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Glycyrrhizin and Long-Term Histopathologic Changes in a Murine Model of Asthma

Abstract Background Licorice root has been widely used to treat bronchial asthma for many years. However, the effect of this herb on lung histopathologic features is not fully understood. Objective In this study, we aimed to determine the effects of oral administration of glycyrrhizin, an active con...

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Published in:Current therapeutic research 2011-12, Vol.72 (6), p.250-261
Main Authors: Hocaoglu, Arzu Babayigit, MD, Karaman, Ozkan, MD, Erge, Duygu Olmez, MD, Erbil, Guven, MD, PhD, Yilmaz, Osman, PhD, Bagriyanik, Alper, MD, PhD, Uzuner, Nevin, MD
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creator Hocaoglu, Arzu Babayigit, MD
Karaman, Ozkan, MD
Erge, Duygu Olmez, MD
Erbil, Guven, MD, PhD
Yilmaz, Osman, PhD
Bagriyanik, Alper, MD, PhD
Uzuner, Nevin, MD
description Abstract Background Licorice root has been widely used to treat bronchial asthma for many years. However, the effect of this herb on lung histopathologic features is not fully understood. Objective In this study, we aimed to determine the effects of oral administration of glycyrrhizin, an active constituent of licorice root, on lung histopathologic features in BALB/c mice, in which the model of chronic asthma was established. Methods Twenty-eight BALB/c mice were divided into 4 groups: control, placebo, dexamethasone, and glycyrrhizin. Mice in the treatment and placebo groups were sensitized with 2 intraperitoneal injections of ovalbumin and then were exposed to aerosolized ovalbumin for 30 minutes per day on 3 days each week for 8 weeks beginning on the 21st study day. In the last week of inhalational exposure, mice in the placebo group received saline and those in the treatment groups received either dexamethasone, 1 mg/kg, or glycyrrhizin, 10 mg/kg, via orogastric gavage for 7 consecutive days. Animals were humanely killed 24 hours after the last ovalbumin and drug exposure. Lung histopathologic findings were evaluated using light and electron microscopy. Results As evaluated in the control, placebo, dexamethasone, and glycyrrhizin groups, respectively, the mean (SD) basement membrane thickness was 306.34 (36.91), 657.52 (98.99), 405.13 (96.1), and 465.01 (121.48) nm; subepithelial smooth muscle thickness was 7.22 (1.37), 11.24 (1.85), 5.62 (1.15), and 7.76 (1.11) μm; epithelium thickness was 19.48 (1.22), 41.62 (5.49), 22.59 (3.18), and 25.54 (4.68) μm; number of mast cells was 1.34 (0.19), 3.62 (0.5), 2.06 (0.77), and 2.77 (0.23)/16,400 μm2 ; and number of goblet cells was 0.32 (0.1), 4.92 (0.82), 0.66 (0.06), and 0.98 (0.15)/100 μm. Evaluation of lung histopathologic features demonstrated that the chronic asthma model of mice was successfully established, with significantly higher numbers of goblet and mast cells and increased thickness of epithelium, basement membrane, and subepithelial smooth muscle layers ( P < 0.001 for all) in the asthma group compared with in the control group. The number of goblet ( P < 0.001) and mast ( P < 0.02) cells and the thickness of basement membrane ( P < 0.001), subepithelial smooth muscle layers ( P ≤ 0.001), and epithelium of the lung ( P < 0.001) were found to be significantly lower in the glycyrrhizin group compared with in the placebo group. When the glycyrrhizin and dexamethasone groups were compared, there was
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However, the effect of this herb on lung histopathologic features is not fully understood. Objective In this study, we aimed to determine the effects of oral administration of glycyrrhizin, an active constituent of licorice root, on lung histopathologic features in BALB/c mice, in which the model of chronic asthma was established. Methods Twenty-eight BALB/c mice were divided into 4 groups: control, placebo, dexamethasone, and glycyrrhizin. Mice in the treatment and placebo groups were sensitized with 2 intraperitoneal injections of ovalbumin and then were exposed to aerosolized ovalbumin for 30 minutes per day on 3 days each week for 8 weeks beginning on the 21st study day. In the last week of inhalational exposure, mice in the placebo group received saline and those in the treatment groups received either dexamethasone, 1 mg/kg, or glycyrrhizin, 10 mg/kg, via orogastric gavage for 7 consecutive days. Animals were humanely killed 24 hours after the last ovalbumin and drug exposure. Lung histopathologic findings were evaluated using light and electron microscopy. Results As evaluated in the control, placebo, dexamethasone, and glycyrrhizin groups, respectively, the mean (SD) basement membrane thickness was 306.34 (36.91), 657.52 (98.99), 405.13 (96.1), and 465.01 (121.48) nm; subepithelial smooth muscle thickness was 7.22 (1.37), 11.24 (1.85), 5.62 (1.15), and 7.76 (1.11) μm; epithelium thickness was 19.48 (1.22), 41.62 (5.49), 22.59 (3.18), and 25.54 (4.68) μm; number of mast cells was 1.34 (0.19), 3.62 (0.5), 2.06 (0.77), and 2.77 (0.23)/16,400 μm2 ; and number of goblet cells was 0.32 (0.1), 4.92 (0.82), 0.66 (0.06), and 0.98 (0.15)/100 μm. Evaluation of lung histopathologic features demonstrated that the chronic asthma model of mice was successfully established, with significantly higher numbers of goblet and mast cells and increased thickness of epithelium, basement membrane, and subepithelial smooth muscle layers ( P &lt; 0.001 for all) in the asthma group compared with in the control group. The number of goblet ( P &lt; 0.001) and mast ( P &lt; 0.02) cells and the thickness of basement membrane ( P &lt; 0.001), subepithelial smooth muscle layers ( P ≤ 0.001), and epithelium of the lung ( P &lt; 0.001) were found to be significantly lower in the glycyrrhizin group compared with in the placebo group. When the glycyrrhizin and dexamethasone groups were compared, there was no statistically significant difference between the 2 groups in the histopathologic parameters, including thickness of basement membrane ( P = 0.514), subepithelial smooth muscle ( P = 0.054), and epithelium ( P = 1.0) and number of mast ( P = 0.075) and goblet ( P = 0.988) cells. Conclusions The results of this study suggest that the group receiving glycyrrhizin had amelioration of all established chronic histopathologic changes of lung in the mouse model of asthma. Further studies are needed to evaluate the efficacy of glycyrrhizin in the management of asthma.</description><identifier>ISSN: 0011-393X</identifier><identifier>EISSN: 1879-0313</identifier><identifier>DOI: 10.1016/j.curtheres.2011.11.002</identifier><identifier>PMID: 24648593</identifier><identifier>CODEN: CTCEA9</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>airway remodeling ; asthma ; BALB/c mice ; Biological and medical sciences ; Chronic obstructive pulmonary disease, asthma ; Glycyrrhiza glabra ; glycyrrhizin ; Internal Medicine ; lung histopathology ; Medical Education ; Medical sciences ; Original Research ; Pharmacology. Drug treatments ; Pneumology</subject><ispartof>Current therapeutic research, 2011-12, Vol.72 (6), p.250-261</ispartof><rights>Elsevier HS Journals, Inc.</rights><rights>2011 Elsevier HS Journals, Inc.</rights><rights>2015 INIST-CNRS</rights><rights>2011 The Authors. Published by Elsevier Inc. All rights reserved. 2011 Elsevier HS Journals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c560t-5920d57584ffbf50eb8cee97db5a2537aee90da38e667f843fbfb808cd87c0233</citedby><cites>FETCH-LOGICAL-c560t-5920d57584ffbf50eb8cee97db5a2537aee90da38e667f843fbfb808cd87c0233</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3957157/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3957157/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=25550259$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24648593$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hocaoglu, Arzu Babayigit, MD</creatorcontrib><creatorcontrib>Karaman, Ozkan, MD</creatorcontrib><creatorcontrib>Erge, Duygu Olmez, MD</creatorcontrib><creatorcontrib>Erbil, Guven, MD, PhD</creatorcontrib><creatorcontrib>Yilmaz, Osman, PhD</creatorcontrib><creatorcontrib>Bagriyanik, Alper, MD, PhD</creatorcontrib><creatorcontrib>Uzuner, Nevin, MD</creatorcontrib><title>Glycyrrhizin and Long-Term Histopathologic Changes in a Murine Model of Asthma</title><title>Current therapeutic research</title><addtitle>Curr Ther Res Clin Exp</addtitle><description>Abstract Background Licorice root has been widely used to treat bronchial asthma for many years. However, the effect of this herb on lung histopathologic features is not fully understood. Objective In this study, we aimed to determine the effects of oral administration of glycyrrhizin, an active constituent of licorice root, on lung histopathologic features in BALB/c mice, in which the model of chronic asthma was established. Methods Twenty-eight BALB/c mice were divided into 4 groups: control, placebo, dexamethasone, and glycyrrhizin. Mice in the treatment and placebo groups were sensitized with 2 intraperitoneal injections of ovalbumin and then were exposed to aerosolized ovalbumin for 30 minutes per day on 3 days each week for 8 weeks beginning on the 21st study day. In the last week of inhalational exposure, mice in the placebo group received saline and those in the treatment groups received either dexamethasone, 1 mg/kg, or glycyrrhizin, 10 mg/kg, via orogastric gavage for 7 consecutive days. Animals were humanely killed 24 hours after the last ovalbumin and drug exposure. Lung histopathologic findings were evaluated using light and electron microscopy. Results As evaluated in the control, placebo, dexamethasone, and glycyrrhizin groups, respectively, the mean (SD) basement membrane thickness was 306.34 (36.91), 657.52 (98.99), 405.13 (96.1), and 465.01 (121.48) nm; subepithelial smooth muscle thickness was 7.22 (1.37), 11.24 (1.85), 5.62 (1.15), and 7.76 (1.11) μm; epithelium thickness was 19.48 (1.22), 41.62 (5.49), 22.59 (3.18), and 25.54 (4.68) μm; number of mast cells was 1.34 (0.19), 3.62 (0.5), 2.06 (0.77), and 2.77 (0.23)/16,400 μm2 ; and number of goblet cells was 0.32 (0.1), 4.92 (0.82), 0.66 (0.06), and 0.98 (0.15)/100 μm. Evaluation of lung histopathologic features demonstrated that the chronic asthma model of mice was successfully established, with significantly higher numbers of goblet and mast cells and increased thickness of epithelium, basement membrane, and subepithelial smooth muscle layers ( P &lt; 0.001 for all) in the asthma group compared with in the control group. The number of goblet ( P &lt; 0.001) and mast ( P &lt; 0.02) cells and the thickness of basement membrane ( P &lt; 0.001), subepithelial smooth muscle layers ( P ≤ 0.001), and epithelium of the lung ( P &lt; 0.001) were found to be significantly lower in the glycyrrhizin group compared with in the placebo group. When the glycyrrhizin and dexamethasone groups were compared, there was no statistically significant difference between the 2 groups in the histopathologic parameters, including thickness of basement membrane ( P = 0.514), subepithelial smooth muscle ( P = 0.054), and epithelium ( P = 1.0) and number of mast ( P = 0.075) and goblet ( P = 0.988) cells. Conclusions The results of this study suggest that the group receiving glycyrrhizin had amelioration of all established chronic histopathologic changes of lung in the mouse model of asthma. Further studies are needed to evaluate the efficacy of glycyrrhizin in the management of asthma.</description><subject>airway remodeling</subject><subject>asthma</subject><subject>BALB/c mice</subject><subject>Biological and medical sciences</subject><subject>Chronic obstructive pulmonary disease, asthma</subject><subject>Glycyrrhiza glabra</subject><subject>glycyrrhizin</subject><subject>Internal Medicine</subject><subject>lung histopathology</subject><subject>Medical Education</subject><subject>Medical sciences</subject><subject>Original Research</subject><subject>Pharmacology. 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Drug treatments</topic><topic>Pneumology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hocaoglu, Arzu Babayigit, MD</creatorcontrib><creatorcontrib>Karaman, Ozkan, MD</creatorcontrib><creatorcontrib>Erge, Duygu Olmez, MD</creatorcontrib><creatorcontrib>Erbil, Guven, MD, PhD</creatorcontrib><creatorcontrib>Yilmaz, Osman, PhD</creatorcontrib><creatorcontrib>Bagriyanik, Alper, MD, PhD</creatorcontrib><creatorcontrib>Uzuner, Nevin, MD</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Current therapeutic research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hocaoglu, Arzu Babayigit, MD</au><au>Karaman, Ozkan, MD</au><au>Erge, Duygu Olmez, MD</au><au>Erbil, Guven, MD, PhD</au><au>Yilmaz, Osman, PhD</au><au>Bagriyanik, Alper, MD, PhD</au><au>Uzuner, Nevin, MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glycyrrhizin and Long-Term Histopathologic Changes in a Murine Model of Asthma</atitle><jtitle>Current therapeutic research</jtitle><addtitle>Curr Ther Res Clin Exp</addtitle><date>2011-12-01</date><risdate>2011</risdate><volume>72</volume><issue>6</issue><spage>250</spage><epage>261</epage><pages>250-261</pages><issn>0011-393X</issn><eissn>1879-0313</eissn><coden>CTCEA9</coden><abstract>Abstract Background Licorice root has been widely used to treat bronchial asthma for many years. However, the effect of this herb on lung histopathologic features is not fully understood. Objective In this study, we aimed to determine the effects of oral administration of glycyrrhizin, an active constituent of licorice root, on lung histopathologic features in BALB/c mice, in which the model of chronic asthma was established. Methods Twenty-eight BALB/c mice were divided into 4 groups: control, placebo, dexamethasone, and glycyrrhizin. Mice in the treatment and placebo groups were sensitized with 2 intraperitoneal injections of ovalbumin and then were exposed to aerosolized ovalbumin for 30 minutes per day on 3 days each week for 8 weeks beginning on the 21st study day. In the last week of inhalational exposure, mice in the placebo group received saline and those in the treatment groups received either dexamethasone, 1 mg/kg, or glycyrrhizin, 10 mg/kg, via orogastric gavage for 7 consecutive days. Animals were humanely killed 24 hours after the last ovalbumin and drug exposure. Lung histopathologic findings were evaluated using light and electron microscopy. Results As evaluated in the control, placebo, dexamethasone, and glycyrrhizin groups, respectively, the mean (SD) basement membrane thickness was 306.34 (36.91), 657.52 (98.99), 405.13 (96.1), and 465.01 (121.48) nm; subepithelial smooth muscle thickness was 7.22 (1.37), 11.24 (1.85), 5.62 (1.15), and 7.76 (1.11) μm; epithelium thickness was 19.48 (1.22), 41.62 (5.49), 22.59 (3.18), and 25.54 (4.68) μm; number of mast cells was 1.34 (0.19), 3.62 (0.5), 2.06 (0.77), and 2.77 (0.23)/16,400 μm2 ; and number of goblet cells was 0.32 (0.1), 4.92 (0.82), 0.66 (0.06), and 0.98 (0.15)/100 μm. Evaluation of lung histopathologic features demonstrated that the chronic asthma model of mice was successfully established, with significantly higher numbers of goblet and mast cells and increased thickness of epithelium, basement membrane, and subepithelial smooth muscle layers ( P &lt; 0.001 for all) in the asthma group compared with in the control group. The number of goblet ( P &lt; 0.001) and mast ( P &lt; 0.02) cells and the thickness of basement membrane ( P &lt; 0.001), subepithelial smooth muscle layers ( P ≤ 0.001), and epithelium of the lung ( P &lt; 0.001) were found to be significantly lower in the glycyrrhizin group compared with in the placebo group. When the glycyrrhizin and dexamethasone groups were compared, there was no statistically significant difference between the 2 groups in the histopathologic parameters, including thickness of basement membrane ( P = 0.514), subepithelial smooth muscle ( P = 0.054), and epithelium ( P = 1.0) and number of mast ( P = 0.075) and goblet ( P = 0.988) cells. Conclusions The results of this study suggest that the group receiving glycyrrhizin had amelioration of all established chronic histopathologic changes of lung in the mouse model of asthma. Further studies are needed to evaluate the efficacy of glycyrrhizin in the management of asthma.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>24648593</pmid><doi>10.1016/j.curtheres.2011.11.002</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record>
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subjects airway remodeling
asthma
BALB/c mice
Biological and medical sciences
Chronic obstructive pulmonary disease, asthma
Glycyrrhiza glabra
glycyrrhizin
Internal Medicine
lung histopathology
Medical Education
Medical sciences
Original Research
Pharmacology. Drug treatments
Pneumology
title Glycyrrhizin and Long-Term Histopathologic Changes in a Murine Model of Asthma
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