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      Research on Anti-inflammatory Targets and Mechanisms of alkaloids in Picrasma quassioides Benn Through Network Pharmacology

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          Abstract

          Abstract This study aimed to investigate the molecular mechanism of Picrasma quassioides Benn against inflammation by means of network pharmacology. The paper will provide a reference for multi-target and multi-channel treatment of inflammation with traditional Chinese medicine. Through screening and analysis, 11 active ingredients and 109 anti-inflammation prediction targets were obtained and constructed a compound-target network. The targets such as VEGFA, TLR4 and STAT3 may play a crucial role. Network enrichment analysis showed that the 109 potential targets constitute a number of pathways or inflammatory reactions closely related to inflammation, including NF-κB signaling pathway and MAPK signaling pathway. The docking results indicated that the binding energy of Picrasidine Y and the inflammatory factors VEGFA is the highest. This study predicted the role of multiple active compounds in the alkaloids of Picrasma in the inflammatory response, and provided a theoretical basis for the anti-inflammatory mechanism of Picrasma.

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          Most cited references25

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          Network pharmacology: the next paradigm in drug discovery.

          The dominant paradigm in drug discovery is the concept of designing maximally selective ligands to act on individual drug targets. However, many effective drugs act via modulation of multiple proteins rather than single targets. Advances in systems biology are revealing a phenotypic robustness and a network structure that strongly suggests that exquisitely selective compounds, compared with multitarget drugs, may exhibit lower than desired clinical efficacy. This new appreciation of the role of polypharmacology has significant implications for tackling the two major sources of attrition in drug development--efficacy and toxicity. Integrating network biology and polypharmacology holds the promise of expanding the current opportunity space for druggable targets. However, the rational design of polypharmacology faces considerable challenges in the need for new methods to validate target combinations and optimize multiple structure-activity relationships while maintaining drug-like properties. Advances in these areas are creating the foundation of the next paradigm in drug discovery: network pharmacology.
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            Traditional Chinese medicine network pharmacology: theory, methodology and application.

            Traditional Chinese medicine (TCM) has a long history of viewing an individual or patient as a system with different statuses, and has accumulated numerous herbal formulae. The holistic philosophy of TCM shares much with the key ideas of emerging network pharmacology and network biology, and meets the requirements of overcoming complex diseases, such as cancer, in a systematic manner. To discover TCM from a systems perspective and at the molecular level, a novel TCM network pharmacology approach was established by updating the research paradigm from the current "one target, one drug" mode to a new "network target, multi-components" mode. Subsequently, a set of TCM network pharmacology methods were created to prioritize disease-associated genes, to predict the target profiles and pharmacological actions of herbal compounds, to reveal drug-gene-disease co-module associations, to screen synergistic multi-compounds from herbal formulae in a high-throughput manner, and to interpret the combinatorial rules and network regulation effects of herbal formulae. The effectiveness of the network-based methods was demonstrated for the discovery of bioactive compounds and for the elucidation of the mechanisms of action of herbal formulae, such as Qing-Luo-Yin and the Liu-Wei-Di-Huang pill. The studies suggest that the TCM network pharmacology approach provides a new research paradigm for translating TCM from an experience-based medicine to an evidence-based medicine system, which will accelerate TCM drug discovery, and also improve current drug discovery strategies. Copyright © 2013 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.
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              A human homologue of the Drosophila Toll protein signals activation of adaptive immunity.

              Induction of the adaptive immune response depends on the expression of co-stimulatory molecules and cytokines by antigen-presenting cells. The mechanisms that control the initial induction of these signals upon infection are poorly understood. It has been proposed that their expression is controlled by the non-clonal, or innate, component of immunity that preceded in evolution the development of an adaptive immune system in vertebrates. We report here the cloning and characterization of a human homologue of the Drosophila toll protein (Toll) which has been shown to induce the innate immune response in adult Drosophila. Like Drosophila Toll, human Toll is a type I transmembrane protein with an extracellular domain consisting of a leucine-rich repeat (LRR) domain, and a cytoplasmic domain homologous to the cytoplasmic domain of the human interleukin (IL)-1 receptor. Both Drosophila Toll and the IL-1 receptor are known to signal through the NF-kappaB pathway. We show that a constitutively active mutant of human Toll transfected into human cell lines can induce the activation of NF-kappaB and the expression of NF-kappaB-controlled genes for the inflammatory cytokines IL-1, IL-6 and IL-8, as well as the expression of the co-stimulatory molecule B7.1, which is required for the activation of naive T cells.
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                Author and article information

                Journal
                bjps
                Brazilian Journal of Pharmaceutical Sciences
                Braz. J. Pharm. Sci.
                Universidade de São Paulo, Faculdade de Ciências Farmacêuticas (São Paulo, SP, Brazil )
                2175-9790
                2023
                : 59
                : e22394
                Affiliations
                [1] Yantai PR orgnameYantai University orgdiv1Key Laboratory of Molecular Pharmacology and Drug Evaluation orgdiv2Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, School of Pharmacy China
                Article
                S1984-82502023000100401 S1984-8250(23)05900000401
                10.1590/s2175-97902023e22394
                9988d0b9-4159-4810-be26-920f32a20689

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 25 April 2023
                : 16 May 2022
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 25, Pages: 0
                Product

                SciELO Brazil

                Categories
                Article

                Alkaloids,Picrasma quassioides (D.Don) Benn,Inflammation,Network pharmacology,Molecular docking.

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