Ershen Zhenwu Decoction suppresses myocardial fibrosis of chronic heart failure with heart–kidney Yang deficiency by down-regulating the Ras Homolog Gene Family Member A/Rho-Associated Coiled-Coil Kinases signaling pathway
The therapeutic efficacy of Ershen Zhenwu Decoction (ESZWD)—a famous formulation from Xin'an for patients with chronic heart failure heart–kidney Yang deficiency (CHF-HKYD)—is well established. Still, the underlying molecular mechanism is not clear. This study investigated mechanisms by which E...
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creator | Cheng, Dan Sheng, Sheng Hu, Jing Cai, Shanshan Liu, Yan Gan, Ruixi Zhu, Zhenpeng Ge, Lan Chen, Weidong Cheng, Xiaoyu |
description | The therapeutic efficacy of Ershen Zhenwu Decoction (ESZWD)—a famous formulation from Xin'an for patients with chronic heart failure heart–kidney Yang deficiency (CHF-HKYD)—is well established. Still, the underlying molecular mechanism is not clear.
This study investigated mechanisms by which ESZWD suppresses cardiac pathology, including myocardial fibrosis, in CHF-HKYD model rats and Ang II-stimulated cardiac fibroblasts (CFs).
The components in ESZWD were analyzed by ultra-high-performance liquid chromatography coupled with Quadrupole Time-Of-Flight mass spectrometry (UHPLC-Q-TOF-MS). CHF-HKYD model was established in the male Sprague–Dawley rats through bilateral thyroidectomy and intraperitoneal administration of 0.02% doxorubicin (DOX), twice weekly for 3 weeks. Subsequently, the CHF-HKYD model rats were randomly categorized into the Model, ESZWD-L (3.96 g/kg/d ESZWD), ESZWD-M (7.92 g/kg/d ESZWD), ESZWD-H (15.84 g/kg/d ESZWD), and Sac/Val (68 mg/kg/d sacubitril/valsartan) groups and treated daily for 4 weeks. As a control, the sham surgery group (Sham) was used. Primary cardiac fibroblasts (CFs) were categorized into Control, Model, ESZWD, and Sac/Val groups. Then, the CFs were stimulated with Ang-II. The ESZWD and Sac/Val groups were incubated with different concentrations of drug-containing sera and their effects on CF viability were assessed via the CCK-8 assay. The ESZWD and Sac/Val groups received drug-containing serum concentrations determined by CCK-8 assay results. The cardioprotective effects of ESZWD were determined using echocardiography, Hematoxylin & Eosin (H&E) staining, Masson staining, and Sirius red staining, and the Enzyme Linked Immunosorbent Assay (ELISA). ESZWD's effects on the Ras Homolog Gene Family Member A (RhoA)/Rho-Associated Coiled-Coil Kinases (ROCKs) signaling pathway and myocardial fibrosis were assessed by Western blotting and Quantitative Real-Time PCR (qRT-PCR) analyses. Immunofluorescence was used to observe fibrotic markers in CFs.
ESZWD treatment improved cardiac function in the CHF-HKYD rats by significantly reducing myocardial fibrosis and ventricular remodeling. ESZWD treatment increased the rats' body temperature (Tb) and 24-h urine volume, left ventricular ejection fraction (LVEF) and LV fractional shortening (LVFS), and decreased LV internal systolic diameter (LVIDs), LV internal diastolic diameter (LVIDd), and heart weight/body weight (HW/BW) compared to the Model group. In comparison to the model rats, ESZW |
doi_str_mv | 10.1016/j.jep.2024.119146 |
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fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3132366740</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0378874124014454</els_id><sourcerecordid>3132366740</sourcerecordid><originalsourceid>FETCH-LOGICAL-c1501-4c14f6c118ba5062edbb4148473f424257a51f12919471b9226b023a227e0ee53</originalsourceid><addsrcrecordid>eNp9kc-O1DAMxisEYoeFB-CCfOTS2ThNm444jYb9g1iEtIIDXKI0dacZ2qYkLaPeeAdeEPEktMzCkYst2Z8_2f5F0XNka2SYXRzWB-rXnHGxRtygyB5EK8wlj2Uqk4fRiiUyj3Mp8Cx6EsKBMSZRsMfRWbJJc4YJrqKflz7U1MHnORxHeE3GmcG6DsLY955CoADt5Iz2pdUNVLbwLtgArgJTe9dZAzVpP0ClbTN6gqMd6lPp1_cfX2zZ0QSfdLeHkiprLHVmgmKC0h272NN-bPRg5-5QE9zpADeudY3bwzV1BFe6tc0E76gtyMP24q528TYEZ6weqISdsw2V8ZLgre30smuw-043i2Ovh_qop6fRo0o3gZ7d5_Po49Xlh91NfPv--s1uexsbTBnGwqCoMoOYFzplGaeyKASKXMikElzwVOoUK-Qb3AiJxYbzrGA80ZxLYkRpch69PPn23n0dKQyqtcFQ0-iO3BhUgglPskwKNkvxJDXzL4OnSvXettpPCplawKqDmsGqBaw6gZ1nXtzbj0VL5b-JvyRnwauTgOYjv1nyKvz5NpXWkxlU6ex_7H8DP_K4NA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3132366740</pqid></control><display><type>article</type><title>Ershen Zhenwu Decoction suppresses myocardial fibrosis of chronic heart failure with heart–kidney Yang deficiency by down-regulating the Ras Homolog Gene Family Member A/Rho-Associated Coiled-Coil Kinases signaling pathway</title><source>Access via ScienceDirect (Elsevier)</source><creator>Cheng, Dan ; Sheng, Sheng ; Hu, Jing ; Cai, Shanshan ; Liu, Yan ; Gan, Ruixi ; Zhu, Zhenpeng ; Ge, Lan ; Chen, Weidong ; Cheng, Xiaoyu</creator><creatorcontrib>Cheng, Dan ; Sheng, Sheng ; Hu, Jing ; Cai, Shanshan ; Liu, Yan ; Gan, Ruixi ; Zhu, Zhenpeng ; Ge, Lan ; Chen, Weidong ; Cheng, Xiaoyu</creatorcontrib><description>The therapeutic efficacy of Ershen Zhenwu Decoction (ESZWD)—a famous formulation from Xin'an for patients with chronic heart failure heart–kidney Yang deficiency (CHF-HKYD)—is well established. Still, the underlying molecular mechanism is not clear.
This study investigated mechanisms by which ESZWD suppresses cardiac pathology, including myocardial fibrosis, in CHF-HKYD model rats and Ang II-stimulated cardiac fibroblasts (CFs).
The components in ESZWD were analyzed by ultra-high-performance liquid chromatography coupled with Quadrupole Time-Of-Flight mass spectrometry (UHPLC-Q-TOF-MS). CHF-HKYD model was established in the male Sprague–Dawley rats through bilateral thyroidectomy and intraperitoneal administration of 0.02% doxorubicin (DOX), twice weekly for 3 weeks. Subsequently, the CHF-HKYD model rats were randomly categorized into the Model, ESZWD-L (3.96 g/kg/d ESZWD), ESZWD-M (7.92 g/kg/d ESZWD), ESZWD-H (15.84 g/kg/d ESZWD), and Sac/Val (68 mg/kg/d sacubitril/valsartan) groups and treated daily for 4 weeks. As a control, the sham surgery group (Sham) was used. Primary cardiac fibroblasts (CFs) were categorized into Control, Model, ESZWD, and Sac/Val groups. Then, the CFs were stimulated with Ang-II. The ESZWD and Sac/Val groups were incubated with different concentrations of drug-containing sera and their effects on CF viability were assessed via the CCK-8 assay. The ESZWD and Sac/Val groups received drug-containing serum concentrations determined by CCK-8 assay results. The cardioprotective effects of ESZWD were determined using echocardiography, Hematoxylin & Eosin (H&E) staining, Masson staining, and Sirius red staining, and the Enzyme Linked Immunosorbent Assay (ELISA). ESZWD's effects on the Ras Homolog Gene Family Member A (RhoA)/Rho-Associated Coiled-Coil Kinases (ROCKs) signaling pathway and myocardial fibrosis were assessed by Western blotting and Quantitative Real-Time PCR (qRT-PCR) analyses. Immunofluorescence was used to observe fibrotic markers in CFs.
ESZWD treatment improved cardiac function in the CHF-HKYD rats by significantly reducing myocardial fibrosis and ventricular remodeling. ESZWD treatment increased the rats' body temperature (Tb) and 24-h urine volume, left ventricular ejection fraction (LVEF) and LV fractional shortening (LVFS), and decreased LV internal systolic diameter (LVIDs), LV internal diastolic diameter (LVIDd), and heart weight/body weight (HW/BW) compared to the Model group. In comparison to the model rats, ESZWD treatment decreased serum levels of B-type natriuretic peptide precursor (NT-proBNP), tumor necrosis factor-alpha (TNF-α), interleukin-11 (IL-11), and IL-17A. ESZWD treatment significantly down-regulated the protein and mRNA expression levels of collagen I A1, α-SMA, RhoA, ROCK1, and ROCK2 in the heart tissues of the CHF-HKYD rats and the Ang II-stimulated CFs.
ESZWD significantly improved cardiac function and attenuated myocardial fibrosis and inflammation in the CHF-HKYD rats by inhibiting the RhoA/ROCKs signaling pathway.
[Display omitted]
•Phytochemical constituents of Ershen Zhenwu Decoction (ESZWD) were analyzed by UHPLC coupled with Q-TOF mass spectrometry.•ESZWD is able to alleviate myocardial fibrosis and inflammation in vivo and in vitro.•ESZWD specifically inhibits the activation of the RhoA/ROCKs signaling pathway.•ESZWD is a potential treatment for treating myocardial fibrosis of Chronic Heart Failure with Heart–Kidney Yang Deficiency.</description><identifier>ISSN: 0378-8741</identifier><identifier>ISSN: 1872-7573</identifier><identifier>EISSN: 1872-7573</identifier><identifier>DOI: 10.1016/j.jep.2024.119146</identifier><identifier>PMID: 39580131</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Chronic heart failure with heart–kidney Yang deficiency4 ; Ershen Zhenwu Decoction1 ; Extracellular matrix5 ; Myocardial fibrosis3 ; RhoA/ROCKs2</subject><ispartof>Journal of ethnopharmacology, 2024-11, Vol.340, p.119146, Article 119146</ispartof><rights>2024</rights><rights>Copyright © 2024. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c1501-4c14f6c118ba5062edbb4148473f424257a51f12919471b9226b023a227e0ee53</cites><orcidid>0009-0008-0339-083X ; 0000-0002-7787-2638 ; 0009-0003-2684-5909</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jep.2024.119146$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39580131$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cheng, Dan</creatorcontrib><creatorcontrib>Sheng, Sheng</creatorcontrib><creatorcontrib>Hu, Jing</creatorcontrib><creatorcontrib>Cai, Shanshan</creatorcontrib><creatorcontrib>Liu, Yan</creatorcontrib><creatorcontrib>Gan, Ruixi</creatorcontrib><creatorcontrib>Zhu, Zhenpeng</creatorcontrib><creatorcontrib>Ge, Lan</creatorcontrib><creatorcontrib>Chen, Weidong</creatorcontrib><creatorcontrib>Cheng, Xiaoyu</creatorcontrib><title>Ershen Zhenwu Decoction suppresses myocardial fibrosis of chronic heart failure with heart–kidney Yang deficiency by down-regulating the Ras Homolog Gene Family Member A/Rho-Associated Coiled-Coil Kinases signaling pathway</title><title>Journal of ethnopharmacology</title><addtitle>J Ethnopharmacol</addtitle><description>The therapeutic efficacy of Ershen Zhenwu Decoction (ESZWD)—a famous formulation from Xin'an for patients with chronic heart failure heart–kidney Yang deficiency (CHF-HKYD)—is well established. Still, the underlying molecular mechanism is not clear.
This study investigated mechanisms by which ESZWD suppresses cardiac pathology, including myocardial fibrosis, in CHF-HKYD model rats and Ang II-stimulated cardiac fibroblasts (CFs).
The components in ESZWD were analyzed by ultra-high-performance liquid chromatography coupled with Quadrupole Time-Of-Flight mass spectrometry (UHPLC-Q-TOF-MS). CHF-HKYD model was established in the male Sprague–Dawley rats through bilateral thyroidectomy and intraperitoneal administration of 0.02% doxorubicin (DOX), twice weekly for 3 weeks. Subsequently, the CHF-HKYD model rats were randomly categorized into the Model, ESZWD-L (3.96 g/kg/d ESZWD), ESZWD-M (7.92 g/kg/d ESZWD), ESZWD-H (15.84 g/kg/d ESZWD), and Sac/Val (68 mg/kg/d sacubitril/valsartan) groups and treated daily for 4 weeks. As a control, the sham surgery group (Sham) was used. Primary cardiac fibroblasts (CFs) were categorized into Control, Model, ESZWD, and Sac/Val groups. Then, the CFs were stimulated with Ang-II. The ESZWD and Sac/Val groups were incubated with different concentrations of drug-containing sera and their effects on CF viability were assessed via the CCK-8 assay. The ESZWD and Sac/Val groups received drug-containing serum concentrations determined by CCK-8 assay results. The cardioprotective effects of ESZWD were determined using echocardiography, Hematoxylin & Eosin (H&E) staining, Masson staining, and Sirius red staining, and the Enzyme Linked Immunosorbent Assay (ELISA). ESZWD's effects on the Ras Homolog Gene Family Member A (RhoA)/Rho-Associated Coiled-Coil Kinases (ROCKs) signaling pathway and myocardial fibrosis were assessed by Western blotting and Quantitative Real-Time PCR (qRT-PCR) analyses. Immunofluorescence was used to observe fibrotic markers in CFs.
ESZWD treatment improved cardiac function in the CHF-HKYD rats by significantly reducing myocardial fibrosis and ventricular remodeling. ESZWD treatment increased the rats' body temperature (Tb) and 24-h urine volume, left ventricular ejection fraction (LVEF) and LV fractional shortening (LVFS), and decreased LV internal systolic diameter (LVIDs), LV internal diastolic diameter (LVIDd), and heart weight/body weight (HW/BW) compared to the Model group. In comparison to the model rats, ESZWD treatment decreased serum levels of B-type natriuretic peptide precursor (NT-proBNP), tumor necrosis factor-alpha (TNF-α), interleukin-11 (IL-11), and IL-17A. ESZWD treatment significantly down-regulated the protein and mRNA expression levels of collagen I A1, α-SMA, RhoA, ROCK1, and ROCK2 in the heart tissues of the CHF-HKYD rats and the Ang II-stimulated CFs.
ESZWD significantly improved cardiac function and attenuated myocardial fibrosis and inflammation in the CHF-HKYD rats by inhibiting the RhoA/ROCKs signaling pathway.
[Display omitted]
•Phytochemical constituents of Ershen Zhenwu Decoction (ESZWD) were analyzed by UHPLC coupled with Q-TOF mass spectrometry.•ESZWD is able to alleviate myocardial fibrosis and inflammation in vivo and in vitro.•ESZWD specifically inhibits the activation of the RhoA/ROCKs signaling pathway.•ESZWD is a potential treatment for treating myocardial fibrosis of Chronic Heart Failure with Heart–Kidney Yang Deficiency.</description><subject>Chronic heart failure with heart–kidney Yang deficiency4</subject><subject>Ershen Zhenwu Decoction1</subject><subject>Extracellular matrix5</subject><subject>Myocardial fibrosis3</subject><subject>RhoA/ROCKs2</subject><issn>0378-8741</issn><issn>1872-7573</issn><issn>1872-7573</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9kc-O1DAMxisEYoeFB-CCfOTS2ThNm444jYb9g1iEtIIDXKI0dacZ2qYkLaPeeAdeEPEktMzCkYst2Z8_2f5F0XNka2SYXRzWB-rXnHGxRtygyB5EK8wlj2Uqk4fRiiUyj3Mp8Cx6EsKBMSZRsMfRWbJJc4YJrqKflz7U1MHnORxHeE3GmcG6DsLY955CoADt5Iz2pdUNVLbwLtgArgJTe9dZAzVpP0ClbTN6gqMd6lPp1_cfX2zZ0QSfdLeHkiprLHVmgmKC0h272NN-bPRg5-5QE9zpADeudY3bwzV1BFe6tc0E76gtyMP24q528TYEZ6weqISdsw2V8ZLgre30smuw-043i2Ovh_qop6fRo0o3gZ7d5_Po49Xlh91NfPv--s1uexsbTBnGwqCoMoOYFzplGaeyKASKXMikElzwVOoUK-Qb3AiJxYbzrGA80ZxLYkRpch69PPn23n0dKQyqtcFQ0-iO3BhUgglPskwKNkvxJDXzL4OnSvXettpPCplawKqDmsGqBaw6gZ1nXtzbj0VL5b-JvyRnwauTgOYjv1nyKvz5NpXWkxlU6ex_7H8DP_K4NA</recordid><startdate>20241122</startdate><enddate>20241122</enddate><creator>Cheng, Dan</creator><creator>Sheng, Sheng</creator><creator>Hu, Jing</creator><creator>Cai, Shanshan</creator><creator>Liu, Yan</creator><creator>Gan, Ruixi</creator><creator>Zhu, Zhenpeng</creator><creator>Ge, Lan</creator><creator>Chen, Weidong</creator><creator>Cheng, Xiaoyu</creator><general>Elsevier B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0009-0008-0339-083X</orcidid><orcidid>https://orcid.org/0000-0002-7787-2638</orcidid><orcidid>https://orcid.org/0009-0003-2684-5909</orcidid></search><sort><creationdate>20241122</creationdate><title>Ershen Zhenwu Decoction suppresses myocardial fibrosis of chronic heart failure with heart–kidney Yang deficiency by down-regulating the Ras Homolog Gene Family Member A/Rho-Associated Coiled-Coil Kinases signaling pathway</title><author>Cheng, Dan ; Sheng, Sheng ; Hu, Jing ; Cai, Shanshan ; Liu, Yan ; Gan, Ruixi ; Zhu, Zhenpeng ; Ge, Lan ; Chen, Weidong ; Cheng, Xiaoyu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1501-4c14f6c118ba5062edbb4148473f424257a51f12919471b9226b023a227e0ee53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Chronic heart failure with heart–kidney Yang deficiency4</topic><topic>Ershen Zhenwu Decoction1</topic><topic>Extracellular matrix5</topic><topic>Myocardial fibrosis3</topic><topic>RhoA/ROCKs2</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cheng, Dan</creatorcontrib><creatorcontrib>Sheng, Sheng</creatorcontrib><creatorcontrib>Hu, Jing</creatorcontrib><creatorcontrib>Cai, Shanshan</creatorcontrib><creatorcontrib>Liu, Yan</creatorcontrib><creatorcontrib>Gan, Ruixi</creatorcontrib><creatorcontrib>Zhu, Zhenpeng</creatorcontrib><creatorcontrib>Ge, Lan</creatorcontrib><creatorcontrib>Chen, Weidong</creatorcontrib><creatorcontrib>Cheng, Xiaoyu</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of ethnopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cheng, Dan</au><au>Sheng, Sheng</au><au>Hu, Jing</au><au>Cai, Shanshan</au><au>Liu, Yan</au><au>Gan, Ruixi</au><au>Zhu, Zhenpeng</au><au>Ge, Lan</au><au>Chen, Weidong</au><au>Cheng, Xiaoyu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ershen Zhenwu Decoction suppresses myocardial fibrosis of chronic heart failure with heart–kidney Yang deficiency by down-regulating the Ras Homolog Gene Family Member A/Rho-Associated Coiled-Coil Kinases signaling pathway</atitle><jtitle>Journal of ethnopharmacology</jtitle><addtitle>J Ethnopharmacol</addtitle><date>2024-11-22</date><risdate>2024</risdate><volume>340</volume><spage>119146</spage><pages>119146-</pages><artnum>119146</artnum><issn>0378-8741</issn><issn>1872-7573</issn><eissn>1872-7573</eissn><abstract>The therapeutic efficacy of Ershen Zhenwu Decoction (ESZWD)—a famous formulation from Xin'an for patients with chronic heart failure heart–kidney Yang deficiency (CHF-HKYD)—is well established. Still, the underlying molecular mechanism is not clear.
This study investigated mechanisms by which ESZWD suppresses cardiac pathology, including myocardial fibrosis, in CHF-HKYD model rats and Ang II-stimulated cardiac fibroblasts (CFs).
The components in ESZWD were analyzed by ultra-high-performance liquid chromatography coupled with Quadrupole Time-Of-Flight mass spectrometry (UHPLC-Q-TOF-MS). CHF-HKYD model was established in the male Sprague–Dawley rats through bilateral thyroidectomy and intraperitoneal administration of 0.02% doxorubicin (DOX), twice weekly for 3 weeks. Subsequently, the CHF-HKYD model rats were randomly categorized into the Model, ESZWD-L (3.96 g/kg/d ESZWD), ESZWD-M (7.92 g/kg/d ESZWD), ESZWD-H (15.84 g/kg/d ESZWD), and Sac/Val (68 mg/kg/d sacubitril/valsartan) groups and treated daily for 4 weeks. As a control, the sham surgery group (Sham) was used. Primary cardiac fibroblasts (CFs) were categorized into Control, Model, ESZWD, and Sac/Val groups. Then, the CFs were stimulated with Ang-II. The ESZWD and Sac/Val groups were incubated with different concentrations of drug-containing sera and their effects on CF viability were assessed via the CCK-8 assay. The ESZWD and Sac/Val groups received drug-containing serum concentrations determined by CCK-8 assay results. The cardioprotective effects of ESZWD were determined using echocardiography, Hematoxylin & Eosin (H&E) staining, Masson staining, and Sirius red staining, and the Enzyme Linked Immunosorbent Assay (ELISA). ESZWD's effects on the Ras Homolog Gene Family Member A (RhoA)/Rho-Associated Coiled-Coil Kinases (ROCKs) signaling pathway and myocardial fibrosis were assessed by Western blotting and Quantitative Real-Time PCR (qRT-PCR) analyses. Immunofluorescence was used to observe fibrotic markers in CFs.
ESZWD treatment improved cardiac function in the CHF-HKYD rats by significantly reducing myocardial fibrosis and ventricular remodeling. ESZWD treatment increased the rats' body temperature (Tb) and 24-h urine volume, left ventricular ejection fraction (LVEF) and LV fractional shortening (LVFS), and decreased LV internal systolic diameter (LVIDs), LV internal diastolic diameter (LVIDd), and heart weight/body weight (HW/BW) compared to the Model group. In comparison to the model rats, ESZWD treatment decreased serum levels of B-type natriuretic peptide precursor (NT-proBNP), tumor necrosis factor-alpha (TNF-α), interleukin-11 (IL-11), and IL-17A. ESZWD treatment significantly down-regulated the protein and mRNA expression levels of collagen I A1, α-SMA, RhoA, ROCK1, and ROCK2 in the heart tissues of the CHF-HKYD rats and the Ang II-stimulated CFs.
ESZWD significantly improved cardiac function and attenuated myocardial fibrosis and inflammation in the CHF-HKYD rats by inhibiting the RhoA/ROCKs signaling pathway.
[Display omitted]
•Phytochemical constituents of Ershen Zhenwu Decoction (ESZWD) were analyzed by UHPLC coupled with Q-TOF mass spectrometry.•ESZWD is able to alleviate myocardial fibrosis and inflammation in vivo and in vitro.•ESZWD specifically inhibits the activation of the RhoA/ROCKs signaling pathway.•ESZWD is a potential treatment for treating myocardial fibrosis of Chronic Heart Failure with Heart–Kidney Yang Deficiency.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>39580131</pmid><doi>10.1016/j.jep.2024.119146</doi><orcidid>https://orcid.org/0009-0008-0339-083X</orcidid><orcidid>https://orcid.org/0000-0002-7787-2638</orcidid><orcidid>https://orcid.org/0009-0003-2684-5909</orcidid></addata></record> |
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subjects | Chronic heart failure with heart–kidney Yang deficiency4 Ershen Zhenwu Decoction1 Extracellular matrix5 Myocardial fibrosis3 RhoA/ROCKs2 |
title | Ershen Zhenwu Decoction suppresses myocardial fibrosis of chronic heart failure with heart–kidney Yang deficiency by down-regulating the Ras Homolog Gene Family Member A/Rho-Associated Coiled-Coil Kinases signaling pathway |
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