Evidence map›Paper›PMID 36216897›Full record

ArticleActa pharmacologica Sinica2023

Oridonin ameliorates caspase-9-mediated brain neuronal apoptosis in mouse with ischemic stroke by inhibiting RIPK3-mediated mitophagy.

Lei Li, Jing-Jing Song, Meng-Xue Zhang, Hui-Wen Zhang, Hai-Yan Zhu, Wei Guo, Cai-Long Pan, Xue Liu, Lu Xu, Zhi-Yuan Zhang

Open access · greenAbstract read
In one paragraph

Article in Acta pharmacologica Sinica, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
3.5field-weighted citation impact, top 6% 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

26 citing papers in PubMed, 42 citations in OpenAlex.

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  13. PANoptosis: a potential target of atherosclerotic cardiovascular disease.Apoptosis : an international journal on programmed cell death · 2025
    Review
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  20. Polyphenolic metabolites inFrontiers in pharmacology · 2025
    Review
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

10 authors at 2 institutions in 1 country.

Lei Li *School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, China.
Jing-Jing Song *School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, China.
Meng-Xue Zhang *School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, China.
Hui-Wen ZhangSchool of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, China.
Hai-Yan ZhuSchool of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, China.
Wei GuoDepartment of Urology, The Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University, Wuxi, 214002, China.
Cai-Long PanSchool of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, China.
Xue LiuSchool of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, China.
Lu XuSchool of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, China. xulu@njmu.edu.cn.
Zhi-Yuan ZhangSchool of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, China. zzy@njmu.edu.cn.
Nanjing Medical University · CNWuxi No.2 People's Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neuronal loss is a primary factor in determining the outcome of ischemic stroke. Oridonin (Ori), a natural diterpenoid compound extracted from the Chinese herb Rabdosia rubescens, has been shown to exert anti-inflammatory and neuroregulatory effects in various models of neurological diseases. In this study we investigated whether Ori exerted a protective effect against reperfusion injury-induced neuronal loss and the underlying mechanisms. Mice were subjected to transient middle cerebral artery occlusion (tMCAO), and were injected with Ori (5, 10, 20 mg/kg, i.p.) at the beginning of reperfusion. We showed that Ori treatment rescued neuronal loss in a dose-dependent manner by specifically inhibiting caspase-9-mediated neuronal apoptosis and exerted neuroprotective effects against reperfusion injury. Furthermore, we found that Ori treatment reversed neuronal mitochondrial damage and loss after reperfusion injury. In N2a cells and primary neurons, Ori (1, 3, 6 μM) exerted similar protective effects against oxygen-glucose deprivation and reoxygenation (OGD/R)-induced injury. We then conducted an RNA-sequencing assay of the ipsilateral brain tissue of tMCAO mice, and identified receptor-interacting protein kinase-3 (RIPK3) as the most significantly changed apoptosis-associated gene. In N2a cells after OGD/R and in the ipsilateral brain region, we found that RIPK3 mediated excessive neuronal mitophagy by activating AMPK mitophagy signaling, which was inhibited by Ori or 3-MA. Using in vitro and in vivo RIPK3 knockdown models, we demonstrated that the anti-apoptotic and neuroprotective effects of Ori were RIPK3-dependent. Collectively, our results show that Ori effectively inhibits RIPK3-induced excessive mitophagy and thereby rescues the neuronal loss in the early stage of ischemic stroke.

Indexed as

Brain IschemiaIschemic StrokeNeuroprotective AgentsReperfusion InjuryStrokeAnimalsApoptosisBrainCaspase 9Diterpenes, KauraneInfarction, Middle Cerebral ArteryMiceMitophagyNeuronsReceptor-Interacting Protein Serine-Threonine KinasesCaspase 9Diterpenes, KauraneNeuroprotective AgentsoridoninReceptor-Interacting Protein Serine-Threonine KinasesRipk3 protein, mouseapoptosisischemic strokemitophagyoridoninRIPK3transient middle cerebral artery occlusion

Identifiers

PMID36216897
PMCPMC10042824
OpenAlexW4303982901

What Socratic 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 Socratic graph.