Evaluation of rosmarinic acid against myocardial infarction in maternally separated rats
Depression and coronary heart diseases are the common comorbid disorder affecting humans globally. The present study evaluated the effectiveness of rosmarinic acid (RA) against myocardial infarction (MI) in comorbid depression induced by maternal separation in rats. Maternal stress is one of the c...
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Depression and coronary heart diseases are the common comorbid disorder affecting humans globally. The present study evaluated the effectiveness of rosmarinic acid (RA) against myocardial infarction (MI) in comorbid depression induced by maternal separation in rats. Maternal stress is one of the childhood crises that may be a potential risk factor for coronary heart disease in later part of life. As per protocol, 70–80% of pups were separated daily for 3 h between postnatal day 1 (PND1) and postnatal day 21 (PND21). Forced-swim test, sucrose preference test, and electrocardiography were performed during the experiment. Body weight was measured on PND0, PND35, and PND55. Orally rosmarinic acid (25 mg/kg and 50 mg/kg) and fluoxetine (10 mg/kg) was done from PND35 to PND55. On PND53 and PND54, isoproterenol (100 mg/kg, subcutaneously) was administered to induce myocardial infarction. On PND55, blood was collected and animals sacrificed, and plasma corticosterone, brain-derived neurotrophic factor, cardiac biomarkers, interleukine-10, and anti-oxidant parameters were measured. Rosmarinic acid and fluoxetine ameliorated the maternal separation–induced increase in immobility period, anhedonia, body weight, ST elevation, corticosterone, creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH). At the same time, both drugs elevated the tissue levels of BDNF, IL-10, glutathione, and superoxide dismutase activity. This study provides the first experimental evidence that maternal stress is an independent risk factor of cardiac abnormalities in rats. Moreover, maternal stress synergistically increases the severity of cardiac abnormalities induced by isoproterenol. Interestingly, fluoxetine and rosmarinic acid effectively ameliorated behavioral anomalies and myocardial infarction in maternally separated rats.
Graphical abstract
Schematic representation of possible molecular mechanism of action of rosmarinic acid against MS-induced myocardial infarction. RA, rosmarinic acid; MS, maternal separation; PND, postnatal days; ISO, isoproterenol; BDNF, brain-derived neurotrophic factor; GSH, glutathione; SOD, superoxide dismutase; IL-10, interleukin-10; MI, myocardial infarction |
| doi_str_mv | 10.1007/s00210-022-02273-9 |
| format | Article |
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Depression and coronary heart diseases are the common comorbid disorder affecting humans globally. The present study evaluated the effectiveness of rosmarinic acid (RA) against myocardial infarction (MI) in comorbid depression induced by maternal separation in rats. Maternal stress is one of the childhood crises that may be a potential risk factor for coronary heart disease in later part of life. As per protocol, 70–80% of pups were separated daily for 3 h between postnatal day 1 (PND1) and postnatal day 21 (PND21). Forced-swim test, sucrose preference test, and electrocardiography were performed during the experiment. Body weight was measured on PND0, PND35, and PND55. Orally rosmarinic acid (25 mg/kg and 50 mg/kg) and fluoxetine (10 mg/kg) was done from PND35 to PND55. On PND53 and PND54, isoproterenol (100 mg/kg, subcutaneously) was administered to induce myocardial infarction. On PND55, blood was collected and animals sacrificed, and plasma corticosterone, brain-derived neurotrophic factor, cardiac biomarkers, interleukine-10, and anti-oxidant parameters were measured. Rosmarinic acid and fluoxetine ameliorated the maternal separation–induced increase in immobility period, anhedonia, body weight, ST elevation, corticosterone, creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH). At the same time, both drugs elevated the tissue levels of BDNF, IL-10, glutathione, and superoxide dismutase activity. This study provides the first experimental evidence that maternal stress is an independent risk factor of cardiac abnormalities in rats. Moreover, maternal stress synergistically increases the severity of cardiac abnormalities induced by isoproterenol. Interestingly, fluoxetine and rosmarinic acid effectively ameliorated behavioral anomalies and myocardial infarction in maternally separated rats.
Graphical abstract
Schematic representation of possible molecular mechanism of action of rosmarinic acid against MS-induced myocardial infarction. RA, rosmarinic acid; MS, maternal separation; PND, postnatal days; ISO, isoproterenol; BDNF, brain-derived neurotrophic factor; GSH, glutathione; SOD, superoxide dismutase; IL-10, interleukin-10; MI, myocardial infarction</description><identifier>ISSN: 0028-1298</identifier><identifier>EISSN: 1432-1912</identifier><identifier>DOI: 10.1007/s00210-022-02273-9</identifier><identifier>PMID: 35876905</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Acids ; Animals ; Biomedical and Life Sciences ; Biomedicine ; Body Weight ; Brain-derived neurotrophic factor ; Brain-Derived Neurotrophic Factor - metabolism ; Cardiovascular disease ; Children ; Cinnamates ; Comorbidity ; Coronary artery disease ; Corticosterone ; Corticosterone - pharmacology ; Creatine ; Creatine kinase ; Depsides ; EKG ; Fluoxetine ; Fluoxetine - pharmacology ; Fluoxetine - therapeutic use ; Glutathione ; Glutathione - metabolism ; Heart attacks ; Heart diseases ; Hedonic response ; Interleukin 10 ; Interleukin-10 - metabolism ; Isoproterenol ; Isoproterenol - pharmacology ; L-Lactate dehydrogenase ; Lactic acid ; Maternal Deprivation ; Myocardial Infarction ; Myocardium - metabolism ; Neurosciences ; Original Article ; Oxidants ; Oxidative Stress ; Pharmacology/Toxicology ; Rats ; Rats, Wistar ; Risk factors ; Rosmarinic Acid ; Sucrose ; Superoxide dismutase ; Superoxide Dismutase - metabolism</subject><ispartof>Naunyn-Schmiedeberg's archives of pharmacology, 2022-10, Vol.395 (10), p.1189-1207</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022</rights><rights>2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-6249fa8be7197dac1a43bfc191dbc4a2e221233cc30274d14cc4c15c50f7d2013</citedby><cites>FETCH-LOGICAL-c375t-6249fa8be7197dac1a43bfc191dbc4a2e221233cc30274d14cc4c15c50f7d2013</cites><orcidid>0000-0002-3641-5633</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00210-022-02273-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00210-022-02273-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,778,782,27911,27912,41475,42544,51306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35876905$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Verma, Himanshu</creatorcontrib><creatorcontrib>Bhattacharjee, Anindita</creatorcontrib><creatorcontrib>Shivavedi, Naveen</creatorcontrib><creatorcontrib>Nayak, Prasanta Kumar</creatorcontrib><title>Evaluation of rosmarinic acid against myocardial infarction in maternally separated rats</title><title>Naunyn-Schmiedeberg's archives of pharmacology</title><addtitle>Naunyn-Schmiedeberg's Arch Pharmacol</addtitle><addtitle>Naunyn Schmiedebergs Arch Pharmacol</addtitle><description>
Depression and coronary heart diseases are the common comorbid disorder affecting humans globally. The present study evaluated the effectiveness of rosmarinic acid (RA) against myocardial infarction (MI) in comorbid depression induced by maternal separation in rats. Maternal stress is one of the childhood crises that may be a potential risk factor for coronary heart disease in later part of life. As per protocol, 70–80% of pups were separated daily for 3 h between postnatal day 1 (PND1) and postnatal day 21 (PND21). Forced-swim test, sucrose preference test, and electrocardiography were performed during the experiment. Body weight was measured on PND0, PND35, and PND55. Orally rosmarinic acid (25 mg/kg and 50 mg/kg) and fluoxetine (10 mg/kg) was done from PND35 to PND55. On PND53 and PND54, isoproterenol (100 mg/kg, subcutaneously) was administered to induce myocardial infarction. On PND55, blood was collected and animals sacrificed, and plasma corticosterone, brain-derived neurotrophic factor, cardiac biomarkers, interleukine-10, and anti-oxidant parameters were measured. Rosmarinic acid and fluoxetine ameliorated the maternal separation–induced increase in immobility period, anhedonia, body weight, ST elevation, corticosterone, creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH). At the same time, both drugs elevated the tissue levels of BDNF, IL-10, glutathione, and superoxide dismutase activity. This study provides the first experimental evidence that maternal stress is an independent risk factor of cardiac abnormalities in rats. Moreover, maternal stress synergistically increases the severity of cardiac abnormalities induced by isoproterenol. Interestingly, fluoxetine and rosmarinic acid effectively ameliorated behavioral anomalies and myocardial infarction in maternally separated rats.
Graphical abstract
Schematic representation of possible molecular mechanism of action of rosmarinic acid against MS-induced myocardial infarction. RA, rosmarinic acid; MS, maternal separation; PND, postnatal days; ISO, isoproterenol; BDNF, brain-derived neurotrophic factor; GSH, glutathione; SOD, superoxide dismutase; IL-10, interleukin-10; MI, myocardial infarction</description><subject>Acids</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Body Weight</subject><subject>Brain-derived neurotrophic factor</subject><subject>Brain-Derived Neurotrophic Factor - metabolism</subject><subject>Cardiovascular disease</subject><subject>Children</subject><subject>Cinnamates</subject><subject>Comorbidity</subject><subject>Coronary artery disease</subject><subject>Corticosterone</subject><subject>Corticosterone - pharmacology</subject><subject>Creatine</subject><subject>Creatine kinase</subject><subject>Depsides</subject><subject>EKG</subject><subject>Fluoxetine</subject><subject>Fluoxetine - pharmacology</subject><subject>Fluoxetine - therapeutic use</subject><subject>Glutathione</subject><subject>Glutathione - metabolism</subject><subject>Heart attacks</subject><subject>Heart diseases</subject><subject>Hedonic response</subject><subject>Interleukin 10</subject><subject>Interleukin-10 - metabolism</subject><subject>Isoproterenol</subject><subject>Isoproterenol - pharmacology</subject><subject>L-Lactate dehydrogenase</subject><subject>Lactic acid</subject><subject>Maternal Deprivation</subject><subject>Myocardial Infarction</subject><subject>Myocardium - metabolism</subject><subject>Neurosciences</subject><subject>Original Article</subject><subject>Oxidants</subject><subject>Oxidative Stress</subject><subject>Pharmacology/Toxicology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Risk factors</subject><subject>Rosmarinic Acid</subject><subject>Sucrose</subject><subject>Superoxide dismutase</subject><subject>Superoxide Dismutase - metabolism</subject><issn>0028-1298</issn><issn>1432-1912</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kMtKAzEUhoMoWqsv4EICbtyM5iSZSbOUUi9QcKPgLpxmMiUyl5rMCH1704sKLlwkIZzv_Cf5CLkAdgOMqdvIGAeWMc43S4lMH5ARSMEz0MAPySjVJxlwPTkhpzG-M8YKyPNjciLyiSo0y0fkbfaJ9YC971raVTR0scHgW28pWl9SXKJvY0-bdWcxlB5r6tsKg902-JY22LvQYl2vaXQrDOla0rTHM3JUYR3d-f4ck9f72cv0MZs_PzxN7-aZFSrvs4JLXeFk4RRoVaIFlGJR2fSBcmElcsc5cCGsFYwrWYK0VlrIbc4qVXIGYkyud7mr0H0MLvam8dG6usbWdUM0vNBSQq6kSujVH_S9GzaPT5QCwbQo9CaQ7yibZMTgKrMKPklZG2Bm493svJvk3Gy9G52aLvfRw6Jx5U_Lt-gEiB0QU6lduvA7-5_YLzy9jc8</recordid><startdate>20221001</startdate><enddate>20221001</enddate><creator>Verma, Himanshu</creator><creator>Bhattacharjee, Anindita</creator><creator>Shivavedi, Naveen</creator><creator>Nayak, Prasanta Kumar</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3641-5633</orcidid></search><sort><creationdate>20221001</creationdate><title>Evaluation of rosmarinic acid against myocardial infarction in maternally separated rats</title><author>Verma, Himanshu ; 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Depression and coronary heart diseases are the common comorbid disorder affecting humans globally. The present study evaluated the effectiveness of rosmarinic acid (RA) against myocardial infarction (MI) in comorbid depression induced by maternal separation in rats. Maternal stress is one of the childhood crises that may be a potential risk factor for coronary heart disease in later part of life. As per protocol, 70–80% of pups were separated daily for 3 h between postnatal day 1 (PND1) and postnatal day 21 (PND21). Forced-swim test, sucrose preference test, and electrocardiography were performed during the experiment. Body weight was measured on PND0, PND35, and PND55. Orally rosmarinic acid (25 mg/kg and 50 mg/kg) and fluoxetine (10 mg/kg) was done from PND35 to PND55. On PND53 and PND54, isoproterenol (100 mg/kg, subcutaneously) was administered to induce myocardial infarction. On PND55, blood was collected and animals sacrificed, and plasma corticosterone, brain-derived neurotrophic factor, cardiac biomarkers, interleukine-10, and anti-oxidant parameters were measured. Rosmarinic acid and fluoxetine ameliorated the maternal separation–induced increase in immobility period, anhedonia, body weight, ST elevation, corticosterone, creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH). At the same time, both drugs elevated the tissue levels of BDNF, IL-10, glutathione, and superoxide dismutase activity. This study provides the first experimental evidence that maternal stress is an independent risk factor of cardiac abnormalities in rats. Moreover, maternal stress synergistically increases the severity of cardiac abnormalities induced by isoproterenol. Interestingly, fluoxetine and rosmarinic acid effectively ameliorated behavioral anomalies and myocardial infarction in maternally separated rats.
Graphical abstract
Schematic representation of possible molecular mechanism of action of rosmarinic acid against MS-induced myocardial infarction. RA, rosmarinic acid; MS, maternal separation; PND, postnatal days; ISO, isoproterenol; BDNF, brain-derived neurotrophic factor; GSH, glutathione; SOD, superoxide dismutase; IL-10, interleukin-10; MI, myocardial infarction</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>35876905</pmid><doi>10.1007/s00210-022-02273-9</doi><tpages>19</tpages><orcidid>https://orcid.org/0000-0002-3641-5633</orcidid></addata></record> |
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| subjects | Acids Animals Biomedical and Life Sciences Biomedicine Body Weight Brain-derived neurotrophic factor Brain-Derived Neurotrophic Factor - metabolism Cardiovascular disease Children Cinnamates Comorbidity Coronary artery disease Corticosterone Corticosterone - pharmacology Creatine Creatine kinase Depsides EKG Fluoxetine Fluoxetine - pharmacology Fluoxetine - therapeutic use Glutathione Glutathione - metabolism Heart attacks Heart diseases Hedonic response Interleukin 10 Interleukin-10 - metabolism Isoproterenol Isoproterenol - pharmacology L-Lactate dehydrogenase Lactic acid Maternal Deprivation Myocardial Infarction Myocardium - metabolism Neurosciences Original Article Oxidants Oxidative Stress Pharmacology/Toxicology Rats Rats, Wistar Risk factors Rosmarinic Acid Sucrose Superoxide dismutase Superoxide Dismutase - metabolism |
| title | Evaluation of rosmarinic acid against myocardial infarction in maternally separated rats |
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