6
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Analyze and Identify Peiminine Target EGFR Improve Lung Function and Alleviate Pulmonary Fibrosis to Prevent Exacerbation of Chronic Obstructive Pulmonary Disease by Phosphoproteomics Analysis

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Chronic obstructive pulmonary disease (COPD) has been a major public health problem and is still a formidable challenge for clinicians. It is urgent to find new compounds for minimizing the risk of disease progression and exacerbation especially in the early phase of COPD. A traditional Chinese medicine (TCM) formula, Chuan Bei Pi Pa dropping pills (CBPP), was tested in this study to investigate its potential mechanisms in preventing the exacerbation of COPD. Phosphoproteomics analysis for a smog stimulated early stage COPD mice model was employed to detect the underlying molecular mechanisms of CBPP. In addition, protein–protein interaction (PPI) and bioinformatics analyses were included to analyze the key proteins and predict the key bioactive compounds. The results indicated that peiminine (PEI) target epidermal growth factor receptor (EGFR) prevented the exacerbation of COPD by inhibiting the EGFR signaling pathway, and ursolic acid (UA) can alleviate inflammation disorders via inhibition of CASP3 on mitogen-activated protein kinase (MAPK) signaling pathway. After in vivo and in vitro evaluations, we revealed that PEI from CBPP, as a lead compound, can improve lung function and alleviate pulmonary fibrosis by acting on the EGFR and MLC2 signaling pathways. Furthermore, the approach described here is an effective way to analyze and identify the bioactive ingredients from a mixture by functional proteomics analysis.

          Related collections

          Most cited references27

          • Record: found
          • Abstract: found
          • Article: not found

          IL-13 signaling through the IL-13alpha2 receptor is involved in induction of TGF-beta1 production and fibrosis.

          Interleukin (IL)-13 is a major inducer of fibrosis in many chronic infectious and autoimmune diseases. In studies of the mechanisms underlying such induction, we found that IL-13 induces transforming growth factor (TGF)-beta(1) in macrophages through a two-stage process involving, first, the induction of a receptor formerly considered to function only as a decoy receptor, IL-13Ralpha(2). Such induction requires IL-13 (or IL-4) and tumor necrosis factor (TNF)-alpha. Second, it involves IL-13 signaling through IL-13Ralpha(2) to activate an AP-1 variant containing c-jun and Fra-2, which then activates the TGFB1 promoter. In vivo, we found that prevention of IL-13Ralpha(2) expression reduced production of TGF-beta(1) in oxazolone-induced colitis and that prevention of IL-13Ralpha(2) expression, Il13ra2 gene silencing or blockade of IL-13Ralpha(2) signaling led to marked downregulation of TGF-beta(1) production and collagen deposition in bleomycin-induced lung fibrosis. These data suggest that IL-13Ralpha(2) signaling during prolonged inflammation is an important therapeutic target for the prevention of TGF-beta(1)-mediated fibrosis.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Ambient air pollution and the risk of acute ischemic stroke.

            The link between daily changes in level of ambient fine particulate matter (PM) air pollution (PM <2.5 μm in diameter [PM(2.5)]) and cardiovascular morbidity and mortality is well established. Whether PM(2.5) levels below current US National Ambient Air Quality Standards also increase the risk of ischemic stroke remains uncertain. We reviewed the medical records of 1705 Boston area patients hospitalized with neurologist-confirmed ischemic stroke and abstracted data on the time of symptom onset and clinical characteristics. The PM(2.5) concentrations were measured at a central monitoring station. We used the time-stratified case-crossover study design to assess the association between the risk of ischemic stroke onset and PM(2.5) levels in the hours and days preceding each event. We examined whether the association with PM(2.5) levels differed by presumed ischemic stroke pathophysiologic mechanism and patient characteristics. The estimated odds ratio (OR) of ischemic stroke onset was 1.34 (95% CI, 1.13-1.58) (P < .001) following a 24-hour period classified as moderate (PM(2.5) 15-40 μg/m(3)) by the US Environmental Protection Agency's (EPA) Air Quality Index compared with a 24-hour period classified as good (≤15 μg/m(3)). Considering PM(2.5) levels as a continuous variable, we found the estimated odds ratio of ischemic stroke onset to be 1.11 (95% CI, 1.03-1.20) (P = .006) per interquartile range increase in PM(2.5) levels (6.4 μg/m(3)). The increase in risk was greatest within 12 to 14 hours of exposure to PM(2.5) and was most strongly associated with markers of traffic-related pollution. These results suggest that exposure to PM(2.5) levels considered generally safe by the US EPA increase the risk of ischemic stroke onset within hours of exposure.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Ursolic acid: an anti- and pro-inflammatory triterpenoid.

              There is growing interest in the elucidation of the biological functions of triterpenoids, ubiquitously distributed throughout the plant kingdom, some of which are used as anticancer and anti-inflammatory agents in Asian countries. Ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, is the major component of some traditional medicine herbs and is well known to possess a wide range of biological functions, such as antioxidative, anti-inflammation, and anticancer activities, that are able to counteract endogenous and exogenous biological stimuli. In contrast to these beneficial properties, some laboratory studies have recently revealed that the effects of UA on normal cells and tissues are occasionally pro-inflammatory. Thus, UA may be designated as a double-edged sword with both positive and negative effects, and further evaluations of the effects of UA on the biological status of target cells or tissues are necessary. This review summarizes previous and current information regarding UA, and provides new insights into the underlying molecular mechanisms of its activities.
                Bookmark

                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                03 July 2019
                2019
                : 10
                : 737
                Affiliations
                [1] 1State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University , Tianjin, China
                [2] 2Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University , Tianjin, China
                [3] 3Tianjin University of Traditional Chinese Medicine , Tianjin, China
                [4] 4First Affiliated Hospital of Henan University of Traditional Chinese Medicine , Zhengzhou, China
                Author notes

                Edited by: Giuseppa Pistritto, Agenzia Italiana del farmaco (AIFA), Italy

                Reviewed by: Min Jiang, Nankai University, China; Guoan Luo, Tsinghua University, China

                *Correspondence: Yuanyuan Hou, houyy@ 123456nankai.edu.cn ; Gang Bai, gangbai@ 123456nankai.edu.cn

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

                Article
                10.3389/fphar.2019.00737
                6620478
                31333459
                d2b2ed2c-565b-4baa-9de2-8e37e45d2eec
                Copyright © 2019 Ma, Liu, Liu, Wang, Chang, Li, Li, Hou and Bai

                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
                : 08 April 2019
                : 07 June 2019
                Page count
                Figures: 5, Tables: 0, Equations: 0, References: 33, Pages: 10, Words: 4584
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                phosphoproteomics,peiminine,egfr,chronic obstructive pulmonary disease,lung function

                Comments

                Comment on this article