Evidence map›Paper›PMID 33947921›Full record

ArticleScientific reports2021

Periplocin and cardiac glycosides suppress the unfolded protein response.

Muneshige Tokugawa, Yasumichi Inoue, Kan'ichiro Ishiuchi, Chisane Kujirai, Michiyo Matsuno, Masaki Ri, Yuka Itoh, Chiharu Miyajima, Daisuke Morishita, Nobumichi Ohoka and 4 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 40% 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

3 citing papers in PubMed, 12 citations in OpenAlex.

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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

14 authors at 3 institutions in 2 countries.

Muneshige TokugawaDepartment of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, 467-8603, Japan.
Yasumichi InoueDepartment of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, 467-8603, Japan. yainoue@phar.nagoya-cu.ac.jp.
Kan'ichiro IshiuchiDepartment of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, 467-8603, Japan.
Chisane KujiraiDepartment of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, 467-8603, Japan.
Michiyo MatsunoThe Kochi Prefectural Makino Botanical Garden, Kochi, 781-8125, Japan.
Masaki RiDepartment of Hematology and Oncology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, 467-8601, Japan.
Yuka ItohDepartment of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, 467-8603, Japan.
Chiharu MiyajimaDepartment of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, 467-8603, Japan.
Daisuke MorishitaDepartment of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, 467-8603, Japan.
Nobumichi OhokaDivision of Molecular Target and Gene Therapy Products, National Institute of Health Sciences, Kawasaki, 210-9501, Japan.
Shinsuke IidaDepartment of Hematology and Oncology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, 467-8601, Japan.
Hajime MizukamiThe Kochi Prefectural Makino Botanical Garden, Kochi, 781-8125, Japan.
Toshiaki MakinoDepartment of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, 467-8603, Japan.
Hidetoshi HayashiDepartment of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, 467-8603, Japan. hhayashi@phar.nagoya-cu.ac.jp.
Nagoya City University · JPMakino Botanical Garden · JPNational Institute of Health Sciences · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The unfolded protein response (UPR) controls protein homeostasis through transcriptional and translational regulation. However, dysregulated UPR signaling has been associated with the pathogenesis of many human diseases. Therefore, the compounds modulating UPR may provide molecular insights for these pathologies in the context of UPR. Here, we screened small-molecule compounds that suppress UPR, using a library of Myanmar wild plant extracts. The screening system to track X-box binding protein 1 (XBP1) splicing activity revealed that the ethanol extract of the Periploca calophylla stem inhibited the inositol-requiring enzyme 1 (IRE1)-XBP1 pathway. We isolated and identified periplocin as a potent inhibitor of the IRE1-XBP1 axis. Periplocin also suppressed other UPR axes, protein kinase R-like endoplasmic reticulum kinase (PERK), and activating transcription factor 6 (ATF6). Examining the structure-activity relationship of periplocin revealed that cardiac glycosides also inhibited UPR. Moreover, periplocin suppressed the constitutive activation of XBP1 and exerted cytotoxic effects in the human multiple myeloma cell lines, AMO1 and RPMI8226. These results reveal a novel suppressive effect of periplocin or the other cardiac glycosides on UPR regulation, suggesting that these compounds will contribute to our understanding of the pathological or physiological importance of UPR.

Indexed as

Cardiac GlycosidesCell LineCell Line, TumorEndoplasmic ReticulumHEK293 CellsHumansPeriplocaPlant ExtractsRNA SplicingSaponinsSignal TransductionSmall Molecule LibrariesUnfolded Protein ResponseX-Box Binding Protein 1Cardiac GlycosidesperiplocinPlant ExtractsSaponinsSmall Molecule LibrariesX-Box Binding Protein 1

Identifiers

PMID33947921
PMCPMC8097017
OpenAlexW3157885272

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Registered trials

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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.