Evidence map›Paper›PMID 35355867›Full record

ArticleOxidative medicine and cellular longevity2022

Cimifugin Ameliorates Lipotoxicity-Induced Hepatocyte Damage and Steatosis through TLR4/p38 MAPK- and SIRT1-Involved Pathways.

Wenwen Yang, Linwensi Zhu, Shanglei Lai, Qinchao Ding, Tiantian Xu, Rui Guo, Xiaobing Dou, Hui Chai, Zhiling Yu, Songtao Li

Open access · hybridAbstract read
In one paragraph

Article in Oxidative medicine and cellular longevity, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

13 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
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  13. Pelargonidin-Antioxidants (Basel, Switzerland) · 2022
    Article
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 2 countries.

Wenwen YangSchool of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, China.ORCID https://orcid.org/0000-0002-6027-7816
Linwensi ZhuThe First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, China.
Shanglei LaiSchool of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Qinchao DingAcademy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China.ORCID https://orcid.org/0000-0001-8664-5368
Tiantian XuSchool of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, China.ORCID https://orcid.org/0000-0002-1499-2392
Rui GuoSchool of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Xiaobing DouSchool of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.ORCID https://orcid.org/0000-0002-2465-3079
Hui ChaiSchool of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Zhiling YuSchool of Chinese Medicine, Hong Kong Baptist University, Hong Kong 999077, China.
Songtao LiSchool of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, China.ORCID https://orcid.org/0000-0002-2926-673X
Zhejiang Chinese Medical University · CNHong Kong Baptist University · HK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Objective: Hepatic metabolic disorder induced by lipotoxicity plays a detrimental role in metabolic fatty liver disease pathogenesis. Cimifugin (Cim), a coumarin derivative extracted from the root of Methods: AML-12, a nontransformed mouse hepatocyte cell line, was employed in this study. The cells were incubated with palmitate or oleate to imitate hepatotoxicity or steatosis model, respectively. Results: Cim significantly reversed palmitate-induced hepatocellular injury in a dose-dependent manner, accompanied by improvements in oxidative stress and mitochondrial damage. Cim pretreatment reversed palmitate-stimulated TLR4/p38 MAPK activation and SIRT1 reduction without affecting JNK, ERK1/2, and AMPK pathways. The hepatoprotective effects of Cim were abolished either through activating TLR4/p38 by their pharmacological agonists or genetical silencing SIRT1 via special siRNA, indicating a mechanistic involvement. Moreover, Cim treatment improved oleate-induced hepatocellular lipid accumulation, which could be blocked by either TLR4 stimulation or SIRT1 knockdown. We observed that SIRT1 was a potential target of TLR4 in palmitate-treated hepatocytes, since TLR4 agonist LPS aggravated, whereas TLR4 antagonist CLI-095 alleviated palmitate-decreased SIRT1 expression. SIRT1 knockdown did not affect palmitate-induced TLR4. In addition, TLR4 activation by LPS significantly abolished Cim-protected SIRT1 reduction induced by palmitate. These results collaboratively indicated that TLR4-regulated SIRT1 pathways was mechanistically involved in the protective effects of Cim against lipotoxicity. Conclusion: In brief, we demonstrate the protective effects of Cim against lipotoxicity-induced cell death and steatosis in hepatocytes. TLR4-regulated p38 MAPK and SIRT1 pathways are involved in Cim-protected hepatic lipotoxicity. Cim is a potential candidate for improving hepatic metabolic disorders mediated by lipotoxicity.

Indexed as

Fatty LiverSirtuin 1AnimalsChromonesHepatocytesMicep38 Mitogen-Activated Protein KinasesToll-Like Receptor 4Chromonescimifuginp38 Mitogen-Activated Protein KinasesSirt1 protein, mouseSirtuin 1Tlr4 protein, mouseToll-Like Receptor 4

Identifiers

PMID35355867
PMCPMC8958062
OpenAlexW4220785217

What OpenQuestion holds

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LicenceCC BY
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.