Sesquiterpene lactones from Hedyosmum brasiliense induce in vitro relaxation of rat aorta and corpus cavernosum

Abstract

Hedyosmum brasiliense Miq., Chloranthaceae, has been used in Southern Brazil as a sedative, antiinflammatory, and aphrodisiac. In this study, endothelium-intact and endothelium-denuded rat aortic rings and strips of corpus cavernosum were used to investigate the relaxant effects of an hexane fraction of leaves of H. brasiliense and its sesquiterpene lactones 13-hydroxy-8,9-dehydroshizukanolide, podoandin, and elemanolide 15-acetoxy-isogermafurenolide. The incubation of hexane fraction of leaves of H. brasiliense resulted in significant relaxation of endothelium-intact aortic rings previously contracted by phenylephrine. In addition, 13-hydroxy-8,9-dehydroshizukanolide and podoandin displayed a clear concentration-dependent ability to relax endothelium-intact (~85 to 90%) and endothelium-denuded (~45 to 55%) rat aortic rings. A less pronounced vascular relaxation was recorded when 15-hydroxy-isogermafurenolide was tested. Interestingly, in tissues previously incubated with the nitric oxide synthase inhibitor L-NAME (100 μM), both 13-hydroxy-8,9-dehydroshizukanolide and podoandin had their effects in endothelium-intact vessels reduced to the same degree of relaxation observed in endothelium-denuded aortic rings. Podoandin, 13-hydroxy-8,9-dehydroshizukanolide, and 15-acetoxy-isogermafurenolide ( 100 μM) were also able to relax precontracted corpus cavernosum strips by 49.5 ±3.9%, 65.9 ±7.3% and 57.9 ±5.5%, respectively. Our results demonstrated that 13-hydroxy-8,9-dehydroshizukanolide, podoandin and 15-acetoxy-isogermafurenolide, isolated from H. brasiliense, generate both endothelium-dependent and -independent relaxation of rat aortic rings, as well as being able to induce in vitro relaxation of rat corpus cavernosum. Importantly, the endothelium-dependent effect is fully dependent on nitric oxide production. Considering that penile erection depends on both relaxation of cavernosal smooth muscle and inflow of blood for the cavernous bodies, this is the first study reporting experimental evidence supporting the aphrodisiac properties of H. brasiliense.

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Acknowledgments

A. Leitolis conducted her M.Sc. studies as recipient of fellowship from CNPq, Brazil. S.K.S. Amoah received a fellowship from CAPES, Brazil. We thank CNPq and Fundação de Amparo a Pesquisa e Inovação de Santa Catarina (FAPESC, SC, Brazil) for previous grants that allowed the development of this research.

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S.K.S.A. worked in the preparation of extracts and isolation of the sesquiterpene lactones during his Ph.D. studies, under supervision of MWB. A.L. performed the in vitro studies and analyzed the results obtained. A.L. and S.K.S.A. drafted the manuscript. JESS was responsible for the conception of the study, including protocols and interpretation of data while supervising A.L. during her graduate studies in Pharmacology, and worked on the manuscript.

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Correspondence to J. Eduardo da Silva-Santos.

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Leitolis, A., Amoah, S.K.S., Biavatti, M.W. et al. Sesquiterpene lactones from Hedyosmum brasiliense induce in vitro relaxation of rat aorta and corpus cavernosum. Rev. Bras. Farmacogn. 26, 363–368 (2016). https://doi.org/10.1016/j.bjp.2016.01.005

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Keywords

  • Vasodilation
  • Nitric oxide
  • Erectile function
  • Aphrodisiac
  • Vascular function
  • Smooth muscle