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Gilsane Lino Von Poser - One of the best experts on this subject based on the ideXlab platform.
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The anti‐Trichomonas vaginalis Phloroglucinol Derivative isoaustrobrasilol B modulates extracellular nucleotide hydrolysis
Chemical biology & drug design, 2017Co-Authors: Camila Braz Menezes, Gilsane Lino Von Poser, Graziela Vargas Rigo, Henrique Bridi, Danielle Da Silva Trentin, Alexandre José Macedo, Tiana TascaAbstract:Trichomonas vaginalis causes trichomoniasis, a neglected sexually transmitted disease. Due to severe health consequences and treatment failure, new therapeutic alternatives are crucial. Phloroglucinols from southern Brazilian Hypericum species demonstrated anti-T. vaginalis and anti-Leishmania amazonensis activities. The modulation of biochemical pathways involved in the control of inflammatory response by ectonucleotidases, NTPDase, and ecto-5′-nucleotidase represents new targets for combating protozoa. This study investigated the activity of Phloroglucinol Derivatives of Hypericum species from southern Brazil against T. vaginalis as well as its ability on modulating parasite ectonucleotidases and, consequently, immune parameters through ATP and adenosine effects. Phloroglucinol Derivatives screening revealed activity for isoaustrobrasilol B (IC50 38 μm) with no hemolytic activity. Although the most active compound induced cytotoxicity against a mammalian cell lineage, the in vivo model evidenced absence of toxicity. Isoaustrobrasilol B significantly inhibited NTPDase and ecto-5′-nucleotidase activities, and the immune modulation attributed to extracellular nucleotide accumulation was evaluated. The production of ROS and IL-6 by T. vaginalis-stimulated neutrophils was not affected by the treatment. Conversely, IL-8 levels were significantly enhanced. The associative mechanism of trophozoites death and ectonucleotidases modulation by isoaustrobrasilol B may increase the susceptibility of T. vaginalis to host innate immune cell like neutrophils consequently, contributing to parasite clearance.
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the anti trichomonas vaginalis Phloroglucinol Derivative isoaustrobrasilol b modulates extracellular nucleotide hydrolysis
Chemical Biology & Drug Design, 2017Co-Authors: Camila Braz Menezes, Gilsane Lino Von Poser, Graziela Vargas Rigo, Henrique Bridi, Danielle Da Silva Trentin, Alexandre José Macedo, Tiana TascaAbstract:Trichomonas vaginalis causes trichomoniasis, a neglected sexually transmitted disease. Due to severe health consequences and treatment failure, new therapeutic alternatives are crucial. Phloroglucinols from southern Brazilian Hypericum species demonstrated anti-T. vaginalis and anti-Leishmania amazonensis activities. The modulation of biochemical pathways involved in the control of inflammatory response by ectonucleotidases, NTPDase, and ecto-5′-nucleotidase represents new targets for combating protozoa. This study investigated the activity of Phloroglucinol Derivatives of Hypericum species from southern Brazil against T. vaginalis as well as its ability on modulating parasite ectonucleotidases and, consequently, immune parameters through ATP and adenosine effects. Phloroglucinol Derivatives screening revealed activity for isoaustrobrasilol B (IC50 38 μm) with no hemolytic activity. Although the most active compound induced cytotoxicity against a mammalian cell lineage, the in vivo model evidenced absence of toxicity. Isoaustrobrasilol B significantly inhibited NTPDase and ecto-5′-nucleotidase activities, and the immune modulation attributed to extracellular nucleotide accumulation was evaluated. The production of ROS and IL-6 by T. vaginalis-stimulated neutrophils was not affected by the treatment. Conversely, IL-8 levels were significantly enhanced. The associative mechanism of trophozoites death and ectonucleotidases modulation by isoaustrobrasilol B may increase the susceptibility of T. vaginalis to host innate immune cell like neutrophils consequently, contributing to parasite clearance.
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uliginosin b a natural Phloroglucinol Derivative with antidepressant like activity increases na k atpase activity in mice cerebral cortex
Revista Brasileira De Farmacognosia-brazilian Journal of Pharmacognosy, 2016Co-Authors: Ana Cristina Stein, Gilsane Lino Von Poser, Liz G. Müller, Andrea G K Ferreira, Andressa Braga, Andresa Heemann Betti, Fernanda Centuriao, Emilene B S Scherer, Janaina Kolling, Angela T S WyseAbstract:Uliginosin B, a Phloroglucinol isolated from Hypericum polyanthemum Klotzsch ex Reichardt, Hypericaceae, has antidepressant-like effect in the forced swimming test in rodents and inhibits monoamines neuronal reuptake without binding to their neuronal carriers. Studies showed the involvement of Na+,K+-ATPase brain activity in depressive disorders, as well as the dependence of neuronal monoamine transport from Na+ gradient generated by Na+,K+-ATPase. This study aimed at evaluating the effect of uliginosin B on Na+,K+-ATPase activity in mice cerebral cortex and hippocampus (1 and 3 h after the last administration) as well as the influence of veratrine, a Na+ channel opener, on the antidepressant-like effect of uliginosin B. Mice were treated (p.o.) with uliginosin B single (10 mg/kg) or repeated doses (10 mg/kg/day, 3 days). Acute administration reduced the immobility in the forced swimming test and tail suspension test and increased Na+,K+-ATPase activity in cerebral cortex 1 h after treating, whereas the repeated treatment induced the antidepressant-like effect and increased the Na+,K+-ATPase activity at both times evaluated. None treatment affected the hippocampus enzyme activity. Veratrine pretreatment prevented uliginosin B antidepressant-like effect in the forced swimming test, suggesting the involvement of Na+ balance regulation on this effect. Altogether, these data indicate that uliginosin B reduces the monoamine uptake by altering Na+ gradient.
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uliginosin b a natural Phloroglucinol Derivative presents a multimediated antinociceptive effect in mice
Journal of Pharmacy and Pharmacology, 2014Co-Authors: Eveline D. Stolz, Gilsane Lino Von Poser, Diego Rafael Hasse, Stela Maris Kuze RatesAbstract:Objective Investigate the involvement of monoaminergic and glutamatergic systems on the antinociceptive and ataxic effects of uliginosin B, which we have already demonstrated to be a promising molecular scaffold to develop new analgesic drugs. Methods Uliginosin B was obtained from hexane extract of aerial parts of Hypericum polyanthemum by chromatographic methods. Uliginosin B antinociceptive and motor coordination effects were evaluated in mice by using hot-plate (15 and 90 mg/kg, i.p.) and rotarod (90 mg/kg, i.p.) tests, respectively. The mechanism of action was investigated through pretreatments with prazosin 1 mg/kg intraperitoneal (α1 receptor antagonist), yohimbine 5 mg/kg intraperitoneal (α2 receptor antagonist), pCPA 300 mg/kg intraperitoneal (serotonin synthesis inhibitor) and MK-801 0.25 mg/kg intraperitoneal (N-methyl-D-aspartic acid receptor antagonist). Key findings The antinociceptive effect of uliginosin B (15 and 90 mg/kg, i.p.) was reduced significantly by pCPA and MK-801. Prazosin and yohimbine improved the antinociceptive effect of the highest dose (90 mg/kg, i.p.) of uliginosin B only. The ataxic effect of uliginosin B (90 mg/kg, i.p.) was completely prevented by pretreatment with pCPA or MK-801, but it was unaffected by pretreatment with prazosin or yohimbine. Conclusion These data confirm the contribution of monoaminergic neurotransmission as well as provide the first evidence of glutamatergic neurotransmission contribution to the uliginosin B effects.
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Determination of pharmacological interactions of uliginosin B, a natural Phloroglucinol Derivative, with amitriptyline, clonidine and morphine by isobolographic analysis
Phytomedicine : international journal of phytotherapy and phytopharmacology, 2014Co-Authors: Eveline D. Stolz, Gilsane Lino Von Poser, Liz G. Müller, Camila B. Antonio, Paola F. Da Costa, François Noël, Stela Maris Kuze RatesAbstract:Uliginosin B is a natural Phloroglucinol Derivative, obtained from Hypericum species native to South America. Previous studies have shown that uliginosin B presents antidepressant-like and antinociceptive effects. Although its mechanism of action is still not completely elucidated, it is known that it involves the activation of monoaminergic neurotransmission. The aim of the current study was to further investigate the antinociceptive mechanism of action of uliginosin B by combining it with different drugs used for treating pain in clinical practice. The intraperitoneal administration of uliginosin B, morphine, amitriptyline and clonidine, alone or in mixture, produced a dose-dependent antinociceptive effect in the hot-plate assay in mice. The effect of the mixtures of drugs was studied using an adapted isobologram analysis at the effect level of 50% of the maximal effect observed. The analysis showed that the interactions between uliginosin B and morphine was synergistic, while the interactions between uliginosin B and amitriptyline or clonidine were additive. These findings point to uliginosin B as a potential adjuvant for pain pharmacotherapy, especially for opioid analgesia.
Tiana Tasca - One of the best experts on this subject based on the ideXlab platform.
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The anti‐Trichomonas vaginalis Phloroglucinol Derivative isoaustrobrasilol B modulates extracellular nucleotide hydrolysis
Chemical biology & drug design, 2017Co-Authors: Camila Braz Menezes, Gilsane Lino Von Poser, Graziela Vargas Rigo, Henrique Bridi, Danielle Da Silva Trentin, Alexandre José Macedo, Tiana TascaAbstract:Trichomonas vaginalis causes trichomoniasis, a neglected sexually transmitted disease. Due to severe health consequences and treatment failure, new therapeutic alternatives are crucial. Phloroglucinols from southern Brazilian Hypericum species demonstrated anti-T. vaginalis and anti-Leishmania amazonensis activities. The modulation of biochemical pathways involved in the control of inflammatory response by ectonucleotidases, NTPDase, and ecto-5′-nucleotidase represents new targets for combating protozoa. This study investigated the activity of Phloroglucinol Derivatives of Hypericum species from southern Brazil against T. vaginalis as well as its ability on modulating parasite ectonucleotidases and, consequently, immune parameters through ATP and adenosine effects. Phloroglucinol Derivatives screening revealed activity for isoaustrobrasilol B (IC50 38 μm) with no hemolytic activity. Although the most active compound induced cytotoxicity against a mammalian cell lineage, the in vivo model evidenced absence of toxicity. Isoaustrobrasilol B significantly inhibited NTPDase and ecto-5′-nucleotidase activities, and the immune modulation attributed to extracellular nucleotide accumulation was evaluated. The production of ROS and IL-6 by T. vaginalis-stimulated neutrophils was not affected by the treatment. Conversely, IL-8 levels were significantly enhanced. The associative mechanism of trophozoites death and ectonucleotidases modulation by isoaustrobrasilol B may increase the susceptibility of T. vaginalis to host innate immune cell like neutrophils consequently, contributing to parasite clearance.
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the anti trichomonas vaginalis Phloroglucinol Derivative isoaustrobrasilol b modulates extracellular nucleotide hydrolysis
Chemical Biology & Drug Design, 2017Co-Authors: Camila Braz Menezes, Gilsane Lino Von Poser, Graziela Vargas Rigo, Henrique Bridi, Danielle Da Silva Trentin, Alexandre José Macedo, Tiana TascaAbstract:Trichomonas vaginalis causes trichomoniasis, a neglected sexually transmitted disease. Due to severe health consequences and treatment failure, new therapeutic alternatives are crucial. Phloroglucinols from southern Brazilian Hypericum species demonstrated anti-T. vaginalis and anti-Leishmania amazonensis activities. The modulation of biochemical pathways involved in the control of inflammatory response by ectonucleotidases, NTPDase, and ecto-5′-nucleotidase represents new targets for combating protozoa. This study investigated the activity of Phloroglucinol Derivatives of Hypericum species from southern Brazil against T. vaginalis as well as its ability on modulating parasite ectonucleotidases and, consequently, immune parameters through ATP and adenosine effects. Phloroglucinol Derivatives screening revealed activity for isoaustrobrasilol B (IC50 38 μm) with no hemolytic activity. Although the most active compound induced cytotoxicity against a mammalian cell lineage, the in vivo model evidenced absence of toxicity. Isoaustrobrasilol B significantly inhibited NTPDase and ecto-5′-nucleotidase activities, and the immune modulation attributed to extracellular nucleotide accumulation was evaluated. The production of ROS and IL-6 by T. vaginalis-stimulated neutrophils was not affected by the treatment. Conversely, IL-8 levels were significantly enhanced. The associative mechanism of trophozoites death and ectonucleotidases modulation by isoaustrobrasilol B may increase the susceptibility of T. vaginalis to host innate immune cell like neutrophils consequently, contributing to parasite clearance.
Danielle Da Silva Trentin - One of the best experts on this subject based on the ideXlab platform.
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The anti‐Trichomonas vaginalis Phloroglucinol Derivative isoaustrobrasilol B modulates extracellular nucleotide hydrolysis
Chemical biology & drug design, 2017Co-Authors: Camila Braz Menezes, Gilsane Lino Von Poser, Graziela Vargas Rigo, Henrique Bridi, Danielle Da Silva Trentin, Alexandre José Macedo, Tiana TascaAbstract:Trichomonas vaginalis causes trichomoniasis, a neglected sexually transmitted disease. Due to severe health consequences and treatment failure, new therapeutic alternatives are crucial. Phloroglucinols from southern Brazilian Hypericum species demonstrated anti-T. vaginalis and anti-Leishmania amazonensis activities. The modulation of biochemical pathways involved in the control of inflammatory response by ectonucleotidases, NTPDase, and ecto-5′-nucleotidase represents new targets for combating protozoa. This study investigated the activity of Phloroglucinol Derivatives of Hypericum species from southern Brazil against T. vaginalis as well as its ability on modulating parasite ectonucleotidases and, consequently, immune parameters through ATP and adenosine effects. Phloroglucinol Derivatives screening revealed activity for isoaustrobrasilol B (IC50 38 μm) with no hemolytic activity. Although the most active compound induced cytotoxicity against a mammalian cell lineage, the in vivo model evidenced absence of toxicity. Isoaustrobrasilol B significantly inhibited NTPDase and ecto-5′-nucleotidase activities, and the immune modulation attributed to extracellular nucleotide accumulation was evaluated. The production of ROS and IL-6 by T. vaginalis-stimulated neutrophils was not affected by the treatment. Conversely, IL-8 levels were significantly enhanced. The associative mechanism of trophozoites death and ectonucleotidases modulation by isoaustrobrasilol B may increase the susceptibility of T. vaginalis to host innate immune cell like neutrophils consequently, contributing to parasite clearance.
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the anti trichomonas vaginalis Phloroglucinol Derivative isoaustrobrasilol b modulates extracellular nucleotide hydrolysis
Chemical Biology & Drug Design, 2017Co-Authors: Camila Braz Menezes, Gilsane Lino Von Poser, Graziela Vargas Rigo, Henrique Bridi, Danielle Da Silva Trentin, Alexandre José Macedo, Tiana TascaAbstract:Trichomonas vaginalis causes trichomoniasis, a neglected sexually transmitted disease. Due to severe health consequences and treatment failure, new therapeutic alternatives are crucial. Phloroglucinols from southern Brazilian Hypericum species demonstrated anti-T. vaginalis and anti-Leishmania amazonensis activities. The modulation of biochemical pathways involved in the control of inflammatory response by ectonucleotidases, NTPDase, and ecto-5′-nucleotidase represents new targets for combating protozoa. This study investigated the activity of Phloroglucinol Derivatives of Hypericum species from southern Brazil against T. vaginalis as well as its ability on modulating parasite ectonucleotidases and, consequently, immune parameters through ATP and adenosine effects. Phloroglucinol Derivatives screening revealed activity for isoaustrobrasilol B (IC50 38 μm) with no hemolytic activity. Although the most active compound induced cytotoxicity against a mammalian cell lineage, the in vivo model evidenced absence of toxicity. Isoaustrobrasilol B significantly inhibited NTPDase and ecto-5′-nucleotidase activities, and the immune modulation attributed to extracellular nucleotide accumulation was evaluated. The production of ROS and IL-6 by T. vaginalis-stimulated neutrophils was not affected by the treatment. Conversely, IL-8 levels were significantly enhanced. The associative mechanism of trophozoites death and ectonucleotidases modulation by isoaustrobrasilol B may increase the susceptibility of T. vaginalis to host innate immune cell like neutrophils consequently, contributing to parasite clearance.
Dan Zhang - One of the best experts on this subject based on the ideXlab platform.
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Novel Phloroglucinol Derivative Compound 21 protects experimental autoimmune encephalomyelitis rats via inhibiting Th1/Th17 cell infiltration.
Brain behavior and immunity, 2020Co-Authors: Zhe Zhao, Xiu-qi Bao, Zihong Zhang, Hui Liu, Dan ZhangAbstract:Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammatory infiltration and demyelination in the central nervous system (CNS). Among the factors involved in the immunological mechanisms of MS, T helper 1 (Th1) cells and T helper 17 (Th17) cells play a critical role. Compound 21, a novel Phloroglucinol Derivative, significantly protected myelin from damage in our previous study. However, it remains unclear whether this compound affects MS. In this study, the experimental autoimmune encephalomyelitis (EAE) rat model was established to mimic the pathological process of MS and evaluate the neuroprotective effect of Compound 21. The results illustrated that Compound 21 treatment notably attenuates neurological deficits, immune infiltration, and demyelination in EAE rats. Our mechanistic investigation revealed that Compound 21 treatment reduces the population of Th1/Th17 cells and inhibits their infiltration into the CNS. Furthermore, we found that the inhibition of Th1/Th17 cell infiltration is related to the direct suppression of Th1/Th17 cell differentiation and the inhibition of proinflammatory microglial cells. Collectively, these results confirm that Compound 21 suppresses infiltrated Th1/Th17 cells to alleviate demyelination in EAE rats, suggesting its potential role as a novel candidate for MS treatment.
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novel Phloroglucinol Derivative compound 21 protects experimental autoimmune encephalomyelitis rats via inhibiting th1 th17 cell infiltration
Brain Behavior and Immunity, 2020Co-Authors: Zhe Zhao, Xiu-qi Bao, Zihong Zhang, Hui Liu, Dan ZhangAbstract:Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammatory infiltration and demyelination in the central nervous system (CNS). Among the factors involved in the immunological mechanisms of MS, T helper 1 (Th1) cells and T helper 17 (Th17) cells play a critical role. Compound 21, a novel Phloroglucinol Derivative, significantly protected myelin from damage in our previous study. However, it remains unclear whether this compound affects MS. In this study, the experimental autoimmune encephalomyelitis (EAE) rat model was established to mimic the pathological process of MS and evaluate the neuroprotective effect of Compound 21. The results illustrated that Compound 21 treatment notably attenuates neurological deficits, immune infiltration, and demyelination in EAE rats. Our mechanistic investigation revealed that Compound 21 treatment reduces the population of Th1/Th17 cells and inhibits their infiltration into the CNS. Furthermore, we found that the inhibition of Th1/Th17 cell infiltration is related to the direct suppression of Th1/Th17 cell differentiation and the inhibition of proinflammatory microglial cells. Collectively, these results confirm that Compound 21 suppresses infiltrated Th1/Th17 cells to alleviate demyelination in EAE rats, suggesting its potential role as a novel candidate for MS treatment.
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novel Phloroglucinol Derivative compound 21 protects experimental autoimmune encephalomyelitis rats via inhibiting th1 th17 cell infiltration
2019Co-Authors: Zhe Zhao, Xiu-qi Bao, Zihong Zhang, Hui Liu, Dan ZhangAbstract:Multiple Sclerosis (MS) is a chronic autoimmune disease characterized by inflammatory infiltration and demyelination in the central nervous system (CNS). Among all the factors that are involved in the immunological mechanisms of MS, T helper 1 (Th1) cells and T helper 17 (Th17) cells play a critical role. Compound 21, a novel Phloroglucinol Derivative, has shown remarkable effects on protecting myelin damage in our previous study. However, whether it has effects on MS remains unclear. In this study, the experimental autoimmune encephalomyelitis (EAE) rat model was established to mimic the pathological process of MS and to evaluate the neuroprotective effect of Compound 21. The results illustrated that Compound 21 treatment notably attenuated the neurological deficits, immune infiltration and demyelination of EAE rats. Mechanistic investigation revealed that Compound 21 treatment reduced the population of Th1/Th17 cells and inhibited their infiltration into the CNS. Further study found that the inhibition of Th1/Th17 cell infiltration was related to the direct suppression of Th1/Th17 cell differentiation and inhibition of pro-inflammatory microglial cells. Collectively, all these results proved that Compound 21 treatment suppressed infiltrated Th1/Th17 cells to alleviate the demyelination of EAE rats, suggesting its potential role as a novel candidate for MS treatment. Funding Statement: This investigation was supported by grants from National Sciences Foundation of China (81630097, 81773718), CAMS Innovation Fund for Medical Sciences (No. 2016-I2M-3-011), CAMS The Fundamental Research Funds for the Central Universities (2018RC350002), National Major Scientific and Technological Special Project for “Significant New Drugs Development” during the Thirteenth Five-year Plan Period (2018ZX09711001-003-005, 2018ZX09711001-008-005, 2018ZX09711001-003-020). Declaration of Interests: The authors declare no competing financial or other interests. Ethics Approval Statement: All the animal experiments were carried out according to the guidelines of the Beijing Municipal Ethic Committee for the care and use of laboratory animals.
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Phloroglucinol Derivative compound 21 attenuates cuprizone-induced multiple sclerosis mice through promoting remyelination and inhibiting neuroinflammation.
Science China. Life sciences, 2019Co-Authors: Zhe Zhao, Xiu-qi Bao, Zihong Zhang, Hui Liu, Dan ZhangAbstract:Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease in the central nervous system. The myelin loss is mainly caused by dysfunction of oligodendrocytes and inflammatory responses of microglia and astrocytes further aggravate the demyelination. Current therapies for MS focus on suppressing the overactivated immune response but cannot halt the disease progress, so effective drugs are urgently needed. Compound 21 is a Phloroglucinol Derivative that has been proved to have an outstanding anti-inflammatory effect. The purpose of the present study is to investigate whether this novel compound is effective in MS. The cuprizone-induced model was used in this study to mimic the pathological progress of MS. The results showed that Compound 21 significantly improved the neurological dysfunction and motor coordination impairment. Luxol Fast Blue staining and myelin basic protein immunostaining demonstrated that Compound 21 remarkably promoted remyelination. In addition, Compound 21 significantly promoted oligodendrocytes differentiation. Furthermore, we found that Compound 21 decreased microglia and astrocytes activities and the subsequent neuroinflammatory response, indicating that the anti-inflammatory effect of Compound 21 was also involved in its neuro-protection. All the data prove that Compound 21 exerts protective effect on MS through promoting remyelination and suppressing neuroinflammation, indicating that Compound 21 might be a potential drug candidate for MS treatment.
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a novel synthetic Derivative of Phloroglucinol inhibits neuroinflammatory responses through attenuating kalirin signaling pathway in murine bv2 microglial cells
Molecular Neurobiology, 2019Co-Authors: Caixia Zang, Xiu-qi Bao, Hanyu Yang, Lu Wang, Yue Wang, Xiaoliang Wang, Dan ZhangAbstract:Neuroinflammation has been implicated as an important factor in the neurodegenerative diseases, and multiple candidates with anti-inflammatory effects have been shown to be beneficial for the treatment of neurodegenerative diseases. Our previous study demonstrated that a novel synthetic Phloroglucinol Derivative from Lysidice rhodostegia roots (code name: Compound 21) exerted neuroprotective effect through suppressing neuroinflammation. The aim of this study was to reveal the underlying molecular mechanism. The results indicated that the anti-inflammatory effects of Compound 21 were mediated through suppression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and the production of reactive oxygen species (ROS). Further study showed that this suppression on NADPH oxidase was mediated by inhibiting the translocation and activity of its subunit Rac1. It is well established that Rac1 activation is regulated by a variety of guanine nucleotide exchange factors (GEFs), so we tried to find out whether GEFs were involved in the anti-inflammatory effects of Compound 21. The results showed that Compound 21 treatment down-regulated the expression and activity of GEF Kalirin, thus modulating the activity of Rac1 GTPase. Altogether, our data suggested that Compound 21 exerted the anti-neuroinflammatory effect through suppressing Kalirin signaling pathways, decreasing Rac1-NADPH oxidase activation and the subsequent pro-inflammatory cytokine production. The present study provided solid evidence to support Compound 21 as a potential candidate of neuroinflammatory inhibitor. Moreover, our findings have shed new light on the role of Rac1 and GEF Kalirin in neuroinflammation, which provides potential targets for neuroinflammation-related diseases, such as neurodegenerative diseases.
Camila Braz Menezes - One of the best experts on this subject based on the ideXlab platform.
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The anti‐Trichomonas vaginalis Phloroglucinol Derivative isoaustrobrasilol B modulates extracellular nucleotide hydrolysis
Chemical biology & drug design, 2017Co-Authors: Camila Braz Menezes, Gilsane Lino Von Poser, Graziela Vargas Rigo, Henrique Bridi, Danielle Da Silva Trentin, Alexandre José Macedo, Tiana TascaAbstract:Trichomonas vaginalis causes trichomoniasis, a neglected sexually transmitted disease. Due to severe health consequences and treatment failure, new therapeutic alternatives are crucial. Phloroglucinols from southern Brazilian Hypericum species demonstrated anti-T. vaginalis and anti-Leishmania amazonensis activities. The modulation of biochemical pathways involved in the control of inflammatory response by ectonucleotidases, NTPDase, and ecto-5′-nucleotidase represents new targets for combating protozoa. This study investigated the activity of Phloroglucinol Derivatives of Hypericum species from southern Brazil against T. vaginalis as well as its ability on modulating parasite ectonucleotidases and, consequently, immune parameters through ATP and adenosine effects. Phloroglucinol Derivatives screening revealed activity for isoaustrobrasilol B (IC50 38 μm) with no hemolytic activity. Although the most active compound induced cytotoxicity against a mammalian cell lineage, the in vivo model evidenced absence of toxicity. Isoaustrobrasilol B significantly inhibited NTPDase and ecto-5′-nucleotidase activities, and the immune modulation attributed to extracellular nucleotide accumulation was evaluated. The production of ROS and IL-6 by T. vaginalis-stimulated neutrophils was not affected by the treatment. Conversely, IL-8 levels were significantly enhanced. The associative mechanism of trophozoites death and ectonucleotidases modulation by isoaustrobrasilol B may increase the susceptibility of T. vaginalis to host innate immune cell like neutrophils consequently, contributing to parasite clearance.
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the anti trichomonas vaginalis Phloroglucinol Derivative isoaustrobrasilol b modulates extracellular nucleotide hydrolysis
Chemical Biology & Drug Design, 2017Co-Authors: Camila Braz Menezes, Gilsane Lino Von Poser, Graziela Vargas Rigo, Henrique Bridi, Danielle Da Silva Trentin, Alexandre José Macedo, Tiana TascaAbstract:Trichomonas vaginalis causes trichomoniasis, a neglected sexually transmitted disease. Due to severe health consequences and treatment failure, new therapeutic alternatives are crucial. Phloroglucinols from southern Brazilian Hypericum species demonstrated anti-T. vaginalis and anti-Leishmania amazonensis activities. The modulation of biochemical pathways involved in the control of inflammatory response by ectonucleotidases, NTPDase, and ecto-5′-nucleotidase represents new targets for combating protozoa. This study investigated the activity of Phloroglucinol Derivatives of Hypericum species from southern Brazil against T. vaginalis as well as its ability on modulating parasite ectonucleotidases and, consequently, immune parameters through ATP and adenosine effects. Phloroglucinol Derivatives screening revealed activity for isoaustrobrasilol B (IC50 38 μm) with no hemolytic activity. Although the most active compound induced cytotoxicity against a mammalian cell lineage, the in vivo model evidenced absence of toxicity. Isoaustrobrasilol B significantly inhibited NTPDase and ecto-5′-nucleotidase activities, and the immune modulation attributed to extracellular nucleotide accumulation was evaluated. The production of ROS and IL-6 by T. vaginalis-stimulated neutrophils was not affected by the treatment. Conversely, IL-8 levels were significantly enhanced. The associative mechanism of trophozoites death and ectonucleotidases modulation by isoaustrobrasilol B may increase the susceptibility of T. vaginalis to host innate immune cell like neutrophils consequently, contributing to parasite clearance.