Vasorelaxing Activity of R-(−)-3′-Hydroxy-2,4,5-trimethoxydalbergiquinol from Dalbergia tonkinensis: Involvement of Smooth Muscle CaV1.2 Channels

Nguyen Manh Cuong; Ninh The Son; Ngu Truong Nhan; Pham Ngoc Khanh; Tran Thu Huong; Nguyen Thi Thu Tram; Giampietro Sgaragli; Amer Ahmed; Alfonso Trezza; Ottavia Spiga; Fabio Fusi

doi:10.1055/a-1099-2929

Planta Medica, Inhaltsverzeichnis

Planta Med 2020; 86(04): 284-293
DOI: 10.1055/a-1099-2929

Biological and Pharmacological Activity

Original Papers

Georg Thieme Verlag KG Stuttgart · New York

Vasorelaxing Activity of R-(−)-3′-Hydroxy-2,4,5-trimethoxydalbergiquinol from Dalbergia tonkinensis: Involvement of Smooth Muscle Ca_V1.2 Channels

Nguyen Manh Cuong

¹Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam

²Graduate University of Science and Technology, Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam

,

Ninh The Son

³Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam

,

Ngu Truong Nhan

²Graduate University of Science and Technology, Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam

⁴Department of Science and Technology, Tay Nguyen University, Daklak, Vietnam

,

Pham Ngoc Khanh

¹Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam

,

Tran Thu Huong

¹Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam

,

Nguyen Thi Thu Tram

⁵Department of Chemistry, Faculty of Science, Can Tho University of Medicine and Pharmacy, Can Tho, Vietnam

,

Giampietro Sgaragli

⁶Dipartimento di Scienze della Vita, Università degli Studi di Siena, Siena, Italy

,

Amer Ahmed

⁶Dipartimento di Scienze della Vita, Università degli Studi di Siena, Siena, Italy

,

Alfonso Trezza

⁷Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Siena, Italy

,

Ottavia Spiga

⁷Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Siena, Italy

,

Fabio Fusi

⁷Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Siena, Italy

› Institutsangaben

Abstract

Dalbergia species heartwood, widely used in traditional medicine to treat various cardiovascular diseases, might represent a rich source of vasoactive agents. In Vietnam, Dalbergia tonkinensis is an endemic tree. Therefore, the aim of the present work was to investigate the vascular activity of R-(−)-3′-hydroxy-2,4,5-trimethoxydalbergiquinol isolated from the heartwood of D. tonkinensis and to provide circular dichroism features of its R absolute configuration. The vascular effects of R-(−)-3′-hydroxy-2,4,5-trimethoxydalbergiquinol were assessed on the in vitro mechanical activity of rat aorta rings, under isometric conditions, and on whole-cell Ba²⁺ currents through Ca_V1.2 channels (I_Ba1.2) recorded in single, rat tail main artery myocytes by means of the patch-clamp technique. R-(−)-3′-Hydroxy-2,4,5-trimethoxydalbergiquinol showed concentration-dependent, vasorelaxant activity on both endothelium-deprived and endothelium intact rings precontracted with the α ₁ receptor agonist phenylephrine. Neither the NO (nitric oxide) synthase inhibitor N^ω-nitro-L-arginine methyl ester nor the cyclooxygenase inhibitor indomethacin affected its spasmolytic activity. R-(−)-3′-Hydroxy-2,4,5-trimethoxydalbergiquinol-induced vasorelaxation was antagonized by (S)-(−)-Bay K 8644 and unaffected by tetraethylammonium plus glibenclamide. In patch-clamp experiments, R-(−)-3′-hydroxy-2,4,5-trimethoxydalbergiquinol inhibited I_Ba1.2 in a concentration-dependent manner and significantly decreased the time constant of current inactivation. R-(−)-3′-Hydroxy-2,4,5-trimethoxydalbergiquinol likely stabilized the channel in its closed state, as suggested by molecular modelling and docking simulation to the Ca_V1.2 channel α _1c subunit. In conclusion, D. tonkinensis species may represent a source of agents potentially useful for the development of novel antihypertensive drugs.

Key words

Dalbergia tonkinensis - Fabaceae - R-(−)-3′-hydroxy-2,4,5-trimethoxydalbergiquinol - rat aorta rings - docking simulation - Ca_V1.2 channel - open-chain neoflavonoid - patch clamp

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Referenzen

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