Evidence mapPaperPMID 41331671Full record

ArticleDiabetology & metabolic syndrome2025

Honokiol attenuates diabetic nephropathy by targeting SIRT3 to suppress mitochondrial ROS-induced pyroptosis.

Ke Yu, Maodong Liu, Tao Zhang, Canghui Guo, Lingyu Du, Min Li, Qian Wang, Ning Han, Yanqing Chi, Ying Li

Abstract read
In one paragraph

Article in Diabetology & metabolic syndrome, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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.

Ke YuDepartment of Nephrology, Hebei Medical University Third Hospital, No. 139, Ziqiang Road, Shijiazhuang, 050051, Hebei Province, China.
Maodong LiuDepartment of Nephrology, Hebei Medical University Third Hospital, No. 139, Ziqiang Road, Shijiazhuang, 050051, Hebei Province, China.
Tao ZhangDepartment of Nephrology, Hebei Medical University Third Hospital, No. 139, Ziqiang Road, Shijiazhuang, 050051, Hebei Province, China.
Canghui GuoDepartment of Nephrology, Hebei Medical University Third Hospital, No. 139, Ziqiang Road, Shijiazhuang, 050051, Hebei Province, China.
Lingyu DuDepartment of Nephrology, Hebei Medical University Third Hospital, No. 139, Ziqiang Road, Shijiazhuang, 050051, Hebei Province, China.
Min LiDepartment of Nephrology, Hebei Medical University Third Hospital, No. 139, Ziqiang Road, Shijiazhuang, 050051, Hebei Province, China.
Qian WangDepartment of Nephrology, Hebei Medical University Third Hospital, No. 139, Ziqiang Road, Shijiazhuang, 050051, Hebei Province, China.
Ning HanDepartment of Nephrology, Hebei Medical University Third Hospital, No. 139, Ziqiang Road, Shijiazhuang, 050051, Hebei Province, China.
Yanqing ChiDepartment of Nephrology, Hebei Medical University Third Hospital, No. 139, Ziqiang Road, Shijiazhuang, 050051, Hebei Province, China. 37300757@hebmu.edu.cn.
Ying LiDepartment of Nephrology, Hebei Medical University Third Hospital, No. 139, Ziqiang Road, Shijiazhuang, 050051, Hebei Province, China. 35500825@hebmu.edu.cn.

Funding

Scientific Research Project of Hebei Administration of Traditional Chinese Medicine 2025333
6 · The paper itself

Abstract

backgroundDiabetic nephropathy (DN) persists as the leading cause of end-stage renal disease worldwide. Growing evidence indicates that mitochondrial dysfunction triggers NLRP3 inflammasome activation and subsequent pyroptosis, which play crucial roles in DN development. Honokiol (HKL), a natural compound with the ability to upregulate SIRT3 expression, shows promise in protecting mitochondrial function. This study investigates HKL's renoprotective effects in DN and explores its mechanism of action through the SIRT3-mediated regulation of mitochondrial ROS, NLRP3 inflammasome, and pyroptosis. MATERIALS AND

methodsdb/db diabetic mice and HK-2 cells subjected to hyperglycemic stimulation were used to assess the therapeutic effects of HKL. Renal function, pyroptosis, and mitochondrial homeostasis were assessed via biochemical assays, histopathological and immunohistochemical analyses, transmission electron microscopy, Western blotting, and immunofluorescence staining. SIRT3 overexpression and knockdown were performed to validate its regulatory role, while the mtROS scavenger MitoTEMPO was utilized to confirm the pivotal involvement of mtROS in the pyroptotic pathway.

resultsHKL treatment significantly ameliorated renal dysfunction and pathological damage in diabetic mice. Mechanistically, HKL upregulated SIRT3 expression, thereby improving mitochondrial function (maintaining structural integrity, stabilizing the membrane potential, and reducing mtROS accumulation), which in turn suppressed NLRP3 inflammasome activation and subsequent GSDMD-mediated pyroptosis. SIRT3 overexpression mimicked the protective effects of HKL, whereas SIRT3 knockdown attenuated its efficacy, confirming the essential role of SIRT3 in this process. Furthermore, mtROS scavenging by MitoTEMPO mitigated pyroptosis, reinforcing the dependence of the effects of HKL on the SIRT3-mtROS axis.

conclusionBy upregulating SIRT3 expression to maintain mitochondrial homeostasis and suppress mtROS-NLRP3-mediated pyroptosis, HKL emerges as a promising therapeutic strategy for DN.

Indexed as

Diabetic nephropathyHonokiolMitochondriaPyroptosisSIRT3

Identifiers

PMID41331671
PMCPMC12777499

What Socratic holds

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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 Socratic graph.