Evidence map›Paper›PMID 42225680›Full record

ArticleScientific reports2026

Harpagide attenuates cerebral ischemic injury by modulating mitochondrial calcium homeostasis associated with the AMPK-MCU axis.

Ke Wang, Huai-Yu Liu, Yue Wang, Gen-Zheng Su, Jin-Lai Gao, Yan-Ping Wang, Zhi He

Abstract read
In one paragraph

Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Ke Wang *Department of Pharmacology, College of Medicine, Jiaxing University, Jiaxing, 314001, People's Republic of China. wangke@zjxu.edu.cn.ORCID http://orcid.org/0000-0002-2795-8556
Huai-Yu Liu *College of Medicine and Health Sciences, China Three Gorges University, Yichang, 443002, People's Republic of China.ORCID http://orcid.org/0009-0009-6941-8599
Yue WangXinmai Pharmaceutical Co., Ltd., Beijing, 100195, People's Republic of China.ORCID http://orcid.org/0009-0006-7387-4587
Gen-Zheng SuCollege of Life Science and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, People's Republic of China.ORCID http://orcid.org/0009-0000-4720-2943
Jin-Lai GaoDepartment of Pharmacology, College of Medicine, Jiaxing University, Jiaxing, 314001, People's Republic of China.ORCID http://orcid.org/0009-0004-0106-1451
Yan-Ping WangJiaXing Key Laboratory of Fundamental and Clinical Research on Cerebral Protection in Acute Ischemic Cerebrovascular Disease(A), Jiaxing, 314001, People's Republic of China.ORCID http://orcid.org/0000-0003-0757-7307
Zhi HeDepartment of Pharmacology, College of Medicine, Jiaxing University, Jiaxing, 314001, People's Republic of China. 329856208@qq.com.ORCID http://orcid.org/0000-0001-7567-8287

Funding

National Natural Science Foundation of China No.82073824National Natural Science Foundation of China No.82204837Natural Science Foundation of Zhejiang, China No. LQ23H290004Natural Science Key Foundation of Zhejiang, China No. LZ25H310002
6 · The paper itself

Abstract

Mitochondrial calcium homeostasis may offer therapeutic benefits for ischemic stroke. Harpagide has been shown to inhibit mitochondrial calcium uptake, but the mechanism remains unclear. In this study, a male ICR mouse model of permanent middle cerebral artery occlusion (pMCAO)-induced focal cerebral ischemia and PC12 and SH-SY5Y cells exposed to oxygen-glucose deprivation (OGD) were used. Apoptosis, lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA), and the ATP levels were measured to assess the neuroprotective effects of harpagide. DCFH-DA, JC-1, and Rhod-2A probes were used to analyze the mitochondrial function. RT-qPCR and western blot were used to determine the mitochondrial calcium uniporter (MCU), the apoptosis-inducing factor (AIF), Endo G, Cyt C, Caspase-3, and AMPK-MCU phosphorylation expression levels. Additionally, Longa scoring and triphenyl tetrazolium chloride (TTC) staining were used. Transmission electron microscopy (TEM) was used to examine the mitochondrial ultrastructural changes. An immunohistochemical analysis was conducted to detect the MCU expression in the temporal cortex. Harpagide attenuated OGD-induced cytotoxicity, as evidenced by reduced lactate LDH leakage, restored ATP generation, and ameliorated mitochondrial ultrastructural damage. Mechanistically, harpagide suppressed oxidative stress and alleviated mitochondrial calcium ([Ca

Indexed as

AMP-Activated Protein KinasesBrain IschemiaCalciumCalcium ChannelsIridoid GlycosidesMitochondriaNeuroprotective AgentsAnimalsApoptosisDisease Models, AnimalHomeostasisHumansInfarction, Middle Cerebral ArteryMaleMiceMice, Inbred ICRAMP-Activated Protein KinasesCalciumCalcium ChannelsIridoid Glycosidesmitochondrial calcium uniporterNeuroprotective AgentsAMPKHarpagideIschemic strokeMCUMitochondrial calcium homeostasis

Identifiers

PMID42225680
PMCPMC13462545

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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.