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      Phytochemical Analysis and Anti-Inflammatory Activity of Different Ethanolic Phyto-Extracts of Artemisia annua L.

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          Abstract

          Artemisia annua L. (AA) has shown for many centuries important therapeutic virtues associated with the presence of artemisinin (ART). The aim of this study was to identify and quantify ART and other secondary metabolites in ethanolic extracts of AA and evaluate the biological activity in the presence of an inflammatory stimulus. In this work, after the extraction of the aerial parts of AA with different concentrations of ethanol, ART was quantified by HPLC and HPLC-MS. In addition, anthocyanins, flavanols, flavanones, flavonols, lignans, low-molecular-weight phenolics, phenolic acids, stilbenes, and terpenes were identified and semi-quantitatively determined by UHPLC-QTOF-MS untargeted metabolomics. Finally, the viability of human neuroblastoma cells (SH-SY5Y) was evaluated in the presence of the different ethanolic extracts and in the presence of lipopolysaccharide (LPS). The results show that ART is more concentrated in AA samples extracted with 90% ethanol. Regarding the other metabolites, only the anthocyanins are more concentrated in the samples extracted with 90% ethanol. Finally, ART and all AA samples showed a protective action towards the pro-inflammatory stimulus of LPS. In particular, the anti-inflammatory effect of the leaf extract of AA with 90% ethanol was also confirmed at the molecular level since a reduction in TNF-α mRNA gene expression was observed in SH-SY5Y treated with LPS.

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          Toll-Like Receptor Signaling Pathways

          Toll-like receptors (TLRs) play crucial roles in the innate immune system by recognizing pathogen-associated molecular patterns derived from various microbes. TLRs signal through the recruitment of specific adaptor molecules, leading to activation of the transcription factors NF-κB and IRFs, which dictate the outcome of innate immune responses. During the past decade, the precise mechanisms underlying TLR signaling have been clarified by various approaches involving genetic, biochemical, structural, cell biological, and bioinformatics studies. TLR signaling appears to be divergent and to play important roles in many aspects of the innate immune responses to given pathogens. In this review, we describe recent progress in our understanding of TLR signaling regulation and its contributions to host defense.
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            Natural products in drug discovery: advances and opportunities

            Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer and infectious diseases. Nevertheless, natural products also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization, which contributed to a decline in their pursuit by the pharmaceutical industry from the 1990s onwards. In recent years, several technological and scientific developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — are addressing such challenges and opening up new opportunities. Consequently, interest in natural products as drug leads is being revitalized, particularly for tackling antimicrobial resistance. Here, we summarize recent technological developments that are enabling natural product-based drug discovery, highlight selected applications and discuss key opportunities.
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              Emerging Roles of Vascular Cell Adhesion Molecule-1 (VCAM-1) in Immunological Disorders and Cancer

              Tumor necrosis factor alpha (TNFα) is a pro-inflammatory cytokine that triggers the expression of inflammatory molecules, including other cytokines and cell adhesion molecules. TNFα induces the expression of intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 (VCAM-1). VCAM-1 was originally identified as a cell adhesion molecule that helps regulate inflammation-associated vascular adhesion and the transendothelial migration of leukocytes, such as macrophages and T cells. Recent evidence suggests that VCAM-1 is closely associated with the progression of various immunological disorders, including rheumatoid arthritis, asthma, transplant rejection, and cancer. This review covers the role and relevance of VCAM-1 in inflammation, and also highlights the emerging potential of VCAM-1 as a novel therapeutic target in immunological disorders and cancer.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Biomolecules
                Biomolecules
                biomolecules
                Biomolecules
                MDPI
                2218-273X
                02 July 2021
                July 2021
                : 11
                : 7
                : 975
                Affiliations
                [1 ]Department of Molecular and Translational Medicine, Division of Pharmacology, University of Brescia, 25123 Brescia, Italy; giulia.abate@ 123456unibs.it (G.A.); m.pucci003@ 123456unibs.it (M.P.); g.morbini001@ 123456studenti.unibs.it (G.M.); e.macsweeney@ 123456studenti.unibs.it (E.M.S.); giuseppina.maccarinelli@ 123456unibs.it (G.M.); giovanni.ribaudo@ 123456unibs.it (G.R.); alessandra.gianoncelli@ 123456unibs.it (A.G.); daniela.uberti@ 123456unibs.it (D.U.); maurizio.memo@ 123456unibs.it (M.M.)
                [2 ]Department for Sustainable Food Process, Università Cattolica del Sacro Cuore, 29122 Piacenza, Italy; leilei.zhang@ 123456unicatt.it
                Author notes
                [†]

                These authors contribute equally to this work.

                [‡]

                These authors contribute equally to this work.

                Author information
                https://orcid.org/0000-0001-9161-3475
                https://orcid.org/0000-0002-9278-0459
                https://orcid.org/0000-0003-3679-5530
                https://orcid.org/0000-0002-0816-5163
                https://orcid.org/0000-0002-5926-9122
                https://orcid.org/0000-0002-5133-9464
                https://orcid.org/0000-0002-8862-2896
                Article
                biomolecules-11-00975
                10.3390/biom11070975
                8301839
                34356599
                5e109d87-9e91-48c5-a8d7-627be466a6e4
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 31 May 2021
                : 29 June 2021
                Categories
                Article

                artemisia annua l.,artemisinin,phenolic compounds,terpenoids,tnf-α

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