Magnolol alleviates hypoxia-induced pulmonary vascular remodeling through inhibition of phenotypic transformation in pulmonary arterial smooth muscle cells

Phenotypic transformation and excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) play an important role in vascular remodeling during pulmonary hypertension (PH). Magnolol (5,5′-diallyl-2,2′-dihydroxybiphenyl) is the major bioactive constituent isolated from the bark of Magno...

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Veröffentlicht in:Biomedicine & pharmacotherapy 2022-06, Vol.150, p.113060-113060, Article 113060
Hauptverfasser: Xiao, Xing-Hua, Luo, Fang-Mei, Wang, E.-Li, Fu, Min-Yi, Li, Tao, Jiang, Yue-Ping, Liu, Shao, Peng, Jun, Liu, Bin
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container_title Biomedicine & pharmacotherapy
container_volume 150
creator Xiao, Xing-Hua
Luo, Fang-Mei
Wang, E.-Li
Fu, Min-Yi
Li, Tao
Jiang, Yue-Ping
Liu, Shao
Peng, Jun
Liu, Bin
description Phenotypic transformation and excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) play an important role in vascular remodeling during pulmonary hypertension (PH). Magnolol (5,5′-diallyl-2,2′-dihydroxybiphenyl) is the major bioactive constituent isolated from the bark of Magnolia Officinalis, which has anti-inflammatory, antioxidant, and cardiovascular protection effects. However, the effect of magnolol on the phenotypic transformation of PASMCs is still unknown. This study aims to evaluate the effects of magnolol on the phenotypic transformation of PASMCs induced by hypoxia. In vivo, Sprague Dawley rats were exposed to hypoxia (10% O2) for four weeks to establish a PH model. The results showed that hypoxia treatment led to an increase in right ventricle systolic pressure, Fulton index, collagen production, accompanied by upregulation in the expression of collagen Ⅰ, collagen Ⅲ, OPN, PCNA, CyclinD1, p-JAK2, and p-STAT3, as well as decreases in expression of SM-22α; these changes were attenuated by magnolol. In vitro, the primary cultured PASMCs were exposed to 3% O2 for 48 h to induce phenotypic transformation. Consistent with the findings in vivo, magnolol treatment could prevent the phenotypic transformation and hyperproliferation of PASMCs induced by hypoxia, accompanied by downregulation in the expression of p-JAK2 and p-STAT3. In summary, this study demonstrated that the protective effect of magnolol on PH vascular remodeling is related to the inhibition of phenotypic transformation and hyperproliferation of PASMCs by inhibiting the JAK2/STAT3 pathway. [Display omitted] •Magnolol inhibits vascular remodeling and collagen deposition in hypoxic PH rats.•Magnolol inhibits the hypoxia-induced phenotypic transformation of PASMCs in vitro.•Magnolol inhibits the hypoxia-induced proliferation and migration of PASMCs in vitro.•The mechanism is related to inhibiting the activation of the JAK2/STAT3 pathway.
doi_str_mv 10.1016/j.biopha.2022.113060
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Magnolol (5,5′-diallyl-2,2′-dihydroxybiphenyl) is the major bioactive constituent isolated from the bark of Magnolia Officinalis, which has anti-inflammatory, antioxidant, and cardiovascular protection effects. However, the effect of magnolol on the phenotypic transformation of PASMCs is still unknown. This study aims to evaluate the effects of magnolol on the phenotypic transformation of PASMCs induced by hypoxia. In vivo, Sprague Dawley rats were exposed to hypoxia (10% O2) for four weeks to establish a PH model. The results showed that hypoxia treatment led to an increase in right ventricle systolic pressure, Fulton index, collagen production, accompanied by upregulation in the expression of collagen Ⅰ, collagen Ⅲ, OPN, PCNA, CyclinD1, p-JAK2, and p-STAT3, as well as decreases in expression of SM-22α; these changes were attenuated by magnolol. In vitro, the primary cultured PASMCs were exposed to 3% O2 for 48 h to induce phenotypic transformation. Consistent with the findings in vivo, magnolol treatment could prevent the phenotypic transformation and hyperproliferation of PASMCs induced by hypoxia, accompanied by downregulation in the expression of p-JAK2 and p-STAT3. In summary, this study demonstrated that the protective effect of magnolol on PH vascular remodeling is related to the inhibition of phenotypic transformation and hyperproliferation of PASMCs by inhibiting the JAK2/STAT3 pathway. [Display omitted] •Magnolol inhibits vascular remodeling and collagen deposition in hypoxic PH rats.•Magnolol inhibits the hypoxia-induced phenotypic transformation of PASMCs in vitro.•Magnolol inhibits the hypoxia-induced proliferation and migration of PASMCs in vitro.•The mechanism is related to inhibiting the activation of the JAK2/STAT3 pathway.</description><identifier>ISSN: 0753-3322</identifier><identifier>EISSN: 1950-6007</identifier><identifier>DOI: 10.1016/j.biopha.2022.113060</identifier><identifier>PMID: 35658230</identifier><language>eng</language><publisher>France: Elsevier Masson SAS</publisher><subject>Hypoxia ; JAK2/STAT3 signaling pathway ; Magnolol ; Phenotypic transformation ; Pulmonary hypertension ; Pulmonary vascular remodeling</subject><ispartof>Biomedicine &amp; pharmacotherapy, 2022-06, Vol.150, p.113060-113060, Article 113060</ispartof><rights>2022 The Authors</rights><rights>Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. 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Magnolol (5,5′-diallyl-2,2′-dihydroxybiphenyl) is the major bioactive constituent isolated from the bark of Magnolia Officinalis, which has anti-inflammatory, antioxidant, and cardiovascular protection effects. However, the effect of magnolol on the phenotypic transformation of PASMCs is still unknown. This study aims to evaluate the effects of magnolol on the phenotypic transformation of PASMCs induced by hypoxia. In vivo, Sprague Dawley rats were exposed to hypoxia (10% O2) for four weeks to establish a PH model. The results showed that hypoxia treatment led to an increase in right ventricle systolic pressure, Fulton index, collagen production, accompanied by upregulation in the expression of collagen Ⅰ, collagen Ⅲ, OPN, PCNA, CyclinD1, p-JAK2, and p-STAT3, as well as decreases in expression of SM-22α; these changes were attenuated by magnolol. In vitro, the primary cultured PASMCs were exposed to 3% O2 for 48 h to induce phenotypic transformation. Consistent with the findings in vivo, magnolol treatment could prevent the phenotypic transformation and hyperproliferation of PASMCs induced by hypoxia, accompanied by downregulation in the expression of p-JAK2 and p-STAT3. In summary, this study demonstrated that the protective effect of magnolol on PH vascular remodeling is related to the inhibition of phenotypic transformation and hyperproliferation of PASMCs by inhibiting the JAK2/STAT3 pathway. [Display omitted] •Magnolol inhibits vascular remodeling and collagen deposition in hypoxic PH rats.•Magnolol inhibits the hypoxia-induced phenotypic transformation of PASMCs in vitro.•Magnolol inhibits the hypoxia-induced proliferation and migration of PASMCs in vitro.•The mechanism is related to inhibiting the activation of the JAK2/STAT3 pathway.</description><subject>Hypoxia</subject><subject>JAK2/STAT3 signaling pathway</subject><subject>Magnolol</subject><subject>Phenotypic transformation</subject><subject>Pulmonary hypertension</subject><subject>Pulmonary vascular remodeling</subject><issn>0753-3322</issn><issn>1950-6007</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp9kU2O1DAQhS0EYpqBGyDkJZs0_okTZ4OERgODNIgNrC3HrnTccuxgO63ps3BZ0mRArFjVot6rqlcfQq8p2VNCm3fHfe_iPOo9I4ztKeWkIU_QjnaCVA0h7VO0I63gFeeMXaEXOR8JIaLh8jm64qIRknGyQz-_6EOIPnqsvYeT0wUyHs9zfHC6csEuBiyeFz_FoNMZn3Q2i9cJJ5iiBe_CAZcxxeUwYhdG17viYsBxwPMIIZbz7AwuSYc8xDTp300X_hmoU4HktMd5irGMeFqy8YANeJ9fomeD9hlePdZr9P3j7bebu-r-66fPNx_uK1MTWdawNfTMUGl5XZOuZ9o00nABDJgB0dpe8rZrmNV9Z5gdpDaSsoHaoQYmDfBr9HabO6f4Y4Fc1OTy5QIdIC5ZsablomtF267SepOaFHNOMKg5uWkNoihRFyzqqDYs6oJFbVhW25vHDUs_gf1r-sNhFbzfBLDmPDlIKhsHYX2-S2CKstH9f8Mv-WSmIg</recordid><startdate>202206</startdate><enddate>202206</enddate><creator>Xiao, Xing-Hua</creator><creator>Luo, Fang-Mei</creator><creator>Wang, E.-Li</creator><creator>Fu, Min-Yi</creator><creator>Li, Tao</creator><creator>Jiang, Yue-Ping</creator><creator>Liu, Shao</creator><creator>Peng, Jun</creator><creator>Liu, Bin</creator><general>Elsevier Masson SAS</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202206</creationdate><title>Magnolol alleviates hypoxia-induced pulmonary vascular remodeling through inhibition of phenotypic transformation in pulmonary arterial smooth muscle cells</title><author>Xiao, Xing-Hua ; Luo, Fang-Mei ; Wang, E.-Li ; Fu, Min-Yi ; Li, Tao ; Jiang, Yue-Ping ; Liu, Shao ; Peng, Jun ; Liu, Bin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-604eb2c18d34409b2ac68c35e2e2ce57db837962dab9c2df8ac812f1df4e28ce3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Hypoxia</topic><topic>JAK2/STAT3 signaling pathway</topic><topic>Magnolol</topic><topic>Phenotypic transformation</topic><topic>Pulmonary hypertension</topic><topic>Pulmonary vascular remodeling</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xiao, Xing-Hua</creatorcontrib><creatorcontrib>Luo, Fang-Mei</creatorcontrib><creatorcontrib>Wang, E.-Li</creatorcontrib><creatorcontrib>Fu, Min-Yi</creatorcontrib><creatorcontrib>Li, Tao</creatorcontrib><creatorcontrib>Jiang, Yue-Ping</creatorcontrib><creatorcontrib>Liu, Shao</creatorcontrib><creatorcontrib>Peng, Jun</creatorcontrib><creatorcontrib>Liu, Bin</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biomedicine &amp; pharmacotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xiao, Xing-Hua</au><au>Luo, Fang-Mei</au><au>Wang, E.-Li</au><au>Fu, Min-Yi</au><au>Li, Tao</au><au>Jiang, Yue-Ping</au><au>Liu, Shao</au><au>Peng, Jun</au><au>Liu, Bin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Magnolol alleviates hypoxia-induced pulmonary vascular remodeling through inhibition of phenotypic transformation in pulmonary arterial smooth muscle cells</atitle><jtitle>Biomedicine &amp; pharmacotherapy</jtitle><addtitle>Biomed Pharmacother</addtitle><date>2022-06</date><risdate>2022</risdate><volume>150</volume><spage>113060</spage><epage>113060</epage><pages>113060-113060</pages><artnum>113060</artnum><issn>0753-3322</issn><eissn>1950-6007</eissn><abstract>Phenotypic transformation and excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) play an important role in vascular remodeling during pulmonary hypertension (PH). 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source Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Access via ScienceDirect (Elsevier)
subjects Hypoxia
JAK2/STAT3 signaling pathway
Magnolol
Phenotypic transformation
Pulmonary hypertension
Pulmonary vascular remodeling
title Magnolol alleviates hypoxia-induced pulmonary vascular remodeling through inhibition of phenotypic transformation in pulmonary arterial smooth muscle cells
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