The Cardiorenal Effects of <i>Piper amalago</i> Are Mediated by the Nitric Oxide/Cyclic Guanosine Monophosphate Pathway and the Voltage-Dependent Potassium Channels
<i>Piper amalago</i> L. is used in Brazilian traditional medicine to treat inflammation, chest pain, and anxiety. This study aimed to investigate the safety and the renal and cardiovascular effects of the volatile oil (VO) and the aqueous (AE) and hydroalcoholic (HE) extracts from <i&...
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| Format: | Article |
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MDPI AG
2023-11-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/11/1630 |
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| author | Luciane M. Monteiro Lislaine M. Klider Aline A. M. Marques Paulo V. Farago Janaína Emiliano Roosevelt I. C. Souza Ariany C. dos Santos Vera L. P. dos Santos Mei Wang Nadla S. Cassemiro Denise B. Silva Ikhlas A. Khan Arquimedes Gasparotto Junior Jane Manfron |
| author_facet | Luciane M. Monteiro Lislaine M. Klider Aline A. M. Marques Paulo V. Farago Janaína Emiliano Roosevelt I. C. Souza Ariany C. dos Santos Vera L. P. dos Santos Mei Wang Nadla S. Cassemiro Denise B. Silva Ikhlas A. Khan Arquimedes Gasparotto Junior Jane Manfron |
| author_sort | Luciane M. Monteiro |
| collection | DOAJ |
| description | <i>Piper amalago</i> L. is used in Brazilian traditional medicine to treat inflammation, chest pain, and anxiety. This study aimed to investigate the safety and the renal and cardiovascular effects of the volatile oil (VO) and the aqueous (AE) and hydroalcoholic (HE) extracts from <i>P. amalago</i>. The gas chromatography-mass spectrometry analyses identified 47 compounds in the VO, with β-cyclogermacrene, spathulenol, β-phellandrene, and α-pinene standing out. Among the 47 compounds also found in AE and HE by liquid chromatography-mass spectrometry, glycosylated flavones, organic acids, amino acids, and amides were highlighted. Some examples of these compounds are methoxy-methylenedioxy <i>cis</i>-cinnamoyl pyrrolidine, methoxy-methylenedioxy <i>trans</i>-cinnamoyl pyrrolidine, and cyclobutene-2,4-<i>bis</i>-(1,3-benzodioxol-5-methoxy-6-yl)-1,3-dicarboxapyrrolidide. The acute toxicity experiments were conducted on female rats (<i>n</i> = 5). The cardiorenal assays (<i>n</i> = 8) and evaluations of vasodilatory effects on the mesenteric vascular bed (<i>n</i> = 5) were conducted on male rats. In either extract or VO, there were no mortality or changes in relative weights or histopathological analysis of the organs. Urinary volume and renal electrolyte excretion were elevated significantly during repeated dose 7-day treatment with different preparations from <i>P. amalago</i>. None of the preparations induced hypotension or changes in cardiac electrical activity. Only HE promoted significant vasodilatory effects in rats’ isolated mesenteric vascular beds. These effects were completely abolished in the presence of L-NAME <i>plus</i> 4-aminopyridine. Therefore, <i>P. amalago</i> leaves are safe and present diuretic activity after acute and repeated dose administration over 7 days. Moreover, the HE induced significant vasodilator response in rats’ mesenteric vascular beds by NO/cGMP pathway and voltage-dependent K<sup>+</sup> channels activation. |
| first_indexed | 2024-03-09T16:32:37Z |
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| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T16:32:37Z |
| publishDate | 2023-11-01 |
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| series | Pharmaceuticals |
| spelling | doaj.art-b882fe97792d4e0e92d794b61093ef682023-11-24T15:00:39ZengMDPI AGPharmaceuticals1424-82472023-11-011611163010.3390/ph16111630The Cardiorenal Effects of <i>Piper amalago</i> Are Mediated by the Nitric Oxide/Cyclic Guanosine Monophosphate Pathway and the Voltage-Dependent Potassium ChannelsLuciane M. Monteiro0Lislaine M. Klider1Aline A. M. Marques2Paulo V. Farago3Janaína Emiliano4Roosevelt I. C. Souza5Ariany C. dos Santos6Vera L. P. dos Santos7Mei Wang8Nadla S. Cassemiro9Denise B. Silva10Ikhlas A. Khan11Arquimedes Gasparotto Junior12Jane Manfron13Graduate Program in Pharmaceutical Sciences, State University of Ponta Grossa, Ponta Grossa 84030-900, PR, BrazilGraduate Program in Pharmaceutical Sciences, State University of Ponta Grossa, Ponta Grossa 84030-900, PR, BrazilLaboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados 79825-070, MS, BrazilGraduate Program in Pharmaceutical Sciences, State University of Ponta Grossa, Ponta Grossa 84030-900, PR, BrazilLaboratory of Natural Products and Mass Spectrometry (LaPNEM), Faculty of Pharmaceutical Sciences, Food and Nutrition (FACFAN), University of Mato Grosso do Sul (UFMS), Campo Grande 79080-190, MS, BrazilLaboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados 79825-070, MS, BrazilLaboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados 79825-070, MS, BrazilSchool of Health, Environment, Sustainability and Humanity, Uninter International University Center, Curitiba 80020-110, PR, BrazilNatural Products Utilization Research Unit, Agricultural Research Service, United States Department of Agriculture, University of Mississippi, University, MS 38677, USALaboratory of Natural Products and Mass Spectrometry (LaPNEM), Faculty of Pharmaceutical Sciences, Food and Nutrition (FACFAN), University of Mato Grosso do Sul (UFMS), Campo Grande 79080-190, MS, BrazilLaboratory of Natural Products and Mass Spectrometry (LaPNEM), Faculty of Pharmaceutical Sciences, Food and Nutrition (FACFAN), University of Mato Grosso do Sul (UFMS), Campo Grande 79080-190, MS, BrazilNational Center for Natural Products Research, University of Mississippi, University, MS 38677, USALaboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados 79825-070, MS, BrazilGraduate Program in Pharmaceutical Sciences, State University of Ponta Grossa, Ponta Grossa 84030-900, PR, Brazil<i>Piper amalago</i> L. is used in Brazilian traditional medicine to treat inflammation, chest pain, and anxiety. This study aimed to investigate the safety and the renal and cardiovascular effects of the volatile oil (VO) and the aqueous (AE) and hydroalcoholic (HE) extracts from <i>P. amalago</i>. The gas chromatography-mass spectrometry analyses identified 47 compounds in the VO, with β-cyclogermacrene, spathulenol, β-phellandrene, and α-pinene standing out. Among the 47 compounds also found in AE and HE by liquid chromatography-mass spectrometry, glycosylated flavones, organic acids, amino acids, and amides were highlighted. Some examples of these compounds are methoxy-methylenedioxy <i>cis</i>-cinnamoyl pyrrolidine, methoxy-methylenedioxy <i>trans</i>-cinnamoyl pyrrolidine, and cyclobutene-2,4-<i>bis</i>-(1,3-benzodioxol-5-methoxy-6-yl)-1,3-dicarboxapyrrolidide. The acute toxicity experiments were conducted on female rats (<i>n</i> = 5). The cardiorenal assays (<i>n</i> = 8) and evaluations of vasodilatory effects on the mesenteric vascular bed (<i>n</i> = 5) were conducted on male rats. In either extract or VO, there were no mortality or changes in relative weights or histopathological analysis of the organs. Urinary volume and renal electrolyte excretion were elevated significantly during repeated dose 7-day treatment with different preparations from <i>P. amalago</i>. None of the preparations induced hypotension or changes in cardiac electrical activity. Only HE promoted significant vasodilatory effects in rats’ isolated mesenteric vascular beds. These effects were completely abolished in the presence of L-NAME <i>plus</i> 4-aminopyridine. Therefore, <i>P. amalago</i> leaves are safe and present diuretic activity after acute and repeated dose administration over 7 days. Moreover, the HE induced significant vasodilator response in rats’ mesenteric vascular beds by NO/cGMP pathway and voltage-dependent K<sup>+</sup> channels activation.https://www.mdpi.com/1424-8247/16/11/1630acute toxicologycardiovascular effectdiuretic effectjaborandi-mansopariparobaPiperaceae |
| spellingShingle | Luciane M. Monteiro Lislaine M. Klider Aline A. M. Marques Paulo V. Farago Janaína Emiliano Roosevelt I. C. Souza Ariany C. dos Santos Vera L. P. dos Santos Mei Wang Nadla S. Cassemiro Denise B. Silva Ikhlas A. Khan Arquimedes Gasparotto Junior Jane Manfron The Cardiorenal Effects of <i>Piper amalago</i> Are Mediated by the Nitric Oxide/Cyclic Guanosine Monophosphate Pathway and the Voltage-Dependent Potassium Channels Pharmaceuticals acute toxicology cardiovascular effect diuretic effect jaborandi-manso pariparoba Piperaceae |
| title | The Cardiorenal Effects of <i>Piper amalago</i> Are Mediated by the Nitric Oxide/Cyclic Guanosine Monophosphate Pathway and the Voltage-Dependent Potassium Channels |
| title_full | The Cardiorenal Effects of <i>Piper amalago</i> Are Mediated by the Nitric Oxide/Cyclic Guanosine Monophosphate Pathway and the Voltage-Dependent Potassium Channels |
| title_fullStr | The Cardiorenal Effects of <i>Piper amalago</i> Are Mediated by the Nitric Oxide/Cyclic Guanosine Monophosphate Pathway and the Voltage-Dependent Potassium Channels |
| title_full_unstemmed | The Cardiorenal Effects of <i>Piper amalago</i> Are Mediated by the Nitric Oxide/Cyclic Guanosine Monophosphate Pathway and the Voltage-Dependent Potassium Channels |
| title_short | The Cardiorenal Effects of <i>Piper amalago</i> Are Mediated by the Nitric Oxide/Cyclic Guanosine Monophosphate Pathway and the Voltage-Dependent Potassium Channels |
| title_sort | cardiorenal effects of i piper amalago i are mediated by the nitric oxide cyclic guanosine monophosphate pathway and the voltage dependent potassium channels |
| topic | acute toxicology cardiovascular effect diuretic effect jaborandi-manso pariparoba Piperaceae |
| url | https://www.mdpi.com/1424-8247/16/11/1630 |
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