Blood pressure-lowering effects of a Bowman-Birk inhibitor and its derived peptides in normotensive and hypertensive rats
Bioactive plant peptides have received considerable interest as potential antihypertensive agents with potentially fewer side effects than antihypertensive drugs. Here, the blood pressure-lowering effects of the Bowman-Birk protease inhibitor, BTCI, and its derived peptides, PepChy and PepTry, were...
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| Veröffentlicht in: | Scientific reports 2020-07, Vol.10 (1), p.11680-11680, Article 11680 |
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| creator | de Freitas, Maria Alzira Garcia Amaral, Nathalia Oda Álvares, Alice da Cunha Morales de Oliveira, Sandriele Aires Mehdad, Azadeh Honda, Diego Elias Bessa, Amanda Sá Martins Ramada, Marcelo Henrique Soller Naves, Lara Marques Pontes, Carolina Nobre Ribeiro Castro, Carlos Henrique Pedrino, Gustavo Rodrigues de Freitas, Sonia Maria |
| description | Bioactive plant peptides have received considerable interest as potential antihypertensive agents with potentially fewer side effects than antihypertensive drugs. Here, the blood pressure-lowering effects of the Bowman-Birk protease inhibitor, BTCI, and its derived peptides, PepChy and PepTry, were investigated using normotensive (Wistar-WR) and spontaneously hypertensive rats (SHR). BTCI inhibited the proteases trypsin and chymotrypsin, respectively, at 6 µM and 40 µM, a 10-fold greater inhibition than observed with PepTry (60 µM) and PepChy (400 µM). These molecules also inhibited angiotensin converting enzyme (ACE) with IC
50
values of 54.6 ± 2.9; 24.7 ± 1.1; and 24.4 ± 1.1 µM, respectively, occluding its catalytic site, as indicated by molecular docking simulation, mainly for PepChy and PepTry. Gavage administration of BTCI and the peptides promoted a decrease of systolic and diastolic blood pressure and an increase of renal and aortic vascular conductance. These effects were more expressive in SHR than in WR. Additionally, BTCI, PepChy and PepTry promoted coronary vasodilation and negative inotropic effects in isolated perfused hearts. The nitric oxide synthase inhibitor blunted the BTCI and PepChy, with no cardiac effects on PepTry. The findings of this study indicate a therapeutic potential of BTCI and its related peptides in the treatment of hypertension. |
| doi_str_mv | 10.1038/s41598-020-66624-3 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7363796</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2423960556</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-d73e01445be8b01ab1836d1e438653ce2e175c13359763f77432bef1d45b8d193</originalsourceid><addsrcrecordid>eNp9kUtv1TAQhS0EolXpH2CBIrFhE2p7_Eg2SNyKR6VKbGBtOfGk1yWxg520uv8e3962FBbMxpbnO2c8OoS8ZvQ9o9CcZcFk29SU01opxUUNz8gxp0LWHDh__uR-RE5zvqalJG8Fa1-SI-BKtYrpY7LbjDG6ak6Y85qwHuMtJh-uKhwG7JdcxaGy1SbeTjbUG59-Vj5sfeeXmCobXOUL4oriBosJzot3mAtShZimuGDIpXMHbnczpoeHZJf8irwY7Jjx9P48IT8-f_p-_rW-_Pbl4vzjZd0LLZbaaUDKhJAdNh1ltmMNKMdQQKMk9MiRadkzANlqBYPWAniHA3NF0TjWwgn5cPCd125C12NYkh3NnPxk085E683fneC35ireGA0KdKuKwbt7gxR_rZgXM_nc4zjagHHNhgsuSoHUBX37D3od1xTKensKWkWl3BvyA9WnmHPC4fEzjJp9uOYQrinhmrtwDRTRm6drPEoeoiwAHIA87wPE9Gf2f2x_A1BEsVs</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2423960556</pqid></control><display><type>article</type><title>Blood pressure-lowering effects of a Bowman-Birk inhibitor and its derived peptides in normotensive and hypertensive rats</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Springer Nature OA Free Journals</source><source>Nature Free</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>de Freitas, Maria Alzira Garcia ; Amaral, Nathalia Oda ; Álvares, Alice da Cunha Morales ; de Oliveira, Sandriele Aires ; Mehdad, Azadeh ; Honda, Diego Elias ; Bessa, Amanda Sá Martins ; Ramada, Marcelo Henrique Soller ; Naves, Lara Marques ; Pontes, Carolina Nobre Ribeiro ; Castro, Carlos Henrique ; Pedrino, Gustavo Rodrigues ; de Freitas, Sonia Maria</creator><creatorcontrib>de Freitas, Maria Alzira Garcia ; Amaral, Nathalia Oda ; Álvares, Alice da Cunha Morales ; de Oliveira, Sandriele Aires ; Mehdad, Azadeh ; Honda, Diego Elias ; Bessa, Amanda Sá Martins ; Ramada, Marcelo Henrique Soller ; Naves, Lara Marques ; Pontes, Carolina Nobre Ribeiro ; Castro, Carlos Henrique ; Pedrino, Gustavo Rodrigues ; de Freitas, Sonia Maria</creatorcontrib><description>Bioactive plant peptides have received considerable interest as potential antihypertensive agents with potentially fewer side effects than antihypertensive drugs. Here, the blood pressure-lowering effects of the Bowman-Birk protease inhibitor, BTCI, and its derived peptides, PepChy and PepTry, were investigated using normotensive (Wistar-WR) and spontaneously hypertensive rats (SHR). BTCI inhibited the proteases trypsin and chymotrypsin, respectively, at 6 µM and 40 µM, a 10-fold greater inhibition than observed with PepTry (60 µM) and PepChy (400 µM). These molecules also inhibited angiotensin converting enzyme (ACE) with IC
50
values of 54.6 ± 2.9; 24.7 ± 1.1; and 24.4 ± 1.1 µM, respectively, occluding its catalytic site, as indicated by molecular docking simulation, mainly for PepChy and PepTry. Gavage administration of BTCI and the peptides promoted a decrease of systolic and diastolic blood pressure and an increase of renal and aortic vascular conductance. These effects were more expressive in SHR than in WR. Additionally, BTCI, PepChy and PepTry promoted coronary vasodilation and negative inotropic effects in isolated perfused hearts. The nitric oxide synthase inhibitor blunted the BTCI and PepChy, with no cardiac effects on PepTry. The findings of this study indicate a therapeutic potential of BTCI and its related peptides in the treatment of hypertension.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-66624-3</identifier><identifier>PMID: 32669617</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/443/592/75/243 ; 631/45/56 ; 64 ; 82 ; 82/16 ; 82/83 ; Angiotensin ; Animals ; Antihypertensive Agents - chemistry ; Antihypertensive Agents - pharmacology ; Antihypertensives ; Aorta ; Binding Sites ; Blood pressure ; Blood Pressure - drug effects ; Chymotrypsin ; Chymotrypsin - chemistry ; Chymotrypsin - metabolism ; Conductance ; Coronary Vessels - drug effects ; Coronary Vessels - physiopathology ; Enzyme Inhibitors - chemistry ; Enzyme Inhibitors - pharmacology ; Humanities and Social Sciences ; Hypertension ; Hypertension - drug therapy ; Hypertension - enzymology ; Hypertension - physiopathology ; Male ; Molecular Docking Simulation ; multidisciplinary ; Myocardial Contraction - drug effects ; NG-Nitroarginine Methyl Ester - chemistry ; NG-Nitroarginine Methyl Ester - pharmacology ; Nitric oxide ; Nitric Oxide Synthase Type III - antagonists & inhibitors ; Nitric Oxide Synthase Type III - chemistry ; Nitric Oxide Synthase Type III - metabolism ; Nitric-oxide synthase ; Peptides ; Peptides - chemical synthesis ; Peptides - pharmacology ; Peptidyl-dipeptidase A ; Peptidyl-Dipeptidase A - chemistry ; Peptidyl-Dipeptidase A - metabolism ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Structure, Secondary ; Proteinase inhibitors ; Rats ; Rats, Inbred SHR ; Rats, Wistar ; Rodents ; Science ; Science (multidisciplinary) ; Side effects ; Trypsin ; Trypsin - chemistry ; Trypsin - metabolism ; Trypsin Inhibitor, Bowman-Birk Soybean - chemistry ; Trypsin Inhibitor, Bowman-Birk Soybean - pharmacology ; Vasodilation ; Vasodilation - drug effects</subject><ispartof>Scientific reports, 2020-07, Vol.10 (1), p.11680-11680, Article 11680</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under 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><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-d73e01445be8b01ab1836d1e438653ce2e175c13359763f77432bef1d45b8d193</citedby><cites>FETCH-LOGICAL-c474t-d73e01445be8b01ab1836d1e438653ce2e175c13359763f77432bef1d45b8d193</cites><orcidid>0000-0001-9738-3412 ; 0000-0002-7562-4980 ; 0000-0001-9806-4376</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363796/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363796/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27922,27923,41118,42187,51574,53789,53791</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32669617$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>de Freitas, Maria Alzira Garcia</creatorcontrib><creatorcontrib>Amaral, Nathalia Oda</creatorcontrib><creatorcontrib>Álvares, Alice da Cunha Morales</creatorcontrib><creatorcontrib>de Oliveira, Sandriele Aires</creatorcontrib><creatorcontrib>Mehdad, Azadeh</creatorcontrib><creatorcontrib>Honda, Diego Elias</creatorcontrib><creatorcontrib>Bessa, Amanda Sá Martins</creatorcontrib><creatorcontrib>Ramada, Marcelo Henrique Soller</creatorcontrib><creatorcontrib>Naves, Lara Marques</creatorcontrib><creatorcontrib>Pontes, Carolina Nobre Ribeiro</creatorcontrib><creatorcontrib>Castro, Carlos Henrique</creatorcontrib><creatorcontrib>Pedrino, Gustavo Rodrigues</creatorcontrib><creatorcontrib>de Freitas, Sonia Maria</creatorcontrib><title>Blood pressure-lowering effects of a Bowman-Birk inhibitor and its derived peptides in normotensive and hypertensive rats</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Bioactive plant peptides have received considerable interest as potential antihypertensive agents with potentially fewer side effects than antihypertensive drugs. Here, the blood pressure-lowering effects of the Bowman-Birk protease inhibitor, BTCI, and its derived peptides, PepChy and PepTry, were investigated using normotensive (Wistar-WR) and spontaneously hypertensive rats (SHR). BTCI inhibited the proteases trypsin and chymotrypsin, respectively, at 6 µM and 40 µM, a 10-fold greater inhibition than observed with PepTry (60 µM) and PepChy (400 µM). These molecules also inhibited angiotensin converting enzyme (ACE) with IC
50
values of 54.6 ± 2.9; 24.7 ± 1.1; and 24.4 ± 1.1 µM, respectively, occluding its catalytic site, as indicated by molecular docking simulation, mainly for PepChy and PepTry. Gavage administration of BTCI and the peptides promoted a decrease of systolic and diastolic blood pressure and an increase of renal and aortic vascular conductance. These effects were more expressive in SHR than in WR. Additionally, BTCI, PepChy and PepTry promoted coronary vasodilation and negative inotropic effects in isolated perfused hearts. The nitric oxide synthase inhibitor blunted the BTCI and PepChy, with no cardiac effects on PepTry. The findings of this study indicate a therapeutic potential of BTCI and its related peptides in the treatment of hypertension.</description><subject>631/443/592/75/243</subject><subject>631/45/56</subject><subject>64</subject><subject>82</subject><subject>82/16</subject><subject>82/83</subject><subject>Angiotensin</subject><subject>Animals</subject><subject>Antihypertensive Agents - chemistry</subject><subject>Antihypertensive Agents - pharmacology</subject><subject>Antihypertensives</subject><subject>Aorta</subject><subject>Binding Sites</subject><subject>Blood pressure</subject><subject>Blood Pressure - drug effects</subject><subject>Chymotrypsin</subject><subject>Chymotrypsin - chemistry</subject><subject>Chymotrypsin - metabolism</subject><subject>Conductance</subject><subject>Coronary Vessels - drug effects</subject><subject>Coronary Vessels - physiopathology</subject><subject>Enzyme Inhibitors - chemistry</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Humanities and Social Sciences</subject><subject>Hypertension</subject><subject>Hypertension - drug therapy</subject><subject>Hypertension - enzymology</subject><subject>Hypertension - physiopathology</subject><subject>Male</subject><subject>Molecular Docking Simulation</subject><subject>multidisciplinary</subject><subject>Myocardial Contraction - drug effects</subject><subject>NG-Nitroarginine Methyl Ester - chemistry</subject><subject>NG-Nitroarginine Methyl Ester - pharmacology</subject><subject>Nitric oxide</subject><subject>Nitric Oxide Synthase Type III - antagonists & inhibitors</subject><subject>Nitric Oxide Synthase Type III - chemistry</subject><subject>Nitric Oxide Synthase Type III - metabolism</subject><subject>Nitric-oxide synthase</subject><subject>Peptides</subject><subject>Peptides - chemical synthesis</subject><subject>Peptides - pharmacology</subject><subject>Peptidyl-dipeptidase A</subject><subject>Peptidyl-Dipeptidase A - chemistry</subject><subject>Peptidyl-Dipeptidase A - metabolism</subject><subject>Protein Binding</subject><subject>Protein Interaction Domains and Motifs</subject><subject>Protein Structure, Secondary</subject><subject>Proteinase inhibitors</subject><subject>Rats</subject><subject>Rats, Inbred SHR</subject><subject>Rats, Wistar</subject><subject>Rodents</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Side effects</subject><subject>Trypsin</subject><subject>Trypsin - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>de Freitas, Maria Alzira Garcia</au><au>Amaral, Nathalia Oda</au><au>Álvares, Alice da Cunha Morales</au><au>de Oliveira, Sandriele Aires</au><au>Mehdad, Azadeh</au><au>Honda, Diego Elias</au><au>Bessa, Amanda Sá Martins</au><au>Ramada, Marcelo Henrique Soller</au><au>Naves, Lara Marques</au><au>Pontes, Carolina Nobre Ribeiro</au><au>Castro, Carlos Henrique</au><au>Pedrino, Gustavo Rodrigues</au><au>de Freitas, Sonia Maria</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Blood pressure-lowering effects of a Bowman-Birk inhibitor and its derived peptides in normotensive and hypertensive rats</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-07-15</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>11680</spage><epage>11680</epage><pages>11680-11680</pages><artnum>11680</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Bioactive plant peptides have received considerable interest as potential antihypertensive agents with potentially fewer side effects than antihypertensive drugs. Here, the blood pressure-lowering effects of the Bowman-Birk protease inhibitor, BTCI, and its derived peptides, PepChy and PepTry, were investigated using normotensive (Wistar-WR) and spontaneously hypertensive rats (SHR). BTCI inhibited the proteases trypsin and chymotrypsin, respectively, at 6 µM and 40 µM, a 10-fold greater inhibition than observed with PepTry (60 µM) and PepChy (400 µM). These molecules also inhibited angiotensin converting enzyme (ACE) with IC
50
values of 54.6 ± 2.9; 24.7 ± 1.1; and 24.4 ± 1.1 µM, respectively, occluding its catalytic site, as indicated by molecular docking simulation, mainly for PepChy and PepTry. Gavage administration of BTCI and the peptides promoted a decrease of systolic and diastolic blood pressure and an increase of renal and aortic vascular conductance. These effects were more expressive in SHR than in WR. Additionally, BTCI, PepChy and PepTry promoted coronary vasodilation and negative inotropic effects in isolated perfused hearts. The nitric oxide synthase inhibitor blunted the BTCI and PepChy, with no cardiac effects on PepTry. The findings of this study indicate a therapeutic potential of BTCI and its related peptides in the treatment of hypertension.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32669617</pmid><doi>10.1038/s41598-020-66624-3</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-9738-3412</orcidid><orcidid>https://orcid.org/0000-0002-7562-4980</orcidid><orcidid>https://orcid.org/0000-0001-9806-4376</orcidid><oa>free_for_read</oa></addata></record> |
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| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7363796 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Springer Nature OA Free Journals; Nature Free; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | 631/443/592/75/243 631/45/56 64 82 82/16 82/83 Angiotensin Animals Antihypertensive Agents - chemistry Antihypertensive Agents - pharmacology Antihypertensives Aorta Binding Sites Blood pressure Blood Pressure - drug effects Chymotrypsin Chymotrypsin - chemistry Chymotrypsin - metabolism Conductance Coronary Vessels - drug effects Coronary Vessels - physiopathology Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology Humanities and Social Sciences Hypertension Hypertension - drug therapy Hypertension - enzymology Hypertension - physiopathology Male Molecular Docking Simulation multidisciplinary Myocardial Contraction - drug effects NG-Nitroarginine Methyl Ester - chemistry NG-Nitroarginine Methyl Ester - pharmacology Nitric oxide Nitric Oxide Synthase Type III - antagonists & inhibitors Nitric Oxide Synthase Type III - chemistry Nitric Oxide Synthase Type III - metabolism Nitric-oxide synthase Peptides Peptides - chemical synthesis Peptides - pharmacology Peptidyl-dipeptidase A Peptidyl-Dipeptidase A - chemistry Peptidyl-Dipeptidase A - metabolism Protein Binding Protein Interaction Domains and Motifs Protein Structure, Secondary Proteinase inhibitors Rats Rats, Inbred SHR Rats, Wistar Rodents Science Science (multidisciplinary) Side effects Trypsin Trypsin - chemistry Trypsin - metabolism Trypsin Inhibitor, Bowman-Birk Soybean - chemistry Trypsin Inhibitor, Bowman-Birk Soybean - pharmacology Vasodilation Vasodilation - drug effects |
| title | Blood pressure-lowering effects of a Bowman-Birk inhibitor and its derived peptides in normotensive and hypertensive rats |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-13T13%3A57%3A46IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Blood%20pressure-lowering%20effects%20of%20a%20Bowman-Birk%20inhibitor%20and%20its%20derived%20peptides%20in%20normotensive%20and%20hypertensive%20rats&rft.jtitle=Scientific%20reports&rft.au=de%20Freitas,%20Maria%20Alzira%20Garcia&rft.date=2020-07-15&rft.volume=10&rft.issue=1&rft.spage=11680&rft.epage=11680&rft.pages=11680-11680&rft.artnum=11680&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/s41598-020-66624-3&rft_dat=%3Cproquest_pubme%3E2423960556%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2423960556&rft_id=info:pmid/32669617&rfr_iscdi=true |