Next Article in Journal
The Potential for Gut Organoid Derived Interstitial Cells of Cajal in Replacement Therapy
Next Article in Special Issue
Achiral Mannich-Base Curcumin Analogs Induce Unfolded Protein Response and Mitochondrial Membrane Depolarization in PANC-1 Cells
Previous Article in Journal
The Phosphoproteomic Response of Rice Seedlings to Cadmium Stress
Previous Article in Special Issue
Self-Nanoemulsifying Drug Delivery System for Resveratrol: Enhanced Oral Bioavailability and Reduced Physical Fatigue in Rats
Article Menu
Issue 10 (October) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(10), 2060; doi:10.3390/ijms18102060

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

1
Department of Pharmacy, University of Pisa, Bonanno Street, 6, 56120 Pisa, Italy
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
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 2 August 2017 / Revised: 21 September 2017 / Accepted: 23 September 2017 / Published: 26 September 2017
(This article belongs to the Special Issue Natural and Semi-Synthetic Small Molecules in Drug Discovery)
View Full-Text   |   Download PDF [2680 KB, uploaded 27 September 2017]   |  

Abstract

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. View Full-Text
Keywords: mitochondria; Stevia rebaudiana Bertoni; tetraphenylphosphonium; isosteviol; cardioprotection mitochondria; Stevia rebaudiana Bertoni; tetraphenylphosphonium; isosteviol; cardioprotection
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

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. Int. J. Mol. Sci. 2017, 18, 2060.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top