Mitochondriotropic and Cardioprotective Effects of Triphenylphosphonium-Conjugated Derivatives of the Diterpenoid Isosteviol

Mitochondriotropic and Cardioprotective Effects of Triphenylphosphonium-Conjugated Derivatives of the Diterpenoid Isosteviol Научная публикация

Журнал

International Journal of Molecular Sciences
ISSN: 1661-6596 , E-ISSN: 1422-0067

Вых. Данные

Год: 2017, Том: 18, Номер: 10, Номер статьи : 2060, Страниц : DOI: 10.3390/ijms18102060

Авторы

Testai Lara ¹ , Strobykina Irina ² , Semenov Victor V. ³ , Semenova Marina ⁴ , Pozzo Eleonora Da ⁵ , Martelli Alma ⁵ , Citi Valentina ⁵ , Martini Claudia ⁵ , Breschi Maria C. ⁵ , Kataev Vladimir E. ² , Calderone Vincenzo ⁵

Организации

1	Department of Pharmacy, University of Pisa, Bonanno Street, 6, 56120 Pisa, Italy. lara.testai@unipi.it.
2	A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center of Russian Academy of Sciences, Arbuzov Street, 8, 420088 Kazan, Russia
3	N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect, 47, 119991 Moscow, Russia
4	N. K. Kol’tsov Institute of Developmental Biology, Russian Academy of Sciences, Vavilov Street, 26, 119334 Moscow, Russia
5	Department of Pharmacy, University of Pisa, Bonanno Street, 6, 56120 Pisa, Italy

Mitochondria play a crucial role in the cell fate; in particular, reducing the accumulation of calcium in the mitochondrial matrix offers cardioprotection. This affect is achieved by a mild depolarization of the mitochondrial membrane potential, which prevents the assembly and opening of the mitochondrial permeability transition pore. For this reason, mitochondria are an attractive target for pharmacological interventions that prevent ischaemia/reperfusion injury. Isosteviol is a diterpenoid created from the acid hydrolysis of Stevia rebaudiana Bertoni (fam. Asteraceae) glycosides that has shown protective effects against ischaemia/reperfusion injury, which are likely mediated through the activation of mitochondrial adenosine tri-phosphate (ATP)-sensitive potassium (mitoKATP) channels. Some triphenylphosphonium (triPP)-conjugated derivatives of isosteviol have been developed, and to evaluate the possible pharmacological benefits that result from these synthetic modifications, in this study, the mitochondriotropic properties of isosteviol and several triPP-conjugates were investigated in rat cardiac mitochondria and in the rat heart cell line H9c2. This study’s main findings highlight the ability of isosteviol to depolarize the mitochondrial membrane potential and reduce calcium uptake by the mitochondria, which are typical functions of mitochondrial potassium channel openings. Moreover, triPP-conjugated derivatives showed a similar behavior to isosteviol but at lower concentrations, indicative of their improved uptake into the mitochondrial matrix. Finally, the cardioprotective property of a selected triPP-conjugated derivative was demonstrated in an in vivo model of acute myocardial infarct.

Testai L. , Strobykina I. , Semenov V.V. , Semenova M. , Pozzo E.D. , Martelli A. , Citi V. , Martini C. , Breschi M.C. , Kataev V.E. , Calderone V.
Mitochondriotropic and Cardioprotective Effects of Triphenylphosphonium-Conjugated Derivatives of the Diterpenoid Isosteviol
International Journal of Molecular Sciences. 2017. V.18. N10. 2060 . DOI: 10.3390/ijms18102060 WOS Scopus OpenAlex

Web of science:	WOS:000414671800044
Scopus:	2-s2.0-85030162885
OpenAlex:	W2759187688

БД	Цитирований
OpenAlex	30
Scopus	28
Web of science	28