Abstract

Sambucus nigra flowers (elderflower) have been widely used in traditional medicine for the relief of early symptoms of common cold. Its chemical composition mainly consists of polyphenolic compounds such as flavonoids, hydroxycinnamic acids, and triterpenes. Although the antioxidant properties of polyphenols are well known, the aim of this study is to assess the antioxidant and protective potentials of Sambucus nigra flowers in the human neuroblastoma (SH-SY5Y) cell line using different in vitro approaches. The antioxidant capacity is first evaluated by the oxygen radical absorbance capacity (ORAC) and the free radical scavenging activity (DPPH) methods. Cell viability is assessed by the crystal violet method; furthermore, the intracellular ROS formation (DCFH-DA method) is determined, together with the effect on the cell antioxidant defenses: reduced glutathione (GSH) and antioxidant enzyme activities (GPx, GR). On the other hand, mTORC1 hyperactivation and autophagy blockage have been associated with an increase in the formation of protein aggregates, this promoting the transference and expansion of neurodegenerative diseases. Then, the ability of Sambucus nigra flowers in the regulation of mTORC1 signaling activity and the reduction in oxidative stress through the activation of autophagy/mitophagy flux is also examined. In this regard, search for different molecules with a potential inhibitory effect on mTORC1 activation could have multiple positive effects either in the molecular pathogenic events and/or in the progression of several diseases including neurodegenerative ones.

Highlights

  • Sambucus nigra L., is a well-known herbaceous species of the Caprifoliaceae family spontaneously growing in Europe, West Asia, and North America

  • This activity may be expressed as the inhibitory concentration 50 (IC50), which expresses the antioxidant concentration required to obtain 50% radical inhibition, or as the antioxidant efficiency (AE), which is calculated as 1/IC50

  • Due to their p3.hDenioscliucsssitoruncture, the main bioactive components of S. nigra, flavonoids and hydroxyBceinnenfiacmiaicl eafcfiedcsts, hoaf veeldaerrfleomwaerkrahbalveeobxeidenanptrsecvaivoeunsglyincgoncafeprarceidtytoreitlastpedolytophtheenohlyicdcorongteennt,dmoaniantliyngflaavboilnitoyidasnadntdhehysdtarboixliytcyinonf athmeicphaceindosx. yTlhreaidr picraelssefnocreminedth[e27te].sOteudrerxetsrauclttss oinf tthheisawntoiorkxiwdaanstccoanpfiarcmiteydi,nwvihtirloewsliitghhrteqauliasntitcitdaotisvees doiffefeldreenrcfleoswweerreexftoraucntds sbeeetmwetoensuthpepaqourtetohuesaanntdioextihdaannotliecffeexcttraocbtsse. rTvheedriensuclutsltoufreHdPcLeCllsinwoiuthr seilmdeirlaflroowrecrosmampaprleasblaegdreoesewsitohf oththoeser pplraenvtioeuxstrlyacrtespaolrstoedric[1h1i,n19f–la2v1o],ntohiids sasasnudr/ionrghthyedrqouxaylictiynnofamsaimc pacleidssan[2d8–re3l1ia].bility of the High-Pressure Liquid Chromatography (HPLC) assay. Their antioxidant capacity was evaluated by two different assays, showing a preventive potential against oxidative stress. Due to their phenolic structure, the main bioactive components of S. nigra, flavonoids and hydroxycinnamic acids, have a remarkable oxidant scavenging capacity related to the hydrogen-donating ability and the stability of the phenoxyl radicals formed [27]

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Summary

Introduction

Sambucus nigra L., (elderflower) is a well-known herbaceous species of the Caprifoliaceae family spontaneously growing in Europe, West Asia, and North America. S. nigra flower extracts have shown to exert different biological activities. Izzo et al [6] confirmed the antibacterial activity of elderflower extracts against both Gram-positive and Gram-negative bacteria; isolated compounds from elderflower have shown immunomodulatory activity through an inhibition of macrophage release of pro-inflammatory cytokines, this effect being attributed to the inhibition of activation of NF-kB and phosphatidylinositol-3-kinase (PI3K) [7]. An aqueous extract of elderflower was able to significantly increase glucose uptake, glucose oxidation, and gluconeogenesis in rat abdominal muscle. Pancreatic cells treated with the elderflower extract showed a dosedependent stimulatory effect on insulin secretion [8]. Elderflower infusion exerted a diuretic effect in experimental animal that was even superior to the one observed with theophylline (5 mg/kg body weight) [9,10]

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