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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id specific-use="scielo-v3" pub-id-type="publisher-id">bWJpsvqmBB9fKgPvJC4VQCF</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2021001401104</article-id>
      <article-id pub-id-type="publisher-id">abc.20210869</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20210869</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Minieditorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Pesquisando Compostos de Ocorr&#234;ncia Natural para Tratar Hipertens&#227;o</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-3508-9776</contrib-id>
          <name>
            <surname>Souza</surname>
            <given-names>Diego Santos</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-2690-912X</contrib-id>
          <name>
            <surname>Roman-Campos</surname>
            <given-names>Danilo</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <aff id="aff1">
          <label>1</label>
          <institution content-type="orgname">Universidade Federal de S&#227;o Paulo</institution>
          <institution content-type="orgdiv1">Escola Paulista de Medicina</institution>
          <institution content-type="orgdiv2">Departamento de Biof&#237;sica</institution>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Laborat&#243;rio de CardioBiologia, Departamento de Biof&#237;sica, Escola Paulista de Medicina, Universidade Federal de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brasil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><bold>Correspond&#234;ncia: Danilo Roman-Campos</bold> &#8226; Rua Botucatu 862, ECB, 2 Andar. CEP <postal-code>04023-062</postal-code>, Departamento de Biof&#237;sica, Escola Paulista de Medicina, UNIFESP. Vila Clementino, S&#227;o Paulo, SP - Brasil. E-mail:<email>drcampos@unifesp.br</email> </corresp>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>03</day>
        <month>12</month>
        <year>2021</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <month>12</month>
        <year>2021</year>
      </pub-date>
      <volume>117</volume>
      <issue>6</issue>
      <fpage>1104</fpage>
      <lpage>1105</lpage>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License</license-p>
        </license>
      </permissions>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave</title>
        <kwd>Doen&#231;as Cardiovasculares</kwd>
        <kwd>Hipertens&#227;o</kwd>
        <kwd>Dieta</kwd>
        <kwd>Produtos Biol&#243;gicos</kwd>
        <kwd>Mortalidade</kwd>
        <kwd>Preven&#231;&#227;o e Controle</kwd>
        <kwd>Sauromatum Gluttatum/uso terap&#234;utico</kwd>
        <kwd>Ratos</kwd>
      </kwd-group>
      <counts>
        <fig-count count="0"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="8"/>
        <page-count count="2"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <p>As doen&#231;as cardiovasculares (DCs) s&#227;o a principal causa de morte em todo o mundo. De forma preocupante, aproximadamente 17,9 milh&#245;es de pessoas morreram de CDs em 2019, representando quase 32% das mortes globais. Al&#233;m disso, quase tr&#234;s quartos das mortes por DC ocorrem em pa&#237;ses de baixa e m&#233;dia renda, o que &#233; um fator de risco para os brasileiros.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Existem v&#225;rios mecanismos subjacentes envolvidos nas DCs, e a hipertens&#227;o &#233; um contribuidor significativo. Hoje, estima-se que cerca de 1,28 bilh&#227;o de adultos com idade entre 30 e 79 anos tenham hipertens&#227;o no mundo. Al&#233;m disso, estima-se que 60&#8211;70% da hipertens&#227;o em adultos seja atribu&#237;da &#224; obesidade, associada &#224; resist&#234;ncia &#224; insulina, dislipidemia e s&#237;ndrome metab&#243;lica.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> Al&#233;m disso, quase 50% dos adultos com hipertens&#227;o desconhecem sua condi&#231;&#227;o e apenas 20% t&#234;m hipertens&#227;o sob controle.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
    <p>De acordo com o American College of Cardiology e a American Heart Association,<sup><xref ref-type="bibr" rid="B4">4</xref></sup> a press&#227;o arterial normal (PA) &#233; considerada quando a press&#227;o arterial sist&#243;lica (PAS) &#233; &lt; 120 mm Hg e &lt;80 mm Hg para a press&#227;o arterial diast&#243;lica (PAD). A PA elevada &#233; considerada quando a PAS &#233; 120-129 e a PAD &#233; &lt;80 mg. Os est&#225;gios 1 e 2 de hipertens&#227;o s&#227;o considerados quando a PAS &#233; 130-139 mm Hg ou &gt; 140 mm Hg, respectivamente, ou PAD &#233; 80-89 mm Hg ou&gt; 90 mm Hg, respectivamente. Esses valores tamb&#233;m seguem a diretriz brasileira mais recente para o diagn&#243;stico de hipertens&#227;o.<sup><xref ref-type="bibr" rid="B5">5</xref></sup></p>
    <p>Os n&#250;meros nos mostram que a busca por novos compostos para amenizar a hipertens&#227;o &#233; de grande import&#226;ncia para o tratamento de pacientes em todo o mundo. As terapias de reaproveitamento s&#227;o uma possibilidade. Por exemplo, um estudo piloto recente demonstrou que uma &#250;nica dose de infliximabe pode reduzir os n&#237;veis m&#233;dios e de PAD imediatamente ap&#243;s sua infus&#227;o, em compara&#231;&#227;o com o placebo em pacientes com hipertens&#227;o. No entanto, nem todo paciente pode se beneficiar com esse tipo de terapia.<sup><xref ref-type="bibr" rid="B6">6</xref></sup></p>
    <p>Nesse cen&#225;rio, os produtos naturais desempenham um papel fundamental. A implementa&#231;&#227;o de produtos naturais tem aumentado nas &#250;ltimas d&#233;cadas. Em um estudo de revis&#227;o aprofundado que cobriu produtos totalmente naturais como fontes de novos medicamentos, de 1981 a 2019 aprovado pela Food and Drug Administration, aproximadamente 1946 novos compostos foram aprovados para tratar doen&#231;as humanas. No &#226;mbito dos anti-hipertensivos, foram autorizados 82 compostos naturais.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> Por&#233;m, apesar do n&#250;mero crescente de compostos naturais autorizados, ainda &#233; necess&#225;rio encontrar novos compostos para o tratamento da hipertens&#227;o, uma vez que os pacientes n&#227;o respondem a uma determinada classe de anti-hipertensivos ou n&#227;o aderem ao tratamento.</p>
    <p>Bibi et al., <sup><xref ref-type="bibr" rid="B8">8</xref></sup> descrevem um novo extrato vegetal bruto de <italic>Sauromatum guttatum</italic> para tratamento experimental da hipertens&#227;o. No manuscrito, os autores avaliam o potencial de aplica&#231;&#227;o terap&#234;utica do extrato vegetal no modelo animal cl&#225;ssico de hipertens&#227;o induzida por sal elevado em ratos (ratos DOCA-hipertensos). Seu estudo descobriu que animais hipertensos tratados diariamente por oito semanas com <italic>S. guttatum</italic> atenuaram significativamente a press&#227;o arterial de uma maneira dependente da dose. Al&#233;m disso, 300 mg/kg de <italic>S. guttatum</italic> tiveram um efeito anti-hipertensivo semelhante ao verapamil 15 mg/kg tratado durante o mesmo per&#237;odo. O uso de an&#233;is a&#243;rticos isolados de ratos hipertensos favoreceu o relaxamento dependente da acetilcolina. &#201; importante ressaltar que os an&#233;is a&#243;rticos isolados de ratos hipertensos tratados por via oral com o extrato bruto de <italic>S. guttatum</italic>. na dose de 300 mg/kg por 28 dias teve uma pot&#234;ncia semelhante sobre o efeito relaxante dependente de acetilcolina contra contra&#231;&#245;es induzidas por fenilefrina que foi observado nos animais controle. Curiosamente, os an&#233;is a&#243;rticos isolados de animais hipertensos tratados com verapamil 15 mg/kg por 28 dias mostraram apenas uma melhora modesta no modelo experimental de hipertens&#227;o. Aparentemente, o mecanismo envolvido no efeito de relaxamento do <italic>S. guttatum</italic> inclui a ativa&#231;&#227;o de receptores muscar&#237;nicos nas c&#233;lulas endoteliais e a estimula&#231;&#227;o da produ&#231;&#227;o de &#243;xido n&#237;trico. Al&#233;m disso, o extrato bruto pode interagir com o canal de c&#225;lcio do tipo L encontrado nos an&#233;is a&#243;rticos, o que tamb&#233;m pode contribuir para o efeito anti-hipertensivo observado. Desta forma, estudos futuros devem isolar o principal agente antipertensivo presente no extrato bruto de <italic>S. guttatum</italic> para desvendar o seu potential uso para o tratamento de hipertens&#227;o, inclusive em outros modelos experimentais.</p>
    <p>Apesar do crescente n&#250;mero de produtos naturais aprovados como agentes terap&#234;uticos, considerando a hipertens&#227;o, ainda &#233; necess&#225;rio encontrar novos compostos que atuem em doses baixas. Al&#233;m disso, um composto natural pode ser &#250;til para pacientes que n&#227;o respondem a terapias convencionais ou que n&#227;o aderem facilmente a determinado regime terap&#234;utico. Como a hipertens&#227;o &#233; um fator comum entre as DCs, os produtos naturais podem fornecer um espectro de tratamento totalmente novo para v&#225;rios pacientes. Assim, gostar&#237;amos de destacar a import&#226;ncia dos produtos naturais e talvez estimular a busca de novos agentes terap&#234;uticos (naturais) que atuem como anti-hipertensivos, fornecendo embasamento cient&#237;fico para seu uso.</p>
  </body>
  <back>
    <fn-group>
      <fn fn-type="other" id="fn1">
        <p>Minieditorial referente ao artigo: O Efeito Anti-Hipertensivo de Sauromatum Guttatum Mediado por Efeitos Vasorrelaxante e Depressivos Mioc&#225;rdicos</p>
      </fn>
    </fn-group>
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  </back>
  <sub-article article-type="translation" id="S01" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Short Editorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Searching Naturally Occurring Compounds to Treat Hypertension</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-3508-9776</contrib-id>
          <name>
            <surname>Souza</surname>
            <given-names>Diego Santos</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-2690-912X</contrib-id>
          <name>
            <surname>Roman-Campos</surname>
            <given-names>Danilo</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <aff id="aff2">
          <label>1</label>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Laborat&#243;rio de CardioBiologia, Departamento de Biof&#237;sica, Escola Paulista de Medicina, Universidade Federal de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brazil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c2"><bold>Mailing Address: Danilo Roman-Campos</bold> &#8226; Rua Botucatu 862, ECB, 2 Andar. Postal Code <postal-code>04023-062</postal-code>, Departamento de Biof&#237;sica, Escola Paulista de Medicina, UNIFESP. Vila Clementino, S&#227;o Paulo, SP - Brazil. E-mail:<email>drcampos@unifesp.br</email> </corresp>
      </author-notes>
      <kwd-group xml:lang="en">
        <title>Keywords</title>
        <kwd>Cardiovascular Diseases</kwd>
        <kwd>Hypertension</kwd>
        <kwd>Diet</kwd>
        <kwd>Biological Products</kwd>
        <kwd>Mortality</kwd>
        <kwd>Prevention and Control</kwd>
        <kwd>Sauromatum Gluttatum/therapeutic use</kwd>
        <kwd>Rats</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>Cardiovascular diseases (CDs) are the major cause of death worldwide. Impressively, approximately 17.9 million people died from CDs in 2019, representing almost 32% of global deaths. Also, nearly three-quarters of deaths due to CDs occur in low- and middle-income countries, which is a risk factor for Brazilians.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> There are several underlying mechanisms involved in CDs, and hypertension is a significant contributor. Today, it is thought that about 1.28 billion adults aged 30-79 years have hypertension in the world. Furthermore, it has been estimated that 60&#8211;70% of hypertension in adults is attributable to obesity, associated with insulin resistance, dyslipidemia and metabolic syndrome.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> Also, almost 50% of adults with hypertension are unaware of its condition, and only 20% have hypertension under control.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
      <p>According to the American College of Cardiology and the American Heart Association,<sup><xref ref-type="bibr" rid="B4">4</xref></sup> Normal Blood pressure (BP) is considering when Systolic Blood Pressure (SBP) is &lt;120 mm Hg and &lt; 80 mm Hg for diastolic blood pressure (DBP). Elevated BP is considered when SBP is 120-129, and DBP is &lt;80 mg. Stage 1 and 2 hypertension are considering when SBP is 130-139 mm Hg or &gt; 140 mm Hg, respectively, or DBP is 80-89 mm Hg or &gt;90 mm Hg, respectively. These values follow the most recent Brazilian guideline to diagnostic hypertension.<sup><xref ref-type="bibr" rid="B5">5</xref></sup></p>
      <p>The numbers show us that the search for new compounds to ameliorate hypertension is of great importance to treat patients worldwide. Repurposing therapies is one possibility. For example, a recent pilot study demonstrated that a single dose of infliximab could reduce mean and DBP levels immediately after its infusion, compared to placebo in patients with hypertension. However, not every patient may benefit from this type of therapy.<sup><xref ref-type="bibr" rid="B6">6</xref></sup></p>
      <p>In this scenario, natural products play an essential part. The implementation of natural products has increased over the last decades. In an in-depth review study that covered all-natural products as sources of new drugs, from 1981 to 2019 approved by the Food and Drug Administration, approximately 1946 new compounds were approved to treat human diseases. In the context of antihypertensive, 82 natural compounds were authorized.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> However, despite the increasing number of natural compounds authorized, it is still necessary to find new compounds to treat hypertension since patients are not responsive to a given antihypertensive class or do not adhere to the treatment.</p>
      <p>Bibi et al.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> describe a novel crude plant extract from <italic>Sauromatum guttatum</italic> to treat experimental hypertension. In the manuscript, the authors evaluate the potential therapeutic application of the plant extract in the classical animal model of High salt-induced hypertension in rats (DOCA-hypertensive rats). Their study found that hypertensive animals daily treated for eight weeks with <italic>S. guttatum</italic> significantly attenuated Arterial Blood Pressure in a dose-dependent manner. Furthermore, 300 mg/kg of <italic>S. guttatum</italic> had a similar antihypertensive effect as Verapamil 15 mg/kg treated during the same time frame. The use of isolated aortic rings from hypertensive rats favored acetylcholine-dependent relaxation. Importantly, aortic Rings isolated from hypertensive rats orally treated with <italic>S. guttatum</italic> crude extract at 300 mg/kg for 28 days had a similar potency for acetylcholine-dependent relaxant effect against phenylephrine-induced contractions that observed for control. Interestingly, aortic rings isolated from hypertensive animals treated with Verapamil at 15 mg/kg for 28 days showed only modest improvement in the same experimental approach. Apparently, the mechanism involved in the relaxation effect of <italic>S. guttatum</italic> involves activating muscarinic receptors in endothelial cells and stimulating nitric oxide production. Also, the crude extract may interact with the L-type calcium channel found in aortic rings, which may also contribute to the antihypertensive effect observed. Thus, future studies should isolate the main antihypertensive active compound found in <italic>S. guttatum</italic> to uncover its potential further to treat hypertension in additional animal models in vivo.</p>
      <p>Despite the growing number of natural products approved as therapeutic agents, considering hypertension, it is still necessary to find new compounds that act at low doses. Also, a natural compound could be helpful for compliance issues and patients who do not respond to a particular class of antihypertensive treatment. As hypertension is a common factor among CDs, natural products can provide a whole new treatment&#8217; spectrum for several patients. Thus, we would like to highlight the importance of natural products and perhaps stimulate the search for new (natural) therapeutic agents that act as antihypertensive, providing a scientific basis for its use.</p>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other" id="fn2">
          <p>Short editorial related to the article: Antihypertensive Activity of Sauromatum guttatum Mediated by Vasorelaxation and Myocardial Depressant Effects</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
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