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Mechanism of vasorelaxation induced by 3′-hydroxy-5,6,7,4′-tetramethoxyflavone in the rats aortic ring assay

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Abstract

Previous studies have demonstrated that 3′-hydroxy-5,6,7,4′-tetramethoxyflavone (TMF) content in Orthosiphon stamineus fractions correlate with its vasorelaxation activity. Even with the availability of previous studies, there is still very little information on the vasorelaxation effect of TMF, and few scientific studies have been carried out. Therefore, the present study was designed to investigate the vasorelaxation activity and mechanism of action of the TMF. The vasorelaxation activity and the underlying mechanisms of TMF were evaluated on thoracic aortic rings isolated from Sprague Dawley rats. TMF caused the relaxation of aortic rings with endothelium pre-contracted with phenylephrine. However, the vasorelaxant effect of TMF was significantly decreased in PE-primed endothelium-denuded and potassium chloride-primed endothelium-intact aortic rings. In the presence of Nω-nitro-l-arginine methyl ester, methylene blue, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, indomethacin, tetraethylammonium, 4-aminopyridine, barium chloride, atropine and propranolol, the relaxation stimulated by TMF was significantly reduced. TMF was also found to reduce Ca2+ release from sarcoplasmic reticulum (via IP3R) and block calcium channels (VOCC). The present study demonstrates the vasorelaxant effect of TMF involves NO/sGC/cGMP and prostacyclin pathways, calcium and potassium channels and muscarinic and beta-adrenergic receptors.

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Pulau Pinang, Malaysia

    Chu Shan Tan & Mun Fei Yam

  2. College of Pharmacy, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Shangjie, Minhou, Fuzhou, Fujian, 350122, China

    Mun Fei Yam

Authors
  1. Chu Shan Tan
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  2. Mun Fei Yam
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Correspondence to Mun Fei Yam.

Ethics declarations

All the procedure described herein were approved by animal ethics committee USM (no. of animal ethics approval: USM/Animal Ethics Approval/2016/(103)(772).

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Highlight of the manuscript:

• TMF might be one of the antihypertensive compounds from Orthosiphon stamineus (Jawa tea).

• TMF exhibits vasorelaxant effect on aortic ring assay.

• The vasorelaxant effect of TMF involves multi-pathways.

• TMF induces vasorelaxation via Kv, Kir and KCa VOCC channels and IP3 receptor.

• The vasorelaxant effect of TMF involves NO/sGC/cGMP pathway

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Tan, C.S., Yam, M.F. Mechanism of vasorelaxation induced by 3′-hydroxy-5,6,7,4′-tetramethoxyflavone in the rats aortic ring assay. Naunyn-Schmiedeberg's Arch Pharmacol 391, 561–569 (2018). https://doi.org/10.1007/s00210-018-1481-9

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  • DOI: https://doi.org/10.1007/s00210-018-1481-9

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