Crude extract and purified components isolated from the stems of Tinospora crispa exhibit positive inotropic effects on the isolated left atrium of rats

Tinospora crispa has been used in folkloric medicine for the control of blood pressure. We previously found that an extract of Tinospora crispa and its constituents effect the heart rate and blood pressure in anesthetized rats. The aim was to investigate the effects and mechanisms of the Tinospora c...

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Veröffentlicht in:Journal of ethnopharmacology 2013-08, Vol.149 (1), p.123-132
Hauptverfasser: Praman, Siwaporn, Mulvany, Michael J., Williams, David E., Andersen, Raymond J., Jansakul, Chaweewan
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container_issue 1
container_start_page 123
container_title Journal of ethnopharmacology
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creator Praman, Siwaporn
Mulvany, Michael J.
Williams, David E.
Andersen, Raymond J.
Jansakul, Chaweewan
description Tinospora crispa has been used in folkloric medicine for the control of blood pressure. We previously found that an extract of Tinospora crispa and its constituents effect the heart rate and blood pressure in anesthetized rats. The aim was to investigate the effects and mechanisms of the Tinospora crispa extract and bioactive components on the rat isolated left atria. Air-dried stems of Tinospora crispa were extracted with water, followed by partitioning with chloroform, ethyl acetate, and finally by n-butanol. The n-butanol soluble material was concentrated and dried under reduced pressure and lyophilized to obtain a crude powder (Tinospora crispa extract). The active components of Tinospora crispa extract were separated by column chromatography and preparative HPLC. The effects and mechanisms of the n-butanol extract and the bioactive purified components (adenine, uridine, adenosine, salsolinol, tyramine, higenamine, syringin, (−)-litcubinine, borapetoside A, borapetoside B, borapetoside D and borapetoside E) were studied in isolated left atria from normal and reserpinized rats. Tinospora crispa extract caused an increase in the force of contraction of the electrical field stimulated left atrium. This effect was inhibited by propranolol, atenolol, ICI-118,551, phentolamine and atropine. The positive inotropic effect on the reserpenized isolated left atrium of the Tinospora crispa extract was significantly inhibited by propranolol, atenolol and ICI-118,551. Phentolamine, on the other hand, caused potentiation and the effect was inhibited when propranolol was also added. Higenamine caused an increase in the force of contraction of the electrical field stimulated left atrium and this effect was significantly inhibited by ICI-118,551 and atenolol but not by phentolamine. Reserpine did not significantly shift the concentration–response curve (C–R curve) of the inotropic effect of the higenamine. ICI-118,551 and atenolol caused a parallel shift of the C–R curve to the right of about 8 and 33 fold, respectively. At low concentrations salsolinol caused a slight increase in the force of contraction of the left atrium, but at higher concentrations a decrease was observed. The negative inotropic effect of salsolinol was significantly inhibited by propranolol and atropine. In the reserpinized isolated left atrium, the negative inotropic effect of salsolinol was potentiated and again this effect was significantly inhibited by propranolol and atropine. Tyramine caused
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We previously found that an extract of Tinospora crispa and its constituents effect the heart rate and blood pressure in anesthetized rats. The aim was to investigate the effects and mechanisms of the Tinospora crispa extract and bioactive components on the rat isolated left atria. Air-dried stems of Tinospora crispa were extracted with water, followed by partitioning with chloroform, ethyl acetate, and finally by n-butanol. The n-butanol soluble material was concentrated and dried under reduced pressure and lyophilized to obtain a crude powder (Tinospora crispa extract). The active components of Tinospora crispa extract were separated by column chromatography and preparative HPLC. The effects and mechanisms of the n-butanol extract and the bioactive purified components (adenine, uridine, adenosine, salsolinol, tyramine, higenamine, syringin, (−)-litcubinine, borapetoside A, borapetoside B, borapetoside D and borapetoside E) were studied in isolated left atria from normal and reserpinized rats. Tinospora crispa extract caused an increase in the force of contraction of the electrical field stimulated left atrium. This effect was inhibited by propranolol, atenolol, ICI-118,551, phentolamine and atropine. The positive inotropic effect on the reserpenized isolated left atrium of the Tinospora crispa extract was significantly inhibited by propranolol, atenolol and ICI-118,551. Phentolamine, on the other hand, caused potentiation and the effect was inhibited when propranolol was also added. Higenamine caused an increase in the force of contraction of the electrical field stimulated left atrium and this effect was significantly inhibited by ICI-118,551 and atenolol but not by phentolamine. Reserpine did not significantly shift the concentration–response curve (C–R curve) of the inotropic effect of the higenamine. ICI-118,551 and atenolol caused a parallel shift of the C–R curve to the right of about 8 and 33 fold, respectively. At low concentrations salsolinol caused a slight increase in the force of contraction of the left atrium, but at higher concentrations a decrease was observed. The negative inotropic effect of salsolinol was significantly inhibited by propranolol and atropine. In the reserpinized isolated left atrium, the negative inotropic effect of salsolinol was potentiated and again this effect was significantly inhibited by propranolol and atropine. Tyramine caused a positive inotropic effect, and this effect was inhibited by propranolol or by pretreatment of the rat with reserpine. Adenosine caused a negative inotropic effect, while uridine caused a slight positive inotropic effect on the left atrium. This effect was significantly inhibited by DPCPX. Crude extracs of Tinospora crispa exert a positive inotropic effect on the electrical field stimulated isolated left atria that results from the concerted action of 5 bioactive compounds: higenamine, salsolinol, tyramine, adenosine and uridine. Higenamine, salsolinol (at low concentration) and tyramine acted via the adrenergic receptors to increase the force of the atrial contraction, whereas a high concentration of salsolinol acted indirectly by stimulating the release of acetylcholine. Adenosine and uridine acted via the purinergic pathways to cause negative inotropic effects on the isolated left atria. Positive inotropic effect of Tinospora crispa extract largely results from higenamine and salsolinol acting via the β-adrenoceptors, tyramine stimulated release of the NA, and uridine acts via A1adenosine receptors. At the same time adenosine acts via the A1adenosine receptors, to modulate its positive inotropic effect on the left atrium. [Display omitted]</description><identifier>ISSN: 0378-8741</identifier><identifier>EISSN: 1872-7573</identifier><identifier>DOI: 10.1016/j.jep.2013.06.010</identifier><identifier>PMID: 23778316</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>acetates ; adenine ; adenosine ; adrenergic receptors ; Animals ; Atrial Function, Left - drug effects ; atropine ; blood pressure ; Cardiotonic Agents - isolation &amp; purification ; Cardiotonic Agents - pharmacology ; chloroform ; DPCPX ; electric field ; Ethnopharmacology ; Female ; Heart Atria - drug effects ; heart rate ; Higenamine ; high performance liquid chromatography ; ICI-118,551 ; In Vitro Techniques ; Left atria ; medicine ; Myocardial Contraction - drug effects ; Plant Extracts - isolation &amp; purification ; Plant Extracts - pharmacology ; Plant Stems - chemistry ; propranolol ; Rats ; Rats, Wistar ; reserpine ; stems ; Tinospora ; Tinospora - chemistry ; Tinospora crispa ; Tyramine ; uridine</subject><ispartof>Journal of ethnopharmacology, 2013-08, Vol.149 (1), p.123-132</ispartof><rights>2013 Elsevier Ireland Ltd</rights><rights>Copyright © 2013 Elsevier Ireland Ltd. 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We previously found that an extract of Tinospora crispa and its constituents effect the heart rate and blood pressure in anesthetized rats. The aim was to investigate the effects and mechanisms of the Tinospora crispa extract and bioactive components on the rat isolated left atria. Air-dried stems of Tinospora crispa were extracted with water, followed by partitioning with chloroform, ethyl acetate, and finally by n-butanol. The n-butanol soluble material was concentrated and dried under reduced pressure and lyophilized to obtain a crude powder (Tinospora crispa extract). The active components of Tinospora crispa extract were separated by column chromatography and preparative HPLC. The effects and mechanisms of the n-butanol extract and the bioactive purified components (adenine, uridine, adenosine, salsolinol, tyramine, higenamine, syringin, (−)-litcubinine, borapetoside A, borapetoside B, borapetoside D and borapetoside E) were studied in isolated left atria from normal and reserpinized rats. Tinospora crispa extract caused an increase in the force of contraction of the electrical field stimulated left atrium. This effect was inhibited by propranolol, atenolol, ICI-118,551, phentolamine and atropine. The positive inotropic effect on the reserpenized isolated left atrium of the Tinospora crispa extract was significantly inhibited by propranolol, atenolol and ICI-118,551. Phentolamine, on the other hand, caused potentiation and the effect was inhibited when propranolol was also added. Higenamine caused an increase in the force of contraction of the electrical field stimulated left atrium and this effect was significantly inhibited by ICI-118,551 and atenolol but not by phentolamine. Reserpine did not significantly shift the concentration–response curve (C–R curve) of the inotropic effect of the higenamine. ICI-118,551 and atenolol caused a parallel shift of the C–R curve to the right of about 8 and 33 fold, respectively. At low concentrations salsolinol caused a slight increase in the force of contraction of the left atrium, but at higher concentrations a decrease was observed. The negative inotropic effect of salsolinol was significantly inhibited by propranolol and atropine. In the reserpinized isolated left atrium, the negative inotropic effect of salsolinol was potentiated and again this effect was significantly inhibited by propranolol and atropine. Tyramine caused a positive inotropic effect, and this effect was inhibited by propranolol or by pretreatment of the rat with reserpine. Adenosine caused a negative inotropic effect, while uridine caused a slight positive inotropic effect on the left atrium. This effect was significantly inhibited by DPCPX. Crude extracs of Tinospora crispa exert a positive inotropic effect on the electrical field stimulated isolated left atria that results from the concerted action of 5 bioactive compounds: higenamine, salsolinol, tyramine, adenosine and uridine. Higenamine, salsolinol (at low concentration) and tyramine acted via the adrenergic receptors to increase the force of the atrial contraction, whereas a high concentration of salsolinol acted indirectly by stimulating the release of acetylcholine. Adenosine and uridine acted via the purinergic pathways to cause negative inotropic effects on the isolated left atria. Positive inotropic effect of Tinospora crispa extract largely results from higenamine and salsolinol acting via the β-adrenoceptors, tyramine stimulated release of the NA, and uridine acts via A1adenosine receptors. At the same time adenosine acts via the A1adenosine receptors, to modulate its positive inotropic effect on the left atrium. [Display omitted]</description><subject>acetates</subject><subject>adenine</subject><subject>adenosine</subject><subject>adrenergic receptors</subject><subject>Animals</subject><subject>Atrial Function, Left - drug effects</subject><subject>atropine</subject><subject>blood pressure</subject><subject>Cardiotonic Agents - isolation &amp; purification</subject><subject>Cardiotonic Agents - pharmacology</subject><subject>chloroform</subject><subject>DPCPX</subject><subject>electric field</subject><subject>Ethnopharmacology</subject><subject>Female</subject><subject>Heart Atria - drug effects</subject><subject>heart rate</subject><subject>Higenamine</subject><subject>high performance liquid chromatography</subject><subject>ICI-118,551</subject><subject>In Vitro Techniques</subject><subject>Left atria</subject><subject>medicine</subject><subject>Myocardial Contraction - drug effects</subject><subject>Plant Extracts - isolation &amp; purification</subject><subject>Plant Extracts - pharmacology</subject><subject>Plant Stems - chemistry</subject><subject>propranolol</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>reserpine</subject><subject>stems</subject><subject>Tinospora</subject><subject>Tinospora - chemistry</subject><subject>Tinospora crispa</subject><subject>Tyramine</subject><subject>uridine</subject><issn>0378-8741</issn><issn>1872-7573</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc2OFCEURonROO3oA7hRlm6qhKKqoOPKdPxLJnHhzJpQcHHoVBUI1ETfxMf1tj3O0hWEnHuA7yPkJWctZ3x8e2yPkNqOcdGysWWcPSI7rmTXyEGKx2THhFSNkj2_IM9KOTLGJO_ZU3LRCSmV4OOO_D7kzQGFnzUbW6lZHU1bDj6AozYuKa6w1kJDibOpeOZzXGi9BVoqLIVGT6_DGkuK2VCbQ0kGXbdhCpWmWEINd0ARqDmmYCl4DxZ1cf3reLDO4PHumsO2nJTZ1PKcPPFmLvDifr0kNx8_XB8-N1dfP305vL9qLP6hNpPoufLjaIz1cnCT6eReOa8Mm7hkArfTJHyn3Lj3Zi860zvfcaUG5Sc7WCMuyZuzN-X4Y4NS9RKKhXk2K8StaN5348AxOo4oP6M2x1IyeJ1yWEz-pTnTp0L0UWMh-lSIZqPGQnDm1b1-mxZwDxP_GkDg9RnwJmrzHSPUN9_Q0OOVverViXh3JgBjuAuQdbEBVgsuZExTuxj-84A_ZKmpCA</recordid><startdate>20130826</startdate><enddate>20130826</enddate><creator>Praman, Siwaporn</creator><creator>Mulvany, Michael J.</creator><creator>Williams, David E.</creator><creator>Andersen, Raymond J.</creator><creator>Jansakul, Chaweewan</creator><general>Elsevier Ireland Ltd</general><scope>FBQ</scope><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>7X8</scope></search><sort><creationdate>20130826</creationdate><title>Crude extract and purified components isolated from the stems of Tinospora crispa exhibit positive inotropic effects on the isolated left atrium of rats</title><author>Praman, Siwaporn ; Mulvany, Michael J. ; Williams, David E. ; Andersen, Raymond J. ; Jansakul, Chaweewan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c377t-b3418f66aacf75dba2798df8a0b17038dfbb3f28d69fa932a4df218858fbc5ca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>acetates</topic><topic>adenine</topic><topic>adenosine</topic><topic>adrenergic receptors</topic><topic>Animals</topic><topic>Atrial Function, Left - drug effects</topic><topic>atropine</topic><topic>blood pressure</topic><topic>Cardiotonic Agents - isolation &amp; purification</topic><topic>Cardiotonic Agents - pharmacology</topic><topic>chloroform</topic><topic>DPCPX</topic><topic>electric field</topic><topic>Ethnopharmacology</topic><topic>Female</topic><topic>Heart Atria - drug effects</topic><topic>heart rate</topic><topic>Higenamine</topic><topic>high performance liquid chromatography</topic><topic>ICI-118,551</topic><topic>In Vitro Techniques</topic><topic>Left atria</topic><topic>medicine</topic><topic>Myocardial Contraction - drug effects</topic><topic>Plant Extracts - isolation &amp; purification</topic><topic>Plant Extracts - pharmacology</topic><topic>Plant Stems - chemistry</topic><topic>propranolol</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>reserpine</topic><topic>stems</topic><topic>Tinospora</topic><topic>Tinospora - chemistry</topic><topic>Tinospora crispa</topic><topic>Tyramine</topic><topic>uridine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Praman, Siwaporn</creatorcontrib><creatorcontrib>Mulvany, Michael J.</creatorcontrib><creatorcontrib>Williams, David E.</creatorcontrib><creatorcontrib>Andersen, Raymond J.</creatorcontrib><creatorcontrib>Jansakul, Chaweewan</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><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>Praman, Siwaporn</au><au>Mulvany, Michael J.</au><au>Williams, David E.</au><au>Andersen, Raymond J.</au><au>Jansakul, Chaweewan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Crude extract and purified components isolated from the stems of Tinospora crispa exhibit positive inotropic effects on the isolated left atrium of rats</atitle><jtitle>Journal of ethnopharmacology</jtitle><addtitle>J Ethnopharmacol</addtitle><date>2013-08-26</date><risdate>2013</risdate><volume>149</volume><issue>1</issue><spage>123</spage><epage>132</epage><pages>123-132</pages><issn>0378-8741</issn><eissn>1872-7573</eissn><abstract>Tinospora crispa has been used in folkloric medicine for the control of blood pressure. We previously found that an extract of Tinospora crispa and its constituents effect the heart rate and blood pressure in anesthetized rats. The aim was to investigate the effects and mechanisms of the Tinospora crispa extract and bioactive components on the rat isolated left atria. Air-dried stems of Tinospora crispa were extracted with water, followed by partitioning with chloroform, ethyl acetate, and finally by n-butanol. The n-butanol soluble material was concentrated and dried under reduced pressure and lyophilized to obtain a crude powder (Tinospora crispa extract). The active components of Tinospora crispa extract were separated by column chromatography and preparative HPLC. The effects and mechanisms of the n-butanol extract and the bioactive purified components (adenine, uridine, adenosine, salsolinol, tyramine, higenamine, syringin, (−)-litcubinine, borapetoside A, borapetoside B, borapetoside D and borapetoside E) were studied in isolated left atria from normal and reserpinized rats. Tinospora crispa extract caused an increase in the force of contraction of the electrical field stimulated left atrium. This effect was inhibited by propranolol, atenolol, ICI-118,551, phentolamine and atropine. The positive inotropic effect on the reserpenized isolated left atrium of the Tinospora crispa extract was significantly inhibited by propranolol, atenolol and ICI-118,551. Phentolamine, on the other hand, caused potentiation and the effect was inhibited when propranolol was also added. Higenamine caused an increase in the force of contraction of the electrical field stimulated left atrium and this effect was significantly inhibited by ICI-118,551 and atenolol but not by phentolamine. Reserpine did not significantly shift the concentration–response curve (C–R curve) of the inotropic effect of the higenamine. ICI-118,551 and atenolol caused a parallel shift of the C–R curve to the right of about 8 and 33 fold, respectively. At low concentrations salsolinol caused a slight increase in the force of contraction of the left atrium, but at higher concentrations a decrease was observed. The negative inotropic effect of salsolinol was significantly inhibited by propranolol and atropine. In the reserpinized isolated left atrium, the negative inotropic effect of salsolinol was potentiated and again this effect was significantly inhibited by propranolol and atropine. Tyramine caused a positive inotropic effect, and this effect was inhibited by propranolol or by pretreatment of the rat with reserpine. Adenosine caused a negative inotropic effect, while uridine caused a slight positive inotropic effect on the left atrium. This effect was significantly inhibited by DPCPX. Crude extracs of Tinospora crispa exert a positive inotropic effect on the electrical field stimulated isolated left atria that results from the concerted action of 5 bioactive compounds: higenamine, salsolinol, tyramine, adenosine and uridine. Higenamine, salsolinol (at low concentration) and tyramine acted via the adrenergic receptors to increase the force of the atrial contraction, whereas a high concentration of salsolinol acted indirectly by stimulating the release of acetylcholine. Adenosine and uridine acted via the purinergic pathways to cause negative inotropic effects on the isolated left atria. Positive inotropic effect of Tinospora crispa extract largely results from higenamine and salsolinol acting via the β-adrenoceptors, tyramine stimulated release of the NA, and uridine acts via A1adenosine receptors. At the same time adenosine acts via the A1adenosine receptors, to modulate its positive inotropic effect on the left atrium. [Display omitted]</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>23778316</pmid><doi>10.1016/j.jep.2013.06.010</doi><tpages>10</tpages></addata></record>
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subjects acetates
adenine
adenosine
adrenergic receptors
Animals
Atrial Function, Left - drug effects
atropine
blood pressure
Cardiotonic Agents - isolation & purification
Cardiotonic Agents - pharmacology
chloroform
DPCPX
electric field
Ethnopharmacology
Female
Heart Atria - drug effects
heart rate
Higenamine
high performance liquid chromatography
ICI-118,551
In Vitro Techniques
Left atria
medicine
Myocardial Contraction - drug effects
Plant Extracts - isolation & purification
Plant Extracts - pharmacology
Plant Stems - chemistry
propranolol
Rats
Rats, Wistar
reserpine
stems
Tinospora
Tinospora - chemistry
Tinospora crispa
Tyramine
uridine
title Crude extract and purified components isolated from the stems of Tinospora crispa exhibit positive inotropic effects on the isolated left atrium of rats
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