Beneficial Effects of Sideritis scardica and Cichorium spinosum against Amyloidogenic Pathway and Tau Misprocessing in Alzheimer’s Disease Neuronal Cell Culture Models

Over the last years, Sideritis extracts were shown to improve memory. However, their potential to promote the generation of new neurons, starting with the neuronal differentiation of neural stem cells, remains unexplored. Therefore, the present study aimed to evaluate the neurogenic effects of different Sideritis infusions in neural stem and precursor cells and their impacts on cell viability. Moreover, the metabolic fingerprints were recorded using LC-DAD, LC-ESIHRMS, and GC-MS. The neurogenic potential from infusions of the eight Sideritis taxa tested was as potent as the classical neuronal inducer combination of retinoic acid and valproic acid. Further cytotoxicity assays revealed that the IC50 values of extracts were comprised between 163 µg/mL and 322 µg/mL. Hierarchical cluster analyses of the metabolic fingerprints unveiled, that the two Sideritis taxa with the lowest IC50 values were the most divergent in the analytical techniques used. As the analysis focused on polyphenols, it is reasonable to assume that these compounds are responsible for the effect on the cell viability of SH-SY5Y neuroblastoma cells. This study is the first report on the neurogenic potential of Sideritis taxa and might support the use of Sideritis herbal preparations in the context of neurodegenerative diseases.

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“…4 c). This is in accordance with previous findings in the specific plants [10,[28][29][30][32][33][34][35][36][37][38][39][40].…”

Section: Accepted Manuscriptsupporting

confidence: 94%

Metabolic Fingerprinting of Different Sideritis Taxa Infusions and Their Neurogenic Activity

et al. 2023

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“…Tau hyperphosphorylation is believed to be crucial in AD pathogenesis by promoting the formation of NFTs and ultimately neural loss. We have previously demonstrated that tau is hyperphosphorylated at Thr231 and Ser199/Ser202 in PC12-htau cells compared to PC12 cells (Chalatsa et al, 2018). We therefore proceeded to assess the effects of trans -crocin 4 and trans -crocetin on this molecular mechanism using differentiated PC12-htau cells expressing hyperphosphorylated human tau.…”

Section: Resultsmentioning

confidence: 93%

The Crocus sativus Compounds trans-Crocin 4 and trans-Crocetin Modulate the Amyloidogenic Pathway and Tau Misprocessing in Alzheimer Disease Neuronal Cell Culture Models

et al. 2019

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Crocus sativus L. natural compounds have been extensively used in traditional medicine for thousands of years. Recent research evidence is now emerging in support of its therapeutic potential for different pathologies including neurodegenerative diseases. Herein, the C. sativus L. natural compounds trans -crocin 4 and trans -crocetin were selected for in depth molecular characterization of their potentially protective effects against Alzheimer’s Disease (AD), utilizing two AD neuronal cell culture models (SH-SY5Y overexpressing APP and PC12 expressing hyperphosphorylated tau). Biologically relevant concentrations, ranging from 0.1 μM to 1 mM, applied for 24 h or 72 h, were well tolerated by differentiated wild type SH-SY5Y and PC12 cells. When tested on neuronally differentiated SH-SY5Y-APP both trans -crocin 4 and trans -crocetin had significant effects against amyloidogenic pathways. Trans -crocin 4 significantly decreased of β-secretase, a key enzyme of the amyloidogenic pathway, and APP-C99, while it decreased γ-secretases that generate toxic beta-amyloid peptides. Similarly, trans -crocetin treatment led to a reduction in β- and γ-secretases, as well as to accumulation of cellular AβPP. When tested on the neuronally differentiated PC12-htau cells, both compounds proved effective in suppressing the active forms of GSK3β and ERK1/2 kinases, as well as significantly reducing total tau and tau phosphorylation. Collectively, our data demonstrate a potent effect of trans -crocin 4 and trans -crocetin in suppressing key molecular pathways of AD pathogenesis, rendering them a promising tool in the prevention and potentially the treatment of AD.

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“…A rapid and accurate method was developed, aiming to detect the major active compounds in the H. perforatum extract, as described elsewhere 30 . For the LC-HRMS, an Orbitrap high resolution mass analyzer was used in negative ionization mode.…”

Section: Resultsmentioning

confidence: 99%

Antimicrobial Photoinactivation Using Visible Light Plus Water-Filtered Infrared-A (VIS + wIRA) and Hypericum Perforatum Modifies In Situ Oral Biofilms

Vollmer

Al‐Ahmad

Argyropoulou

et al. 2019

Sci Rep

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Due to increasing antibiotic resistance, the application of antimicrobial photodynamic therapy (aPDT) is gaining increasing popularity in dentistry. The aim of this study was to investigate the antimicrobial effects of aPDT using visible light (VIS) and water-filtered infrared-A (wIRA) in combination with a Hypericum perforatum extract on in situ oral biofilms. The chemical composition of H. perforatum extract was analyzed using ultra-high-performance liquid chromatography coupled with high resolution mass spectrometry (UPLC-HRMS). To obtain initial and mature oral biofilms in situ, intraoral devices with fixed bovine enamel slabs (BES) were carried by six healthy volunteers for two hours and three days, respectively. The ex situ exposure of biofilms to VIS + wIRA (200 mWcm−2) and H. perforatum (32 mg ml−1, non-rinsed or rinsed prior to aPDT after 2-min preincubation) lasted for five minutes. Biofilm treatment with 0.2% chlorhexidine gluconate solution (CHX) served as a positive control, while untreated biofilms served as a negative control. The colony-forming units (CFU) of the aPDT-treated biofilms were quantified, and the surviving microorganisms were identified using MALDI-TOF biochemical tests as well as 16 S rDNA-sequencing. We could show that the H. perforatum extract had significant photoactivation potential at a concentration of 32 mg ml−1. When aPDT was carried out in the presence of H. perforatum, all biofilms (100%) were completely eradicated (p = 0.0001). When H. perforatum was rinsed off prior to aPDT, more than 92% of the initial viable bacterial count and 13% of the mature oral biofilm were killed. Overall, the microbial composition in initial and mature biofilms was substantially altered after aPDT, inducing a shift in the synthesis of the microbial community. In conclusion, H. perforatum-mediated aPDT using VIS + wIRA interferes with oral biofilms, resulting in their elimination or the substantial alteration of microbial diversity and richness. The present results support the evaluation of H. perforatum-mediated aPDT for the adjunctive treatment of biofilm-associated oral diseases.

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Beneficial Effects of Sideritis scardica and Cichorium spinosum against Amyloidogenic Pathway and Tau Misprocessing in Alzheimer’s Disease Neuronal Cell Culture Models

Abstract: These findings suggest that C. spinosum and S. scardica could have a notable potential in the prevention and/or treatment of AD, and merit further investigations at the in vivo level.

Cited by 14 publications

References 93 publications

Metabolic Fingerprinting of Different Sideritis Taxa Infusions and Their Neurogenic Activity

Metabolic Fingerprinting of Different Sideritis Taxa Infusions and Their Neurogenic Activity

The Crocus sativus Compounds trans-Crocin 4 and trans-Crocetin Modulate the Amyloidogenic Pathway and Tau Misprocessing in Alzheimer Disease Neuronal Cell Culture Models

Antimicrobial Photoinactivation Using Visible Light Plus Water-Filtered Infrared-A (VIS + wIRA) and Hypericum Perforatum Modifies In Situ Oral Biofilms

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