Evidence map›Paper›PMID 38378659›Full record

ArticleCell communication and signaling : CCS2024

Chemoproteomics-based profiling reveals potential antimalarial mechanism of Celastrol by disrupting spermidine and protein synthesis.

Peng Gao, Jianyou Wang, Huan Tang, Huanhuan Pang, Jiemei Liu, Chen Wang, Fei Xia, Honglin Chen, Liting Xu, Junzhe Zhang and 4 more

Open access · goldAbstract readVideo-Audio Media
In one paragraph

Article in Cell communication and signaling : CCS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
6.0field-weighted citation impact, top 4% 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

6 citing papers in PubMed, 11 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 4 institutions in 1 country.

Peng Gao *Department of rehabilitation medicine, Shunde Hospital, Southern Medical University, Foshan, 528300, China.
Jianyou Wang *State Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng, 475004, China.
Huan Tang *State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
Huanhuan Pang *State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
Jiemei LiuDepartment of rehabilitation medicine, Shunde Hospital, Southern Medical University, Foshan, 528300, China.
Chen WangState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
Fei XiaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
Honglin ChenState Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng, 475004, China.
Liting XuState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
Junzhe ZhangState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
Lixia YuanSchool of Traditional Chinese Medicine and School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. cnylxtcm@smu.edu.cn.
Guang HanState Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng, 475004, China. hang@henu.edu.cn.
Jigang WangState Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng, 475004, China. jgwang@icmm.ac.cn.
Gang LiuDepartment of rehabilitation medicine, Shunde Hospital, Southern Medical University, Foshan, 528300, China. lg2781@smu.edu.cn.
Chinese Academy of Medical Sciences & Peking Union Medical College · CNHenan University · CNThe First People's Hospital of Shunde · CNGuangzhou University of Chinese Medicine · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMalaria remains a global health burden, and the emergence and increasing spread of drug resistance to current antimalarials poses a major challenge to malaria control. There is an urgent need to find new drugs or strategies to alleviate this predicament. Celastrol (Cel) is an extensively studied natural bioactive compound that has shown potentially promising antimalarial activity, but its antimalarial mechanism remains largely elusive.

methodsWe first established the Plasmodium berghei ANKA-infected C57BL/6 mouse model and systematically evaluated the antimalarial effects of Cel in conjunction with in vitro culture of Plasmodium falciparum. The potential antimalarial targets of Cel were then identified using a Cel activity probe based on the activity-based protein profiling (ABPP) technology. Subsequently, the antimalarial mechanism was analyzed by integrating with proteomics and transcriptomics. The binding of Cel to the identified key target proteins was verified by a series of biochemical experiments and functional assays.

resultsThe results of the pharmacodynamic assay showed that Cel has favorable antimalarial activity both in vivo and in vitro. The ABPP-based target profiling showed that Cel can bind to a number of proteins in the parasite. Among the 31 identified potential target proteins of Cel, PfSpdsyn and PfEGF1-α were verified to be two critical target proteins, suggesting the role of Cel in interfering with the de novo synthesis of spermidine and proteins of the parasite, thus exerting its antimalarial effects.

conclusionsIn conclusion, this study reports for the first time the potential antimalarial targets and mechanism of action of Cel using the ABPP strategy. Our work not only support the expansion of Cel as a potential antimalarial agent or adjuvant, but also establishes the necessary theoretical basis for the development of potential antimalarial drugs with pentacyclic triterpenoid structures, as represented by Cel. Video Abstract.

Indexed as

AntimalarialsMalariaAnimalsMiceMice, Inbred C57BLPentacyclic TriterpenesSpermidineAntimalarialscelastrolPentacyclic TriterpenesSpermidineAntimalarialCelastrolProtein synthesisSpermidine

Identifiers

PMID38378659
PMCPMC10877925
OpenAlexW4391969121

What Socratic holds

Textmetadata
LicenceCC BY
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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.