Paeonol attenuates heart failure induced by transverse aortic constriction via ERK1/2 signalling

Paeonol (PAE) is the main phytochemical from Cortex Moutan. Its main pharmacological effects are anti-inflammatory and antioxidant, but its cardioprotective effect is unclear. The study investigates the effects and underlying mechanisms of PAE on transverse aortic constriction (TAC)-induced heart fa...

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Veröffentlicht in:Pharmaceutical biology 2022-12, Vol.60 (1), p.562-569
Hauptverfasser: Chen, Xu, Zhang, Zhiyu, Zhang, Xiaowei, Jia, Zhi, Liu, Jun, Chen, Xinpei, Xu, Aiqing, Liang, Xue, Li, Guangping
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container_issue 1
container_start_page 562
container_title Pharmaceutical biology
container_volume 60
creator Chen, Xu
Zhang, Zhiyu
Zhang, Xiaowei
Jia, Zhi
Liu, Jun
Chen, Xinpei
Xu, Aiqing
Liang, Xue
Li, Guangping
description Paeonol (PAE) is the main phytochemical from Cortex Moutan. Its main pharmacological effects are anti-inflammatory and antioxidant, but its cardioprotective effect is unclear. The study investigates the effects and underlying mechanisms of PAE on transverse aortic constriction (TAC)-induced heart failure (HF) in mice. C57BL/6 mice were randomly divided into five groups: sham, TAC, PAE10 (TAC + PAE 10 mg/kg), PAE20 (TAC + PAE 20 mg/kg) and PAE 50 (TAC + PAE 50 mg/kg). Paeonol was intragastrically administered to mice for 4 weeks. Mice were anaesthetized with pentobarbital sodium and underwent cardiac echocardiography using echocardiography system. Serum levels of atrial natriuretic peptide (ANP), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). Myocardial apoptosis was detected with terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining. Haematoxylin-eosin (H&E) and Masson's staining were used for histopathological evaluation. Western and quantitative real-time PCR (qRT-PCR) were performed to detect levels of apoptosis and fibrosis-related proteins. Echocardiography showed PAE improved cardiac function (LVEF: TAC, 52.3±6.8%; PAE20, 65.8±3.6%; PAE50, 71.4±2.5%) and H&E staining showed PAE alleviated myocardial injury (TAC: 1170.3 ± 134.6 μm 2 ; PAE50: 576.0 ± 53.5 μm 2 ). Western and qRT-PCR results showed that PAE down-regulated the levels of ANP, BNP and α-MHC. In addition, TUNEL and western results showed PAE significantly inhibited apoptosis. Masson and western results showed PAE inhibited cardiac hypertrophy. Western results showed the ERK1/2/JNK pathway could be inhibited by PAE. Paeonol regulates ERK1/2/JNK to improve cardiac function, which provides theoretical support for the extensive clinical treatment of HF.
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Its main pharmacological effects are anti-inflammatory and antioxidant, but its cardioprotective effect is unclear. The study investigates the effects and underlying mechanisms of PAE on transverse aortic constriction (TAC)-induced heart failure (HF) in mice. C57BL/6 mice were randomly divided into five groups: sham, TAC, PAE10 (TAC + PAE 10 mg/kg), PAE20 (TAC + PAE 20 mg/kg) and PAE 50 (TAC + PAE 50 mg/kg). Paeonol was intragastrically administered to mice for 4 weeks. Mice were anaesthetized with pentobarbital sodium and underwent cardiac echocardiography using echocardiography system. Serum levels of atrial natriuretic peptide (ANP), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). Myocardial apoptosis was detected with terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining. Haematoxylin-eosin (H&amp;E) and Masson's staining were used for histopathological evaluation. Western and quantitative real-time PCR (qRT-PCR) were performed to detect levels of apoptosis and fibrosis-related proteins. Echocardiography showed PAE improved cardiac function (LVEF: TAC, 52.3±6.8%; PAE20, 65.8±3.6%; PAE50, 71.4±2.5%) and H&amp;E staining showed PAE alleviated myocardial injury (TAC: 1170.3 ± 134.6 μm 2 ; PAE50: 576.0 ± 53.5 μm 2 ). Western and qRT-PCR results showed that PAE down-regulated the levels of ANP, BNP and α-MHC. In addition, TUNEL and western results showed PAE significantly inhibited apoptosis. Masson and western results showed PAE inhibited cardiac hypertrophy. Western results showed the ERK1/2/JNK pathway could be inhibited by PAE. Paeonol regulates ERK1/2/JNK to improve cardiac function, which provides theoretical support for the extensive clinical treatment of HF.</description><identifier>ISSN: 1388-0209</identifier><identifier>EISSN: 1744-5116</identifier><identifier>DOI: 10.1080/13880209.2022.2040543</identifier><identifier>PMID: 35249458</identifier><language>eng</language><publisher>England: Taylor &amp; Francis</publisher><subject>Acetophenones - pharmacology ; Animals ; Aorta ; Aorta - physiopathology ; Apoptosis ; Apoptosis - drug effects ; Atrial natriuretic peptide ; cardiac fibrosis ; Cardiac function ; Cardiomegaly - prevention &amp; control ; Cardiotonic Agents - pharmacology ; Congestive heart failure ; Constriction, Pathologic - complications ; Disease Models, Animal ; DNA nucleotidylexotransferase ; Echocardiography ; Enzyme-linked immunosorbent assay ; ERK1/2 ; Extracellular signal-regulated kinase ; Fibrosis ; Heart failure ; Heart Failure - drug therapy ; Heart Failure - physiopathology ; Hypertrophy ; Inflammation ; Interleukin 6 ; Labeling ; Major histocompatibility complex ; Male ; MAP Kinase Signaling System - drug effects ; Mice ; Mice, Inbred C57BL ; Paeonol ; Pentobarbital ; Serum levels ; Signal transduction ; Signal Transduction - drug effects ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α ; Tumors</subject><ispartof>Pharmaceutical biology, 2022-12, Vol.60 (1), p.562-569</ispartof><rights>2022 The Author(s). Published by Informa UK Limited, trading as Taylor &amp; Francis Group. 2022</rights><rights>2022 The Author(s). Published by Informa UK Limited, trading as Taylor &amp; Francis Group. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 The Author(s). Published by Informa UK Limited, trading as Taylor &amp; Francis Group. 2022 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c562t-c8747bde3ab4aacbbd757726a4640492f9fb9d64ace028bdf838ed2f7825e4603</citedby><cites>FETCH-LOGICAL-c562t-c8747bde3ab4aacbbd757726a4640492f9fb9d64ace028bdf838ed2f7825e4603</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/PMC8903794/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8903794/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,866,887,2106,27511,27933,27934,53800,53802,59152,59153</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35249458$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Xu</creatorcontrib><creatorcontrib>Zhang, Zhiyu</creatorcontrib><creatorcontrib>Zhang, Xiaowei</creatorcontrib><creatorcontrib>Jia, Zhi</creatorcontrib><creatorcontrib>Liu, Jun</creatorcontrib><creatorcontrib>Chen, Xinpei</creatorcontrib><creatorcontrib>Xu, Aiqing</creatorcontrib><creatorcontrib>Liang, Xue</creatorcontrib><creatorcontrib>Li, Guangping</creatorcontrib><title>Paeonol attenuates heart failure induced by transverse aortic constriction via ERK1/2 signalling</title><title>Pharmaceutical biology</title><addtitle>Pharm Biol</addtitle><description>Paeonol (PAE) is the main phytochemical from Cortex Moutan. Its main pharmacological effects are anti-inflammatory and antioxidant, but its cardioprotective effect is unclear. The study investigates the effects and underlying mechanisms of PAE on transverse aortic constriction (TAC)-induced heart failure (HF) in mice. C57BL/6 mice were randomly divided into five groups: sham, TAC, PAE10 (TAC + PAE 10 mg/kg), PAE20 (TAC + PAE 20 mg/kg) and PAE 50 (TAC + PAE 50 mg/kg). Paeonol was intragastrically administered to mice for 4 weeks. Mice were anaesthetized with pentobarbital sodium and underwent cardiac echocardiography using echocardiography system. Serum levels of atrial natriuretic peptide (ANP), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). Myocardial apoptosis was detected with terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining. Haematoxylin-eosin (H&amp;E) and Masson's staining were used for histopathological evaluation. Western and quantitative real-time PCR (qRT-PCR) were performed to detect levels of apoptosis and fibrosis-related proteins. Echocardiography showed PAE improved cardiac function (LVEF: TAC, 52.3±6.8%; PAE20, 65.8±3.6%; PAE50, 71.4±2.5%) and H&amp;E staining showed PAE alleviated myocardial injury (TAC: 1170.3 ± 134.6 μm 2 ; PAE50: 576.0 ± 53.5 μm 2 ). Western and qRT-PCR results showed that PAE down-regulated the levels of ANP, BNP and α-MHC. In addition, TUNEL and western results showed PAE significantly inhibited apoptosis. Masson and western results showed PAE inhibited cardiac hypertrophy. Western results showed the ERK1/2/JNK pathway could be inhibited by PAE. Paeonol regulates ERK1/2/JNK to improve cardiac function, which provides theoretical support for the extensive clinical treatment of HF.</description><subject>Acetophenones - pharmacology</subject><subject>Animals</subject><subject>Aorta</subject><subject>Aorta - physiopathology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Atrial natriuretic peptide</subject><subject>cardiac fibrosis</subject><subject>Cardiac function</subject><subject>Cardiomegaly - prevention &amp; control</subject><subject>Cardiotonic Agents - pharmacology</subject><subject>Congestive heart failure</subject><subject>Constriction, Pathologic - complications</subject><subject>Disease Models, Animal</subject><subject>DNA nucleotidylexotransferase</subject><subject>Echocardiography</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>ERK1/2</subject><subject>Extracellular signal-regulated kinase</subject><subject>Fibrosis</subject><subject>Heart failure</subject><subject>Heart Failure - drug therapy</subject><subject>Heart Failure - physiopathology</subject><subject>Hypertrophy</subject><subject>Inflammation</subject><subject>Interleukin 6</subject><subject>Labeling</subject><subject>Major histocompatibility complex</subject><subject>Male</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Paeonol</subject><subject>Pentobarbital</subject><subject>Serum levels</subject><subject>Signal transduction</subject><subject>Signal Transduction - drug effects</subject><subject>Tumor necrosis factor-TNF</subject><subject>Tumor necrosis factor-α</subject><subject>Tumors</subject><issn>1388-0209</issn><issn>1744-5116</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>0YH</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>DOA</sourceid><recordid>eNp9kk1vVCEUhm-MxtbqT9CQuHEzLd9wN8amqdrYRGN0jVw-pkwYqMAdM_9expk21oUbIPCc95zDeYfhJYKnCEp4hoiUEMPxFEOM-0Iho-TRcIwEpQuGEH_cz51Z7KCj4VmtKwghI4Q9HY4Iw3SkTB4PP75ol1OOQLfm0qybq-DG6dKA1yHOxYGQ7GycBdMWtKJT3bhSHdC5tGCAyam2EkwLOYFN0ODy6yd0hkENy6RjDGn5fHjidazuxWE_Gb6_v_x28XFx_fnD1cX59cIwjtvCSEHFZB3RE9XaTJMVTAjMNeUU0hH70U-j5VQbB7GcrJdEOou9kJg5yiE5Ga72ujbrlbotYa3LVmUd1J-LXJZK70qOTgkuiYDQTqNH1EyjZEgaaqTBTHIufdd6u9e6nae1s8al3nl8IPrwJYUbtcwbJUdIxEi7wJuDQMk_Z1ebWodqXIw6uTxXhTnhUtI-gY6-_gdd5bn0z-uU4IhijLjoFNtTpuRai_P3xSCodn5Qd35QOz-ogx963Ku_O7mPujNAB97tgZB8Lmv9K5doVdPbmIvv4zahKvL_HL8Bn7vFKg</recordid><startdate>202212</startdate><enddate>202212</enddate><creator>Chen, Xu</creator><creator>Zhang, Zhiyu</creator><creator>Zhang, Xiaowei</creator><creator>Jia, Zhi</creator><creator>Liu, Jun</creator><creator>Chen, Xinpei</creator><creator>Xu, Aiqing</creator><creator>Liang, Xue</creator><creator>Li, Guangping</creator><general>Taylor &amp; 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Jia, Zhi ; Liu, Jun ; Chen, Xinpei ; Xu, Aiqing ; Liang, Xue ; Li, Guangping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c562t-c8747bde3ab4aacbbd757726a4640492f9fb9d64ace028bdf838ed2f7825e4603</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Acetophenones - pharmacology</topic><topic>Animals</topic><topic>Aorta</topic><topic>Aorta - physiopathology</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Atrial natriuretic peptide</topic><topic>cardiac fibrosis</topic><topic>Cardiac function</topic><topic>Cardiomegaly - prevention &amp; control</topic><topic>Cardiotonic Agents - pharmacology</topic><topic>Congestive heart failure</topic><topic>Constriction, Pathologic - complications</topic><topic>Disease Models, Animal</topic><topic>DNA nucleotidylexotransferase</topic><topic>Echocardiography</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>ERK1/2</topic><topic>Extracellular signal-regulated kinase</topic><topic>Fibrosis</topic><topic>Heart failure</topic><topic>Heart Failure - drug therapy</topic><topic>Heart Failure - physiopathology</topic><topic>Hypertrophy</topic><topic>Inflammation</topic><topic>Interleukin 6</topic><topic>Labeling</topic><topic>Major histocompatibility complex</topic><topic>Male</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Paeonol</topic><topic>Pentobarbital</topic><topic>Serum levels</topic><topic>Signal transduction</topic><topic>Signal Transduction - drug effects</topic><topic>Tumor necrosis factor-TNF</topic><topic>Tumor necrosis factor-α</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Xu</creatorcontrib><creatorcontrib>Zhang, Zhiyu</creatorcontrib><creatorcontrib>Zhang, Xiaowei</creatorcontrib><creatorcontrib>Jia, Zhi</creatorcontrib><creatorcontrib>Liu, Jun</creatorcontrib><creatorcontrib>Chen, Xinpei</creatorcontrib><creatorcontrib>Xu, Aiqing</creatorcontrib><creatorcontrib>Liang, Xue</creatorcontrib><creatorcontrib>Li, Guangping</creatorcontrib><collection>Access via Taylor &amp; 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Its main pharmacological effects are anti-inflammatory and antioxidant, but its cardioprotective effect is unclear. The study investigates the effects and underlying mechanisms of PAE on transverse aortic constriction (TAC)-induced heart failure (HF) in mice. C57BL/6 mice were randomly divided into five groups: sham, TAC, PAE10 (TAC + PAE 10 mg/kg), PAE20 (TAC + PAE 20 mg/kg) and PAE 50 (TAC + PAE 50 mg/kg). Paeonol was intragastrically administered to mice for 4 weeks. Mice were anaesthetized with pentobarbital sodium and underwent cardiac echocardiography using echocardiography system. Serum levels of atrial natriuretic peptide (ANP), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). Myocardial apoptosis was detected with terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining. Haematoxylin-eosin (H&amp;E) and Masson's staining were used for histopathological evaluation. Western and quantitative real-time PCR (qRT-PCR) were performed to detect levels of apoptosis and fibrosis-related proteins. Echocardiography showed PAE improved cardiac function (LVEF: TAC, 52.3±6.8%; PAE20, 65.8±3.6%; PAE50, 71.4±2.5%) and H&amp;E staining showed PAE alleviated myocardial injury (TAC: 1170.3 ± 134.6 μm 2 ; PAE50: 576.0 ± 53.5 μm 2 ). Western and qRT-PCR results showed that PAE down-regulated the levels of ANP, BNP and α-MHC. In addition, TUNEL and western results showed PAE significantly inhibited apoptosis. Masson and western results showed PAE inhibited cardiac hypertrophy. Western results showed the ERK1/2/JNK pathway could be inhibited by PAE. Paeonol regulates ERK1/2/JNK to improve cardiac function, which provides theoretical support for the extensive clinical treatment of HF.</abstract><cop>England</cop><pub>Taylor &amp; Francis</pub><pmid>35249458</pmid><doi>10.1080/13880209.2022.2040543</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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subjects Acetophenones - pharmacology
Animals
Aorta
Aorta - physiopathology
Apoptosis
Apoptosis - drug effects
Atrial natriuretic peptide
cardiac fibrosis
Cardiac function
Cardiomegaly - prevention & control
Cardiotonic Agents - pharmacology
Congestive heart failure
Constriction, Pathologic - complications
Disease Models, Animal
DNA nucleotidylexotransferase
Echocardiography
Enzyme-linked immunosorbent assay
ERK1/2
Extracellular signal-regulated kinase
Fibrosis
Heart failure
Heart Failure - drug therapy
Heart Failure - physiopathology
Hypertrophy
Inflammation
Interleukin 6
Labeling
Major histocompatibility complex
Male
MAP Kinase Signaling System - drug effects
Mice
Mice, Inbred C57BL
Paeonol
Pentobarbital
Serum levels
Signal transduction
Signal Transduction - drug effects
Tumor necrosis factor-TNF
Tumor necrosis factor-α
Tumors
title Paeonol attenuates heart failure induced by transverse aortic constriction via ERK1/2 signalling
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