Glycyrrhizic acid increases glucagon like peptide-1 secretion via TGR5 activation in type 1-like diabetic rats

Wang, Lin-Yu; Cheng, Kai‐Chun; Li, Yingxiao; Niu, Chiang‐Shan; Niu, Ho‐Shan

doi:10.1016/j.biopha.2017.08.087

Cited by 26 publications

(14 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is no doubt that ROS induced by high glucose are responsible for STAT3 activation, similar to previous views. 13,19,27 Expression of the Enho gene is promoted by STAT3 11 and we confirmed it in HepG2 cells by silencing STAT3 with a specific inhibitor (Stattic). Therefore, hyperglycemia produced ROS to activate STAT3 to induce higher expression of Enho gene in HepG2 cells.…”

Section: Discussionsupporting

confidence: 52%

“…24 Activated STAT3 in the nucleus binds to specific DNA promoter sequences to regulate Enho gene expression. 11 Hyperglycemia activated STAT3 expression 25 additionally increased tissue damage. 9 It has been reported that high glucose conditions increased STAT3 phosphorylation and nuclear translocation.…”

Section: Discussionmentioning

confidence: 99%

“…10 STAT3 may promote the transcription of target genes, including adropin. 11 However, the role of STAT3 and adropin in glycemic control in diabetes remains unclear.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

<p>Promotion of Adropin Expression by Hyperglycemia Is Associated with STAT3 Activation in Diabetic Rats</p>

Kuo¹,

Cheng²,

Li³

et al. 2020

DMSO

Self Cite

View full text Add to dashboard Cite

Background: Adropin is a secreted polypeptide that has been demonstrated to play an important role in energy homeostasis and lipid metabolism. Signal transducer and activator of transcription 3 (STAT3) may promote the transcription of target genes including adropin. In the current study, we investigated the effect of adropin on glucose metabolism in diabetic rats and the mechanism that governs this effect was subsequently assessed. Materials and Methods: Rats received a single injection of streptozotocin to induce type 1 diabetes. The diabetic rats were treated with insulin or phloridzin, another antidiabetic agent through inhibition of glucose reabsorption, for 7 days. Plasma glucose levels and adropin levels were measured. The interaction between STAT3 and adropin was evaluated using the human hepatoma HepG2 cell line. HepG2 cells were pretreated with the specific antagonist Stattic or with STAT3-specific siRNAs to knockout STAT3. Changes in energy homeostasisassociated gene expression were measured using real-time PCR. The protein expression levels of pSTAT3 and STAT3 were measured using Western blotting. Results: In diabetic rats, the serum concentrations of adropin were increased in the vehicletreated group and decreased in the insulin-or phloridzin-treated group. In liver tissues, the Enho expression level and the activity of STAT3 also showed similar tendencies. After HepG2 cells were treated with medium containing high glucose, the ratio of p-STAT3 to STAT3, Enho mRNA levels and reactive oxygen species expression levels in HepG2 cells were significantly increased in conjunction with increased glucose levels. The effect was inhibited after pretreatment with Stattic or knockdown with STAT3-specific siRNAs. Conclusion: STAT3 is involved in the genetic regulation of adropin, increasing the levels of circulating adropin and promoting Enho expression in the livers of diabetic rats.

show abstract

Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

<p>Promotion of Adropin Expression by Hyperglycemia Is Associated with STAT3 Activation in Diabetic Rats</p>

Kuo¹,

Cheng²,

Li³

et al. 2020

DMSO

Self Cite

View full text Add to dashboard Cite

show abstract

“…Because the above mentioned triterpenoids have been identified as natural ligands for two bile acid activated receptors, the Farnesoid-X-Receptor (FXR) and G protein Bile Acid Receptor (GPBAR)-1 (Sepe et al, 2015;De Marino et al, 2019;Fiorucci and Distrutti, 2019), we have further investigated whether mammalian ligands of these receptors were also endowed with the ability to bind the above mentioned RBD's pockets. More specifically, oleanolic, betulinic and ursolic acids have been proved to act as selective and potent GPBAR1 agonists (Sato et al, 2007;Genet et al, 2010;Lo et al, 2016), while glycyrrhetinic acid, the major metabolic component of licorice, and its corresponding saponin, glycyrrhizic acid, have been shown to act as dual FXR and GPBAR1 agonists in transactivation assay (Distrutti et al, 2015), also promoting GLP-1 secretion in type 1-like diabetic rats (Wang et al, 2017).…”

Section: Virtual Screening Of the Fda-approved Drug Librarymentioning

confidence: 99%

Hijacking SARS-CoV-2/ACE2 Receptor Interaction by Natural and Semi-synthetic Steroidal Agents Acting on Functional Pockets on the Receptor Binding Domain

et al. 2020

View full text Add to dashboard Cite

The coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by the severe acute respiratory syndrome coronavirus (SARS)-CoV-2. In light of the urgent need to identify novel approaches to be used in the emergency phase, we have embarked on an exploratory campaign aimed at repurposing natural substances and clinically available drugs as potential anti-SARS-CoV2-2 agents by targeting viral proteins. Here we report on a strategy based on the virtual screening of druggable pockets located in the central β-sheet core of the SARS-CoV-2 Spike's protein receptor binding domain (RBD). By combining an in silico approach and molecular in vitro testing we have been able to identify several triterpenoid/steroidal agents that inhibit interaction of the Spike RBD with the carboxypeptidase domain of the Angiotensin Converting Enzyme (ACE2). In detail, we provide evidence that potential binding sites exist in the RBD of the SARS CoV-2 Spike protein and that occupancy of these pockets reduces the ability of the RBD to bind to the ACE2 consensus in vitro. Naturally occurring and clinically available triterpenoids such as glycyrrhetinic and oleanolic acids, as well as primary and secondary bile acids and their amidated derivatives such as glyco-ursodeoxycholic acid and semi-synthetic derivatives such as obeticholic acid reduces the RBD/ACE2 binding. In aggregate, these results might help to define novel approaches to COVID-19 based on SARS-CoV-2 entry inhibitors.

show abstract

“…Moreover, reduction of hyperglycemia by TQ treatment was potentiated in diabetic rats receiving sitagliptin at a dose sufficient to inhibit DPP-4 [28]. It is similar to that induced by activation of TGR5 [25]. Additionally, blockade of GLP-1 receptor using Ex9-39 [29] also diminished the effects of TQ on hyperglycemia in diabetic rats that received sitagliptin and those that did not.…”

Section: Discussionmentioning

confidence: 77%

Thymoquinone activates imidazoline receptor to enhance glucagon-like peptide-1 secretion in diabetic rats

Lee

Kuo

2019

Arch Med Sci

Self Cite

View full text Add to dashboard Cite

Introduction: Thymoquinone (TQ) is one of the principal bioactive ingredients proven to exhibit anti-diabetic effects. Recently, glucagon-like peptide-1 (GLP-1) has been found to be involved in antidiabetic effects in rats. The aim of this study was to evaluate the mediation of GLP-1 in the antidiabetic effect of TQ and to understand the possible mechanisms. Material and methods: NCI-H716 cells and CHO-K1 cells were used to investigate the effects of TQ on GLP-1 secretion in vitro. In type 1 diabetic rats, the changes in plasma glucose and GLP-1 levels were evaluated with TQ treatment. Results: The direct effect of TQ on imidazoline receptors (I-Rs) was identified in CHO-K1 cells overexpressing I-Rs. Additionally, in the intestinal NCI-H716 cells that may secrete GLP-1, TQ treatment enhanced GLP-1 secretion in a dose-dependent manner. However, these effects of TQ were reduced by ablation of I-Rs with siRNA in NCI-H716 cells. Moreover, these effects were inhibited by BU224, the imidazoline I2 receptor (I-2R) antagonist. In diabetic rats, TQ increased plasma GLP-1 levels, which were inhibited by BU-224 treatment. Functionally, TQ-attenuated hyperglycemia is also evidenced through GLP-1 using pharmacological manipulations. Conclusions: This report demonstrates that TQ may promote GLP-1 secretion through I-R activation to reduce hyperglycemia in type-1 diabetic rats.

show abstract

Glycyrrhizic acid increases glucagon like peptide-1 secretion via TGR5 activation in type 1-like diabetic rats

Cited by 26 publications

References 42 publications

<p>Promotion of Adropin Expression by Hyperglycemia Is Associated with STAT3 Activation in Diabetic Rats</p>

<p>Promotion of Adropin Expression by Hyperglycemia Is Associated with STAT3 Activation in Diabetic Rats</p>

Hijacking SARS-CoV-2/ACE2 Receptor Interaction by Natural and Semi-synthetic Steroidal Agents Acting on Functional Pockets on the Receptor Binding Domain

Thymoquinone activates imidazoline receptor to enhance glucagon-like peptide-1 secretion in diabetic rats

Contact Info

Product

Resources

About