Evidence map›Paper›PMID 35203528›Full record

ArticleBiomedicines2022

Metformin Inhibits ROS Production by Human M2 Macrophages via the Activation of AMPK.

Rana M Nassif, Elias Chalhoub, Pia Chedid, Margarita Hurtado-Nedelec, Elia Raya, Pham My-Chan Dang, Jean-Claude Marie, Jamel El-Benna

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomedicines, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
4.2field-weighted citation impact, top 5% 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

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.

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  17. Oxidative Stress in Cardiovascular Diseases: Mechanisms and Exploring Advanced Therapies.Cardiovascular & hematological agents in medicinal chemistry · 2025
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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

8 authors at 2 institutions in 2 countries.

Rana M NassifFaculty of Health Sciences, University of Balamand, P.O. Box 55251 Sin El Fil, Beirut 1100-2807, Lebanon.ORCID 0000-0002-8929-5911
Elias ChalhoubFaculty of Health Sciences, University of Balamand, P.O. Box 55251 Sin El Fil, Beirut 1100-2807, Lebanon.ORCID 0000-0003-1465-4681
Pia ChedidFaculty of Health Sciences, University of Balamand, P.O. Box 55251 Sin El Fil, Beirut 1100-2807, Lebanon.ORCID 0000-0003-0578-7415
Margarita Hurtado-NedelecCentre de Recherche sur l'Inflammation (CRI), Laboratoire d'Excellence Inflamex, Faculté de Médecine Xavier Bichat, Université de Paris, INSERM-U1149, CNRS-ERL8252, 75018 Paris, France.
Elia RayaFaculty of Health Sciences, University of Balamand, P.O. Box 55251 Sin El Fil, Beirut 1100-2807, Lebanon.
Pham My-Chan DangCentre de Recherche sur l'Inflammation (CRI), Laboratoire d'Excellence Inflamex, Faculté de Médecine Xavier Bichat, Université de Paris, INSERM-U1149, CNRS-ERL8252, 75018 Paris, France.
Jean-Claude MarieCentre de Recherche sur l'Inflammation (CRI), Laboratoire d'Excellence Inflamex, Faculté de Médecine Xavier Bichat, Université de Paris, INSERM-U1149, CNRS-ERL8252, 75018 Paris, France.
Jamel El-BennaCentre de Recherche sur l'Inflammation (CRI), Laboratoire d'Excellence Inflamex, Faculté de Médecine Xavier Bichat, Université de Paris, INSERM-U1149, CNRS-ERL8252, 75018 Paris, France.ORCID 0000-0001-5733-216X
Centre National de la Recherche Scientifique · FRUniversity of Balamand · LB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Metformin (1,1-dimethylbiguanide hydrochloride) is the most commonly used drug to treat type II diabetic patients. It is believed that this drug has several other beneficial effects, such as anti-inflammatory and anticancer effects. Here, we wanted to evaluate the effect of metformin on the production of reactive oxygen species (ROS) by human macrophages. Macrophages are generated in vivo from circulating monocytes depending on the local tissue environment. In vitro proinflammatory macrophages (M1) and anti-inflammatory macrophages (M2) can be generated by culturing monocytes in the presence of different cytokines, such as GM-CSF or M-CSF, respectively. We show that metformin selectively inhibited human monocyte differentiation into proinflammatory macrophages (M1) without inhibiting their differentiation into anti-inflammatory macrophages (M2). Moreover, we demonstrate that, in response to LPS, M2 macrophages produced ROS, which could be very harmful for nearby tissues, and metformin inhibited this process. Interestingly, metformin with LPS induced activation of the adenosine-monophosphate-activated protein kinase (AMPK) and pharmacological activation of AMPK by AICAR, a known AMPK activator, decreased ROS production, whereas the deletion of AMPK in mice dramatically enhanced ROS production in different types of immune cells. These results suggest that metformin exhibits anti-inflammatory effects by inhibiting the differentiation of human monocytes into M1 macrophages and by limiting ROS production by macrophages via the activation of AMPK.

Indexed as

AMPKinflammationmacrophagemetforminNADPH oxidaseNOX2ROS

Identifiers

PMID35203528
PMCPMC8869356
OpenAlexW4210604230

What OpenQuestion holds

Textmetadata
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.