Metformin as a Potential Treatment Option for Endometriosis

Kimber-Trojnar, Żaneta; Dłuski, Dominik; Wierzchowska-Opoka, Magdalena; Ruszała, Monika; Leszczyńska‐Gorzelak, Bożena

doi:10.3390/cancers14030577

Cited by 15 publications

(12 citation statements)

References 165 publications

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“…In addition, there are few plaque-stabilizing drugs targeting MMP-9. Metformin interferes with the pathophysiology of multiple cancers and diabetes by reducing MMP-9 expression [ 31 , 32 , 33 ]. However, there are still many studies showing that metformin can increase MMP-9 expression [ 34 ], including some clinical trials [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Metformin Directly Binds to MMP-9 to Improve Plaque Stability

Chen

Wang

et al. 2023

JCDD

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Vulnerable atherosclerotic plaque rupture is the principal mechanism that accounts for myocardial infarction and stroke. High matrix metalloproteinase-9 (MMP-9) expression and activity have been proven to lead to plaque instability. Metformin, a first-line treatment for type 2 diabetes, is beneficial to plaque vulnerability. However, the mechanism underlying its anti-atherogenic effect remains unclear. Molecular docking and surface plasmon resonance experiments showed that metformin directly interacts with MMP-9, and incubated MMP-9 overexpressing HEK293A cells with metformin (1 μmol·L−1) significantly attenuates MMP-9’s activity using zymography and MMP activity assays. Moreover, metformin treatment drives MMP-9 degradation. Next, we constructed a carotid artery atherosclerotic plaque model and administered consecutive 14-day metformin (200 mg·kg−1·d−1) treatment by intragastric gavage. Immunofluorescence staining of the right carotid common artery and serum MMP activity assay results showed that metformin treatment decreased local plaque MMP-9 protein level and circulating MMP-9 activity, respectively. Histochemical staining revealed that after metformin treatment, the collagen content in plaque was significantly preserved, and the plaque vulnerability index decreased. These findings suggested that metformin improved atherosclerotic plaque stability by directly binding to MMP-9 and driving its degradation.

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Section: Discussionmentioning

confidence: 99%

Metformin Directly Binds to MMP-9 to Improve Plaque Stability

Chen

Wang

et al. 2023

JCDD

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“…Indeed, metformin administration in STZ-diabetic rats resulted in improved testosterone, LH and FSH hormones levels (Nasrolahi et al 2013 ). Various studies have shown that treatment with metformin is effective in reproductive system diseases, including female and male reproduction in endocrine pathologies (Lee et al 2019 ; Shpakov 2021 , ul haq Shah, Shrivastava et al 2022 ), endometriosis (Zhao et al 2018 , Mu et al 2020 , Stochino-Loi et al 2021 , Kimber-Trojnar et al 2022 ), polycystic ovary syndrome (Chen et al 2019 ; Fornes et al 2022 , Xu et al 2022 ) and prostate (Sun et al 2018 , Chen, Wang et al 2021a , b , c , Aydın et al 2022 , Morale et al 2022 ).…”

Section: Metformin and Therapeutic Goalsmentioning

confidence: 99%

The role of AMPK-dependent pathways in cellular and molecular mechanisms of metformin: a new perspective for treatment and prevention of diseases

Hasanvand

2022

Inflammopharmacol

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Metformin can suppress gluconeogenesis and reduce blood sugar by activating adenosine monophosphate-activated protein kinase (AMPK) and inducing small heterodimer partner (SHP) expression in the liver cells. The main mechanism of metformin’s action is related to its activation of the AMPK enzyme and regulation of the energy balance. AMPK is a heterothermic serine/threonine kinase made of a catalytic alpha subunit and two subunits of beta and a gamma regulator. This enzyme can measure the intracellular ratio of AMP/ATP. If this ratio is high, the amino acid threonine 172 available in its alpha chain would be activated by the phosphorylated liver kinase B1 (LKB1), leading to AMPK activation. Several studies have indicated that apart from its significant role in the reduction of blood glucose level, metformin activates the AMPK enzyme that in turn has various efficient impacts on the regulation of various processes, including controlling inflammatory conditions, altering the differentiation pathway of immune and non-immune cell pathways, and the amelioration of various cancers, liver diseases, inflammatory bowel disease (IBD), kidney diseases, neurological disorders, etc. Metformin’s activation of AMPK enables it to control inflammatory conditions, improve oxidative status, regulate the differentiation pathways of various cells, change the pathological process in various diseases, and finally have positive therapeutic effects on them. Due to the activation of AMPK and its role in regulating several subcellular signalling pathways, metformin can be effective in altering the cells’ proliferation and differentiation pathways and eventually in the prevention and treatment of certain diseases. Graphical abstract

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“…Unfortunately, despite following the recommendations discussed above, as much as 15–30% of patients with GDM will require pharmacotherapy. The treatment of hyperglycemia in patients with GDM includes insulin, as well as oral medications, including metformin and glyburide [ 10 , 21 , 22 , 23 , 24 ]. Due to its structure, insulin is considered a safer drug than metformin and glyburide [ 25 ].…”

Section: Management Of Gdmmentioning

confidence: 99%

Incretins as a Potential Treatment Option for Gestational Diabetes Mellitus

Pilszyk

Niebrzydowska

Pilszyk

et al. 2022

IJMS

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Gestational diabetes mellitus (GDM) is a metabolic disease affecting an increasing number of pregnant women around the world. It is not only associated with numerous perinatal complications but also has long-term consequences impacting maternal health and fetal development. To prevent them, it is important to keep glucose levels under control. As much as 15–30% of GDM patients will require treatment with insulin, metformin, or glyburide. With that in mind, it is crucial to keep searching for novel and improved pharmacotherapies. Nowadays, there are ongoing studies investigating the use of other groups of drugs that have proven successful in the treatment of T2DM. Glucagon-like peptide-1 (GLP-1) receptor agonist and dipeptidyl peptidase-4 (DPP-4) inhibitor are among the drugs targeting the incretin system and are currently receiving significant attention. The aim of our review is to demonstrate the potential of these medications in treating GDM and preventing its later complications. It seems that both groups may be successful in the GDM management used alone or as an addition to better-known drugs, including metformin and glyburide. However, more clinical trials are needed to confirm their importance in GDM treatment and to demonstrate effective therapeutic strategies.

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Metformin as a Potential Treatment Option for Endometriosis

Cited by 15 publications

References 165 publications

Metformin Directly Binds to MMP-9 to Improve Plaque Stability

Metformin Directly Binds to MMP-9 to Improve Plaque Stability

The role of AMPK-dependent pathways in cellular and molecular mechanisms of metformin: a new perspective for treatment and prevention of diseases

Incretins as a Potential Treatment Option for Gestational Diabetes Mellitus

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