Effects of medicinal herbs on contraction rate of cultured cardiomyocyte. Possible mechanisms involved in the chronotropic effects of hawthorn and berberine in neonatal murine cardiomyocyte Public Deposited

http://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/n870zw293

Descriptions

Attribute NameValues
Alternative Title
  • Possible mechanisms involved in the chronotropic effects of hawthorn and berberine in neonatal murine cardiomyocyte
Creator
Abstract or Summary
  • Herbs have been used for many centuries in diverse civilizations for the treatment of heart disease. Only a few natural supplements claim to have direct cardiovascular actions including hawthorn (Crataegus spp.) and berberine derived from the Berberidaceae family. Several different studies indicate important cardiovascular effects of hawthorn and berberine. For example, both exert positive inotropic effects and have been used in the treatment of congestive heart failure. Recently, it was shown that hawthorn extract preparations cause negative chronotropic effects in a cultured neonatal murine cardiomyocyte assay independent of beta-adrenergic receptor blockade. The aim of this study was to further characterize the effect of hawthorn extract to decrease the contraction rate of cultured cardiomyocytes. We hypothesized that hawthorn extract may be acting through muscarinic receptors to decrease contraction rate of cardiomyocytes. Atrial and ventricular cardiomyocytes were treated with hawthorn extract in the presence of atropine or himbacine. Changes in the contraction rate of cultured cardiomyocytes revealed that both muscarinic antagonists significantly attenuated the negative chronotropic activity of hawthorn extract. Using quinuclidinyl benzilate, L-[benzylic-4,4'-3H] ([³H]-QNB) as a radioligand antagonist, the effect of a partially purified hawthorn extract fraction to inhibit muscarinic receptor binding was quantified. Hawthorn extract fraction 3 dose-dependently inhibited [³H]-QNB binding to mouse heart membranes. These findings suggest that muscarinic receptors may be involved in the negative chronotropic effect of hawthorn extracts in neonatal murine cardiomyocytes. Berberine exhibits variable positive and negative chronotropic effects in different species. Our first aim was to examine the effect of berberine in a cultured neonatal murine cardiomyocyte assay. Our study demonstrates that berberine has significant negative chronotropic actions on cardiomyocytes which is not an effect of beta-adrenergic receptor blockade. Pertussis toxin (PTX), a Gi/o protein inhibitor, blocked the negative chronotropic activity of berberine. Muscarinic, adenosine, opioid, and α₂ receptors are coupled through a G-protein (Gi/o) to adenylyl cyclase in an inhibitory fashion. Activation of these receptors are primarily responsible for PTX-sensitive negative chronotropic effects in heart. We hypothesized that berberine may be acting through one of these receptor type to decrease contraction rate of cardiomyocytes. For this purpose, we studied the effects of the muscarinic-receptor antagonists, atropine, himbacine, or AF- DX 116 on the negative chronotropic activity of berberine. Muscarinic antagonists completely blocked the effect of berberine on contraction rate of cardiomyocytes, whereas the bradycardic effect of berberine was not inhibited by the opioid, adenosine, or α2 receptor antagonists naloxone, CGS 15943, or phentolamine, respectively. Using [³H]QNB as a radioligand, we demonstrated that berberine bound to muscarinic receptors of adult mouse heart membranes with relatively high affinity. Furthermore, berberine dose-dependently inhibited [³H]QNB binding to muscarinic M2 receptors exogenously expressed in HEK 293 cells. Therefore, the findings of the present study suggest that berberine has muscarinic agonist effects in cultured neonatal murine cardiomyocytes, potentially explaining reported physiological effects of berberine. Cardiac hypertrophy represents the most important factor in the development of congestive heart failure. We investigated the inhibitory effect of berberine on hypertrophy of H9c2 cells. In rat heart-derived H9c2 myoblast cells treated with different hypertrophic agonists such as insulin growth factor II (IGF-II), arginine vasopressin (AVP), phenylephrine, and isoproterenol, protein content and size of cells were significantly increased compared to control group. However, the number of H9c2 cells after treatment with hypertrophic agonists did not differ significantly compared to control. The increases in area of cells and protein content induced by the hypertrophic agonists were inhibited by treatment with berberine in a concentration-dependent manner. Our findings have provided the first scientific evidence that berberine may have an inhibitory effect on hypertrophy of heart-derived cells, and provide a rationale for further studies to evaluate berberine's cardiac activity.
Resource Type
Date Available
Date Copyright
Date Issued
Degree Level
Degree Name
Degree Field
Degree Grantor
Commencement Year
Advisor
Committee Member
Academic Affiliation
Non-Academic Affiliation
Keyword
Subject
Rights Statement
Language
Replaces
Additional Information
  • description.provenance : Submitted by Satin Salehi (salehis@onid.orst.edu) on 2009-09-22T04:34:07Z No. of bitstreams: 2 Pretext pages.pdf: 108090 bytes, checksum: 3dd62abc3e3e861dd3779fb238888953 (MD5) SalehiSatin2009.doc: 7159296 bytes, checksum: 41b631227e002d8185eac654a56460e2 (MD5)
  • description.provenance : Submitted by Satin Salehi (salehis@onid.orst.edu) on 2009-09-24T22:48:42Z No. of bitstreams: 1 SalehiSatin2009.pdf: 803629 bytes, checksum: bbfd9f5edd78bb7603b2c3614bcba036 (MD5)
  • description.provenance : Approved for entry into archive by Laura Wilson(laura.wilson@oregonstate.edu) on 2009-09-29T17:30:22Z (GMT) No. of bitstreams: 1 SalehiSatin2009.pdf: 803629 bytes, checksum: bbfd9f5edd78bb7603b2c3614bcba036 (MD5)
  • description.provenance : Made available in DSpace on 2009-09-29T17:30:23Z (GMT). No. of bitstreams: 1 SalehiSatin2009.pdf: 803629 bytes, checksum: bbfd9f5edd78bb7603b2c3614bcba036 (MD5)
  • description.provenance : Approved for entry into archive by Julie Kurtz(julie.kurtz@oregonstate.edu) on 2009-09-25T16:28:32Z (GMT) No. of bitstreams: 1 SalehiSatin2009.pdf: 803629 bytes, checksum: bbfd9f5edd78bb7603b2c3614bcba036 (MD5)
  • description.provenance : Rejected by Julie Kurtz(julie.kurtz@oregonstate.edu), reason: Rejecting because dissertation was submitted with one PDF and one Word document. The requirements are to submit one PDF of the entire dissertation. Once revised, open the item that was rejected. Replace the attached file with the revised file and resubmit. Thanks, Julie on 2009-09-22T15:56:50Z (GMT)

Relationships

Parents:

This work has no parents.

Last modified

Downloadable Content

Download PDF

Items