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1
Serafini, Mauro, Ilaria Peluso, and Anna Raguzzini. "Flavonoids as anti-inflammatory agents." Proceedings of the Nutrition Society 69, no. 3 (June 23, 2010): 273–78. http://dx.doi.org/10.1017/s002966511000162x.
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Epidemiological evidence suggests that a high intake of plant foods is associated with lower risk of chronic diseases. However, the mechanism of action and the components involved in this effect have not been identified clearly. In recent years, the scientific community has agreed to focus its attention on a class of secondary metabolites extensively present in a wide range of plant foods: the flavonoids, suggested as having different biological roles. The anti-inflammatory actions of flavonoids in vitro or in cellular models involve the inhibition of the synthesis and activities of different pro-inflammatory mediators such as eicosanoids, cytokines, adhesion molecules and C-reactive protein. Molecular activities of flavonoids include inhibition of transcription factors such as NF-κB and activating protein-1 (AP-1), as well as activation of nuclear factor-erythroid 2-related factor 2 (Nrf2). However, the in vitro evidence might be somehow of limited impact due to the non-physiological concentrations utilized and to the fact that in vivo flavonoids are extensively metabolized to molecules with different chemical structures and activities compared with the ones originally present in the food. Human studies investigating the effect of flavonoids on markers of inflammation are insufficient, and are mainly focused on flavonoid-rich foods but not on pure molecules. Most of the studies lack assessment of flavonoid absorption or fail to associate an effect on inflammation with a change in circulating levels of flavonoids. Human trials with appropriate placebo and pure flavonoid molecules are needed to clarify if flavonoids represent ancillary ingredients or key molecules involved in the anti-inflammatory properties of plant foods.
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Murray, P. J. "STAT3-mediated anti-inflammatory signalling." Biochemical Society Transactions 34, no. 6 (October 25, 2006): 1028–31. http://dx.doi.org/10.1042/bst0341028.
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IL-1O (interleukin-10) negatively regulates inflammation through a mechanism that blocks the expression of pro-inflammatory genes encoding cytokines, chemokines, cell-surface molecules and other molecules required for the full activation of the innate and adaptive immune responses. The signalling pathway used by the IL-10 receptor to generate the anti-inflammatory response requires STAT3 (signal transducer and activator of transcription 3) and is indirect. Thus STAT3 activates other genes whose task is to selectively control transcription of inflammatory targets. Here, I summarize current knowledge of the key features of IL-10 signalling and make predictions concerning the mechanism of IL-10 at the level of inflammatory genes. Understanding IL-10 signalling should be a gateway to the development of broadly acting anti-inflammatory agents.
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Bucciantini, Monica, Manuela Leri, Pamela Nardiello, Fiorella Casamenti, and Massimo Stefani. "Olive Polyphenols: Antioxidant and Anti-Inflammatory Properties." Antioxidants 10, no. 7 (June 29, 2021): 1044. http://dx.doi.org/10.3390/antiox10071044.
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Oxidative stress and inflammation triggered by increased oxidative stress are the cause of many chronic diseases. The lack of anti-inflammatory drugs without side-effects has stimulated the search for new active substances. Plant-derived compounds provide new potential anti-inflammatory and antioxidant molecules. Natural products are structurally optimized by evolution to serve particular biological functions, including the regulation of endogenous defense mechanisms and interaction with other organisms. This property explains their relevance for infectious diseases and cancer. Recently, among the various natural substances, polyphenols from extra virgin olive oil (EVOO), an important element of the Mediterranean diet, have aroused growing interest. Extensive studies have shown the potent therapeutic effects of these bioactive molecules against a series of chronic diseases, such as cardiovascular diseases, diabetes, neurodegenerative disorders and cancer. This review begins from the chemical structure, abundance and bioavailability of the main EVOO polyphenols to highlight the effects and the possible molecular mechanism(s) of action of these compounds against inflammation and oxidation, in vitro and in vivo. In addition, the mechanisms of inhibition of molecular signaling pathways activated by oxidative stress by EVOO polyphenols are discussed, together with their possible roles in inflammation-mediated chronic disorders, also taking into account meta-analysis of population studies and clinical trials.
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Al-Khayri, Jameel M., Gandasi Ravikumar Sahana, Praveen Nagella, Biljo V. Joseph, Fatima M. Alessa, and Muneera Q. Al-Mssallem. "Flavonoids as Potential Anti-Inflammatory Molecules: A Review." Molecules 27, no. 9 (May 2, 2022): 2901. http://dx.doi.org/10.3390/molecules27092901.
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Hydroxylated polyphenols, also called flavonoids, are richly present in vegetables, fruits, cereals, nuts, herbs, seeds, stems, and flowers of numerous plants. They possess numerous medicinal properties such as antioxidant, anti-cancer, anti-microbial, neuroprotective, and anti-inflammation. Studies show that flavonoids activate antioxidant pathways that render an anti-inflammatory effect. They inhibit the secretions of enzymes such as lysozymes and β-glucuronidase and inhibit the secretion of arachidonic acid, which reduces inflammatory reactions. Flavonoids such as quercetin, genistein, apigenin, kaempferol, and epigallocatechin 3-gallate modulate the expression and activation of a cytokine such as interleukin-1beta (IL-1β), Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8); regulate the gene expression of many pro-inflammatory molecules such s nuclear factor kappa-light chain enhancer of activated B cells (NF-κB), activator protein-1 (AP-1), intercellular adhesion molecule-1 (ICAM), vascular cell adhesion molecule-1 (VCAM), and E-selectins; and also inhibits inducible nitric oxide (NO) synthase, cyclooxygenase-2, and lipoxygenase, which are pro-inflammatory enzymes. Understanding the anti-inflammatory action of flavonoids provides better treatment options, including coronavirus disease 2019 (COVID-19)-induced inflammation, inflammatory bowel disease, obstructive pulmonary disorder, arthritis, Alzheimer’s disease, cardiovascular disease, atherosclerosis, and cancer. This review highlights the sources, biochemical activities, and role of flavonoids in enhancing human health.
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Kubes, Paul. "Polymorphonuclear leukocyte – endothelium interactions: a role for pro-inflammatory and anti-inflammatory molecules." Canadian Journal of Physiology and Pharmacology 71, no. 1 (January 1, 1993): 88–97. http://dx.doi.org/10.1139/y93-013.
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The movement of polymorphonuclear leukocytes (PMNs) from the mainstream of blood to the extravascular space is a characteristic feature of the inflammatory response. This process requires that the PMN initially contacts the endothelium, then adheres firmly to the vessel wall, and finely migrates out of the microvasculature. Each of these events requires signals or pro-inflammatory molecules that direct the PMN to the potential site of inflammation. These molecules include histamine, which appears to be of importance in the initial recruitment of PMNs, leukotriene B4, which promotes PMN adhesion, and platelet-activating factor, which may contribute to both the adhesion process as well as the migration through the endothelial barrier. Although many other pro-inflammatory molecules have been identified, including the cytokines and complement, the three aforementioned molecules are used in this review as paradigms of the varying functions that pro-inflammatory molecules have in the inflammatory process. There is a growing body of evidence that in addition to the many pro-inflammatory agents found in the body there are a number of important anti-inflammatory molecules, including nitric oxide, prostacyclin, and adenosine. Each of these molecules possess important properties that serve to interrupt or protect against the ongoing inflammatory process. The anti-inflammatory potential of these endogenous molecules is discussed.Key words: nitric oxide, histamine, platelet-activating factor, prostacyclin, leukotriene B4, adenosine.
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JOHNSTON, M. J. G., J. A. MacDONALD, and D. M. McKAY. "Parasitic helminths: a pharmacopeia of anti-inflammatory molecules." Parasitology 136, no. 2 (December 15, 2008): 125–47. http://dx.doi.org/10.1017/s0031182008005210.
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SUMMARYInfection with parasitic helminths takes a heavy toll on the health and well-being of humans and their domestic livestock, concomitantly resulting in major economic losses. Analyses have consistently revealed bioactive molecules in extracts of helminths or in their excretory/secretory products that modulate the immune response of the host. It is our view that parasitic helminths are an untapped source of immunomodulatory substances that, in pure form, could become new drugs (or models for drug design) to treat disease. Here, we illustrate the range of immunomodulatory molecules in selected parasitic trematodes, cestodes and nematodes, their impact on the immune cells in the host and how the host may recognize these molecules. There are many examples of the partial characterization of helminth-derived immunomodulatory molecules, but these have not yet translated into new drugs, reflecting the difficulty of isolating and fully characterizing proteins, glycoproteins and lipid-based molecules from small amounts of parasite material. However, this should not deter the investigator, since analytical techniques are now being used to accrue considerable structural information on parasite-derived molecules, even when only minute quantities of tissue are available. With the introduction of methodologies to purify and structurally-characterize molecules from small amounts of tissue and the application of high throughput immunological assays, one would predict that an assessment of parasitic helminths will yield a variety of novel drug candidates in the coming years.
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Yang, Shih-Chun, Ahmed Alalaiwe, Zih-Chan Lin, Yu-Chih Lin, Ibrahim A. Aljuffali, and Jia-You Fang. "Anti-Inflammatory microRNAs for Treating Inflammatory Skin Diseases." Biomolecules 12, no. 8 (August 3, 2022): 1072. http://dx.doi.org/10.3390/biom12081072.
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Skin inflammation occurs due to immune dysregulation because of internal disorders, infections, and allergic reactions. The inflammation of the skin is a major sign of chronic autoimmune inflammatory diseases, such as psoriasis, atopic dermatitis (AD), and lupus erythematosus. Although there are many therapies for treating these cutaneous inflammation diseases, their recurrence rates are high due to incomplete resolution. MicroRNA (miRNA) plays a critical role in skin inflammation by regulating the expression of protein-coding genes at the posttranscriptional level during pathogenesis and homeostasis maintenance. Some miRNAs possess anti-inflammatory features, which are beneficial for mitigating the inflammatory response. miRNAs that are reduced in inflammatory skin diseases can be supplied transiently using miRNA mimics and agomir. miRNA-based therapies that can target multiple genes in a given pathway are potential candidates for the treatment of skin inflammation. This review article offers an overview of the function of miRNA in skin inflammation regulation, with a focus on psoriasis, AD, and cutaneous wounds. Some bioactive molecules can target and modulate miRNAs to achieve the objective of inflammation suppression. This review also reports the anti-inflammatory efficacy of these molecules through modulating miRNA expression. The main limitations of miRNA-based therapies are rapid biodegradation and poor skin and cell penetration. Consideration was given to improving these drawbacks using the approaches of cell-penetrating peptides (CPPs), nanocarriers, exosomes, and low-frequency ultrasound. A formulation design for successful miRNA delivery into skin and target cells is also described in this review. The possible use of miRNAs as biomarkers and therapeutic modalities could open a novel opportunity for the diagnosis and treatment of inflammation-associated skin diseases.
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Bansal, Yogita, Purva Sethi, and Gulshan Bansal. "Coumarin: a potential nucleus for anti-inflammatory molecules." Medicinal Chemistry Research 22, no. 7 (November 10, 2012): 3049–60. http://dx.doi.org/10.1007/s00044-012-0321-6.
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Côrtes Filho, Aldo Barbosa, Danyo Maia Lima, Pâmala Évelin Pires Cedro, Tátilla Putumujú Santana Mendes, Alana Caise dos Anjos Miranda, Maíra Mercês Barreto, Evely Rocha Lima, Baraquizio Braga do Nascimento Junior, and Gildomar Lima Valasques Junior. "In silico screening of brazilian semiarid compounds to identify potential drugs with glucocorticoid receptor interaction." Research, Society and Development 9, no. 9 (September 5, 2020): e734997865. http://dx.doi.org/10.33448/rsd-v9i9.7865.
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The glucocorticoid receptor regulates the anti-inflammatory response, and prevents transcription of anti-inflammatory substances such as nuclear factor kB and lipocortin-1, IL-2, IL-6, TNF and prostaglandins. Thus, a search for new molecules with potential interaction with the glucocorticoid receptor is an interesting strategy for the treatment of inflammatory diseases. Virtual screening has proven to be a viable tool for discovering new products at lower cost and practicality. Thus, the aim of this study is to identify and evaluate brazilian semiarid compounds with anti-inflammatory potential with glucocorticoid receptor action through molecular coupling. Protein selection was performed by searching the 3D structure database, Protein Data Bank. A total of 382 semi-arid molecules available in the ZINC database of State University of Feira de Santana (UEFS) were used. Molecular docking was performed using Autodock Vina and as interaction clouds analyzed by the Discovery Studio Visualizer program. Mometasone furoate shows a binding energy of -12.7 Kcal.mol-1. A ZINC 69481862 molecule fits Lipinski and Veber rules, however, the best interaction was the ZINC 69482012 molecule, evidenced by the binding energy -11.2 Kcal.mol-1. Analyses of intermolecular interactions have shown that Van der Waals interactions and electrostatic bonds are crucial for the binding of the molecule at the receptor's active site. It is necessary to test in vitro to verify the viability and toxicity of the potential drug.
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Peyrottes, Agathe, Garance Coquant, Loïc Brot, Dominique Rainteau, Philippe Seksik, Jean-Pierre Grill, and Jean-Maurice Mallet. "Anti-Inflammatory Effects of Analogues of N-Acyl Homoserine Lactones on Eukaryotic Cells." International Journal of Molecular Sciences 21, no. 24 (December 11, 2020): 9448. http://dx.doi.org/10.3390/ijms21249448.
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Background: Since acyl-homoserine lactone (AHL) profiling has been described in the gut of healthy subjects and patients with inflammatory bowel disease (IBD), the potential effects of these molecules on host cells have raised interest in the medical community. In particular, natural AHLs such as the 3-oxo-C12-HSL exhibit anti-inflammatory properties. Our study aimed at finding stable 3-oxo-C12-HSL-derived analogues with improved anti-inflammatory effects on epithelial and immune cells. Methods: We first studied the stability and biological properties of the natural 3-oxo-C12-HSL on eukaryotic cells and a bacterial reporter strain. We then constructed and screened a library of 22 AHL-derived molecules. Anti-inflammatory effects were assessed by cytokine release in an epithelial cell model, Caco-2, and a murine macrophage cell line, RAW264.7, (respectively, IL-8 and IL-6) upon exposure to the molecule and after appropriate stimulation (respectively, TNF-α 50 ng/mL and IFN-γ 50 ng/mL, and LPS 10 ng/mL and IFN-γ 20 U/mL). Results: We found two molecules of interest with amplified anti-inflammatory effects on mammalian cells without bacterial-activating properties in the reporter strain. The molecules furthermore showed improved stability in biological medium compared to the native 3-oxo-C12-HSL. Conclusions: We provide new bio-inspired AHL analogues with strong anti-inflammatory properties that will need further study from a therapeutic perspective.
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Montero-Lobato, Zaida, María Vázquez, Francisco Navarro, Juan Fuentes, Elisabeth Bermejo, Inés Garbayo, Carlos Vílchez, and María Cuaresma. "Chemically-Induced Production of Anti-Inflammatory Molecules in Microalgae." Marine Drugs 16, no. 12 (November 30, 2018): 478. http://dx.doi.org/10.3390/md16120478.
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Microalgae have been widely recognized as a valuable source of natural, bioactive molecules that can benefit human health. Some molecules of commercial value synthesized by the microalgal metabolism have been proven to display anti-inflammatory activity, including the carotenoids lutein and astaxanthin, the fatty acids EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), and sulphated polysaccharides. These molecules can accumulate to a certain extent in a diversity of microalgae species. A production process could become commercially feasible if the productivity is high and the overall production process costs are minimized. The productivity of anti-inflammatory molecules depends on each algal species and the cultivation conditions, the latter being mostly related to nutrient starvation and/or extremes of temperature and/or light intensity. Furthermore, novel bioprocess tools have been reported which might improve the biosynthesis yields and productivity of those target molecules and reduce production costs simultaneously. Such novel tools include the use of chemical triggers or enhancers to improve algal growth and/or accumulation of bioactive molecules, the algal growth in foam and the surfactant-mediated extraction of valuable compounds. Taken together, the recent findings suggest that the combined use of novel bioprocess strategies could improve the technical efficiency and commercial feasibility of valuable microalgal bioproducts production, particularly anti-inflammatory compounds, in large scale processes.
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Nunes, Clara dos Reis, Mariana Barreto Arantes, Silvia Menezes de Faria Pereira, Larissa Leandro da Cruz, Michel de Souza Passos, Luana Pereira de Moraes, Ivo José Curcino Vieira, and Daniela Barros de Oliveira. "Plants as Sources of Anti-Inflammatory Agents." Molecules 25, no. 16 (August 15, 2020): 3726. http://dx.doi.org/10.3390/molecules25163726.
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Plants represent the main source of molecules for the development of new drugs, which intensifies the interest of transnational industries in searching for substances obtained from plant sources, especially since the vast majority of species have not yet been studied chemically or biologically, particularly concerning anti-inflammatory action. Anti-inflammatory drugs can interfere in the pathophysiological process of inflammation, to minimize tissue damage and provide greater comfort to the patient. Therefore, it is important to note that due to the existence of a large number of species available for research, the successful development of new naturally occurring anti-inflammatory drugs depends mainly on a multidisciplinary effort to find new molecules. Although many review articles have been published in this regard, the majority presented the subject from a limited regional perspective. Thus, the current article presents highlights from the published literature on plants as sources of anti-inflammatory agents.
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Wallace, John L. "Novel Targets for Anti-Inflammatory Therapy in Inflammatory Bowel Disease." Canadian Journal of Gastroenterology 8, no. 6 (1994): 373–78. http://dx.doi.org/10.1155/1994/765272.
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Until the cause(s) of inflammatory bowel disease are identified, improvements in therapy will likely come from improved anti-inflammatory therapy or improved drug delivery systems. There are many potential targets for anti-inflammatory therapy, including the synthesis of specific inflammatory mediators. This review focuses on the potential for developing therapy aimed at three targets: nerves and neuropeptides; coagulation and thrombosis; and adhesion molecules. In each case, evidence is presented from clinical and/or experimental studies that supports the hypothesis that these are rational targets for anti-inflammatory drug development.
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Mohammed, Mona S., Wadah J. A. Osman, Elrashied A. E. Garelnabi, Zuheir Osman, Bashier Osman, Hassan S. Khalid, and Magdi A. Mohamed. "Secondary metabolites as anti-inflammatory agents." Journal of Phytopharmacology 3, no. 4 (August 25, 2014): 275–85. http://dx.doi.org/10.31254/phyto.2014.3409.
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Inflammation is a complex pathophysiological process mediated by a variety of signaling molecules and can be classified as either acute or chronic. Anti inflammatory drugs are broadly classified into two categories: Steroidal and Non steroidal anti-inflammatory agents (NSAIDs) some of them are no longer used due to their severe adverse effects. Traditionally, people have been using powerful anti-inflammatory plants for thousands of years as part of their diet and pharmaceutical arsenal, and secondary compounds derived from these plants may offer important sources of anti-inflammatory agents.
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Salvemini, Daniela. "SUPEROXIDE DISMUTASE MIMETICS: NOVEL SMALL MOLECULES ANTI-INFLAMMATORY AGENTS." Shock 21, Supplement (March 2004): 126. http://dx.doi.org/10.1097/00024382-200403001-00504.
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Shokuhfar, Tolou, Suman Sinha-Ray, Cortino Sukotjo, and Alexander L. Yarin. "Intercalation of anti-inflammatory drug molecules within TiO2 nanotubes." RSC Advances 3, no. 38 (2013): 17380. http://dx.doi.org/10.1039/c3ra42173b.
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Hanke, Thomas, Daniel Merk, Dieter Steinhilber, Gerd Geisslinger, and Manfred Schubert-Zsilavecz. "Small molecules with anti-inflammatory properties in clinical development." Pharmacology & Therapeutics 157 (January 2016): 163–87. http://dx.doi.org/10.1016/j.pharmthera.2015.11.011.
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Bozrova, S. V., V. A. Levitsky, S. A. Nedospasov, and M. S. Drutskaya. "Imiquimod: the biochemical mechanisms of immunomodulatory and anti-inflammatory activity." Biomeditsinskaya Khimiya 59, no. 3 (2013): 249–66. http://dx.doi.org/10.18097/pbmc20135903249.
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Imidazoquinolins represent a new group of compounds that recently entered into clinical practice as anti-tumor and anti-viral immune modulators. They are low molecular weight synthetic guanosine-like molecules. Although imiquimod, the most widely used imidazoquinolin, is recommended for the treatment of several forms of skin cancer and papillomas, the molecular mechanisms of its action are not fully understood. In particular, imiquimod has been characterized as a specific agonist of Toll-like receptor 7 (TLR7) and is widely used in this capacity in a large number of experimental studies and clinical trials. However, detailed analysis of the published data with the use of imiquimod, suggests that its biological activity can not be explained only by interaction with TLR7. There are indications of a direct interaction of imiquimod with adenosine receptors and other molecules that regulate the synthesis of cyclic adenosine monophosphate. A detailed understanding of the biochemical basis of imiquimod immunomodulating and antitumor effect will increase its clinical effectiveness and accelerate the development of new drugs with similar but improved medical properties. This review summarizes the published data concerning the effects of imiquimod on a variety of intracellular biochemical processes and signaling pathways.
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Manish S. Junagade and Anju Goyal. "‘Mutual Prodrug’ and approach to increase the effectiveness of Non-Steroidal Anti-inflammatory Drugs." World Journal of Biological and Pharmaceutical Research 1, no. 1 (June 30, 2021): 035–45. http://dx.doi.org/10.53346/wjbpr.2021.1.1.0011.
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A clinically useful drug may have limitations in practice because of undesirable side effects, poor solubility, and poor bioavailability, short duration of action, first-pass effect, poor absorption & adverse effects. There are increased efforts in research to increase the therapeutic efficacy of drugs by eliminating or minimizing the undesirable properties of drug molecules. Some of the problems can be solved using a formulation development approach but in some cases, chemical modification in the molecule is necessary to correct the pharmacokinetic parameters. One of the approaches to convert the existing molecule to a more efficient molecule is prodrug design. Mutual Prodrug is the molecule in which an active drug molecule is attached to a carrier molecule having pharmacological activity. So a mutual prodrug consists of two pharmacologically active molecules connected by a bio labile linkage. Both molecules in this act as a pro moiety of each other. The design of mutual prodrug is very fruitful in the area of research & has given successful results in increasing the clinical & therapeutic effectiveness of the drugs. The present article takes a review of various applications of mutual prodrugs & development in this field in the last few decades.
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González, Yisett, Daniel Torres-Mendoza, Gillian E. Jones, and Patricia L. Fernandez. "Marine Diterpenoids as Potential Anti-Inflammatory Agents." Mediators of Inflammation 2015 (2015): 1–14. http://dx.doi.org/10.1155/2015/263543.
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The inflammatory response is a highly regulated process, and its dysregulation can lead to the establishment of chronic inflammation and, in some cases, to death. Inflammation is the cause of several diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and asthma. The search for agents inhibiting inflammation is a great challenge as the inflammatory response plays an important role in the defense of the host to infections. Marine invertebrates are exceptional sources of new natural products, and among those diterpenoids secondary metabolites exhibit notable anti-inflammatory properties. Novel anti-inflammatory diterpenoids, exclusively produced by marine organisms, have been identified and synthetic molecules based on those structures have been obtained. The anti-inflammatory activity of marine diterpenoids has been attributed to the inhibition of Nuclear Factor-κB activation and to the modulation of arachidonic acid metabolism. However, more research is necessary to describe the mechanisms of action of these secondary metabolites. This review is a compilation of marine diterpenoids, mainly isolated from corals, which have been described as potential anti-inflammatory molecules.
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Zappavigna, Silvia, Alessia Maria Cossu, Anna Grimaldi, Marco Bocchetti, Giuseppe Andrea Ferraro, Giovanni Francesco Nicoletti, Rosanna Filosa, and Michele Caraglia. "Anti-Inflammatory Drugs as Anticancer Agents." International Journal of Molecular Sciences 21, no. 7 (April 9, 2020): 2605. http://dx.doi.org/10.3390/ijms21072605.
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Inflammation is strictly associated with cancer and plays a key role in tumor development and progression. Several epidemiological studies have demonstrated that inflammation can predispose to tumors, therefore targeting inflammation and the molecules involved in the inflammatory process could represent a good strategy for cancer prevention and therapy. In the past, several clinical studies have demonstrated that many anti-inflammatory agents, including non-steroidal anti-inflammatory drugs (NSAIDs), are able to interfere with the tumor microenvironment by reducing cell migration and increasing apoptosis and chemo-sensitivity. This review focuses on the link between inflammation and cancer by describing the anti-inflammatory agents used in cancer therapy, and their mechanisms of action, emphasizing the use of novel anti-inflammatory agents with significant anticancer activity.
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Sarmadi, Negar, Hossein Poustchi, Fatemeh Ali Yari, Amir Reza Radmard, Sara Karami, Abbas Pakdel, Parisa Shabani, and Ali Khaleghian. "Anti-inflammatory function of apolipoprotein B-depleted plasma is impaired in non-alcoholic fatty liver disease." PLOS ONE 17, no. 4 (April 12, 2022): e0266227. http://dx.doi.org/10.1371/journal.pone.0266227.
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Background Non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular events. HDL exerts various protective functions on the cardiovascular system including anti-inflammatory activity by suppressing adhesion molecules expression in inflammation-induced endothelial cells. This study was designed to search if the anti-inflammatory capacity of apolipoprotein B-depleted plasma (apoB-depleted plasma) is altered in NAFLD patients. Methods A total of 83 subjects including 42 NAFLD and 41 control subjects were included in this cross-sectional study. Anti-inflammatory function of HDL was determined as the ability of apoB-depleted plasma to inhibit tumor necrosis factor-α (TNF-α)-induced expression of adhesion molecules in human umbilical vein endothelial cells (HUVECs). Results Incubation of inflammation-stimulated HUVECs with the NAFLD patients’ apo-B depleted plasma led to higher levels of expression of adhesion molecules compared to the control subjects’ plasma samples, reflecting an impaired anti-inflammatory capacity of apoB-depleted plasma in the NAFLD patients. Impaired anti-inflammatory capacity of apoB-depleted plasma was correlated with fatty liver and obesity indices. After adjustment with obesity indices, the association of anti-inflammatory capacity of apoB-depleted plasma with NAFLD remained significant. Conclusion Impaired anti-inflammatory activity of apoB-depleted plasma was independently associated with NAFLD.
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Peritore, Alessio Filippo, Rosalba Siracusa, Rosalia Crupi, and Salvatore Cuzzocrea. "Therapeutic Efficacy of Palmitoylethanolamide and Its New Formulations in Synergy with Different Antioxidant Molecules Present in Diets." Nutrients 11, no. 9 (September 11, 2019): 2175. http://dx.doi.org/10.3390/nu11092175.
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The use of a complete nutritional approach seems increasingly promising to combat chronic inflammation. The choice of healthy sources of carbohydrates, fats, and proteins, associated with regular physical activity and avoidance of smoking is essential to fight the war against chronic diseases. At the base of the analgesic, anti-inflammatory, or antioxidant action of the diets, there are numerous molecules, among which some of a lipidic nature very active in the inflammatory pathway. One class of molecules found in diets with anti-inflammatory actions are ALIAmides. Among all, one is particularly known for its ability to counteract the inflammatory cascade, the Palmitoylethanolamide (PEA). PEA is a molecular that is present in nature, in numerous foods, and is endogenously produced by our body, which acts as a balancer of inflammatory processes, also known as endocannabionoid-like. PEA is often used in the treatment of both acute and chronic inflammatory pathologies, either alone or in association with other molecules with properties, such as antioxidants or analgesics. This review aims to illustrate an overview of the different diets that are involved in the process of opposition to the inflammatory cascade, focusing on capacity of PEA and new formulations in synergy with other molecules.
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Motterlini, R. "Carbon monoxide-releasing molecules (CO-RMs): vasodilatory, anti-ischaemic and anti-inflammatory activities." Biochemical Society Transactions 35, no. 5 (October 25, 2007): 1142–46. http://dx.doi.org/10.1042/bst0351142.
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The well-known adverse effects of CO (carbon monoxide) intoxication are counterbalanced by its positive actions when small amounts are produced intracellularly by the cytoprotective enzyme HO-1 (haem oxygenase-1). As compelling scientific evidence accumulated to sustain that HO-1 plays a fundamental role in counteracting vascular and inflammatory disorders, we began to appreciate that a controlled delivery of CO to mammals may provide therapeutic benefits in a number of pathological states. This is the rationale for the recent development of CO-RMs (CO-releasing molecules), a group of compounds capable of carrying and liberating controlled quantities of CO in cellular systems, which offer a plausible tool for studying the pharmacological effects of this gas and identifying its mechanism(s) of action. The present review will highlight the encouraging results obtained so far on the vasodilatory, anti-ischaemic and anti-inflammatory effects elicited by CO-RMs in in vitro and in vivo models with an emphasis on the prospect of converting chemical CO carriers into CO-based pharmaceuticals.
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Hoshino, M., and Y. Nakamura. "The effect of inhaled sodium cromoglycate on cellular infiltration into the bronchial mucosa and the expression of adhesion molecules in asthmatics." European Respiratory Journal 10, no. 4 (April 1, 1997): 858–65. http://dx.doi.org/10.1183/09031936.97.10040858.
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There is no direct evidence of the anti-inflammatory effect of inhaled sodium cromoglycate (SCG). To investigate whether inhaled SCG has any effect on cellular infiltration into the bronchial mucosa and the expression of adhesion molecules in patients with asthma, biopsies of the bronchial mucosa were taken from nine patients with atopic bronchial asthma before and after treatment with inhaled SCG (8 mg x day(-1)) from a metered-dose inhaler (MDI). Eosinophils were stained with anti-EG2, neutrophils with anti-NP57, mast cells with anti-AA1, T-lymphocytes with anti-CD4, CD8 and CD3, and macrophages with anti-CD68. Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1) and P-selectin were stained at the same time as adhesion molecules expressed in vascular endothelium. The intensity of ICAM-1 expression in the bronchial epithelium was also evaluated. The numbers of eosinophils, mast cells, T-lymphocytes and macrophages were significantly reduced as a result of SCG administration, and the expression of ICAM-1, VCAM-1 and ELAM-1 was also significantly inhibited. A significant correlation was found between ICAM-1 expression and T-lymphocytes and between VCAM-1 expression and eosinophils. It was concluded that sodium cromoglycate does have an effect on the infiltration of the bronchial mucosa by inflammatory cells and also on the expression of adhesion molecules.
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Lee, Tae Hoon. "Lactoferrin inhibits immune cell adhesion via suppression of cell adhesion molecules expression in hypoxia/reoxygenation animal model." Journal of Immunology 200, no. 1_Supplement (May 1, 2018): 42.10. http://dx.doi.org/10.4049/jimmunol.200.supp.42.10.
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Abstract Lactoferrin (Lf), an 80 kDa iron binding protein, belongs to transferrin family found in secretions such as milk and in plasma secreted from neutrophils granules upon inflammatory stimulation. Lf is a multifunctional protein mainly involved in both the innate and adaptive immune defenses. In this study, we investigated the anti-adherent activity of Lf in hypoxia/reoxygenation (H/R)-stimulated human endothelial cells (HUVECs). Lf dramatically reduced the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) by hypoxia-situation HUVECs. Our results also demonstrated that Lf was reduced the expression of cell adhesion molecules on H/R-induced vascular inflammation mouse model. Lf significantly reduced the gene expression of pro-inflammatory cytokine such as IL-6, IL-1β and TNF-α in hypoxia-induced HUVECs. These results demonstrate that Lf inhibits the expression of cell adhesion molecules including ICAM-1, VCAM-1 and pro-inflammatory cytokines. It also suggests that Lf may play an important role in the development of drug for anti-vascular inflammation by inhibiting the expression of cell adhesion molecules.
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Chae, Hae-Jung, Jong Bae Seo, Sung-Hak Kim, Ei Joung Youn, Sanghee Kim, and Sung-Suk Suh. "Antarctic Freshwater Microalga, Micractinium simplicissimum, Suppresses Inflammation." Journal of Nanoscience and Nanotechnology 21, no. 7 (July 1, 2021): 4098–103. http://dx.doi.org/10.1166/jnn.2021.19158.
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Inflammation mediated by the innate immune system is the organism’s protective mechanism against infectious environmental risk factors. Uncontrolled acute inflammation can become chronic, contributing to various chronic inflammatory diseases such as arthritis, asthma, autoimmune diseases, and atherosclerosis. Although microalgae are increasingly receiving attention as a source of bioactive molecules with therapeutic potential for various human diseases, the underlying mechanisms are not yet well understood. In the present study, we investigated the molecular mechanisms underlying the anti-inflammatory and anti-aging activities of ethanol extracts of Antarctic freshwater microalga Micractinium simplicissimum. Using RAW 264.7 macrophages, microalgal extracts exerted anti-inflammatory activity by regulating the major inflammatory indicators including cyclooxy-genase (COX)-2, interleukin (IL)-6, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α and nitric oxide (NO). Besides, we observed the anti-aging activity of the microalgal extract by suppressing MMP-1 production in human dermal fibroblast. Taken together, these data suggest that anti-inflammatory and anti-aging activities of Antarctic freshwater microalga, Micractinium simplicissimum, can provide new clues to understanding the molecular link between inflammation and diseases, and be a potential anti-inflammatory agent.
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Cerón-Carrasco, José Pedro, Horacio Pérez-Sánchez, José Zúñiga, and Alberto Requena. "Antibodies as Carrier Molecules: Encapsulating Anti-Inflammatory Drugs inside Herceptine." Journal of Physical Chemistry B 122, no. 7 (February 8, 2018): 2064–72. http://dx.doi.org/10.1021/acs.jpcb.7b10749.
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WALLACE, G. "Endogenous production of anti-inflammatory molecules maintaining ocular immune privilege." Acta Ophthalmologica 92 (August 20, 2014): 0. http://dx.doi.org/10.1111/j.1755-3768.2014.3753.x.
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Nworu, Chukwuemeka Sylvester, and Peter Achunike Akah. "ANTI-INFLAMMATORY HERBS AND THEIR MOLECULAR MECHANISMS OF ACTION." African Journal of Traditional, Complementary and Alternative Medicines 12 (November 3, 2015): 52–61. http://dx.doi.org/10.21010/ajtcam.v12i6.3s.
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Background: Medicinal plant and plant products have shown tremendous potentials and are used beneficially in the treatment of inflammation and in the management of diseases with significant inflammatory components. Many medicinal plants employed as anti-inflammatory and anti-phlogistic remedies lack the gastro-erosive side effects of non-steroidal anti-inflammatory drugs (NSAID) or the plethora of unwanted side effects associated with steroidal anti-inflammatory drugs. In order to harness and optimise the applications of these herbs in inflammatory diseases, there is a need to understand how these herbs produce their anti-inflammatory actions.
Materials and Methods: This paper is a review of some anti-inflammatory herbs and their molecular mechanisms of action. A literature search and analysis of published manuscript was employed to x-ray research findings that show how medicinal plants produce anti-inflammatory activities.
Results: Many studies have shown that anti-inflammatory activities of herbal extracts and herb-derived compounds are mainly due to their inhibition of arachidonic acid (AA) metabolism, cyclo-oxygenase (COX), lipo-oxygenase (LOX), pro-inflammatory cytokines, inducible nitric oxide, and transcription activation factor (NF-κB). Some anti-inflammatory medicinal herbs are reported to stabilize lysosomal membrane and some cause the uncoupling of oxidative phosphorylation of intracellular signalling molecules. Many have also been shown to possess strong oxygen radical scavenging activities.
Conclusion: Most of the mechanisms by which anti-inflammatory medicinal plants act are related and many herbal products have been shown to act through a combination of these molecular pathways.
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D'Amico, Ferdinando, Giulia Roda, Laurent Peyrin-Biroulet, and Silvio Danese. "Anti-adhesion Molecules in IBD: Does Gut Selectivity Really Make the Difference?" Current Pharmaceutical Design 25, no. 1 (May 23, 2019): 19–24. http://dx.doi.org/10.2174/1381612825666190307165703.
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Inflammatory Bowel Disease is lifetime chronic progressive inflammatory disease. A considerable portion of patients, do not respond or lose response or experience side effect to “traditional” biological treatment such as anti-tumor necrosis factor (TNF)-α agents. The concept that the blockade of T cell traffic to the gut controls inflammation has stimulated the development of new drugs which selectively targets molecules involved in controlling cell homing to the intestine. The result is the reduction of the chronic inflammatory infiltration in the gut. In this regard, anti-adhesion molecules represent a new class of drugs for patients who don’t respond or lose response to traditional therapy. Moreover, some of these molecules such as vedolizumab, offer the advantage to target the delivery of a drug to the gut (gut selectivity) which could increase clinical efficacy and limit potential adverse events. In this article, we will give an overview of the current data on anti-adhesion molecules in Inflammatory Bowel Diseases.
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Ungurianu, Anca, Anca Zanfirescu, Georgiana Nițulescu, and Denisa Margină. "Vitamin E beyond Its Antioxidant Label." Antioxidants 10, no. 5 (April 21, 2021): 634. http://dx.doi.org/10.3390/antiox10050634.
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Vitamin E, comprising tocopherols and tocotrienols, is mainly known as an antioxidant. The aim of this review is to summarize the molecular mechanisms and signaling pathways linked to inflammation and malignancy modulated by its vitamers. Preclinical reports highlighted a myriad of cellular effects like modulating the synthesis of pro-inflammatory molecules and oxidative stress response, inhibiting the NF-κB pathway, regulating cell cycle, and apoptosis. Furthermore, animal-based models have shown that these molecules affect the activity of various enzymes and signaling pathways, such as MAPK, PI3K/Akt/mTOR, JAK/STAT, and NF-κB, acting as the underlying mechanisms of their reported anti-inflammatory, neuroprotective, and anti-cancer effects. In clinical settings, not all of these were proven, with reports varying considerably. Nonetheless, vitamin E was shown to improve redox and inflammatory status in healthy, diabetic, and metabolic syndrome subjects. The anti-cancer effects were inconsistent, with both pro- and anti-malignant being reported. Regarding its neuroprotective properties, several studies have shown protective effects suggesting vitamin E as a potential prevention and therapeutic (as adjuvant) tool. However, source and dosage greatly influence the observed effects, with bioavailability seemingly a key factor in obtaining the preferred outcome. We conclude that this group of molecules presents exciting potential for the prevention and treatment of diseases with an inflammatory, redox, or malignant component.
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Puthia, Manoj, Jan K. Marzinek, Ganna Petruk, Gizem Ertürk Bergdahl, Peter J. Bond, and Jitka Petrlova. "Antibacterial and Anti-Inflammatory Effects of Apolipoprotein E." Biomedicines 10, no. 6 (June 17, 2022): 1430. http://dx.doi.org/10.3390/biomedicines10061430.
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Apolipoprotein E (APOE) is a lipid-transport protein that functions as a key mediator of lipid transport and cholesterol metabolism. Recent studies have shown that peptides derived from human APOE display anti-inflammatory and antimicrobial effects. Here, we applied in vitro assays and fluorescent microscopy to investigate the anti-bacterial effects of full-length APOE. The interaction of APOE with endotoxins from Escherichia coli was explored using surface plasmon resonance, binding assays, transmission electron microscopy and all-atom molecular dynamics (MD) simulations. We also studied the immunomodulatory activity of APOE using in vitro cell assays and an in vivo mouse model in combination with advanced imaging techniques. We observed that APOE exhibits anti-bacterial activity against several Gram-negative bacterial strains of Pseudomonas aeruginosa and Escherichia coli. In addition, we showed that APOE exhibits a significant binding affinity for lipopolysaccharide (LPS) and lipid A as well as heparin. MD simulations identified the low-density lipoprotein receptor (LDLR) binding region in helix 4 of APOE as a primary binding site for these molecules via electrostatic interactions. Together, our data suggest that APOE may have an important role in controlling inflammation during Gram-negative bacterial infection.
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Schindler, J. F., J. B. Monahan, and W. G. Smith. "p38 Pathway Kinases as Anti-inflammatory Drug Targets." Journal of Dental Research 86, no. 9 (September 2007): 800–811. http://dx.doi.org/10.1177/154405910708600902.
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Mitogen-activated protein kinases (MAPK) are intracellular signaling molecules involved in cytokine synthesis. Several classes of mammalian MAPK have been identified, including extracellular signal-regulated kinase, c-jun N-terminal kinase, and p38 MAP kinase. p38α is a key MAPK involved in tumor necrosis factor α and other cytokine production, as well as enzyme induction (cyclooxygenase-2, inducible nitric oxide synthase, and matrix metalloproteinases) and adhesion molecule expression. An understanding of the broad biologic and pathophysiological roles of p38 MAPK family members has grown significantly over the past decade, as has the complexity of the signaling network leading to their activation. Downstream substrates of MAPK include other kinases ( e.g., mitogen-activated protein-kinase-activated protein kinase 2) and factors that regulate transcription, nuclear export, and mRNA stability and translation. The high-resolution crystal structure of p38α has led to the design of selective inhibitors that have good pharmacological activity. Despite the strong rationale for MAPK inhibitors in human disease, direct proof of concept in the clinic has yet to be demonstrated, with most compounds demonstrating dose-limiting adverse effects. The role of MAPK in inflammation makes them attractive targets for new therapies, and efforts are continuing to identify newer, more selective inhibitors for inflammatory diseases.
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Gejjalagere Honnappa, Chethan, and Unnikrishnan Mazhuvancherry Kesavan. "A concise review on advances in development of small molecule anti-inflammatory therapeutics emphasising AMPK: An emerging target." International Journal of Immunopathology and Pharmacology 29, no. 4 (October 6, 2016): 562–71. http://dx.doi.org/10.1177/0394632016673369.
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Inflammatory diseases are complex, multi-factorial outcomes of evolutionarily conserved tissue repair processes. For decades, non-steroidal anti-inflammatory drugs and cyclooxygenase inhibitors, the primary drugs of choice for the management of inflammatory diseases, addressed individual targets in the arachidonic acid pathway. Unsatisfactory safety and efficacy profiles of the above have necessitated the development of multi-target agents to treat complex inflammatory diseases. Current anti-inflammatory therapies still fall short of clinical needs and the clinical trial results of multi-target therapeutics are anticipated. Additionally, new drug targets are emerging with improved understanding of molecular mechanisms controlling the pathophysiology of inflammation. This review presents an outline of small molecules and drug targets in anti-inflammatory therapeutics with a summary of a newly identified target AMP-activated protein kinase, which constitutes a novel therapeutic pathway in inflammatory pathology.
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Tzara, Ariadni, George Lambrinidis, and Angeliki Kourounakis. "Design of Multifaceted Antioxidants: Shifting towards Anti-Inflammatory and Antihyperlipidemic Activity." Molecules 26, no. 16 (August 14, 2021): 4928. http://dx.doi.org/10.3390/molecules26164928.
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Oxidative stress and inflammation are two conditions that coexist in many multifactorial diseases such as atherosclerosis and neurodegeneration. Thus, the design of multifunctional compounds that can concurrently tackle two or more therapeutic targets is an appealing approach. In this study, the basic NSAID structure was fused with the antioxidant moieties 3,5-di-tert-butyl-4-hydroxybenzoic acid (BHB), its reduced alcohol 3,5-di-tert-butyl- 4-hydroxybenzyl alcohol (BHBA), or 6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid (Trolox), a hydrophilic analogue of α-tocopherol. Machine learning algorithms were utilized to validate the potential dual effect (anti-inflammatory and antioxidant) of the designed analogues. Derivatives 1–17 were synthesized by known esterification methods, with good to excellent yields, and were pharmacologically evaluated both in vitro and in vivo for their antioxidant and anti-inflammatory activity, whereas selected compounds were also tested in an in vivo hyperlipidemia protocol. Furthermore, the activity/binding affinity of the new compounds for lipoxygenase-3 (LOX-3) was studied not only in vitro but also via molecular docking simulations. Experimental results demonstrated that the antioxidant and anti-inflammatory activities of the new fused molecules were increased compared to the parent molecules, while molecular docking simulations validated the improved activity and revealed the binding mode of the most potent inhibitors. The purpose of their design was justified by providing a potentially safer and more efficient therapeutic approach for multifactorial diseases.
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Yeo, Jiwon, Junseok Lee, Seonyeong Yoon, and Won Jong Kim. "Tannic acid-based nanogel as an efficient anti-inflammatory agent." Biomaterials Science 8, no. 4 (2020): 1148–59. http://dx.doi.org/10.1039/c9bm01384a.
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Martins, Luana Mota, Ana Raquel Soares Oliveira, Kyria Jayanne Clímaco Cruz, Francisco Leonardo Torres-Leal, and Dilina do Nascimento Marreiro. "Obesity, inflammation, and insulin resistance." Brazilian Journal of Pharmaceutical Sciences 50, no. 4 (December 2014): 677–92. http://dx.doi.org/10.1590/s1984-82502014000400003.
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White adipose tissue (WAT) is considered an endocrine organ. When present in excess, WAT can influence metabolism via biologically active molecules. Following unregulated production of such molecules, adipose tissue dysfunction results, contributing to complications associated with obesity. Previous studies have implicated pro- and anti-inflammatory substances in the regulation of inflammatory response and in the development of insulin resistance. In obese individuals, pro-inflammatory molecules produced by adipose tissue contribute to the development of insulin resistance and increased risk of cardiovascular disease. On the other hand, the molecules with anti-inflammatory action, that have been associated with the improvement of insulin sensitivity, have your decreased production. Imbalance of these substances contributes significantly to metabolic disorders found in obese individuals. The current review aims to provide updated information regarding the activity of biomolecules produced by WAT.
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Allijn, Iris E., René P. Brinkhuis, Gert Storm, and Raymond M. Schiffelers. "Anti-Inflammatory Properties of Plant Derived Natural Products – A Systematic Review." Current Medicinal Chemistry 26, no. 24 (October 11, 2019): 4506–36. http://dx.doi.org/10.2174/0929867325666190523123357.
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Traditionally, natural medicines have been administered as plant extracts, which are composed of a mixture of molecules. The individual molecular species in this mixture may or may not contribute to the overall medicinal effects and some may even oppose the beneficial activity of others. To better control therapeutic effects, studies that characterized specific molecules and describe their individual activity that have been performed over the past decades. These studies appear to underline that natural products are particularly effective as antioxidants and anti-inflammatory agents. In this systematic review we aimed to identify potent anti-inflammatory natural products and relate their efficacy to their chemical structure and physicochemical properties. To identify these compounds, we performed a comprehensive literature search to find those studies, in which a dose-response description and a positive control reference compound was used to benchmark the observed activity. Of the analyzed papers, 7% of initially selected studies met these requirements and were subjected to further analysis. This analysis revealed that most selected natural products indeed appeared to possess anti-inflammatory activities, in particular anti-oxidative properties. In addition, 14% of the natural products outperformed the remaining natural products in all tested assays and are attractive candidates as new anti-inflammatory agents.
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Barnes, Peter J. "Anti-inflammatory Actions of Glucocorticoids: Molecular Mechanisms." Clinical Science 94, no. 6 (June 1, 1998): 557–72. http://dx.doi.org/10.1042/cs0940557.
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1. Glucocorticoids are widely used for the suppression of inflammation in chronic inflammatory diseases such as asthma, rheumatoid arthritis, inflammatory bowel disease and autoimmune diseases, all of which are associated with increased expression of inflammatory genes. The molecular mechanisms involved in this antiinflammatory action of glucocorticoids is discussed, particularly in asthma, which accounts for the highest clinical use of these agents. 2. Glucocorticoids bind to glucocorticoid receptors in the cytoplasm which then dimerize and translocate to the nucleus, where they bind to glucocorticoid response elements (GRE) on glucocorticoid-responsive genes, resulting in increased transcription. Glucocorticoids may increase the transcription of genes coding for antiinflammatory proteins, including lipocortin-1, interleukin-10, interleukin-1 receptor antagonist and neutral endopeptidase, but this is unlikely to account for all of the widespread anti-inflammatory actions of glucocorticoids. 3. The most striking effect of glucocorticoids is to inhibit the expression of multiple inflammatory genes (cytokines, enzymes, receptors and adhesion molecules). This cannot be due to a direct interaction between glucocorticoid receptors and GRE, as these binding sites are absent from the promoter regions of most inflammatory genes. It is more likely to be due to a direct inhibitory interaction between activated glucocorticoid receptors and activated transcription factors, such as nuclear factor-κB and activator protein-1, which regulate the inflammatory gene expression. 4. It is increasingly recognized that glucocorticoids change the chromatin structure. Glucocorticoid receptors also interact with CREB-binding protein (CBP), which acts as a co-activator of transcription, binding several other transcription factors that compete for binding sites on this molecule. Increased transcription is associated with uncoiling of DNA wound around histone and this is secondary to acetylation of the histone residues by the enzymic action of CBP. Glucocorticoids may lead to deacetylation of histone, resulting in tighter coiling of DNA and reduced access of transcription factors to their binding sites, thereby suppressing gene expression. 5. Rarely patients with chronic inflammatory diseases fail to respond to glucocorticoids, although endocrine function of steroids is preserved. This may be due to excessive formation of activator protein-1 at the inflammatory site, which consumes activated glucocorticoid receptors so that they are not available for suppressing inflammatory genes. 6. This new understanding of glucocorticoid mechanisms may lead to the development of novel steroids with less risk of side effects (which are due to the endocrine and metabolic actions of steroids). ‘Dissociated’ steroids which are more active in transrepression (interaction with transcription factors) than transactivation (GRE binding) have now been developed. Some of the transcription factors that are inhibited by glucocorticoid, such as nuclear factor-κB, are also targets for novel anti-inflammatory therapies.
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Chen, Xiangxiu, Xu Song, Xinghong Zhao, Yu Zhang, Yiming Wang, Renyong Jia, Yuanfeng Zou, Lixia Li, and Zhongqiong Yin. "Insights into the Anti-inflammatory and Antiviral Mechanisms of Resveratrol." Mediators of Inflammation 2022 (August 12, 2022): 1–11. http://dx.doi.org/10.1155/2022/7138756.
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Resveratrol is a naturally occurring stilbene phytoalexin phenolic compound, which has been extensively studied on its biological activity. It has been widely accepted that resveratrol possesses anti-inflammatory and antiviral activities. In this review, we summarize the anti-inflammatory dosages and mechanism and antiviral mechanism of resveratrol. Since viral infections are often accompanied by inflammation, we propose that the NF-κB signaling pathway is a key and common molecular mechanism of resveratrol to exert anti-inflammatory and antiviral effects. For future studies, we believe that resveratrol’s anti-inflammatory and antiviral mechanisms can consider the upstream signaling molecules of the NF-κB signaling pathway. For resveratrol antivirus, future studies can be conducted on the interaction of resveratrol with key proteins or important enzymes of the virus. In addition, we also think that the clinical application of resveratrol is very important. In short, resveratrol is a promising anti-inflammatory and antiviral drug, and research on it needs to be expanded.
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Lee, Woo-Ram, Soo-Jung Kim, Ji-Hyun Park, Kyung-Hyun Kim, Young-Chae Chang, Yoon-Yup Park, Kwang-Gill Lee, et al. "Bee Venom Reduces Atherosclerotic Lesion Formation via Anti-Inflammatory Mechanism." American Journal of Chinese Medicine 38, no. 06 (January 2010): 1077–92. http://dx.doi.org/10.1142/s0192415x10008482.
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The components of bee venom (BV) utilized in the current study were carefully scrutinized with chromatography. Despite its well documented anti-inflammatory property, there are no reports regarding the influence of BV on the expression of cellular adhesion molecules in the vascular endothelium. A great amount of information exists concerning the effects of an atherogenic diet on atherosclerotic changes in the aorta, but little is known about the molecular mechanisms and the levels of gene regulation involved in the anti-inflammatory process induced by BV. The experimental atherosclerosis was induced in mice by a lipopolysaccharide (LPS) injection and an atherogenic diet. The animals were divided into three groups, the NC groups of animals that were fed with a normal diet, the LPS/fat group was fed with the atherogenic diet and received intraperitoneal injections of LPS, and the LPS/fat + BV group was given LPS, an atherogenic diet and intraperitoneal BV injections. At the end of each treatment period, the LPS/fat + BV group had decreased levels of total cholesterol (TC) and triglyceride (TG) in their serum, compared to the LPS/fat group. The LPS/fat group had significant expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the serum, compared with the NC group ( p < 0.05). The amount of cytokines reduced consistently in the BV treatment groups compared with those in LPS/fat group. BV significantly reduced the amount of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), transforming growth factor-β1 (TGF-β1) and fibronectin in the aorta, compared with the LPS/fat group ( p < 0.05). A similar pattern was also observed in the heart. In conclusion, BV has anti-atherogenic properties via its lipid-lowering and anti-inflammatory mechanisms.
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Ziadlou, Barbero, Stoddart, Wirth, Li, Martin, Wang, Qin, Alini, and Grad. "Regulation of Inflammatory Response in Human Osteoarthritic Chondrocytes by Novel Herbal Small Molecules." International Journal of Molecular Sciences 20, no. 22 (November 15, 2019): 5745. http://dx.doi.org/10.3390/ijms20225745.
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In this study, 34 Traditional Chinese Medicine (TCM) compounds were screened for potential anabolic and anti-inflammatory properties on human osteoarthritic (OA) chondrocytes. The anabolic effects were assessed by measuring the glycosaminoglycan (GAG) relative to the DNA content using a 3D pellet culture model. The most chondrogenic compounds were tested in an inflammatory model consisting of 3 days of treatment with cytokines (IL-1β/TNF-α) with or without supplementation of TCM compounds. The anti-inflammatory effects were assessed transcriptionally, biochemically and histologically. From the 34 compounds, Vanilic acid (VA), Epimedin A (Epi A) and C (Epi C), 2′′-O-rhamnosylicariside II (2-O-rhs II), Icariin, Psoralidin (PS), Protocatechuicaldehyde (PCA), 4-Hydroxybenzoic acid (4-HBA) and 5-Hydroxymethylfurfural (5-HMF) showed the most profound anabolic effects. After induction of inflammation, pro-inflammatory and catabolic genes were upregulated, and GAG/DNA was decreased. VA, Epi C, PS, PCA, 4-HBA and 5-HMF exhibited anti-catabolic and anti-inflammatory effects and prevented the up-regulation of pro-inflammatory markers including metalloproteinases and cyclooxygenase 2. After two weeks of treatment with TCM compounds, the GAG/DNA ratio was restored compared with the negative control group. Immunohistochemistry and Safranin-O staining confirmed superior amounts of cartilaginous matrix in treated pellets. In conclusion, VA, Epi C, PS, PCA, 4-HBA and 5-HMF showed promising anabolic and anti-inflammatory effects.
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P, Purkait. "Interaction of Inflammatory Molecules in Tuberculosis and Sars Cov-2 Infection." Virology & Immunology Journal 6, no. 1 (February 17, 2022): 1–13. http://dx.doi.org/10.23880/vij-16000286.
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The Hyper-inflammatory immune response is a chief reason for disease severity and mortality in patients. Generally, macrophages and dendritic cells sense and react to microbial or viral invasion by making inflammatory molecules that remove pathogens and help in tissue repair. During tuberculosis infection, alveolar macrophages activate alveolar dendritic cells, which move to lymph nodes. In lymph nodes, the proliferation of CD4+ T cells, CD8+ cells and γδ T cells occur. Mycobacterium tuberculosis (MTB) bacteria further modify the host's immune system for their long survival period. Meanwhile, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infects alveolar macrophages and releases inflammatory cytokine to produce and activate T-cells. MTB and SARS-CoV-2 infections together lead to an increase in the rate of pathogenesis. This type of co-infection in macrophages causes the production of pro- and anti-inflammatory cytokines, which further play an important role in immune-pathogenesis. However, the abnormal or dysregulated response of macrophages leads to harmful effects of the host, as observed in the macrophage activation syndrome induced by severe infections, including the virus SARSCoV-2. Unlike macrophages, dendritic cells (DCs) act as antigen presenting cells. They connect innate and adaptive immunity cells. They are susceptible to cytokine-mediated activation and lead to cytokine production. The cytokine Interleukin-6 (IL6) is an important and unique molecule that can act pro- as well as anti-inflammatory and helps in the development and differentiation of macrophages associated with numerous inflammatory diseases. In this review paper, we have emphasized the vital pathological role of macrophages, dendritic cells and IL-6 in tuberculosis and SARS-CoV-2 infection and prospective therapeutic strategies based upon IL-6 as the main target for preventing the cytokine storm and associated organ failure.
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S. J., Rahitha Devi, and Prakash Kumar B. "In Silico Screening for Anti-inflammatory Bioactive Molecules from Ayurvedic Decoction, Balaguluchyadi kashayam." Current Computer-Aided Drug Design 16, no. 4 (September 3, 2020): 435–50. http://dx.doi.org/10.2174/1573409915666191015113753.
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Background: Balaguluchyadi kashayam, a polyherbal Ayurvedic decoction prepared from Sidacordifolia L., Tinospora cordifolia (Willd.) Miers, and Cedrusdeodara (Roxb. ex D.Don) G.Don, is used in Ayurveda for the treatment of chronic inflammatory conditions. Although this herbal decoction has been used for a long period for treating chronic inflammatory conditions, the mechanism of action of the decoction in reducing inflammatory conditions associated with chronic inflammation has not been clearly understood. Mass spectroscopy-based identification of bioactive molecules present in the decoction and its interaction with enzymes/proteins involved in the pathogenesis of chronic inflammation has been carried and reported in this study. Introduction: Polyherbalism is one of the major principles of Ayurveda. Various phytoconstituents with different activities in the polyherbal decoction act on multi targets of a wide range of diseases. Balaguluchyadi kashayam is a polyherbal decoction prescribed for chronic inflammatory etiologies and the present study aims to evaluate the binding potential of the compounds, identified from Balaguluchyadi kashayam to enzymes/proteins involved in the development and progression of chronic inflammation. Methods: The bioactive compounds present in the Balaguluchyadi Kashayam fractions were extracted by preparative HPLC and identified using UPLC MS Q-TOF. The physicochemical characteristics and ADMET properties of the compounds were calculated using Mol soft, Swiss ADME and OSIRIS data warrior software. Then the binding interactions between the molecules and the proinflammatory mediators such as 5 Lipoxygenase, Cyclooxygenase 2, Tumor necrosis factoralpha convertase enzyme (TACE) and Caspase 1 were determined using molecular docking software Auto Dock 4.0 (http://autodock.scripps.edu/downloads). Results: The identified bioactive molecules in the decoction showed a good binding affinity towards the enzymes/proteins involved in the development and progression of chronic inflammation compared to the binding affinity of known inhibitors/drugs to the respective enzymes/proteins. Conclusion: The bioactive molecules identified in Balaguluchyadi Kashayam could be developed as potential therapeutic molecules against enzymes/proteins involved in the development and progression of chronic inflammation.
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Liu, Fu-Chao, and Huang-Ping Yu. "Red wine extract, resveratrol, on maintenance of organ function following trauma-hemorrhage." Functional Foods in Health and Disease 2, no. 10 (October 23, 2012): 351. http://dx.doi.org/10.31989/ffhd.v2i10.76.
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Resveratrol, is a polyphenol that can be extracted from grapes and red wine, possess potential anti-inflammatory effects, which would result in the reduction of cytokine production, the alteration of the expression of adhesion molecule molecules, and the inhibition of neutrophil function. Resveratrol might also act as an antioxidant, anti-aging, and control of cell cycle and apoptosis. Resveratrol has been shown to have protective effects for patients in shock-like states. Such protective phenomenon is reported to be implicated in a variety of intracellular signaling pathways including the regulation of the mitogen-activated protein kinases (MAPK)/ hemeoxygenase-1 (HO-1) pathway, activates estrogen receptor (ER), and the mediation of pro-inflammatory cytokines, reactive oxygen species (ROS) formation and reactive. Moreover, through anti-inflammatory effects and antioxidant properties, the resveratrol is believed to maintain organ function following trauma-hemorrhage.Key words: resveratrol, anti-inflammatory, trauma-hemorrhage.
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Anthwal, Amit, Kundan Singh, M. S. M. Rawat, Amit K. Tyagi, Bharat B. Aggarwal, and Diwan S. Rawat. "C5-curcuminoid-dithiocarbamate based molecular hybrids: synthesis and anti-inflammatory and anti-cancer activity evaluation." RSC Adv. 4, no. 54 (2014): 28756–64. http://dx.doi.org/10.1039/c4ra03655g.
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The C5-curcumin-dithiocarbamate analogues were synthesized in search of new molecules with anti-proliferation potential against cancer cells. These new compounds demonstrated higher anti-proliferation and anti-inflammatory activity against cancer cell lines in comparison to curcumin.
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Lauritano, Chiara, Kirsti Helland, Gennaro Riccio, Jeanette H. Andersen, Adrianna Ianora, and Espen H. Hansen. "Lysophosphatidylcholines and Chlorophyll-Derived Molecules from the Diatom Cylindrotheca closterium with Anti-Inflammatory Activity." Marine Drugs 18, no. 3 (March 17, 2020): 166. http://dx.doi.org/10.3390/md18030166.
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Microalgae have been shown to be excellent producers of lipids, pigments, carbohydrates, and a plethora of secondary metabolites with possible applications in the pharmacological, nutraceutical, and cosmeceutical sectors. Recently, various microalgal raw extracts have been found to have anti-inflammatory properties. In this study, we performed the fractionation of raw extracts of the diatom Cylindrotheca closterium, previously shown to have anti-inflammatory properties, obtaining five fractions. Fractions C and D were found to significantly inhibit tumor necrosis factor alpha (TNF-⍺) release in LPS-stimulated human monocyte THP-1 cells. A dereplication analysis of these two fractions allowed the identification of their main components. Our data suggest that lysophosphatidylcholines and a breakdown product of chlorophyll, pheophorbide a, were probably responsible for the observed anti-inflammatory activity. Pheophorbide a is known to have anti-inflammatory properties. We tested and confirmed the anti-inflammatory activity of 1-palmitoyl-sn-glycero-3-phosphocholine, the most abundant lysophosphatidylcholine found in fraction C. This study demonstrated the importance of proper dereplication of bioactive extracts and fractions before isolation of compounds is commenced.
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Calder, Philip C. "Omega-3 fatty acids and inflammatory processes: from molecules to man." Biochemical Society Transactions 45, no. 5 (September 12, 2017): 1105–15. http://dx.doi.org/10.1042/bst20160474.
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Inappropriate, excessive or uncontrolled inflammation contributes to a range of human diseases. Inflammation involves a multitude of cell types, chemical mediators and interactions. The present article will describe nutritional and metabolic aspects of omega-6 (n-6) and omega-3 (n-3) fatty acids and explain the roles of bioactive members of those fatty acid families in inflammatory processes. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n-3 fatty acids found in oily fish and fish oil supplements. These fatty acids are capable of partly inhibiting many aspects of inflammation including leucocyte chemotaxis, adhesion molecule expression and leucocyte–endothelial adhesive interactions, production of eicosanoids like prostaglandins and leukotrienes from the n-6 fatty acid arachidonic acid and production of pro-inflammatory cytokines. In addition, EPA gives rise to eicosanoids that often have lower biological potency than those produced from arachidonic acid, and EPA and DHA give rise to anti-inflammatory and inflammation resolving mediators called resolvins, protectins and maresins. Mechanisms underlying the anti-inflammatory actions of EPA and DHA include altered cell membrane phospholipid fatty acid composition, disruption of lipid rafts, inhibition of activation of the pro-inflammatory transcription factor nuclear factor κB so reducing expression of inflammatory genes and activation of the anti-inflammatory transcription factor peroxisome proliferator-activated receptor γ. Animal experiments demonstrate benefit from EPA and DHA in a range of models of inflammatory conditions. Human trials demonstrate benefit of oral n-3 fatty acids in rheumatoid arthritis and in stabilizing advanced atherosclerotic plaques. Intravenous n-3 fatty acids may have benefits in critically ill patients through reduced inflammation. The anti-inflammatory and inflammation resolving actions of EPA, DHA and their derivatives are of clinical relevance.
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Gera, Ankur, Chander Mohan, Jitender Madan, and Sandeep Arora. "Molecular Hybrids of N-Phthaloylglycyl Hydrazide and Hydrazinecarbothioamide with Anti-inflammatory and Anti-oxidant Activities." Current Organic Synthesis 16, no. 7 (December 26, 2019): 1055–66. http://dx.doi.org/10.2174/1570179416666190306141318.
Full textAbstract:
Background: Oxidative stress due to high levels of reactive organic species is the cause of the progression of inflammation in various diseases. The molecules possessing both anti-inflammatory and antioxidant activity can be the promising key to treat inflammatory diseases. Phthalimide and hydrazinecarbothioamide are anti-inflammatory and anti-oxidant pharmacophores. Objective: Molecular hybrids possessing above two pharmacophores were designed. A series of N-phenyl substituted 2-(2-(1,3-dioxoisoindolin-2-yl)acetyl)-N-phenylhydrazine-1-carbothioamide (CGS compounds) was synthesized and evaluated for biological activities. Methods: N-phthaloylglycyl hydrazide was reacted with unsubstituted/substituted phenyl isothiocyanates to yield CGS compounds. Synthesized compounds were evaluated for in vivo anti-inflammatory activity in carrageenan rat paw edema model, and in vitro anti-oxidant activity by DPPH assay. Levels of TNF-α and oxidative stress at the site of inflammation were measured. The genetic algorithm-PLS regression based QSAR model correlating the effect of N-phenyl substituent on the anti-inflammatory activity was developed. Further, the interaction of the active compound in the TNF-α binding pocket was studied by in silico docking. Results: Compound containing the 2-OCH3, 4-NO2 (CGS-5); 4-CF3 (CGS-9); 4-NO2 (CGS-3) showed significant anti-inflammatory activity (percentage inhibition of paw edema after 3 hour = 58.24, 50.38, 40.05, respectively) and potent anti-oxidant activity (IC50 =0.045, 0.998, 0.285 μg/ml, respectively). Reduced levels of TNF- α and increased levels of GSH were observed for the above three compounds. Descriptors for QSAR model identified by GA-PLS were WPSA1, Weta1unity, WDunity, SC3, VC5, MlogP, and WTPT3. The identified model was highly predictive, and value of root mean square error of prediction for internal (leave one out) and external validation was: 1.579, 1.325. Conclusion: Molecular hybrids of phthalimide and hydrazinecarbothioamide were synthesized. Some of the compounds possessed promising anti-inflammatory and anti-oxidant activities.