Evidence map›Paper›PMID 30756299›Full record

ArticleMolecular neurobiology2019

Hesperetin Confers Neuroprotection by Regulating Nrf2/TLR4/NF-κB Signaling in an Aβ Mouse Model.

Muhammad Ikram, Tahir Muhammad, Shafiq Ur Rehman, Amjad Khan, Min Gi Jo, Tahir Ali, Myeong Ok Kim

Abstract read
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In one paragraph

Article in Molecular neurobiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
111citing papers in PubMed, 2 pooled it
12.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

111 citing papers in PubMed, 2 syntheses or guidelines pooled it, 183 citations in OpenAlex.

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  5. Vitamin D Promotes Neuronal Survival via Nrf2 Upregulation in D-Galactose-Induced Mice: An In-Vivo and In-Silico Study.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026
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51 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Muhammad IkramDivision of Life Science and Applied Life Science (BK21 plus), College of Natural Sciences, Gyeongsang National University, Jinju, 52828, Republic of Korea.
Tahir MuhammadDivision of Life Science and Applied Life Science (BK21 plus), College of Natural Sciences, Gyeongsang National University, Jinju, 52828, Republic of Korea.
Shafiq Ur RehmanDivision of Life Science and Applied Life Science (BK21 plus), College of Natural Sciences, Gyeongsang National University, Jinju, 52828, Republic of Korea.
Amjad KhanDivision of Life Science and Applied Life Science (BK21 plus), College of Natural Sciences, Gyeongsang National University, Jinju, 52828, Republic of Korea.
Min Gi JoDivision of Life Science and Applied Life Science (BK21 plus), College of Natural Sciences, Gyeongsang National University, Jinju, 52828, Republic of Korea.
Tahir AliDivision of Life Science and Applied Life Science (BK21 plus), College of Natural Sciences, Gyeongsang National University, Jinju, 52828, Republic of Korea.
Myeong Ok KimDivision of Life Science and Applied Life Science (BK21 plus), College of Natural Sciences, Gyeongsang National University, Jinju, 52828, Republic of Korea. mokim@gnu.ac.kr.ORCID http://orcid.org/0000-0003-2492-5369
Gyeongsang National University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hesperetin is a bioactive flavonoid in the body, produced from hesperidin. No comprehensive studies have shown its protective effects in neurodegenerative disorders. Here, we hypothesized that hesperetin may protect the mice brain against Aβ-induced neurodegeneration. Twenty-four hours after intracerebroventricular injection of Aβ1-42, the treated group was injected hesperetin. For in vitro experiments, HT22 and BV-2 cells were used. Immunoblot, immunofluorescence, and behavioral analyses were used to evaluate the different parameters. Our results indicated that hesperetin significantly attenuated oxidative stress, as assessed by the expression of Nrf2/HO-1 and LPO and ROS assays, in the hippocampus, cortex, and in vitro HT22 cells. Similarly, activated glial cells were regulated by hesperetin, as assessed by the expression of GFAP and Iba-1. Moreover, the expression of TLR4, p-NF-κB, and downstream targets was analyzed; the results showed that hesperetin reinstated the expression of these markers. The effects of hesperetin were further confirmed by using specific TLR4 and p-NF-κB inhibitors in BV-2 cells. Next, we evaluated Aβ pathology in the cortex, hippocampus, and HT22 cells, showing that hesperetin significantly reduced the Aβ pathology. Furthermore, the antiapoptotic effects of hesperetin were assessed, which showed strong antiapoptotic effects. Overall, the neuroprotective effect of hesperetin was found to be a multipotent effect, involving the inhibition of oxidative stress, neuroinflammation, apoptotic cell death, and cognitive consolidation. Given antioxidant, anti-inflammatory, and antiapoptotic potentials against Aβ-induced neurodegeneration and memory impairment, hesperetin may be a promising therapeutic agent for Alzheimer's disease-like neurological disorders.

Indexed as

Signal TransductionAlzheimer DiseaseAmyloid beta-PeptidesAnimalsApoptosisAstrocytesBiomarkersCell LineCognitive DysfunctionDisease Models, AnimalHesperidinHippocampusMaleMemoryMemory DisordersMice, Inbred C57BLAmyloid beta-PeptidesBiomarkershesperetinHesperidinNerve Tissue ProteinsNF-E2-Related Factor 2NF-kappa BToll-Like Receptor 4Amyloid betaHesperetinNeurodegenerationNeuroinflammationNeuroprotection

Identifiers

PMID30756299
OpenAlexW2913268298

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.