Biotechnologically-Produced Myconoside and Calceolarioside E Induce Nrf2 Expression in Neutrophils.

Kristiana M Amirova,Milen I Georgiev,Slaveya V Krustanova,Kalina I Alipieva,Andrey S Marchev,Svetlana D Simova,Petya A Dimitrova

doi:10.3390/ijms22041759

Abstract

The pathological manifestation of various diseases can be suppressed by the activation of nuclear factor erythroid 2 p45-related factor 2 (Nrf2), a transcriptional regulator of the cellular redox balance. Haberlea rhodopensis Friv. is a resurrection plant species endemic for Bulgaria, containing biologically active phenylethanoid glycosides that might possess antioxidant or redox activity. This study aimed to analyze the metabolic profile of in vitro cultured H. rhodopensis and to identify molecules that increase Nrf2 expression in bone marrow neutrophils. Fractions B, D, and E containing myconoside, or myconoside and calceolarioside E in ratios 1:0.6 and 0.25:1 were found to be the most active ones. Fraction B (200 µg/mL) improved neutrophil survival and strongly increased the Nrf2 intracellular level, while D and E, as well as, myconoside and calceolarioside E at the same ratios had a superior effect. Calceolarioside E (32 µg/mL) had stronger activity than myconoside, the effect of which was very similar to that of 2-cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me), used as a positive control. These data indicate that both molecules, used alone or in combination have stimulatory activity on the endogenous Nrf2 level, indicating their therapeutic potential to regulate the cellular redox homeostasis oxidative stress-associated pathologies.

Highlights

Haberlea rhodopensis Friv., commonly known as Rhodope silivriak or Orpheus’ flower, is a rare resurrection plant of the northern hemisphere spread all over Europe in the past and nowadays found only in the mountains of the Balkan Peninsula as a glacial relict from the Tertiary period
Several phenylethanoid glycosides-rich fractions have been obtained from the crude methanolic extract of H. rhodopensis
Their contents were characterized by nuclear magnetic resonance (NMR) analysis and the two main molecules myconoside and calceolarioside E were found in different ratios in the fractions

Summary

Introduction

Haberlea rhodopensis Friv. (family Gesneriaceae), commonly known as Rhodope silivriak or Orpheus’ flower, is a rare resurrection plant of the northern hemisphere spread all over Europe in the past and nowadays found only in the mountains of the Balkan Peninsula as a glacial relict from the Tertiary period. (family Gesneriaceae), commonly known as Rhodope silivriak or Orpheus’ flower, is a rare resurrection plant of the northern hemisphere spread all over Europe in the past and nowadays found only in the mountains of the Balkan Peninsula as a glacial relict from the Tertiary period It is a native plant, endemic to Bulgaria and Greece. North-facing shady rocky slopes with high humidity at altitudes between 100 and 1700 m a.s.l. are the characteristic habitats of H. rhodopensis [1,2] This plant species is included in the Red Data Book of Bulgaria in three categories, such as Rare species, Balkan endemic species, and Tertiary relicts, as well as, listed in the European Rare species category and in Appendix I of the Bern Convention [3]. NMR-based metabolite profiling has been used to identify a specific group of molecules and compare their variations in different plant parts in Sambucus ebulus L. [6], Rhodiola rosea L. [7], and commercial preparations [8]

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