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https://www.readbyqxmd.com/read/29238967/potent-anti-inflammatory-and-pro-resolving-effects-of-anabasum-in-a-human-model-of-self-resolving-acute-inflammation
#1
Madhur P Motwani, Frances Bennett, Paul C Norris, Alexander A Maini, Marc J George, Justine Newson, Alice Henderson, Adrian J Hobbs, Mark Tepper, Barbara White, Charles N Serhan, Raymond MacAllister, Derek W Gilroy
Anabasum is a synthetic analogue of Δ8 - tetrahydrocannabinol (THC)-11-oic acid that in pre-clinical models of experimental inflammation exerts potent anti-inflammatory actions with minimal CNS cannabimimetic activity. Here we used a novel model of acute inflammation driven by i.d. UV-killed E. coli in healthy humans and found that Anabasum (5mg) exerted a potent anti-inflammatory effect equivalent to that of prednisolone in terms of inhibiting neutrophil infiltration, the hallmark of acute inflammation. These effects arose from the inhibition of the neutrophil chemoattractant LTB4 , while the inhibition of anti-phagocytic prostanoids (PGE2 , TxB2 and PGF2 α) resulted in enhanced clearance of inflammatory stimulus from the injected site...
December 14, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29238467/neuroprotection-of-a-sesamin-derivative-1-2-bis-3-methoxyphenyl-methyl-ethane-1-2-dicaroxylic-acid-mmeda-against-ischemic-and-hypoxic-neuronal-injury
#2
Chang-Tsen Hung, Li-Dian Chen, Chien-Wei Hou
Objectives: Stroke may cause severe neuronal damage. The sesamin have been demonstrated to possess neuroprotection by its antioxidant and anti-inflammatory properties. One sesamin derivative was artificially composited, 1, 2-bis [(3-methoxyphenyl) methyl] ethane-1, 2-dicaroxylic acid (MMEDA) had been developed to study its antioxidative activity and neuroprotection. Materials and Methods: The infaction of Sprague Dawley (SD) rats and hypoxia models of BV-2 microglia or PC12 cells were investigated for in vivo and in vitro test respectively...
December 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29238213/first-evidence-of-the-conversion-of-paracetamol-to-am404-in-human-cerebrospinal-fluid
#3
Chhaya V Sharma, Jamie H Long, Seema Shah, Junia Rahman, David Perrett, Samir S Ayoub, Vivek Mehta
Paracetamol is arguably the most commonly used analgesic and antipyretic drug worldwide, however its mechanism of action is still not fully established. It has been shown to exert effects through multiple pathways, some actions suggested to be mediated via N-arachidonoylphenolamine (AM404). AM404, formed through conjugation of paracetamol-derived p-aminophenol with arachidonic acid in the brain, is an activator of the capsaicin receptor, TRPV1, and inhibits the reuptake of the endocannabinoid, anandamide, into postsynaptic neurons, as well as inhibiting synthesis of PGE2 by COX-2...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/29237778/mpges1-dependent-prostaglandin-e2-pge2-controls-antigen-specific-th17-and-th1-responses-by-regulating-t-autocrine-and-paracrine-pge2-production
#4
Damian Maseda, Elizabeth M Johnson, Lindsay E Nyhoff, Bridgette Baron, Fumiaki Kojima, Ashley J Wilhelm, Martin R Ward, Jerold G Woodward, David D Brand, Leslie J Crofford
The integration of inflammatory signals is paramount in controlling the intensity and duration of immune responses. Eicosanoids, particularly PGE2, are critical molecules in the initiation and resolution of inflammation and in the transition from innate to acquired immune responses. Microsomal PGE synthase 1 (mPGES1) is an integral membrane enzyme whose regulated expression controls PGE2 levels and is highly expressed at sites of inflammation. PGE2 is also associated with modulation of autoimmunity through altering the IL-23/IL-17 axis and regulatory T cell (Treg) development...
December 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29237478/am404-paracetamol-metabolite-prevents-prostaglandin-synthesis-in-activated-microglia-by-inhibiting-cox-activity
#5
Soraya Wilke Saliba, Ariel R Marcotegui, Ellen Fortwängler, Johannes Ditrich, Juan Carlos Perazzo, Eduardo Muñoz, Antônio Carlos Pinheiro de Oliveira, Bernd L Fiebich
BACKGROUND: N-arachidonoylphenolamine (AM404), a paracetamol metabolite, is a potent agonist of the transient receptor potential vanilloid type 1 (TRPV1) and low-affinity ligand of the cannabinoid receptor type 1 (CB1). There is evidence that AM404 exerts its pharmacological effects in immune cells. However, the effect of AM404 on the production of inflammatory mediators of the arachidonic acid pathway in activated microglia is still not fully elucidated. METHOD: In the present study, we investigated the effects of AM404 on the eicosanoid production induced by lipopolysaccharide (LPS) in organotypic hippocampal slices culture (OHSC) and primary microglia cultures using Western blot, immunohistochemistry, and ELISA...
December 13, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29234949/curc-mpeg454-a-pegylated-curcumin-derivative-improves-anti-inflammatory-and-antioxidant-activities-a-comparative-study
#6
Fei Cheng, Yuhe Chen, Zhu Zhan, Yu Liu, Peng Hu, Hong Ren, Huadong Tang, Mingli Peng
We previously demonstrated that a PEGylated curcumin (Curc-mPEG454) significantly inhibited cyclooxygenase 2 (COX-2) expression and improved the progression of liver fibrosis. The current study systematically evaluates its anti-inflammatory and antioxidant activities in vitro in a comparative study with curcumin, aspirin, NS-398, and vitamin C. RAW264.7 murine macrophages were pretreated with Curc-mPEG454, curcumin, aspirin, NS-398, or vitamin C at the indicated concentration for 2 h; then, the cells were stimulated with 1 μg/mL lipopolysaccharide (LPS) for 24 h...
December 13, 2017: Inflammation
https://www.readbyqxmd.com/read/29234444/the-effects-of-thai-herbal-ha-rak-formula-on-cox-isoform-expression-in-human-umbilical-vein-endothelial-cells-induced-by-il-1%C3%AE
#7
Titchaporn Palo, Athiwat Thaworn, Phornnapa Charoenkij, Onusa Thamsermsang, Sirikul Chotewuttakorn, Pinpat Tripatara, Tawee Laohapand, Pravit Akarasereenont
Objective: To investigate the modulated effects of HRF on cyclooxygenase isoform expression and its activity, using the human umbilical vein endothelial cell (HUVEC) model induced by interleukin-1 beta (IL-1β). Methods: Cells were treated with indomethacin (positive control), HRF, and its components at various concentrations prior to treatment with IL-1β at 24 h. Cell viability was determined by MTT assay. Moreover, the anti-inflammatory effects of HRF and its components through mRNA and protein expression were established using real-time quantitative PCR and Western blot, respectively...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29232190/the-effects-of-curcuma-longa-and-curcumin-on-reproductive-systems
#8
R Mohebbati, A Anaeigoudari, M R Khazdair
OBJECTIVE: Curcuma longa (C. longa) was used in some countries such as China and India for various medicinal purposes. Curcumin, the active component of C. longa, is commonly used as a coloring agent in foods, drugs, and cosmetics. C. longa and curcumin have been known to act as antioxidant, anti-inflammatory, anti-mutagen, and anti-carcinogenic agents. Th e attempt of the present review was to give an effort on a detailed literature survey concentrated on the protective effects of C...
October 26, 2017: Endocrine Regulations
https://www.readbyqxmd.com/read/29231542/-clinical-research-of-electroacupuncture-on-the-analgesic-effect-of-thoracic-perioperative-stage
#9
Mintao Zhou, Yu Li, Xuechang Han, Qunzhi Xing, Yiyao Wang, Xu Dong, Junxiao Chang
OBJECTIVE: To discuss the clinical therapeutic effects of electroacupuncture at Neimadian (Extra) and Neiguan (PC 6) on the analgesic effect of thoracic perioperative stage and its effect mechanism. METHODS: Sixty cases of esophageal cancer with elective radical resection under general anesthesia were divided into an observation group and a control group according to the operation sequence, 30 cases in each one. In the control group, the general anesthesia was simply applied and sufentanil was administered for patient controlled intravenous analgesia (PCIA) after operation...
July 12, 2017: Zhongguo Zhen Jiu, Chinese Acupuncture & Moxibustion
https://www.readbyqxmd.com/read/29231216/aronia-citrus-juice-polyphenol-rich-juice-intake-and-elite-triathlon-training-a-lipidomic-approach-using-representative-oxylipins-in-urine
#10
Libia Alejandra García-Flores, Sonia Medina, Cristina Gómez, Craig E Wheelock, Roberto Cejuela, José Miguel Martínez-Sanz, Camille Oger, Jean-Marie Galano, Thierry Durand, Álvaro Hernández-Sáez, Federico Ferreres, Ángel Gil-Izquierdo
In the present study, we examined whether particular urinary oxylipins (isoprostanes (IsoPs), leukotrienes (LTs), prostaglandins (PGs), and thromboxanes (TXs)) in 16 elite triathletes could alter during 145 days of training. Within this time span, 45 days were dedicated to examining the effects of the intake of a beverage rich in polyphenols (one serving: 200 mL per day) supplemented in their diet. The beverage was a mixture of citrus juice (95%) and Aronia melanocarpa juice (5%) (ACJ). Fifty-two oxylipins were analyzed in the urine...
December 12, 2017: Food & Function
https://www.readbyqxmd.com/read/29229421/the-amino-analogue-of-%C3%AE-boswellic-acid-efficiently-attenuates-the-release-of-pro-inflammatory-mediators-than-its-parent-compound-through-the-suppression-of-nf-%C3%AE%C2%BAb-i%C3%AE%C2%BAb%C3%AE-signalling-axis
#11
Shilpa Gupta, Aitizaz Ul Ahsan, Abubakar Wani, Vidushi Khajuria, Lone A Nazir, Simmi Sharma, Asha Bhagat, Parduman Raj Sharma, Subhash Bhardwaj, Kaiser J Peerzada, Bhahwal Ali Shah, Zabeer Ahmed
Natural product derivatives have proven to be cutting edge window for drug discovery and development. BA-25 (3-α-o-acetoxy-4β-amino-11-oxo-24-norurs-12-ene) an amino analogue of β-boswellic acid exhibited inhibition of TNF-α and IL-6 in THP-1 cells as demonstrated previously, however, the effect on principal inflammatory mediators such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and the pathways that mediate this function remains unknown. This study was designed to examine the comparative anti-inflammatory activity of BA-25 with its parent compound, β boswellic acid both in vitro and in vivo...
December 8, 2017: Cytokine
https://www.readbyqxmd.com/read/29229270/intratracheal-instillation-of-alveolar-type-ii-cells-enhances-recovery-from-acute-lung-injury-in-rats
#12
Raquel Guillamat-Prats, Ferranda Puig, Marta Camprubí-Rimblas, Raquel Herrero, Anna Serrano-Mollar, Maria Nieves Gómez, Jessica Tijero, Michael A Matthay, Lluís Blanch, Antonio Artigas
BACKGROUND: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by excess production of inflammatory factors. Alveolar type II (ATII) cells help repair damaged lung tissue, rapidly proliferating and differentiating into alveolar type I cells after epithelial cell injury. In ALI, the lack of viable ATII favors progression to more severe lung injury. ATII cells regulate the immune response by synthesizing surfactant and other anti-inflammatory proteins and lipids...
November 8, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/29226622/pde4-inhibitor-rolipram-inhibits-the-expression-of-microsomal-prostaglandin-e-synthase-1-by-a-mechanism-dependent-on-map-kinase-phosphatase-1
#13
Lauri Tuure, Mari Hämäläinen, Eeva Moilanen
Phosphodiesterase-4 (PDE4) inhibitors have recently been introduced to the treatment of COPD and psoriatic arthritis. Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible enzyme synthesizing PGE2 , the most abundant prostanoid related to inflammation and inflammatory pain. mPGES-1 is a potential drug target for novel anti-inflammatory treatments aiming at an improved safety profile as compared to NSAIDs. Here we investigated the effect of the PDE4 inhibitor rolipram on the expression of mPGES-1 in macrophages; and a potential mediator role in the process for MAP kinase phosphatase-1 (MKP-1) which is an endogenous factor limiting the activity of the proinflammatory MAP kinases p38 and JNK...
December 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/29226424/activation-of-ep2-receptor-suppresses-poly-i-c-and-lps-mediated-inflammation-in-primary-microglia-and-organotypic-hippocampal-slice-cultures-contributing-role-for-mapks
#14
Nizar M Yousif, Antonio Carlos Pinheiro de Oliveira, Simone Brioschi, Michael Huell, Knut Biber, Bernd L Fiebich
Brain inflammation is a critical factor involved in neurodegeneration. Recently, the prostaglandin E2 (PGE2 ) downstream members were suggested to modulate neuroinflammatory responses accompanying neurodegenerative diseases. In this study, we investigated the protective effects of prostaglandin E2 receptor 2 (EP2 ) during TLR3 and TLR4-driven inflammatory response using in vitro primary microglia and ex vivo organotypic hippocampal slice cultures (OHSCs). Depletion of microglia from OHSCs differentially affected TLR3 and TLR4 receptor expression...
December 11, 2017: Glia
https://www.readbyqxmd.com/read/29224225/down-regulation-of-15-pgdh-by-interleukin-1-beta-from-activated-macrophages-leads-to-poor-prognosis-in-pancreatic-cancer
#15
Kota Arima, Yoshihiro Komohara, Luke Bu, Masayo Tsukamoto, Rumi Itoyama, Keisuke Miyake, Tomoyuki Uchihara, Yoko Ogata, Shigeki Nakagawa, Hirohisa Okabe, Katsunori Imai, Daisuke Hashimoto, Akira Chikamoto, Yo-Ichi Yamashita, Hideo Baba, Takatsugu Ishimoto
Chronic inflammation has a crucial role in cancer development and the progression of various tumors, including pancreatic ductal adenocarcinoma (PDAC). The arachidonate cascade is a major inflammatory pathway that produces several metabolites, such as prostaglandin E2 (PGE2 ). The enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) degrades prostaglandin and is frequently decreased in several types of cancer; however, the molecular mechanisms of 15-PGDH suppression are unclear. The current study was conducted to elucidate the molecular mechanisms and clinical significance of 15-PGDH suppression in PDAC...
December 10, 2017: Cancer Science
https://www.readbyqxmd.com/read/29223540/protective-effect-of-coptisine-free-base-on-indomethacin-induced-gastric-ulcers-in-rats-characterization-of-potential-molecular-mechanisms
#16
Chaodan Luo, Hanbin Chen, Yongfu Wang, Guosheng Lin, Cailan Li, Lihua Tan, Ziren Su, Xiaoping Lai, Jianhui Xie, Huifang Zeng
AIMS: The aim of this study was to comparatively investigate the potential gastroprotective effect and underlying mechanisms of coptisine free base (CFB, 8-hydroxy-7, 8-dihydrocoptisine), berberine and lansoprazole against indomethacin-induced gastric ulcer in rats. MATERIALS AND METHODS: CFB (10, 20 and 40mg/kg), berberine (20mg/kg) and lansoprazole (30mg/kg) were orally administrated to rats prior to indometacin ingestion, and gastric lesions were evaluated macroscopically and histologically, and further analyzed by ELISA, qRT-PCR and Western blot...
December 6, 2017: Life Sciences
https://www.readbyqxmd.com/read/29223154/antiinflammatory-effect-of-rosiglitazone-via-modulation-of-mrna-stability-of-interleukin-10-and-cyclooxygenase-2-in-astrocytes
#17
E V Pankevich, A A Astakhova, D V Chistyakov, M G Sergeeva
Investigation of molecular mechanisms of proinflammatory stimuli signaling in astrocytes is important for understanding their role in pathogenesis of central nervous system diseases as well as in functioning of the innate immunity system in non-immune cells. Here we show that lipopolysaccharide (LPS) stimulation of primary rat astrocytes led to conventional inflammatory response: increase in both proinflammatory (tumor necrosis factor, TNFα; prostaglandin E2, PGE2) and antiinflammatory marker (interleukin 10, IL-10) levels...
November 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/29221883/anti-neuroinflammatory-effects-of-sesquiterpenoids-isolated-from-nardostachys-jatamansi
#18
Chi-Su Yoon, Kwan-Woo Kim, Sang-Chan Lee, Youn-Chul Kim, Hyuncheol Oh
Two new nardosinone-type sesquiterpenoids, namely kanshone J (1) and kanshone K (2) along with seven known terpenoids (3-9) were isolated from the rhizomes and roots of Nardostachys jatamansi DC (Valerianaceae). The structures of these compounds were determined mainly by analysis of 1D-, 2D-NMR and MS data. In addition, the absolute configuration of compound 1 was assigned by application of the modified Mosher's method. In an initial assay to evaluate their anti-neuroinflammatory effects, compounds 1-5 and 9 exhibited dose-dependent inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 cells, with IC50 values ranging from 2...
November 24, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29217623/prostaglandins-d2-and-e2-have-opposite-effects-on-alveolar-macrophage-infected-with-histoplasma-capsulatum
#19
Priscilla A T Pereira, Patrícia A Assis, Morgana K B Prado, Simone Gusamão Ramos, David M Aronoff, Francisco W G Paula-Silva, Carlos A Sorgi, Lúcia H Faccioli
PGE2 suppresses macrophage effector mechanisms; however, little is known about the function of PGD2 in infected alveolar macrophages (AMs). Using serum opsonized Histoplasma capsulatum (ops-H. capsulatum) in vitro, we demonstrated that AMs produced PGE2 and PGD2 in a time-dependent manner, with PGE2 levels exceeding those of PGD2 by 48 h post-infection. Comparison of the effects of both exogenous PGs on AMs revealed that PGD2 increased phagocytosis and killing through the DP2 receptor, whereas PGE2 had opposite effects, through EP2/EP4-dependent mechanisms...
December 7, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/29217133/pge2-suppresses-human-group-2-innate-lymphoid-cell-function
#20
Jovana Maric, Avinash Ravindran, Luca Mazzurana, Åsa K Björklund, Aline Van Acker, Anna Rao, Danielle Friberg, Sven-Erik Dahlén, Akos Heinemann, Viktoria Konya, Jenny Mjösberg
BACKGROUND: Group 2 innate lymphoid cells (ILC2) are involved in the initial phase of type 2 inflammation and can amplify allergic immune responses by orchestrating other type 2 immune cells. PGE2 is a bioactive lipid that plays protective roles in the lung, particularly during allergic inflammation. OBJECTIVE: We set out to investigate how PGE2 regulates human ILC2 function. METHODS: The effects of PGE2 on human ILC2 proliferation, intracellular cytokine and transcription factor expression were assessed by flow cytometry...
December 4, 2017: Journal of Allergy and Clinical Immunology
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