Secondary Metabolites in Ramalina terebrata Detected by UHPLC/ESI/MS/MS and Identification of Parietin as Tau Protein Inhibitor

Cornejo, Alberto; Salgado, Francisco; Caballero, Julio; Vargas, Reinaldo; Simirgiotis, Mario J.; Areche, Carlos

doi:10.3390/ijms17081303

Cited by 53 publications

(71 citation statements)

References 49 publications

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“…Most of the obtained fragments correlated with those found previously for protocetraric acid [35] [36] Compound 19 exhibits a pseudo-molecular ion at m/z 371.04021 (C 18 H 11 O 9 ). [38] Depsone A depsone, picrolichenic acid (compound 34), has been detected for the first time in R. farinacea. Furthermore, fragmentation gave rise to other ions at m/z 243.0297 and 227.0350 corresponding to losses of C-CO and CH 3 -CH-CO groups, respectively, from the [M À H À 2CO 2 ] À .…”

Section: Depsidonesmentioning

confidence: 99%

UHPLC‐HRMS/MS Based Profiling of Algerian Lichens and Their Antimicrobial Activities

Rafika

Ahmed

Burger

et al. 2018

Chemistry & Biodiversity

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Lichens are complex symbiotic organisms able to produce a vast array of compounds. The Algerian lichen diversity has only prompted little interest even given the 1085 species listed. Herein, the chemodiversity of four Algerian lichens including Cladonia rangiformis, Ramalina farinaceae, R. fastigiata, and Roccella phycopsis was investigated. A dereplication strategy, using ultra high performance liquid chromatography-high resolution-electrospray ionization-mass spectrometry (UHPLC-HRMS/MS), was carried out for a comprehensive characterization of their substances including phenolics, depsides, depsidones, depsones, dibenzofurans, and aliphatic acids. Some known compounds were identified for the first time in some species. Additionally, the lichenic extracts were evaluated for their antifungal and antimicrobial activities on human pathogenic strains (Candida albicans, C. glabrata, Aspergillus fumigatus, Staphylococcus aureus, and Escherichia coli). Cyclohexane extracts were found particularly active against human pathogenic fungi with MIC values ranging from 8 to 62.5 μg/mL, without cytotoxicity. This study highlights the therapeutic and prophylactic potential of lichenic extracts as antibacterial and antifungal agents.

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Section: Depsidonesmentioning

confidence: 99%

UHPLC‐HRMS/MS Based Profiling of Algerian Lichens and Their Antimicrobial Activities

Rafika

Ahmed

Burger

et al. 2018

Chemistry & Biodiversity

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“…The ThT fluorescence was done as described . Briefly, to examine the inhibition of tau aggregation, the total volume of the reaction mixture was 100 μl, which included 20 μM 4R, 5 μM heparin in 100 mM sodium acetate, pH 6.0 with compound 2.…”

Section: Methodsmentioning

confidence: 99%

Anthraquinone Derivative Reduces Tau Oligomer Progression by Inhibiting Cysteine‐Cysteine Interaction

Areche

Zapata²,

González³

et al. 2019

ChemistryOpen

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Tau protein is a natively unfolded protein whose primary role is to participate in axonal transport closely associated with microtubules. Neurodegenerative disorders including Alzheimer's disease and Tauopathies involved tau protein that is found hyperphosphorylated in vivo ; then, tau is detached from microtubules to form toxic aggregates or oligomers, which have a deleterious effect on membranes, triggering an inflammatory response. Considering finding tau inhibitors, we isolated two compounds in the ethyl acetate extract from Xanthoria ectaneoides (Nyl.) Zahlbr; ergosterol peroxide ( 1 ) and a new anthraquinone ( 2 ). We established the structure through spectroscopic data and biogenic considerations, and we named it “2‐hydroxy‐3‐((8‐hydroxy‐3‐methoxy‐6‐methylanthraquinonyl)oxy)propanoic acid”. This new anthraquinone was evaluated as a tau inhibitor by ThT fluorescence, dot blot assays and total internal reflection fluorescence microscopy. Our results strongly suggest that this anthraquinone remodels soluble oligomers and diminishes β‐sheet content. Moreover, through the fluorescence labeling of cysteine inside of the microtubule‐binding domain (4R), we showed that this anthraquinone could reduce the oligomers progression by inhibiting cysteine interactions.

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“…Alternatively, a derivative plant polyphenol, curcumin, has been useful, since curcumin exerts a pleiotropic effect by combining both anti-aggregate and antioxidant activities. Recently, we have characterized that parietin, an anthraquinone, isolated from Ramalina terebrata, lichen collected in the Antarctic region of "Península Fildes", has effect on tau aggregation [40]. Docking studies of parietin and 306 VQIVYK 311 hexapeptide suggest that parietin bind steric zippers preventing β-sheet assembly [40].…”

Section: Lichens As Antioxidants and Tau Inhibitors Sourcementioning

confidence: 99%

“…According to the docking model, there are both types of interaction: hydrogen bond (HB) among phenolic groups, methoxy motif and lysine side chains. Besides this, hydrophobic interaction also occurs between methyl group of methoxy substituent and valine [40]. Interestingly, another anthraquinone, emodin, which inhibits tau aggregation has lower IC 50 instead of parietin, we hypothesize that could be due to methoxy group at C-3 position in parietin (Figure 1).…”

mentioning

confidence: 91%

“…Recently, we have characterized that parietin, an anthraquinone, isolated from Ramalina terebrata, lichen collected in the Antarctic region of "Península Fildes", has effect on tau aggregation [40]. Docking studies of parietin and 306 VQIVYK 311 hexapeptide suggest that parietin bind steric zippers preventing β-sheet assembly [40]. According to the docking model, there are both types of interaction: hydrogen bond (HB) among phenolic groups, methoxy motif and lysine side chains.…”

mentioning

confidence: 99%

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Secondary Metabolites of Lichens as Both Anti-aggregative and Antioxidant Agents in Tauopathies

Cornejo¹,

Areche²

2017

J Clin Cell Immunol

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This commentary described our findings of parietin, an anthraquinone, isolated from Ramalina terebrata as inhibitor of tau protein. Moreover, we considered important to link tauopathies with reactive oxygen species since oligomers and fibril-forming elements are responsible for activating reactive oxygen species, which cause inflammatory response and neurodegeneration. Together, we considered important to find naturally occurring compounds that might be able to stop aggregation and reduce ROS cells damage.Keywords: Tauopathies; Secondary metabolites; Lichens; Reactive oxygen species; Inflammatory response; Neurodegeneration Tauopathies and NeurotoxicityTaoupathies are neurodegenerative disorders involving tau protein, such as progressive nuclear palsy (PSP), corticobasal degeneration (CBD), Pick´s disease among others. Tau is an unfolded protein which is found mainly in axons of mature and physiologically is involved in microtubule stability and axonal transport [1]. However, once tau becomes hyperphosphorylated it detaches from microtubule starting the aggregation process [2,3]. Pathological tau aggregates are able to activate glia cells that release cytotoxic factors, which cause pro inflammatory cytokines such as TNF-α, IL-1 and IL-6 and chemokines [4]. Tau phosphorylation is increased in both physiologically and pathological state [5], however phosphorylation is increased during development, suggesting that process is needed for neuronal plasticity [6]. Tau phosphorylation is an event highly regulated by kinases and phosphatases. Its balance is deregulated due to several stimuli such as oxidative stress [7]. Tau is able to form paired helical filaments closely related to neurofibrillary tangles [8,9]. Hyperphosphorylated tau protein is found in patients suffering with tauopathies in cerebrospinal fluid (CNS), which correlates well with hypocampal atrophy [10]. In addition, tauopathies have tau hyperphosphorylated as a hallmark; however, the degree of phosphorylation differs among them. In addition, it is important to notice that there is no single phosphorylation site associated to a particular tauopathy [5]. Moreover, tau has the propensity to form aggregates, since inside the full length protein (441 aminoacids) resides a region known as 4R (four microtubule binding domain) containing two hexapeptides 275 VQIINK 280 and 306 VQIVYK 311 both associated to β sheet formation [11]. Increased tau phosphorylation decreased its binding for microtubules. These species prone to form aggregates which are toxic in both cell and transgenic mouse model [12,13]. Despite that fact, there are evidences showing that soluble species and pre fibrils which are more related to toxicity [14]. An interesting UV raman spectroscopy study showed that at early stages, within the first hour, fibrillar aggregates possess a mixture of β-sheet and disordered content. Afterward, the UVRR spectra shows a consolidation in fibril structure, augmenting the content of β sheet [15], interesting is to remark that toxicity apparently reli...

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Secondary Metabolites in Ramalina terebrata Detected by UHPLC/ESI/MS/MS and Identification of Parietin as Tau Protein Inhibitor

Cited by 53 publications

References 49 publications

UHPLC‐HRMS/MS Based Profiling of Algerian Lichens and Their Antimicrobial Activities

UHPLC‐HRMS/MS Based Profiling of Algerian Lichens and Their Antimicrobial Activities

Anthraquinone Derivative Reduces Tau Oligomer Progression by Inhibiting Cysteine‐Cysteine Interaction

Secondary Metabolites of Lichens as Both Anti-aggregative and Antioxidant Agents in Tauopathies

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