Download PDF
Planta Med 2020; 86(09): 631-642
DOI: 10.1055/a-1154-8832
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Vasorelaxing Activity of Stilbenoid and Phenanthrene Derivatives from Brasiliorchis porphyrostele: Involvement of Smooth Muscle CaV1.2 Channels

Watcharee Waratchareeyakul
1   Natural Products Research Group, Department of Chemistry, University of Surrey, Guildford, United Kingdom
2   Department of Chemistry, Rambhai Barni Rajabhat University, Chanthaburi, Thailand
,
Fabio Fusi
3   Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Siena, Italy
,
Miriam Durante
4   Dipartimento di Scienze della Vita, Università degli Studi di Siena, Siena, Italy
,
Amer Ahmed
4   Dipartimento di Scienze della Vita, Università degli Studi di Siena, Siena, Italy
,
Walter Knirsch
5   Institute of Plant Sciences, Karl-Franzens-University, Graz, Austria
,
Eduard Mas-Claret
1   Natural Products Research Group, Department of Chemistry, University of Surrey, Guildford, United Kingdom
,
Dulcie A. Mulholland
1   Natural Products Research Group, Department of Chemistry, University of Surrey, Guildford, United Kingdom
6   School of Chemistry and Physics, University of KwaZulu-Natal, Durban, South Africa
› Author AffiliationsSupported by: National Science and Technology Development Agency, Thailand
Supported by: National Research Council of Thailand
Further Information

Publication History

received 18 January 2020
revised 29 March 2020

accepted 04 April 2020

Publication Date:
29 April 2020 (online)

    Permissions and Reprints

Abstract

Five compounds, 3,4′-dihydroxy-3′,5,5′-trimethoxydihydrostilbene, 1; 3,4′-ihydroxy-3′,5′-dimethoxydihydrostilbene, 2; 3,4′-dihydroxy-5,5′-dimethoxydihydrostilbene, 3; 9,10-dihydro-2,7-dihydroxy-4,6-dimethoxyphenanthrene, 4; and the previously unreported 1,2,6,7-tetrahydroxy-4-methoxyphenanthrene, 5 were isolated from the South American orchid, Brasiliorchis porphyrostele. An in-depth analysis of their vascular effects was performed on in vitro rat aorta rings and tail main artery myocytes. Compounds 1 – 4 were shown to possess vasorelaxant activity on rings pre-contracted by the α 1 receptor agonist phenylephrine, the CaV1.2 stimulator (S)-(−)-Bay K 8644, or depolarized with high K+ concentrations. However, compound 5 was active solely on rings stimulated by 25 mM but not 60 mM K+. The spasmolytic activity of compounds 1 and 4 was significantly affected by the presence of an intact endothelium. The KATP channel blocker glibenclamide and the KV channel blocker 4-aminopyridine significantly antagonized the vasorelaxant activity of compounds 4 and 1, respectively. In patch-clamp experiments, compounds 1 – 4 inhibited Ba2+ current through CaV1.2 channels in a concentration-dependent manner, whereas neither compound 4 nor compound 1 affected K+ currents through KATP and KV channels, respectively. The present in vitro, comprehensive study demonstrates that Brasiliorchis porphyrostele may represent a source of vasoactive agents potentially useful for the development of novel antihypertensive agents that has now to be validated in vivo in animal models of hypertension.

Key words

Brasiliorchis porphyrostele - phenanthrenes - stilbenoids - vasorelaxing - vascular CaV1.2 channel - vascular endothelium - Orchidaceae

Supporting Information

    Plant material, isolation procedure, NMR data for compounds 1 – 5, NMR and UV spectra for compound 5, and the effect of 2 mM TEA, 3 mM 4-aminopyridine, and 5 µM glibenclamide on K 25-induced contraction (endothelium denuded rat aorta rings) are available as Supporting Information.

  • Supporting Information
 

  • References

  • 1 Singer R, Koehler S, Carnevali G. Brasiliorchis: a new genus for the Maxillaria picta alliance (Orchidaceae, Maxillariinae). Novon 2009; 17: 91-99
    PubMedGoogle Scholar
  • 2 Hossain MM. Therapeutic orchids: traditional uses and recent advances – an overview. Fitoterapia 2011; 82: 102-140
    CrossrefPubMedGoogle Scholar
  • 3 Kovacs A, Vasas A, Hohmann J. Natural phenanthrenes and their biological activity. Phytochemistry 2008; 69: 1084-1110
    CrossrefPubMedGoogle Scholar
  • 4 Estrada S, Lopez-Guerrero JJ, Villalobos-Molina R, Mata R. Spasmolytic stilbenoids from Maxillaria densa . Fitoterapia 2004; 75: 690-695
    CrossrefPubMedGoogle Scholar
  • 5 Nopo-Olazabal C, Hubstenberger J, Nopo-Olazabal L, Medina-Bolivar F. Antioxidant activity of selected stilbenoids and their bioproduction in hairy root cultures of muscadine grape (Vitis rotundifolia Michx.). J Agric Food Chem 2013; 61: 11744-11758
    CrossrefPubMedGoogle Scholar
  • 6 Sonkusare S, Palade PT, Marsh JD, Telemaque S, Pesic A, Rusch NJ. Vascular calcium channels and high blood pressure: pathophysiology and therapeutic implications. Vascul Pharmacol 2006; 44: 131-142
    CrossrefPubMedGoogle Scholar
  • 7 Bulpitt CJ. The uses and misuses of orchids in medicine. Q J Med 2005; 98: 625-631
    CrossrefPubMedGoogle Scholar
  • 8 Dixon N, Wong LS, Geerlings TH, Micklefield J. Cellular targets of natural products. Nat Prod Rep 2007; 24: 1288-1310
    CrossrefPubMedGoogle Scholar
  • 9 Fusi F, Trezza A, Spiga O, Sgaragli G, Bova S. CaV1.2 channel current block by the PKA inhibitor H-89 in rat tail artery myocytes via a PKA-independent mechanism: electrophysiological, functional, and molecular docking studies. Biochem Pharmacol 2017; 140: 53-63
    CrossrefPubMedGoogle Scholar
  • 10 Saponara S, Testai L, Iozzi D, Martinotti E, Martelli A, Chericoni S, Sgaragli G, Fusi F, Calderone V. (±)-Naringenin as large conductance Ca2+-activated K+ (BKCa) channel opener in vascular smooth muscle cells. Br J Pharmacol 2006; 149: 1013-1021
    CrossrefPubMedGoogle Scholar
  • 11 Tang G, Wang R. Differential expression of KV and KCa channels in vascular smooth muscle cells during 1-day culture. Pflugers Arch 2001; 442: 124-135
    CrossrefPubMedGoogle Scholar
  • 12 Low AM, Darby PJ, Kwan CY, Daniel EE. Effects of thapsigargin and ryanodine on vascular contractility: cross-talk between sarcoplasmic reticulum and plasmalemma. Eur J Pharmacol 1993; 230: 53-62
    PubMedGoogle Scholar
  • 13 Gurney AM. Mechanisms of drug-induced vasodilation. J Pharm Pharmacol 1994; 46: 242-251
    CrossrefPubMedGoogle Scholar
  • 14 Kuga T, Sadoshima J, Tomoike H, Kanaide H, Akaike N, Nakamura M. Actions of Ca2+ antagonists on two types of Ca2+ channels in rat aorta smooth muscle cells in primary culture. Circ Res 1990; 67: 469-480
    CrossrefPubMedGoogle Scholar
  • 15 Timin EN, Berjukow S, Hering S. Concepts of state-dependent Pharmacology of Calcium Channels. In: McDonough SI. ed. Calcium Channel Pharmacology. New York: Kluwer Academic/Plenum Publishers; 2004: 1-19
    CrossrefGoogle Scholar
  • 16 Rendon-Vallejo P, Hernandez-Abreu O, Vergara-Galicia J, Millan-Pacheco C, Mejia A, Ibarra-Barajas M, Estrada-Soto S. Ex vivo study of the vasorelaxant activity induced by phenanthrene derivatives isolated from Maxillaria densa . J Nat Prod 2012; 75: 2241-2245
    CrossrefPubMedGoogle Scholar
  • 17 Lerman LO, Kurtz TW, Touyz RM, Ellison DH, Chade AR, Crowley SD, Mattson DL, Mullins JJ, Osborn J, Eirin A, Reckelhoff JF, Iadecola C, Coffman TM. Animal models of hypertension: a scientific statement from the American Heart Association. Hypertension 2019; 73: e87
    PubMedGoogle Scholar
  • 18 Juneja RK, Sharma SC, Tandon JS. Two substituted bibenzyls and a dihydrophenanthrene from Cymbidium aloifolium . Phytochemistry 1987; 26: 1123-1125
    CrossrefPubMedGoogle Scholar
  • 19 Leong YW, Kang CC, Harrison LJ, Powell AD. Phenanthrenes, dihydrophenanthrenes and bibenzyls from the orchid Bulbophyllum vaginatum . Phytochemistry 1997; 44: 157-165
    CrossrefPubMedGoogle Scholar
  • 20 Majumder PL, Banerjee S, Sen S. Three stilbenoids from the orchid Agrostophyllum callosum . Phytochemistry 1996; 42: 847-852
    CrossrefPubMedGoogle Scholar
  • 21 Singh SB, Pettit GR. Antineoplastic agents. 166. Isolation, structure, and synthesis of combretastatin C-1. J Org Chem 1989; 54: 4105-4114
    CrossrefPubMedGoogle Scholar
  • 22 Cuong NM, Khanh PN, Duc HV, Huong TT, Tai BH, Binh NQ, Durante M, Fusi F. Vasorelaxing activity of two coumarins from Murraya paniculata leaves. Biol Pharm Bull 2014; 37: 694-697
    CrossrefPubMedGoogle Scholar
  • 23 Fusi F, Ferrara A, Zalatnai A, Molnar J, Sgaragli G, Saponara S. Vascular activity of two silicon compounds, ALIS 409 and ALIS 421, novel multidrug-resistance reverting agents in cancer cells. Cancer Chemother Pharmacol 2008; 61: 443-451
    CrossrefPubMedGoogle Scholar
  • 24 Fusi F, Durante M, Sgaragli G, Khanh PN, Son NT, Huong TT, Huong NV, Cuong NM. In vitro vasoactivity of zerumbone from Zingiber zerumbet . Planta Med 2015; 81: 298-304
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Fusi F, Saponara S, Sgaragli G, Cargnelli G, Bova S. Ca2+ entry blocking and contractility promoting actions of norbormide in single rat caudal artery myocytes. Br J Pharmacol 2002; 137: 323-328
    CrossrefPubMedGoogle Scholar
  • 26 Fusi F, Sgaragli G, Saponara S. Mechanism of myricetin stimulation of vascular L-type Ca2+ current. J Pharmacol Exp Ther 2005; 313: 790-797
    CrossrefPubMedGoogle Scholar
  • 27 Mugnai P, Durante M, Sgaragli G, Saponara S, Paliuri G, Bova S, Fusi F. L-type Ca2+ channel current characteristics are preserved in rat tail artery myocytes after one-day storage. Acta Physiol 2014; 211: 334-345
    CrossrefPubMedGoogle Scholar
  • 28 Budriesi R, Cosimelli B, Ioan P, Ugenti MP, Carosati E, Frosini M, Fusi F, Spisani R, Saponara S, Cruciani G, Novellino E, Spinelli D, Chiarini A. L-Type calcium channel blockers: from diltiazem to 1,2,4-oxadiazol-5-ones via thiazinooxadiazol-3-one derivatives. J Med Chem 2009; 52: 2352-2362
    CrossrefPubMedGoogle Scholar
  • 29 Iozzi D, Schubert R, Kalenchuk VU, Neri A, Sgaragli G, Fusi F, Saponara S. Quercetin relaxes rat tail main artery partly via a PKG-mediated stimulation of KCa1.1 channels. Acta Physiol 2013; 208: 329-339
    CrossrefPubMedGoogle Scholar
  • 30 Magnon M, Calderone V, Floch A, Cavero I. Influence of depolarization on vasorelaxant potency and efficacy of Ca2+ entry blockers, K+ channel openers, nitrate derivatives, salbutamol and papaverine in rat aortic rings. Naunyn-Schmiedebergʼs Arch Pharmacol 1998; 358: 452-463
    PubMedGoogle Scholar