Evidence map›Paper›PMID 36085573›Full record

ArticleJournal of cachexia, sarcopenia and muscle2022

Atractylenolide I ameliorates cancer cachexia through inhibiting biogenesis of IL-6 and tumour-derived extracellular vesicles.

Meng Fan, Xiaofan Gu, Wanli Zhang, Qiang Shen, Ruiqin Zhang, Qiaoyu Fang, Yueping Wang, Xiaodong Guo, Xiongwen Zhang, Xuan Liu

Open access · goldAbstract read
In one paragraph

Article in Journal of cachexia, sarcopenia and muscle, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
4.4field-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

36 citing papers in PubMed, 55 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

10 authors at 2 institutions in 1 country.

Meng FanShanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.ORCID 0000-0002-3761-4431
Xiaofan GuShanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China.ORCID 0000-0002-2441-3489
Wanli ZhangShanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China.ORCID 0000-0003-2555-6577
Qiang ShenShanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.ORCID 0000-0002-0867-6668
Ruiqin ZhangShanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.ORCID 0000-0002-3758-7429
Qiaoyu FangShanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.ORCID 0000-0002-6519-3427
Yueping WangShanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.ORCID 0000-0003-1133-7875
Xiaodong GuoDepartment of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.ORCID 0000-0002-3986-694X
Xiongwen ZhangShanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China.ORCID 0000-0002-6514-4190
Xuan LiuShanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.ORCID 0000-0002-7356-7898
Shanghai University of Traditional Chinese Medicine · CNEast China Normal University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAtractylenolide I (AI) is a natural sesquiterpene lactone isolated from Atractylodes macrocephala Koidz, known as Baizhu in traditional Chinese medicine. AI has been found to ameliorate cancer cachexia in clinic cancer patients and in tumour-bearing mice. Here, we checked the influence of AI on biogenesis of IL-6 and extracellular vesicles (EVs) in cancer cachexia mice and then focused on studying mechanisms of AI in inhibiting the production of tumour-derived EVs, which contribute to the ameliorating effects of AI on cancer cachexia.

methodsC26 tumour-bearing BALB/c mice were applied as animal model to examine the effects of AI (25 mg/kg) in attenuating cachexia symptoms, serum IL-6 and EVs levels. IL-6 and EVs secretion of C26 tumour cells treated with AI (0.31-5 μM) was further observed in vitro. The in vitro cultured C2C12 myotubes and 3T3-L1 mature adipocytes were used to check the potency of conditioned medium of C26 cells treated with AI (0.625-5 μM) in inducing muscle atrophy and lipolysis. The glycolysis potency of C26 cells under AI (0.31-5 μM) treatment was evaluated by measuring the extracellular acidification rate using Seahorse XFe96 Analyser. Levels of related signal proteins in both in vitro and in vivo experiments were examined using western blotting to study the possible mechanisms. STAT3 overexpression or knockout C26 cells were also used to confirm the effects of AI (5 μM).

resultsAI ameliorated cancer cachexia symptoms (P < 0.05), improved grip strength (P < 0.05) and decreased serum EVs (P < 0.05) and IL-6 (P < 0.05) levels of C26 tumour-bearing mice. AI directly inhibited EVs biogenesis (P < 0.001) and IL-6 secretion (P < 0.01) of cultured C26 cells. The potency of C26 medium in inducing C2C12 myotube atrophy (+59.54%, P < 0.001) and 3T3-L1 adipocyte lipolysis (+20.73%, P < 0.05) was significantly attenuated when C26 cells were treated with AI. AI treatment inhibited aerobic glycolysis and the pathway of STAT3/PKM2/SNAP23 in C26 cells. Furthermore, overexpression of STAT3 partly antagonized the effects of AI in suppressing STAT3/PKM2/SNAP23 pathway, EVs secretion, glycolysis and the potency of C26 medium in inducing muscle atrophy and lipolysis, whereas knockout of STAT3 enhanced the inhibitory effect of AI on these values. The inhibition of AI on STAT3/PKM2/SNAP23 pathway was also observed in C26 tumour tissues.

conclusionsAI ameliorates cancer cachexia by decreasing the production of IL-6 and EVs of tumour cells. The decreasing effects of AI on EVs biogenesis are based on its inhibition on STAT3/PKM2/SNAP23 pathway.

Indexed as

Extracellular VesiclesNeoplasmsAnimalsCachexiaCell Line, TumorDrugs, Chinese HerbalInterleukin-6LactonesMiceMuscular AtrophySesquiterpenesatractylenolide IBaizhuDrugs, Chinese HerbalInterleukin-6LactonesSesquiterpenesatractylenolide Icancer cachexiaextracellular vesiclelipolysismuscle atrophySTAT3

Identifiers

PMID36085573
PMCPMC9745491
OpenAlexW4297731256

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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 OpenQuestion graph.