Evidence map›Paper›PMID 39238115›Full record

ArticleCNS neuroscience & therapeutics2024

Betulin ameliorates neuronal apoptosis and oxidative injury via DJ-1/Akt/Nrf2 signaling pathway after subarachnoid hemorrhage.

Xiaoyang Lu, Shu Yang, Qixiong Lu, Yuansheng Zhang, Zaihong Cha, Wei Huang, Tao Li

Abstract read
In one paragraph

Article in CNS neuroscience & therapeutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

  1. Article
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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.

Xiaoyang LuDepartment of Neurosurgery, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
Shu YangDepartment of Neurology, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
Qixiong LuThe Affiliated Hospital of Kunming University of Science and Technology. Department of Neurosurgery, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China.
Yuansheng ZhangThe Affiliated Hospital of Kunming University of Science and Technology. Department of Neurosurgery, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China.
Zaihong ChaThe Affiliated Hospital of Kunming University of Science and Technology. Department of Neurosurgery, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China.
Wei HuangDepartment of Neurosurgery, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
Tao LiDepartment of Neurosurgery, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.ORCID 0000-0003-0792-003X

Funding

Innovation Research Projects on Cerebrovascular Diseases for Young Doctors, China International Medical Foundation Z-2016-20-2101Joint Projects of Yunnan Provincial Science and Technology Department and Kunming Medical University for Applied Basic Research 202101AY070001-252Joint Projects of Yunnan Provincial Science and Technology Department and Kunming University of Science and Technology KUST-KH2023005ZNational Natural Science Foundation of China 82001278The Fund for Young Doctors with the First People's Hospital of Yunnan Province KHBS-2022-018Yunnan Fundamental Research Projects 202401CF070007
6 · The paper itself

Abstract

aimsWe aimed to resolve the uncertainty as to whether betulin exerted neuroprotection on early brain injury (EBI) caused by subarachnoid hemorrhage (SAH), and to investigate the related molecular mechanisms.

methodsBioinformatic analysis was performed to pre-study the differently expressed genes (DEGs) and the possible signaling pathways. Rat and cellular model of SAH were introduced in this study, and betulin, an activator of DJ-1 protein, was administered to reveal the effect. Gross assessment regarding mortality, neurofunctions, SAH grade, brain water content (BWC) along with multiple cellular and molecular studies in vivo or/and in vitro such as immunofluorescence (IF) staining, western blot (WB), reactive oxygen species (ROS) assay, and flow cytometry (FCM) were all conducted after SAH induction to verify the protective effect and the relevant mechanisms of DJ-1 in diverse levels. In addition, MK2206 (selective inhibitor of Akt) and iRNADj-1 (interfering RNA to Dj-1) were utilized to confirm the mechanisms of the effect.

resultsThe data from our study showed that DJ-1 protein was moderately expressed in neurons, microglia, and astrocytes; its level in brain tissue elevated and peaked at 24-72 h after SAH induction. Betulin could efficaciously induce the expression of DJ-1 which in turn activated Akt and Bcl-2, and anti-oxidative enzymes SOD2 and HO-1, functioning to reduce the activation of cleaved caspase-3 (c-Casp-3) and reactive oxygen species (ROS). The induced DJ-1 could upregulate the expression of Nrf2. However, Akt seemed no direct effect on elevating the expression of Nrf2. DJ-1 alone could as well activate Akt-independent antiapoptotic pathway via suppressing the activation of caspase-8 (Casp-8).

conclusionsBetulin which was a potent agonist of DJ-1 had the ability to induce its expression in brain tissue. DJ-1 had neuroprotective effect on EBI through comprehensive mechanisms, including facilitating intrinsic and extrinsic antiapoptotic pathway, and reducing oxidative injury by upregulating the expression of redox proteins. Betulin as an inexpensive drug showed the potential for SAH treatment.

Indexed as

ApoptosisNeuronsNF-E2-Related Factor 2Oxidative StressProtein Deglycase DJ-1Proto-Oncogene Proteins c-aktRats, Sprague-DawleySignal TransductionSubarachnoid HemorrhageTriterpenesAnimalsBetulinic AcidMaleNeuroprotective AgentsRatsReactive Oxygen SpeciesbetulinBetulinic AcidNeuroprotective AgentsNfe2l2 protein, ratNF-E2-Related Factor 2PARK7 protein, ratProtein Deglycase DJ-1Proto-Oncogene Proteins c-aktReactive Oxygen SpeciesTriterpenesbetulinDJ‐1early brain injuryneuronal apoptosisoxidative injurysubarachnoid hemorrhage

Identifiers

PMID39238115
PMCPMC11377304

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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.