NLRP3 inflammasome inhibition and M1-to-M2 microglial polarization shifting via scoparone-inhibited TLR4 axis in ovariectomy/D-galactose Alzheimer's disease rat model

Ibrahim, Weam W.; Skalicka‐Woźniak, Krystyna; Budzyńska, Barbara; Sayed, Nesrine S. El

doi:10.1016/j.intimp.2023.110239

Cited by 9 publications

(2 citation statements)

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“…In the present study, OVX/D-Gal group rats exhibited spatial learning memory impairments, as evidenced by the results of the MWM test, which is in line with former findings (Kamel et al 2018 ; Ibrahim et al 2019 , 2023 ). However, treatment with E. bonariensis extract (100 or 200 mg/kg) markedly improved the memory performance of OVX/D-Gal group rats, producing effects equivalent to those of donepezil.…”

Section: Discussionsupporting

confidence: 93%

Neuroprotective potential of Erigeron bonariensis ethanolic extract against ovariectomized/D-galactose-induced memory impairments in female rats in relation to its metabolite fingerprint as revealed using UPLC/MS

Ibrahim,

Sayed,

Abdelhameed

et al. 2024

Inflammopharmacol

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Erigeron bonariensis is widely distributed throughout the world's tropics and subtropics. In folk medicine, E. bonariensis has historically been used to treat head and brain diseases. Alzheimer’s disease (AD) is the most widespread form of dementia initiated via disturbances in brain function. Herein, the neuroprotective effect of the chemically characterized E. bonariensis ethanolic extract is reported for the first time in an AD animal model. Chemical profiling was conducted using UPLC–ESI-MS analysis. Female rats underwent ovariectomy (OVX) followed by 42 days of D-galactose (D-Gal) administration (150 mg/kg/day, i.p) to induce AD. The OVX/D-Gal-subjected rats received either donepezil (5 mg/kg/day) or E. bonariensis at 50, 100, and 200 mg/kg/day, given 1 h prior to D-Gal. UPLC–ESI-MS analysis identified 42 chemicals, including flavonoids, phenolic acids, terpenes, and nitrogenous constituents. Several metabolites, such as isoschaftoside, casticin, velutin, pantothenic acid, xanthurenic acid, C18-sphingosine, linoleamide, and erucamide, were reported herein for the first time in Erigeron genus. Treatment with E. bonariensis extract mitigated the cognitive decline in the Morris Water Maze test and the histopathological alterations in cortical and hippocampal tissues of OVX/D-Gal-subjected rats. Moreover, E. bonariensis extract mitigated OVX/D-Gal-induced Aβ aggregation, Tau hyperphosphorylation, AChE activity, neuroinflammation (NF-κBp65, TNF-α, IL-1β), and apoptosis (Cytc, BAX). Additionally, E. bonariensis extract ameliorated AD by increasing α7-nAChRs expression, down-regulating GSK-3β and FOXO3a expression, and modulating Jak2/STAT3/NF-ĸB p65 and PI3K/AKT signaling cascades. These findings demonstrate the neuroprotective and memory-enhancing effects of E. bonariensis extract in the OVX/D-Gal rat model, highlighting its potential as a promising candidate for AD management. Graphical Abstract

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Section: Discussionsupporting

confidence: 93%

Neuroprotective potential of Erigeron bonariensis ethanolic extract against ovariectomized/D-galactose-induced memory impairments in female rats in relation to its metabolite fingerprint as revealed using UPLC/MS

Ibrahim,

Sayed,

Abdelhameed

et al. 2024

Inflammopharmacol

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“…It been demonstrated to possess antiinflammatory, antioxidant, and antitumor properties in diverse cancer types. [14][15][16] Therefore, Scoparone exhibits promising therapeutic potential not only in glioma but also in other diseases. Further investigations are warranted to explore its therapeutic efficacy and mechanisms of action in various disease contexts.…”

Section: Discussionmentioning

confidence: 99%

Scoparone attenuates glioma progression and improves the toxicity of temozolomide by suppressing RhoA/ROCK1 signaling

Zhou

Han

Zhao

et al. 2023

Environmental Toxicology

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BackgroundGlioma, a type of malignant brain tumor, has become a challenging health issue globally in recent years.MethodsIn this study, we investigated the potential therapeutic role of scoparone in glioma and the underlying mechanism. Initially, transcriptome sequencing was conducted to identify genes that exhibited differential expression in glioma cells treated with scoparone compared to untreated cells. Subsequently, the impact of scoparone on the proliferation, migration, and invasion of glioma cells was assessed in vitro using a range of assays including cell viability, colony formation, wound healing, and transwell assays. Moreover, the apoptotic effects of scoparone on glioma cells were evaluated through flow cytometry and western blot analysis. Furthermore, we established a glioma xenograft mouse model to assess the in vivo antitumor activity of scoparone. Lastly, by integrating transcriptome analysis, we endeavored to unravel the molecular mechanisms underlying the observed antitumor effects of scoparone by examining the expression levels of RhoA/ROCK1 signaling pathway components using western blot analysis and qRT‐PCR.ResultsOur transcriptome sequencing results revealed that scoparone significantly downregulated RhoA/ROCK1 signaling in glioma cells. Furthermore, scoparone treatment inhibited glioma cell proliferation, migration, and invasion, and promoted cell apoptosis in vitro. Moreover, scoparone reduced tumor growth and prolonged survival in a glioma xenograft mouse model, and improved the toxicity of temozolomide. Finally, our results showed that the antitumor effects of scoparone were mediated by the suppression of RhoA/ROCK1 signaling.ConclusionScoparone could be a promising therapeutic agent for glioma by suppressing RhoA/ROCK1 signaling. These findings pave the way for future research endeavors aimed at the development and optimization of scoparone‐based therapeutic strategies.

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Exploring the Therapeutic Potential of BBB‐Penetrating Phytochemicals With p38 MAPK Modulatory Activity in Addressing Oxidative Stress‐Induced Neurodegenerative Disorders, With a Focus on Alzheimer's Disease

Hosseini,

Sheibani,

Valipour

2024

Phytotherapy Research

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Oxidative stress plays an important role in the occurrence of neurodegenerative diseases. Previous studies indicate a strong connection between oxidative stress, inappropriate activation of the p38 MAPK signaling pathway, and the pathogenesis of neurodegenerative diseases. Although antioxidant therapy is a valid strategy to alleviate these problems, the most important limitation of this approach is the ineffectiveness of drug administration due to the limited permeability of the BBB. Therefore, BBB‐penetrating p38 MAPK modulators with proper antioxidant capacity could be useful in preventing/reducing the complications of neurodegenerative disorders. The current manuscript aims to review the therapeutic capabilities of some recently reviewed naturally occurring p38 MAPK inhibitors in the management of neurodegenerative problems such as Alzheimer's disease. In data collection, we tried to use more recent studies published in high‐quality journals indexed in databases Scopus, Web of Science, PubMed, and so on, but no specific time frame was considered due to the nature of the study. Our evaluations indicate that natural compounds tanshinones, protoberberines, pinocembrin, osthole, rhynchophylline, oxymatrine, schisandrin, piperine, paeonol, ferulic acid, 6‐gingerol, obovatol, and trolox have significant potential for use as supplements/adjuvants in the reduction of neurodegenerative‐related problems. Our findings emphasize the usefulness of BBB‐penetrating phytochemicals with p38 MAPK modulatory activity as potential therapeutic options against neurodegenerative disorders. Of course, the proper use of these compounds depends on considering their toxicity/safety profile and pharmacokinetic characteristics as well as the clinical conditions of users.

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NLRP3 inflammasome inhibition and M1-to-M2 microglial polarization shifting via scoparone-inhibited TLR4 axis in ovariectomy/D-galactose Alzheimer's disease rat model

Cited by 9 publications

References 68 publications

Neuroprotective potential of Erigeron bonariensis ethanolic extract against ovariectomized/D-galactose-induced memory impairments in female rats in relation to its metabolite fingerprint as revealed using UPLC/MS

Neuroprotective potential of Erigeron bonariensis ethanolic extract against ovariectomized/D-galactose-induced memory impairments in female rats in relation to its metabolite fingerprint as revealed using UPLC/MS

Scoparone attenuates glioma progression and improves the toxicity of temozolomide by suppressing RhoA/ROCK1 signaling

Exploring the Therapeutic Potential of BBB‐Penetrating Phytochemicals With p38 MAPK Modulatory Activity in Addressing Oxidative Stress‐Induced Neurodegenerative Disorders, With a Focus on Alzheimer's Disease

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