A rare olive compound oleacein functions as a TrkB agonist and mitigates neuroinflammation both in vitro and in vivo

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: June 4, 2024

Abstract Background Neuroinflammation is widely acknowledged as a characteristic feature of almost all neurological disorders and specifically in depression- anxiety-like disorders. In recent years, there has been significant attention on natural compounds with potent anti-inflammatory effects due to their potential mitigating neuroinflammation neuroplasticity. Methods the present study, we aimed evaluate neuroprotective oleacein (OC), rare secoiridoid derivative found extra virgin olive oil. Our goal was explore BDNF/TrkB neurotrophic activity OC subsequently assess its for modulating neuroinflammatory response using human neuroblastoma cells (SH-SY5Y cells) an vivo model depression induced by lipopolysaccharide (LPS)-mediated inflammation. Results SH-SY5Y cells, exhibited dose-dependent increase BDNF expression. This enhancement absent when were co-treated inhibitors BDNF's receptor TrkB, well downstream molecules PI3K MEK. Whole-transcriptomics analysis revealed that upregulated cell cycle-related genes under normal conditions, while downregulating inflammation-associated LPS-induced conditions. Furthermore, surface plasmon resonance (SPR) assays demonstrated stronger more stable binding affinity TrkB compared positive control, 7,8-dihydroxyflavone. Importantly, bioluminescence imaging single oral dose significantly increased expression brains Bdnf-IRES-AkaLuc mice. administration at dosage 10 mg/kg body weight days reduced immobility time tail suspension test LPS-treated group. RT-qPCR decreased pro-inflammatory cytokines Tnfα , Il6 Il1β simultaneously enhancing Bdnf expression, both pro mature protein levels mice hippocampus. These changes comparable those control antidepressant drug fluoxetine. Additionally, microarray mouse confirmed could counteract inflammatory biological events. Conclusion Altogether, our study represents first report antineuroinflammatory properties via modulation activity. finding underscores therapeutic agent anxiety-related

Language: Английский

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Biosynthesized Selenium-hydroxytyrosol nanoparticles attenuate hepatocellular carcinoma in rats

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Hepatocellular carcinoma (HCC) is a life-threatening disease with global impact, underscoring the urgent need for development of new therapeutic agents. This study evaluates effect selenium-hydroxytyrosol nanoparticles (Se-HTNPs) in rat model HCC induced by diethylnitrosamine (DEN). In vitro, Se-HTNPs treatment reduced viability Hep G2 cells dose-dependent manner, an IC₅₀ value 61.29 ± 1.12 µg/mL. The results confirmed antioxidant, anti-inflammatory, and anti-carcinogenic properties Se-HTNPs, demonstrating their effectiveness against DEN-induced HCC. effects were validated inhibiting serum ALT, AST, ALP enzyme activities reducing total bilirubin levels. Simultaneously, enhanced albumin protein Additionally, alleviated oxidative stress significantly lowering hepatic lipid peroxidation (MDA) levels markedly increasing antioxidant marker (GSH, SOD, TAC) compared to DEN-administered rats. also inflammatory markers (TNFα, IL-6, IL-1β), apoptotic (p53 caspase 3), VEGF Furthermore, DEN group, distinctly suppressed c-JNK mRNA NF-κB gene expression Moreover, Se-HTNP improved histological alterations DEN. conclusion, these findings suggest that mitigate rats through potent properties.

Language: Английский

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Morinda officinalis oligosaccharides alleviate chronic unpredictable mild stress-induced depression through the BDNF/TrkB/CREB pathway and symptoms of sexual dysfunction in mice

Frontiers in Neuroscience, Journal Year: 2025, Volume and Issue: 18

Published: Jan. 8, 2025

In recent years, depression has become a global public health concern, and one of the common concomitant symptoms are diminished sexual motivation impaired performance. The aim this study was to investigate potential effects Morinda officinalis oligosaccharides (MOO) on its symptom, dysfunction. Chronic unpredictable mild stress (CUMS)-induced model constructed, MOO abilities were evaluated. results revealed that able alleviate CUMS-induced depression-like behavior in mice, inhibit hippocampal neuron apoptosis, reverse monoamine neurotransmitter imbalance, increase Brain-derived neurotrophic factor (BDNF) expression levels hippocampus, modulate composition distribution gut microbiota, abundance probiotics after continuous gavage for 28 days. further confirmed dysfunction is closely related development by improving lack low performance depressed modulating disruption sex hormone secretion serum, alleviating sperm morphology functional defects epididymis. These findings provide basis exploring antidepressant mechanism, use improve hypogonadotropic symptoms, future new drug improves symptoms.

Language: Английский

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

Nutraceuticals, Journal Year: 2025, Volume and Issue: 5(1), P. 5 - 5

Published: Jan. 21, 2025

The aim of the present study was to investigate phenolic composition and efficacy an innovative formulation based on Mg, Vitamin B6, water extracts from Vitex agnus-castus, Crocus sativus, Melissa officinalis, Betula pendula, pubescens developed as effective tool face neuroinflammation depression symptoms occurring in premenstrual syndrome (PMS). analyzed through colorimetric liquid chromatography methods for determining content phenols flavonoids. Additionally, scavenging/reducing properties were investigated via 2,2-diphenyl-1-picrylhydrazyl (DPPH,) 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), horseradish peroxidase assays. biocompatible limits determined allelopathy, brine shrimp lethality test, Daphnia magna cardiotoxicity assay. then assayed experimental model constituted by isolated mouse cortex specimens exposed K+ 60 mM Krebs–Ringer buffer, a toxic depolarizing stimulus able reproduce burden inflammation/oxidative stress increased serotonin (5-hydroxytryptamine, 5-HT) impoverishment different neurological psychiatric conditions, including depression. results phytochemical analysis showed that is rich benzoic acids, namely gentisic acid (155.31 µg/mL) phenylethanoid compounds, hydroxytyrosol (39.79 support antioxidant effects measured DPPH (IC50: 1.48 mg/mL), ABTS 0.42 2.02 mg/mL) ecotoxicological models indicated non-toxic, permitting identification concentration (1000 be used buffer. In this model, gene expression cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), estrogen receptor-1 (ESR1), prolactin receptor (PRLR), brain-derived neurotrophic factor (BDNF), transporter (SERT) real-time PCR. cortex, formula reduced COX-2, IL-6, SERT, ESR1, PRLR BDNF IL-10 expression. Overall, corroborated use contrast inflammation, oxidative stress, neurotransmitter impairment associated with PMS.

Language: Английский

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Green-synthesized selenium-hydroxytyrosol nanocomposites attenuate hepatocellular carcinoma in rats by modulating oxidative stress, inflammation, and apoptosis

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Language: Английский

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Hydroxytyrosol: A Promising Therapeutic Agent for Mitigating Inflammation and Apoptosis

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(12), P. 1504 - 1504

Published: Nov. 22, 2024

Inflammation and apoptosis are interrelated biological processes that have a significant impact on the advancement growth of certain chronic diseases, such as cardiovascular problems, neurological conditions, osteoarthritis. Recent research has emphasized focusing these mechanisms could result in novel therapeutic approaches aim to decrease severity diseases enhance patient outcomes. Hydroxytyrosol (HT), which is well-known for its ability prevent oxidation, been identified possible candidate regulating both inflammation apoptosis. In this review, we will highlight multifaceted benefits HT agent mitigating inflammation, apoptosis, associated conditions. This review provides comprehensive overview latest vitro vivo anti-inflammatory antiapoptotic effects by it works. Based studies, strongly advised use bioactive ingredient pharmaceutical products intended well those with applications.

Language: Английский

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Impact of pharmacokinetic enhancement strategies on the antimicrobial and antioxidant activities of hydroxytyrosol

RSC Advances, Journal Year: 2025, Volume and Issue: 15(5), P. 3448 - 3464

Published: Jan. 1, 2025

Investigation of the impact two approaches, chemical modification by lipophilization and liposomal encapsulation, on antioxidant antimicrobial properties hydroxytyrosol.

Language: Английский

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