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      Drug Design, Development and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the design and development of drugs, as well as the clinical outcomes, patient safety, and programs targeted at the effective and safe use of medicines. Sign up for email alerts here.

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      Network Pharmacology Integrated with Transcriptomics Analysis Reveals Ermiao Wan Alleviates Atopic Dermatitis via Suppressing MAPK and Activating the EGFR/AKT Signaling

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          Abstract

          Background

          Ermiao Wan (EMW) is commonly used to treat atopic dermatitis (AD) in China. However, the pharmacological mechanisms underlying the action of EMW against AD remain unclear.

          Purpose

          We aimed to determine the mechanisms underlying the effectiveness of EMW in the treatment of AD.

          Methods

          We evaluated the effect of EMW on AD induced by dinitrochlorobenzene (DNCB) in BALB/C mice. To clarify the key components of EMW in AD treatment, the main components of EMW were identified using HPLC. Serum pharmacochemistry was used to analyze the absorbed ingredients from blood. Based on the phytochemical results, network pharmacology and molecular docking were used to predict the action of EMW. Skin transcriptomic analysis was used to validate the network pharmacology results. RT-qPCR,ELISA, and immunohistochemical were performed to validate the results of skin transcriptomics.

          Results

          EMW improved the symptoms of AD, with less rashes, less spontaneous scratching, less inflammatory cell infiltration, and fewer allergic reactions. The established HPLC method is simple and reliable. Chlorogenic acid, phellodendrine, magnoflorine, jatrorrhizine, palmatine, berberine, and atractylodin were the key effective ingredients with a high blood concentration. Fifty-seven primary causal targets of EMW against AD were identified. These targets are mainly involved in ErbB signaling pathways including EGFR, AKT1, MAPK8, JUN, MAPK1. Molecular docking showed that EGFR, AKT1, MAPK8, JUN, MAPK1 had good binding force with EMW. In AD mice, EMW regulated the EGFR/AKT signaling through upregulation of Grb2, GAB1, Raf-1, EGFR, and AKT, and downregulation of MAPK1 and JUN, compared to that in the MD group.

          Conclusion

          EMW could alleviate AD through activating EGFR/AKT signaling and suppressing MAPK. This study provides a theoretical basis for the clinical use of EMW.

          Most cited references48

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          Traditional Chinese medicine network pharmacology: theory, methodology and application.

          Shao Li, Bo Zhang (2013)
          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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            Skin damage among health care workers managing coronavirus disease-2019

            Jiajia Lan, Zexing Song, Xiaoping Miao … (2020)
            To the Editor: Since the outbreak of coronavirus disease-2019 (COVID-19) in December 2019, more than 200,000 health care workers from all over China have been participating in the fight against this highly contagious disease in Hubei province, which is the center of infection in China. Skin damage caused by enhanced infection-prevention measures among health care workers, which could reduce their enthusiasm for overloaded work and make them anxious, has been reported frequently. Previous studies have revealed that hand eczema is quite common in health care workers, 1 , 2 and the risk factors include frequent hand hygiene and wearing gloves for a long time. 3 , 4 Considering the frequent hand hygiene and long-time wearing of tertiary protective devices (N95 mask, goggles, face shield, and double layers of gloves) among health care workers during the epidemic period of COVID-19, we aimed to estimate the prevalence, clinical features, and risk factors of this skin damage among them. From January to February 2020, self-administered online questionnaires were distributed to 700 individuals, consisting of physicians and nurses who worked in the designated departments of tertiary hospitals in Hubei, China. The questionnaire included questions about the condition of skin damage and the frequency or duration of several infection-prevention measures (Supplemental Material 1, available via Mendeley at https://data.mendeley.com/datasets/zknvry83v5/2). Finally, 542 individuals (Supplemental Material 2) completed the study (response rate, 77.4%), with 71.4% (387 of 542) working in isolation wards and 28.6% (155 of 542) working in fever clinics. The general prevalence rate of skin damage caused by enhanced infection-prevention measures was 97.0% (526 of 542) among first-line health care workers. The affected sites included the nasal bridge, hands, cheek, and forehead, with the nasal bridge the most commonly affected (83.1%). Among a series of symptoms and signs, dryness/tightness and desquamation were the most common symptom (70.3%) and sign (62.2%), respectively (Table I ). The health care workers who wore some medical devices more than 6 hours had higher risks of skin damage in corresponding sites than those who did for less time (N95 masks: odds ratio [OR], 2.02; 95% confidence interval [CI], 1.35-3.01; P  10 times daily) hand hygiene could increase the risk of hand skin damage (OR, 2.17; 95% CI, 1.38-3.43; P  6 h/d 317 (58.5) Cheek: 259 (81.7) 2.02 1.35-3.01 6 h/d 265 (58.8) Nasal bridge: 233 (87.9) 2.32 1.41-3.83 6 h/d 157 (59.2) Forehead: 92 (58.6) 1.52 0.93-2.50 .66 Gloves 113∗ ≤6 h/d 52 (46.0) Hands: 29 (55.8) 1 [Ref] >6 h/d 61 (54.0) Hands: 39 (63.9) 1.41 0.66-3.00 .44 321† ≤6 h/d 131 (40.8) Hands: 100 (76.3) 1 [Ref] >6 h/d 190 (59.2) Hands: 146 (76.8) 1.03 0.61-1.74 >.99 Hand hygiene 434 ≤10 times/d 113 (26.0) Hands: 68 (60.2) 1 [Ref] >10 times/d 321 (74.0) Hands: 246 (76.6) 2.17 1.38-3.43 10 times/d. Our study has some limitations. Firstly, we only studied 1 site with a single exposure factor, but some sites could be related to more than 1 factor. The nasal bridge, for example, could be compressed by the N95 mask and goggles simultaneously, although goggles were the main factor. Secondly, possible risk factors such as participants wearing the N95 mask after work in daily life were not included. In conclusion, our study demonstrated that the prevalence of skin damage of first-line health care workers was very high. Moreover, we found that longer exposure time was a significant risk factor, which highlights that the working time of first-line staff should be arranged reasonably. Besides, prophylactic dressings could be considered to alleviate the device-related pressure injuries, according to a prior study. 5
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              New insights into the epidemiology of childhood atopic dermatitis.

              C Flohr, Graham Mann (2013)
              There is a growing desire to explain the worldwide rise in the prevalence of atopic dermatitis (AD). Trend data on the burden of AD suggest that the picture in the developing world may soon resemble that of wealthier nations, where AD affects over 20% of children. This, combined with significant variations in prevalence within countries, emphasizes the importance of environmental factors. Many hypotheses have been explored, from the modulation of immune priming by hygiene, gut microbiota diversity, and exposure to endotoxins through farm animals to the effects of pollution, climate, and diet. The discovery of the filaggrin skin barrier gene and its importance in AD development and severity has brought the focus on gene-environment interactions and the identification of environmental factors that impact on skin barrier function. This article reviews our current understanding of the epidemiology of AD, with an emphasis on the findings reported in the international literature over the last 5 years. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Drug Des Devel Ther
                Journal ID (iso-abbrev): Drug Des Devel Ther
                Journal ID (publisher-id): dddt
                Title: Drug Design, Development and Therapy
                Publisher: Dove
                ISSN (Electronic): 1177-8881
                Publication date (Electronic): 21 December 2022
                Publication date Collection: 2022
                Volume: 16
                Pages: 4325-4341
                Affiliations
                [1 ]School of Traditional Chinese Medicine, Southern Medical University , Guangzhou, 510515, People’s Republic of China
                [2 ]Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University , Guangzhou, 510515, People’s Republic of China
                [3 ]Guangdong Provincial Engineering Laboratory of Chinese Medicine Preparation Technology , Guangzhou, 510515, People’s Republic of China
                [4 ]School of Pharmaceutical Sciences, Guilin Medical University , Guilin, 541199, People’s Republic of China
                Author notes
                Correspondence: Xiao-Mei Tan, Tel/Fax + 86-020-61648265, Email tanxm_smu@163.com
                Author information
                https://orcid.org/http://orcid.org/0000-0003-2841-1795
                Article
                Publisher ID: 384927
                DOI: 10.2147/DDDT.S384927
                PMC ID: 9790806
                PubMed ID: 36578822
                SO-VID: 01702b64-4f0f-41d8-a4d3-5427429428ee
                Copyright statement: © 2022 Xia et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 10 August 2022
                Date accepted : 08 December 2022
                Page count
                Figures: 10, Tables: 3, References: 48, Pages: 17
                Funding
                Funded by: the National Key R&D Program of China;
                This work is supported by grants from the National Key R&D Program of China (2018YFC1704500; 2018YFC1704503).
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: ermiao wan,atopic dermatitis,network pharmacology,serum pharmacochemistry,skin transcriptome,egfr/akt signaling
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: ermiao wan, atopic dermatitis, network pharmacology, serum pharmacochemistry, skin transcriptome, egfr/akt signaling

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