ArticlePharmacological research2015
The effects of (-)-epicatechin on endothelial cells involve the G protein-coupled estrogen receptor (GPER).
Article in Pharmacological research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 4 of them syntheses that pooled it.
What it found
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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.
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.
Who cites it
35 citing papers in PubMed, 4 syntheses or guidelines pooled it, 67 citations in OpenAlex.
- The role of cocoa flavanols in modulating peripheral and cerebral microvascular function in healthy individuals and populations at-risk of cardiovascular disease: a systematic review.Nutrition journal · 2025Pooled it
- Pooled it
- Pooled it
- Effects of Cocoa-Derived Polyphenols on Cognitive Function in Humans. Systematic Review and Analysis of Methodological Aspects.Plant foods for human nutrition (Dordrecht, Netherlands) · 2020Pooled it
- Dietary flavanols preserve upper- and lower-limb endothelial function during sitting in high- and low-fit young healthy males.The Journal of physiology · 2026Trial
- The Impact of Cocoa Flavanols in Modulating Resting Cerebral Blood Flow During Prolonged Sitting in Healthy Young and Older Adults.Nutrients · 2025Trial
- Cocoa Flavanols Improve Vascular Responses to Acute Mental Stress in Young Healthy Adults.Nutrients · 2021Trial
- Effects of Cacao By-Products and a Modest Weight Loss Intervention on the Concentration of Serum Triglycerides in Overweight Subjects: Proof of Concept.Journal of medicinal food · 2020Trial
- A pilot study on clinical pharmacokinetics and preclinical pharmacodynamics of (+)-epicatechin on cardiometabolic endpoints.Food & function · 2018Trial
- Beneficial effects of dark chocolate on exercise capacity in sedentary subjects: underlying mechanisms. A double blind, randomized, placebo controlled trial.Food & function · 2016Trial
- (-)-Epicatechin metabolites as a GPER ligands: a theoretical perspective.Molecular diversity · 2025Article
- Sea buckthorn flavonoids and their derivatives: potential natural compounds for the treatment of diabetic cardiomyopathy.Frontiers in pharmacology · 2025Review
- The G protein-coupled oestrogen receptor GPER in health and disease: an update.Nature reviews. Endocrinology · 2023Review
- G Protein-Coupled Estrogen Receptor GPER: Molecular Pharmacology and Therapeutic Applications.Annual review of pharmacology and toxicology · 2023Review
- (-)-Epicatechin Is a Biased Ligand of Apelin Receptor.International journal of molecular sciences · 2022Article
- Estrogen and G protein-coupled estrogen receptor accelerate the progression of benign prostatic hyperplasia by inducing prostatic fibrosis.Cell death & disease · 2022Article
- G-Protein-Coupled Estrogen Receptor Expression in Rat Uterine Artery Is Increased by Pregnancy and Induces Dilation in a CaInternational journal of molecular sciences · 2022Article
- Association of Dietary Intake of Polyphenols with an Adequate Nutritional Profile in Postpartum Women from Argentina.Preventive nutrition and food science · 2022Article
- (-)-Epicatechin Alters Reactive Oxygen and Nitrogen Species Production Independent of Mitochondrial Respiration in Human Vascular Endothelial Cells.Oxidative medicine and cellular longevity · 2022Article
- ( -)-Epicatechin and cardiometabolic risk factors: a focus on potential mechanisms of action.Pflugers Archiv : European journal of physiology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
We have provided evidence that the stimulatory effects of (-)-epicatechin ((-)-EPI) on endothelial cell nitric oxide (NO) production may involve the participation of a cell-surface receptor. Thus far, such entity(ies) has not been fully elucidated. The G protein-coupled estrogen receptor (GPER) is a cell-surface receptor that has been linked to protective effects on the cardiovascular system and activation of intracellular signaling pathways (including NO production) similar to those reported with (-)-EPI. In bovine coronary artery endothelial cells (BCAEC) by the use of confocal imaging, we evidence the presence of GPER at the cell-surface and on F-actin filaments. Using in silico studies we document the favorable binding mode between (-)-EPI and GPER. Such binding is comparable to that of the GPER agonist, G1. By the use of selective blockers, we demonstrate that the activation of ERK 1/2 and CaMKII by (-)-EPI is dependent on the GPER/c-SRC/EGFR axis mimicking those effects noted with G1. We also evidence by the use of siRNA the role that GPER has on mediating ERK1/2 activation by (-)-EPI. GPER appears to be coupled to a non Gαi/o or Gαs, protein subtype. To extrapolate our findings to an ex vivo model, we employed phenylephrine pre-contracted aortic rings evidencing that (-)-EPI can mediate vasodilation through GPER activation. In conclusion, we provide evidence that suggests the GPER as a potential mediator of (-)-EPI effects and highlights the important role that GPER may have on cardiovascular system protection.
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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 OpenQuestion graph.