class of anti-T2 D drugs with an increasingly described neuroprotective potential, the already marketed liraglutide emerged as a GLP-1R agonist highly resistant to dipeptidyl peptidase-4 degradation(thereby having an increased half-life) and whose systemic GLP-1R activity is comparable to that of native GLP-1. Importantly, several preclinical studies showed anti-apoptotic, anti-inflammatory, anti-oxidant and neuroprotective effects of liraglutide against T2 D, stroke and Alzheimer disease(AD), whereas several clinical trials, demonstrated some surprising benefits of liraglutide on weight loss, microglia in

关键词： Type 2 diabetes Glucagon-like peptide-1 Gut Brain Insulin Liraglutide Alzheimer disease Neuroprotection

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Punica granatum Leaf Lipophilic Fraction Favours Mortality by Attenuating Inflammation in Mice with Polymicrobial Sepsis

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Journal of Pharmacy and Pharmacology 2019年第7期7卷 355-367页

作者： Nagila Caroline Fialho Sousa Isabella Fernandes da Silva Figueiredo Mizael Calacio de Araujo Elaine Pereira de Andrade Thais Costa Alves Bruna Letícia Rosa da Silva Domingos Magno Santos Pereira Saulo JoseFigueiredo Mendes Joao Francisco Silva Rodrigues Jaqueline Pessoa Pontes Simone Aparecida teixeira AndreAlvares Marques Vale Marcus Vinicius Dias-Souza Lidio Goncalves Lima-Neto Vera Lucia dos Santos ana paula Azevedo-Santos Marcelo Nicolas Muscara Valerio Monteiro-Neto Andrea de Souza Monteiro Luis Claudio Nascimento da Silva Elizabeth Soares Fernandes Programa de Pos-graduacao Universidade CEUMARua JosueMontellon°1RenascencaSao LuisMA 65075-120Brazil departamento de Farmacologia Universidade de Sao PauloAv.Prof.Lineu Prestesn°1524Sala 326ButantanSao PauloSP 05508-900Brazil Programa de Pos-graduacao em Ciências em Saude Universidade Federal do MaranhaoAvenida dos Portuguesesn°1966BacangaSao LuisMA 65080-805Brazil departamento de Microbiologia Universidade Federal de Minas GeraisAv.Antonio Carlosn°6627PampulhaBelo HorizonteMG 31270-901Brazil departamento de Patologia Universidade Federal do MaranhaoAvenida dos Portuguesesn°1966BacangaSao LuísMA 65080-805Brazil

Punica granatum *** known antimicrobial and anti-inflammatory *** of different parts of this plant have been commonly used in the folk medicine to prevent and treat infections;and studies have supported the use of *** extracts for this ***,little is known of the effects of ***-derived fractions in severe infectious diseases such as ***,we investigated the actions of the hexane fraction(HF),rich in lipophilic compounds,obtained from the leaves of this plant,in a murine model of polymicrobial *** pre-treatment with HF increased mortality in septic *** same animals presented with lower levels of interleukin-6,nitric oxide and hydrogen peroxide in their peritoneal lavage samples than vehicle *** also increased polymorphonuclear cell accumulation in to the peritoneum of mice with ***-derived nitric oxide upon lipopolysaccharide stimuli was markedly reduced by incubation with ***,triterpenes,phytosterols,vitamin E and ascorbyl palmitate were detected in the *** results indicate that *** leaf lipophilic fractions may worsen sepsis *** effect may be associated with its bioactive compounds which act synergistically or not,increasing sepsis mortality in vivo.

关键词： P.granatum infection inflammation

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