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      Bioactivity, Compounds Isolated, Chemical Qualitative, and Quantitative Analysis of Cymbaria daurica Extracts

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          Abstract

          Cymbaria daurica L. is widely used in traditional Mongolian medicine for the treatment of impetigo, psoriasis, pruritus, fetotoxicity, and diabetes. Therefore, the anti-inflammatory and α-glucosidase-inhibitory activities of four polar C. daurica extracts (water, n-butanol, ethyl acetate, and petroleum ether extract) were preliminarily evaluated to identify the active extracts. We also investigated the chemical composition of the active extracts by phytochemical analysis. The n-butanol and ethyl acetate extracts exhibited significant ( p < 0.05) anti-inflammatory activities by inhibiting lipopolysaccharide-induced nitric oxide (NO) production in RAW 264.7 cells. None of the tested extracts exhibited cytotoxic effects at the effective concentrations. The ethyl acetate extract significantly inhibited α-glucosidase activity, and the inhibition potency was equivalent to that of acarbose ( p > 0.05). The n-Butanol extract presented the second highest inhibitory activity. As the n-butanol and ethyl acetate extracts were found to have potent anti-inflammatory and α-glucosidase-inhibitory activities, we separated and identified 10 compounds from the extracts. Among them, vanillic acid, cistanoside F, echinacoside, arenarioside, verbascoside, isoacteoside, and tricin were isolated from C. daurica for the first time. Further, 30 compounds from the n-butanol and ethyl acetate extracts of C. daurica were identified using UHPLC-Q-Exactive. The present study demonstrates for the first time that C. daurica contains phenylethanoid glycosides. In addition, this novel HPLC method was subsequently used for simultaneous identification of five compounds in the n-butanol and ethyl acetate extracts of C. daurica. This study provides a chemical basis for further characterization and utilization of C. daurica, which could be a potential source of novel anti-diabetic and anti-inflammatory agents.

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          Most cited references49

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          Anti-inflammatory effects of flavonoids in neurodegenerative disorders

          Neuroinflammation is one of the main mechanisms involved in the progression of several neurodegenerative diseases, such as Parkinson, Alzheimer, multiple sclerosis, amyotrophic lateral sclerosis and others. The activation of microglia is the main feature of neuroinflammation, promoting the release of pro-inflammatory cytokines and resulting in the progressive neuronal cell death. Natural compounds, such as flavonoids, possess neuroprotective potential probably related to their ability to modulate the inflammatory responses involved in neurodegenerative diseases. In fact, pure flavonoids (e.g., quercetin, genistein, hesperetin, epigallocatechin-3-gallate) or enriched-extracts, can reduce the expression of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β and COX-2), down-regulate inflammatory markers and prevent neural damage. This anti-inflammatory activity is primarily related to the regulation of microglial cells, mediated by their effects on MAPKs and NF-κB signalling pathways, as demonstrated by in vivo and in vitro data. The present work reviews the role of inflammation in neurodegenerative diseases, highlighting the potential therapeutic effects of flavonoids as a promising approach to develop innovative neuroprotective strategy.
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            Rosmarinic acid inhibits the formation of reactive oxygen and nitrogen species in RAW264.7 macrophages.

            Antioxidant action of Rosmarinic acid (Ros A), a natural phenolic ingredient in many Lamiaceae herbs such as Perilla frutescens, sage, basil and mint, was analyzed in relation to the Ikappa-B activation in RAW264.7 macrophages. Ros A inhibited nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) protein synthesis induced by lipopolysaccharide (LPS), and also effectively suppressed phorbol 12-myristate 13-acetate (PMA)-induced superoxide production in RAW264.7 macrophages in a dose-dependent manner. Peroxynitrite-induced formation of 3-nitrotyrosine in bovine serum albumin and RAW264.7 macrophages were also inhibited by Ros A. Moreover, Western blot analysis demonstrated that LPS-induced phosphorylation of Ikappa-Balpha was abolished by Ros A. Ros A can act as an effective protector against peroxynitrite-mediated damage, and as a potent inhibitor of superoxide and NO synthesis; the inhibition of the formation of reactive oxygen and nitrogen species are partly based on its ability to inhibit the serine phosphorylation of Ikappa-Balpha.
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              Verbascoside down-regulates some pro-inflammatory signal transduction pathways by increasing the activity of tyrosine phosphatase SHP-1 in the U937 cell line

              Polyphenols are the major components of many traditional herbal remedies, which exhibit several beneficial effects including anti-inflammation and antioxidant properties. Src homology region 2 domain-containing phosphatase-1 (SHP-1) is a redox sensitive protein tyrosine phosphatase that negatively influences downstream signalling molecules, such as mitogen-activated protein kinases, thereby inhibiting inflammatory signalling induced by lipopolysaccharide (LPS). Because a role of transforming growth factor β-activated kinase-1 (TAK1) in the upstream regulation of JNK molecule has been well demonstrated, we conjectured that SHP-1 could mediate the anti-inflammatory effect of verbascoside through the regulation of TAK-1/JNK/AP-1 signalling in the U937 cell line. Our results demonstrate that verbascoside increased the phosphorylation of SHP-1, by attenuating the activation of TAK-1/JNK/AP-1 signalling. This leads to a reduction in the expression and activity of both COX and NOS. Moreover, SHP-1 depletion deletes verbascoside inhibitory effects on pro-inflammatory molecules induced by LPS. Our data confirm that SHP-1 plays a critical role in restoring the physiological mechanisms of inducible proteins such as COX2 and iNOS, and that the down-regulation of TAK-1/JNK/AP-1 signalling by targeting SHP-1 should be considered as a new therapeutic strategy for the treatment of inflammatory diseases.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                07 February 2020
                2020
                : 11
                : 48
                Affiliations
                [1] 1 Department of Pharmacy, Baotou Medical College , Baotou, China
                [2] 2 Clinical Laboratory, The First Affiliated Hospital of Baotou Medical College of Inner Mongolia University of Science and Technology , Baotou, China
                [3] 3 Pharmaceutical Laboratory, Inner Mongolia Autonomous Region Academy of Chinese Medicine , Hohhot, China
                [4] 4 Guangxi Key Laboratory of Medicinal Resources Protection and Genetic Improvement, Guangxi Botanical Garden of Medicinal Plants , Nanning, China
                [5] 5 Inner Mongolia Key Laboratory of Characteristic Geoherbs Resources Protection and Utilization, Baotou Medical College , Baotou, China
                Author notes

                Edited by: Lie-Fen Shyur, Academia Sinica, Taiwan

                Reviewed by: Aline Carvalho Pereira, Universidade Federal de Lavras, Brazil; Souaibou Yaouba, Université de Lorraine, France

                *Correspondence: Minhui Li, prof_liminhui@ 123456yeah.net ; Chunhong Zhang, zchlhh@ 123456126.com

                This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2020.00048
                7019114
                409bd520-a311-4bd6-b32c-2d2375f99a90
                Copyright © 2020 Gong, Wang, Zhang, Wang, Wang, Shi, Zang, Zhang, Zhang and Li

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 20 September 2019
                : 14 January 2020
                Page count
                Figures: 6, Tables: 6, Equations: 0, References: 52, Pages: 12, Words: 5878
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Funded by: Agriculture Research System of China 10.13039/501100010203
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                cymbaria daurica l.,scrophulariaceae,anti-inflammatory activity,inhibition of α-glucosidase activity,uhplc-q-exactive orbitrap hrms,phenylethanoid glycoside,verbascoside

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