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      The Protective Effects of 2,3,5,4′-Tetrahydroxystilbene-2- O-β-d-Glucoside in the OVA-Induced Asthma Mice Model

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          Abstract

          Asthma is an inflammatory disease caused by an imbalance of Th1 and Th2 cells. In general, asthma is characterized by a stronger Th2 response. Most conventional asthma treatment focuses on improving airway flow or suppression of airway inflammation. To reduce the side effects of currently used asthma medicines, we have conducted studies on natural products that have no side effects. 2,3,5,4′-tetrahydroxystilbene-2-O-β- d-glucoside (TSG), the main compound of Polygonum multiflorum (PM), has various biological activities, including anti-inflammation and anti-oxidation activities. However, the effect of TSG on asthma has not been studied yet. We examined the effects of TSG on Th2 immune responses using an OVA-induced asthma animal model. OVA-sensitized mice were treated with TSG. 24 h after the last intranasal challenge, airway hyperresponsiveness (AHR) was measured or serum and bronchoalveolar lavage fluid (BALF) were harvested. We measured typical Th1 and Th2 cytokines in serum and BALF. As a result, TSG suppressed Th2 responses, as shown by the lower levels of IL-4, IL-5, total IgE, OVA-specific IgE, and OVA-specific IgG1. On the other hand, TSG increased Th1 responses, as shown by the levels of IFN-gamma. Collectively, these results confirm the potential of TSG for asthma treatment through modulation of inflammatory responses. Considering that the cytotoxic effect of PM extract is due to the cis isomer of TSG, if the effect of TSG on asthma treatment is found to be non-toxic in clinical trials, it would be more effective to use it as a purified component than PM extract as an asthma treatment agent.

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          Most cited references33

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          Discovery and resupply of pharmacologically active plant-derived natural products: A review

          Medicinal plants have historically proven their value as a source of molecules with therapeutic potential, and nowadays still represent an important pool for the identification of novel drug leads. In the past decades, pharmaceutical industry focused mainly on libraries of synthetic compounds as drug discovery source. They are comparably easy to produce and resupply, and demonstrate good compatibility with established high throughput screening (HTS) platforms. However, at the same time there has been a declining trend in the number of new drugs reaching the market, raising renewed scientific interest in drug discovery from natural sources, despite of its known challenges. In this survey, a brief outline of historical development is provided together with a comprehensive overview of used approaches and recent developments relevant to plant-derived natural product drug discovery. Associated challenges and major strengths of natural product-based drug discovery are critically discussed. A snapshot of the advanced plant-derived natural products that are currently in actively recruiting clinical trials is also presented. Importantly, the transition of a natural compound from a “screening hit” through a “drug lead” to a “marketed drug” is associated with increasingly challenging demands for compound amount, which often cannot be met by re-isolation from the respective plant sources. In this regard, existing alternatives for resupply are also discussed, including different biotechnology approaches and total organic synthesis. While the intrinsic complexity of natural product-based drug discovery necessitates highly integrated interdisciplinary approaches, the reviewed scientific developments, recent technological advances, and research trends clearly indicate that natural products will be among the most important sources of new drugs also in the future.
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            Th2 cytokines and asthma — Interleukin-4: its role in the pathogenesis of asthma, and targeting it for asthma treatment with interleukin-4 receptor antagonists

            Interleukin-4 (IL-4) mediates important pro-inflammatory functions in asthma including induction of the IgE isotype switch, expression of vascular cell adhesion molecule-1 (VCAM-1), promotion of eosinophil transmigration across endothelium, mucus secretion, and differentiation of T helper type 2 lymphocytes leading to cytokine release. Asthma is a complex genetic disorder that has been linked to polymorphisms in the IL-4 gene promoter and proteins involved in IL-4 signaling. Soluble recombinant IL-4 receptor lacks transmembrane and cytoplasmic activating domains and can therefore sequester IL-4 without mediating cellular activation. We report the results of initial clinical trials, which demonstrate clinical efficacy of this naturally occurring IL-4 antagonist as a therapeutic agent in asthma.
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              Effects of long-term treatment with an inhaled corticosteroid on growth and pulmonary function in asthmatic children.

              In a controlled prospective study we have measured growth and pulmonary function in children with asthma during long-term treatment with inhaled budesonide and compared these findings with those obtained from children not treated with corticosteroids. Two hundred and sixteen children were followed at 6 monthly intervals for 1-2 years without inhaled budesonide and then for 3-6 years on inhaled budesonide. Sixty-two children treated with theophylline, beta 2-agonists and sodium-cromoglycate but not with inhaled steroids were also followed for 3-7 years (controls). During the period of budesonide therapy the mean daily dose decreased from 710 to 430 micrograms (P < 0.01) and no signs of tachyphylaxis to the treatment were seen. Budesonide treatment was associated with a significant reduction in the number of annual hospital admissions due to acute severe asthma (from 0.03 to 0.004 per child, P < 0.001). In patients not treated with budesonide an annual decrease in % predicted FEV1 of 1-3% was seen. In contrast FEV1 improved significantly with time during budesonide treatment, both compared with the run-in period and with the control group (P < 0.01). Furthermore, there was a significant (P = 0.01) relationship between the duration of asthma at the start of budesonide and the annual increase in FEV1 during budesonide therapy. After 3 years of treatment with budesonide, children who started this therapy later than 5 years after the onset of asthma had significantly lower FEV1 (96%) than the children who received budesonide within the first 2 years after the onset of asthma (101%) (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                12 December 2018
                December 2018
                : 19
                : 12
                : 4013
                Affiliations
                [1 ]College of Pharmacy, Sunchon National University, 255 Jungangno, Suncheon 540-950, Korea; hyh7733@ 123456naver.com (Y.-H.H.); ksz1353@ 123456naver.com (S.-J.K.); hangunkim@ 123456sunchon.ac.kr (H.K.)
                [2 ]Suncheon Research Center for Natural Medicines, Suncheon 540-950, Korea
                Author notes
                [* ]Correspondence: sungtae@ 123456sunchon.ac.kr ; Tel.: +82-61-750-3752; Fax: +82-61-750-3708
                Article
                ijms-19-04013
                10.3390/ijms19124013
                6321435
                30545126
                03d0861e-b2aa-4031-ba29-2b90951c77b7
                © 2018 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 ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 29 October 2018
                : 10 December 2018
                Categories
                Article

                Molecular biology
                2,3,5,4′-tetrahydroxystilbene-2-o-β-d-glucoside (tsg),asthma,airway hyperresponsiveness (ahr),inflammation

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