ArticleDrug design, development and therapy2016
Development of betulinic acid as an agonist of TGR5 receptor using a new in vitro assay.
Article in Drug design, development and therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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.
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
17 citing papers in PubMed, 30 citations in OpenAlex.
- Structure-Based Insights into TGR5 Activation by Natural Compounds: Therapeutic Implications and Emerging Strategies for Obesity Management.Biomedicines · 2025Review
- Crosstalk Between Bile Acids and Intestinal Epithelium: Multidimensional Roles of Farnesoid X Receptor and Takeda G Protein Receptor 5.International journal of molecular sciences · 2025Review
- Recent advancements in the structural exploration of TGR5 agonists for diabetes treatment.RSC medicinal chemistry · 2024Review
- Mechanism of action of the bile acid receptor TGR5 in obesity.Acta pharmaceutica Sinica. B · 2024Review
- Identification of Andrographolide as an Agonist of Bile Acid TGR5 Receptor in a Cell Line to Demonstrate the Reduction in Hyperglycemia in Type-1 Diabetic Rats.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Saponins fromNutrients · 2022Article
- A clickable photoaffinity probe of betulinic acid identifies tropomyosin as a target.Acta pharmaceutica Sinica. B · 2022Article
- TGR5 Expression Is Associated with Changes in the Heart and Urinary Bladder of Rats with Metabolic Syndrome.Life (Basel, Switzerland) · 2021Article
- Therapeutic Opportunities of GPBAR1 in Cholestatic Diseases.Frontiers in pharmacology · 2021Review
- Hijacking SARS-CoV-2/ACE2 Receptor Interaction by Natural and Semi-synthetic Steroidal Agents Acting on Functional Pockets on the Receptor Binding Domain.Frontiers in chemistry · 2020Article
- TGR5 activation ameliorates hyperglycemia-induced cardiac hypertrophy in H9c2 cells.Scientific reports · 2019Article
- Regulation of bile acid receptor activityLiver research (Beijing, China) · 2018Article
- miR-192 is upregulated in T1DM, regulates pancreatic β-cell development and inhibits insulin secretion through suppressing GLP-1 expression.Experimental and therapeutic medicine · 2018Article
- Ursolic acid activates the TGR5 receptor to enhance GLP-1 secretion in type 1-like diabetic rats.Naunyn-Schmiedeberg's archives of pharmacology · 2017Article
- The Dietary Furocoumarin Imperatorin Increases Plasma GLP-1 Levels in Type 1-Like Diabetic Rats.Nutrients · 2017Article
- Identification of morin as an agonist of imidazoline I-3 receptor for insulin secretion in diabetic rats.Naunyn-Schmiedeberg's archives of pharmacology · 2017Article
- Investigation of triamterene as an inhibitor of the TGR5 receptor: identification in cells and animals.Drug design, development and therapy · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundG-protein-coupled bile acid receptor 1, also known as TGR5 is known to be involved in glucose homeostasis. In animal models, treatment with a TGR5 agonist induces incretin secretion to reduce hyperglycemia. Betulinic acid, a triterpenoid present in the leaves of white birch, has been introduced as a selective TGR5 agonist. However, direct activation of TGR5 by betulinic acid has not yet been reported.
methodsTransfection of TGR5 into cultured Chinese hamster ovary (CHO-K1) cells was performed to establish the presence of TGR5. Additionally, TGR5-specific small interfering RNA was employed to silence TGR5 in cells (NCI-H716 cells) that secreted incretins. Uptake of glucose by CHO-K1 cells was evaluated using a fluorescent indicator. Amounts of cyclic adenosine monophosphate and glucagon-like peptide were quantified using enzyme-linked immunosorbent assay kits.
resultsBetulinic acid dose-dependently increases glucose uptake by CHO-K1 cells transfected with TGR5 only, which can be considered an alternative method instead of radioligand binding assay. Additionally, signals coupled to TGR5 activation are also increased by betulinic acid in cells transfected with TGR5. In NCI-H716 cells, which endogenously express TGR5, betulinic acid induces glucagon-like peptide secretion via increasing calcium levels. However, the actions of betulinic acid were markedly reduced in NCI-H716 cells that received TGR5-silencing treatment. Therefore, the present study demonstrates the activation of TGR5 by betulinic acid for the first time.
conclusionSimilar to the positive control lithocholic acid, which is the established agonist of TGR5, betulinic acid has been characterized as a useful agonist of TGR5 and can be used to activate TGR5 in the future.
Indexed as
Identifiers
What OpenQuestion holds
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.