Unravelling the Neuroprotective Effects of a Novel Formulation Based on Plant Extracts, Mg, and Vitamin B6

The aim of the present study was to investigate the phenolic composition and the efficacy of an innovative formulation based on Mg, Vitamin B6, and water extracts from <i>Vitex agnus-castus</i>, <i>Crocus sativus</i>, <i>Melissa officinalis</i>, <i>Betula pe...

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Main Authors: Simonetta Cristina Di Simone, Alessandra Acquaviva, Maria Loreta Libero, Nilofar Nilofar, Fatma Tunali, Paola Angelini, Giancarlo Angeles Flores, Gaia Cusumano, Lucia Recinella, Sheila Leone, Giustino Orlando, Gokhan Zengin, Luigi Menghini, Claudio Ferrante, Annalisa Chiavaroli
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Language:English
Published: MDPI AG 2025-01-01
Series:Nutraceuticals
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Online Access:https://www.mdpi.com/1661-3821/5/1/5
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author Simonetta Cristina Di Simone
Alessandra Acquaviva
Maria Loreta Libero
Nilofar Nilofar
Fatma Tunali
Paola Angelini
Giancarlo Angeles Flores
Gaia Cusumano
Lucia Recinella
Sheila Leone
Giustino Orlando
Gokhan Zengin
Luigi Menghini
Claudio Ferrante
Annalisa Chiavaroli
author_facet Simonetta Cristina Di Simone
Alessandra Acquaviva
Maria Loreta Libero
Nilofar Nilofar
Fatma Tunali
Paola Angelini
Giancarlo Angeles Flores
Gaia Cusumano
Lucia Recinella
Sheila Leone
Giustino Orlando
Gokhan Zengin
Luigi Menghini
Claudio Ferrante
Annalisa Chiavaroli
author_sort Simonetta Cristina Di Simone
collection DOAJ
description The aim of the present study was to investigate the phenolic composition and the efficacy of an innovative formulation based on Mg, Vitamin B6, and water extracts from <i>Vitex agnus-castus</i>, <i>Crocus sativus</i>, <i>Melissa officinalis</i>, <i>Betula pendula</i>, and <i>Betula pubescens</i> developed as an effective tool to face neuroinflammation and depression symptoms occurring in premenstrual syndrome (PMS). The formulation was analyzed through colorimetric and liquid chromatography methods for determining the content in phenols and flavonoids. Additionally, scavenging/reducing properties were investigated via 2,2-diphenyl-1-picrylhydrazyl (DPPH,) 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and horseradish peroxidase assays. The biocompatible limits were determined via allelopathy, the brine shrimp lethality test, and <i>Daphnia magna</i> cardiotoxicity assay. The formulation was then assayed in an experimental model constituted by isolated mouse cortex specimens exposed to K<sup>+</sup> 60 mM Krebs–Ringer buffer, a toxic depolarizing stimulus able to reproduce the burden of inflammation/oxidative stress and the increased serotonin (5-hydroxytryptamine, 5-HT) impoverishment occurring in different neurological and psychiatric conditions, including depression. The results of the phytochemical analysis showed that the formulation is rich in benzoic acids, namely gentisic acid (155.31 µg/mL) and phenylethanoid compounds, namely hydroxytyrosol (39.79 µg/mL) that support the antioxidant effects measured via DPPH (IC<sub>50</sub>: 1.48 mg/mL), ABTS (IC<sub>50</sub>: 0.42 mg/mL), and horseradish peroxidase (IC<sub>50</sub>: 2.02 mg/mL) assays. The ecotoxicological models indicated the formulation as non-toxic, permitting the identification of a biocompatible concentration (1000 µg/mL) to be used in isolated mouse cortex exposed to K<sup>+</sup> 60 mM Krebs–Ringer buffer. In this model, the gene expression of cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), estrogen receptor-1 (ESR1), prolactin receptor (PRLR), brain-derived neurotrophic factor (BDNF), and serotonin transporter (SERT) was determined by real-time PCR. In the isolated mouse cortex, the formula reduced COX-2, IL-6, SERT, ESR1, and PRLR gene expression and increased BDNF and IL-10 gene expression. Overall, the study corroborated the use of the formulation as an innovative tool to contrast inflammation, oxidative stress, and neurotransmitter impairment associated with PMS.
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spelling doaj-art-e4ae05a979cf4c4fac18e34ed299e6ff2025-08-20T02:42:28ZengMDPI AGNutraceuticals1661-38212025-01-0151510.3390/nutraceuticals5010005Unravelling the Neuroprotective Effects of a Novel Formulation Based on Plant Extracts, Mg, and Vitamin B6Simonetta Cristina Di Simone0Alessandra Acquaviva1Maria Loreta Libero2Nilofar Nilofar3Fatma Tunali4Paola Angelini5Giancarlo Angeles Flores6Gaia Cusumano7Lucia Recinella8Sheila Leone9Giustino Orlando10Gokhan Zengin11Luigi Menghini12Claudio Ferrante13Annalisa Chiavaroli14Botanic Garden “Giardino dei Semplici”, Department of Pharmacy, “G. d’Annunzio” University, 66100 Chieti, ItalyBotanic Garden “Giardino dei Semplici”, Department of Pharmacy, “G. d’Annunzio” University, 66100 Chieti, ItalyBotanic Garden “Giardino dei Semplici”, Department of Pharmacy, “G. d’Annunzio” University, 66100 Chieti, ItalyBotanic Garden “Giardino dei Semplici”, Department of Pharmacy, “G. d’Annunzio” University, 66100 Chieti, ItalyBotanic Garden “Giardino dei Semplici”, Department of Pharmacy, “G. d’Annunzio” University, 66100 Chieti, ItalyDepartment of Chemistry, Biology and Biotechnology, University of Perugia, 06122 Perugia, ItalyBotanic Garden “Giardino dei Semplici”, Department of Pharmacy, “G. d’Annunzio” University, 66100 Chieti, ItalyDepartment of Chemistry, Biology and Biotechnology, University of Perugia, 06122 Perugia, ItalyBotanic Garden “Giardino dei Semplici”, Department of Pharmacy, “G. d’Annunzio” University, 66100 Chieti, ItalyBotanic Garden “Giardino dei Semplici”, Department of Pharmacy, “G. d’Annunzio” University, 66100 Chieti, ItalyBotanic Garden “Giardino dei Semplici”, Department of Pharmacy, “G. d’Annunzio” University, 66100 Chieti, ItalyPhysiology and Biochemistry Research Laboratory, Department of Biology, Science Faculty, Selcuk University, Konya 42130, TurkeyBotanic Garden “Giardino dei Semplici”, Department of Pharmacy, “G. d’Annunzio” University, 66100 Chieti, ItalyBotanic Garden “Giardino dei Semplici”, Department of Pharmacy, “G. d’Annunzio” University, 66100 Chieti, ItalyBotanic Garden “Giardino dei Semplici”, Department of Pharmacy, “G. d’Annunzio” University, 66100 Chieti, ItalyThe aim of the present study was to investigate the phenolic composition and the efficacy of an innovative formulation based on Mg, Vitamin B6, and water extracts from <i>Vitex agnus-castus</i>, <i>Crocus sativus</i>, <i>Melissa officinalis</i>, <i>Betula pendula</i>, and <i>Betula pubescens</i> developed as an effective tool to face neuroinflammation and depression symptoms occurring in premenstrual syndrome (PMS). The formulation was analyzed through colorimetric and liquid chromatography methods for determining the content in phenols and flavonoids. Additionally, scavenging/reducing properties were investigated via 2,2-diphenyl-1-picrylhydrazyl (DPPH,) 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and horseradish peroxidase assays. The biocompatible limits were determined via allelopathy, the brine shrimp lethality test, and <i>Daphnia magna</i> cardiotoxicity assay. The formulation was then assayed in an experimental model constituted by isolated mouse cortex specimens exposed to K<sup>+</sup> 60 mM Krebs–Ringer buffer, a toxic depolarizing stimulus able to reproduce the burden of inflammation/oxidative stress and the increased serotonin (5-hydroxytryptamine, 5-HT) impoverishment occurring in different neurological and psychiatric conditions, including depression. The results of the phytochemical analysis showed that the formulation is rich in benzoic acids, namely gentisic acid (155.31 µg/mL) and phenylethanoid compounds, namely hydroxytyrosol (39.79 µg/mL) that support the antioxidant effects measured via DPPH (IC<sub>50</sub>: 1.48 mg/mL), ABTS (IC<sub>50</sub>: 0.42 mg/mL), and horseradish peroxidase (IC<sub>50</sub>: 2.02 mg/mL) assays. The ecotoxicological models indicated the formulation as non-toxic, permitting the identification of a biocompatible concentration (1000 µg/mL) to be used in isolated mouse cortex exposed to K<sup>+</sup> 60 mM Krebs–Ringer buffer. In this model, the gene expression of cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), estrogen receptor-1 (ESR1), prolactin receptor (PRLR), brain-derived neurotrophic factor (BDNF), and serotonin transporter (SERT) was determined by real-time PCR. In the isolated mouse cortex, the formula reduced COX-2, IL-6, SERT, ESR1, and PRLR gene expression and increased BDNF and IL-10 gene expression. Overall, the study corroborated the use of the formulation as an innovative tool to contrast inflammation, oxidative stress, and neurotransmitter impairment associated with PMS.https://www.mdpi.com/1661-3821/5/1/5medicinal plantphenolic compoundsneuroprotectiongene expression
spellingShingle Simonetta Cristina Di Simone
Alessandra Acquaviva
Maria Loreta Libero
Nilofar Nilofar
Fatma Tunali
Paola Angelini
Giancarlo Angeles Flores
Gaia Cusumano
Lucia Recinella
Sheila Leone
Giustino Orlando
Gokhan Zengin
Luigi Menghini
Claudio Ferrante
Annalisa Chiavaroli
Unravelling the Neuroprotective Effects of a Novel Formulation Based on Plant Extracts, Mg, and Vitamin B6
Nutraceuticals
medicinal plant
phenolic compounds
neuroprotection
gene expression
title Unravelling the Neuroprotective Effects of a Novel Formulation Based on Plant Extracts, Mg, and Vitamin B6
title_full Unravelling the Neuroprotective Effects of a Novel Formulation Based on Plant Extracts, Mg, and Vitamin B6
title_fullStr Unravelling the Neuroprotective Effects of a Novel Formulation Based on Plant Extracts, Mg, and Vitamin B6
title_full_unstemmed Unravelling the Neuroprotective Effects of a Novel Formulation Based on Plant Extracts, Mg, and Vitamin B6
title_short Unravelling the Neuroprotective Effects of a Novel Formulation Based on Plant Extracts, Mg, and Vitamin B6
title_sort unravelling the neuroprotective effects of a novel formulation based on plant extracts mg and vitamin b6
topic medicinal plant
phenolic compounds
neuroprotection
gene expression
url https://www.mdpi.com/1661-3821/5/1/5
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