ArticleExperimental and therapeutic medicine2018
Metformin and pioglitazone combination therapy ameliorate polycystic ovary syndrome through AMPK/PI3K/JNK pathway.
Article in Experimental and therapeutic medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 41 citations in OpenAlex.
- Metformin versus metformin plus pioglitazone on gonadal and metabolic profiles in normal-weight women with polycystic ovary syndrome: a single-center, open-labeled prospective randomized controlled trial.Journal of ovarian research · 2024Trial
- Comparative evaluation of metformin & sitaformin in classic PCOS patients undergoing intracytoplasmic sperm injection: A randomized controlled pilot study.The Indian journal of medical research · 2023Trial
- Pioglitazone Metformin Complex Improves Polycystic Ovary Syndrome Comorbid Psychological Distress via Inhibiting NLRP3 Inflammasome Activation: A Prospective Clinical Study.Mediators of inflammation · 2020Trial
- Exploring the key ingredients and mechanisms of Banxia Xiexin decoction for the treatment of polycystic ovary syndrome based on network pharmacology and experimental validation.Annals of medicine · 2025Article
- The roles of MAPK signaling pathway in ovarian folliculogenesis.Journal of ovarian research · 2025Review
- Role of Granulosa Cell Dysfunction in Women Infertility Associated with Polycystic Ovary Syndrome and Obesity.Biomolecules · 2025Review
- Chiglitazar ameliorates dehydroepiandrosterone-induced polycystic ovary syndrome in rats.Journal of ovarian research · 2024Article
- Posttranslational modifications in pathogenesis of PCOS.Frontiers in endocrinology · 2022Review
- HB-EGF induces mitochondrial dysfunction via estrogen hypersecretion in granulosa cells dependent on cAMP-PKA-JNK/ERK-CaInternational journal of biological sciences · 2022Article
- Insulin resistance, autophagy and apoptosis in patients with polycystic ovary syndrome: Association with PI3K signaling pathway.Frontiers in endocrinology · 2022Review
- Repurposing new drug candidates and identifying crucial molecules underlying PCOS Pathogenesis Based On Bioinformatics Analysis.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2021Article
- proBDNF expression induces apoptosis and inhibits synaptic regeneration by regulating the RhoA-JNK pathway in an in vitro post-stroke depression model.Translational psychiatry · 2021Article
- Metformin Prevents Follicular Atresia in Aging Laying Chickens through Activation of PI3K/AKT and Calcium Signaling Pathways.Oxidative medicine and cellular longevity · 2020Article
- Panax ginseng improves glucose metabolism in streptozotocin-induced diabetic rats through 5' adenosine monophosphate kinase up-regulation.Saudi journal of biological sciences · 2019Article
- Metformin and sitagliptin combination therapy ameliorates polycystic ovary syndrome with insulin resistance through upregulation of lncRNA H19.Cell cycle (Georgetown, Tex.) · 2019Article
- Total flavonoids extracted fromBioscience reports · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder, which results in health problems such as menstrual disorders, hyperandrogenism and persistent anovulation. Hyperandrogenism and insulin resistance are the basic characteristics of PCOS. To investigate the combined effect of metformin and pioglitazone on POCS and the potential mechanisms, a rat model of PCOS was established by intramuscular injection of estradiol valerate (EV). The effect of metformin and pioglitazone monotherapy or combination therapy in control rats and PCOS rats was evaluated, involving the testosterone level, follicular development and insulin resistance. The potential mechanism for the therapeutic effect of metformin and pioglitazone on POCS was explored through using three inhibitors of the 5'adenosine monophosphate-activated protein kinase (AMPK)/phosphoinositide-3 kinase (PI3K)/c-Jun N-terminal kinase (JNK) pathway (Compound C, Wortmannin and SP600125). The results showed that EV-induced PCOS rats demonstrated hyperandrogenemia, hyperinsulinemia and follicular dysplasia. Metformin or pioglitazone monotherapy significantly suppressed the high level of testosterone, reduced the raised percentage of cystic follicles and primary follicles, promoted the number of early antral follicles, and markedly decreased the high concentration of fasting insulin and homeostatic model assessment for insulin resistance index in PCOS rats. In addition, metformin and pioglitazone combination therapy demonstrated greater efficacy than its individual components. Furthermore, individual or joint treatment with metformin and pioglitazone affected the phosphorylation level of JNK in PCOS rats. Compound C and Wortmannin eliminated the effect of metformin and pioglitazone combination therapy on improving the follicular growth in PCOS rats, whereas SP600125 treatment enhanced this combination therapy effect. These data suggested that metformin and pioglitazone combination therapy demonstrated great efficacy in ameliorating PCOS through regulating the AMPK/PI3K/JNK pathway.
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Registered trials
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.