2-Formyl-komarovicine promotes adiponectin production in human mesenchymal stem cells through PPARγ partial agonism

Ahn, Soon Kil; Lee, Moon Young; An, Seungchan; Hyun, Sooyeol; Hwang, Jiho; Lee, Jong-Kook; Noh, Minsoo

doi:10.1016/j.bmc.2018.01.019

Cited by 19 publications

(14 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast to a full agonist, a partial agonist functions as an antagonist by competing with a full agonist ( Ahn et al ., 2018 ). To validate the different PPARγ docking models, the competitive effects of magnolol, honokiol and 4- O -methylhonokiol on troglitazone were investigated during adipogenesis in hBM-MSCs ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Lanthascreen TM time resolved fluorescence resonance energy transfer (TR-FRET) competitive binding assay kits (Invitrogen) were used to evaluate PPARα, PPARδ and PPARγ binding activities of chemical ligands as described ( Ahn et al ., 2018 ). All assay measurements were performed using a CLARIOstar plate reader (BMG LABTECH, Ortenberg, Germany).…”

Section: Methodsmentioning

confidence: 99%

“…Adiponectin, also referred to as an adipocyte complement-related protein of 30 kDa, is an anti-inflammatory adipocytokine mainly produced in mammalian adipocytes ( Straub and Scherer, 2019 ). Hypoadiponectinemia has been reported in various metabolic diseases such as obesity, diabetes, and cardiovascular metabolic syndrome ( Ahn et al ., 2018 ; Waragai et al ., 2018 ). Serum adiponectin levels are lower in diabetic and proinflammatory conditions than in healthy population ( Kershaw and Flier, 2004 ).…”

Section: Introductionmentioning

confidence: 99%

“…Adiponectin production is also upregulated by sulfonylurea anti-diabetic drugs during adipogenesis ( Iwaki et al ., 2003 ). Non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin and indomethacin are widely known to increase adiponectin production in hBM-MSCs when treated with IDX ( Shin et al ., 2009 ; Ahn et al ., 2018 ). Monoamine oxidase inhibitors (MAOIs) like moclobemide significantly promote adiponectin production during adipogenesis in hBM-MSCs, although its pharmacological mechanism has not been fully elucidated ( Byun et al ., 2013 ).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Diallyl Biphenyl-Type Neolignans Have a Pharmacophore of PPARα/γ Dual Modulators

Han

Liu

Ahn

et al. 2020

Biomolecules & Therapeutics

Self Cite

View full text Add to dashboard Cite

Adiponectin secretion-promoting compounds have therapeutic potentials in human metabolic diseases. Diallyl biphenyl-type neolignan compounds, magnolol, honokiol, and 4- O -methylhonokiol, from a Magnolia officinalis extract were screened as adiponectin-secretion promoting compounds in the adipogenic differentiation model of human bone marrow mesenchymal stem cells (hBM-MSCs). In a target identification study, magnolol, honokiol, and 4- O -methylhonokiol were elucidated as PPARα and PPARγ dual modulators. Diallyl biphenyl-type neolignans affected the transcription of lipid metabolism-associated genes in a different way compared to those of specific PPAR ligands. The diallyl biphenyl-type neolignan structure provides a novel pharmacophore of PPARα/γ dual modulators, which may have unique therapeutic potentials in diverse metabolic diseases.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Diallyl Biphenyl-Type Neolignans Have a Pharmacophore of PPARα/γ Dual Modulators

Han

Liu

Ahn

et al. 2020

Biomolecules & Therapeutics

Self Cite

View full text Add to dashboard Cite

show abstract

“…In fact, many pharmacological drugs enhance adiponectin biosynthesis during adipogenesis in hBM-MSCs [16]. Anti-diabetic peroxisome proliferator-activated receptor γ (PPARγ) agonists, such as troglitazone and pioglitazone, as well as sulfonylureas, such as glibenclamide, significantly enhance adiponectin production during adipogenesis in hBM-MSCs [17,18]. Although a direct molecular target has not been identified yet, aspirin upregulates adiponectin production in the differentiated adipocytes in a concentration-dependent manner [19,20].…”

Section: Introductionmentioning

confidence: 99%

Cyclin-Dependent Kinase 5 Inhibitor Butyrolactone I Elicits a Partial Agonist Activity of Peroxisome Proliferator-Activated Receptor γ

et al. 2020

Self Cite

View full text Add to dashboard Cite

Adiponectin is an adipocyte-derived cytokine having an insulin-sensitizing activity. During the phenotypic screening of secondary metabolites derived from the marine fungus Aspergillus terreus, a poly cyclin-dependent kinase (CDK) inhibitor butyrolactone I affecting CDK1 and CDK5 was discovered as a potent adiponectin production-enhancing compound in the adipogenesis model of human bone marrow-derived mesenchymal stem cells (hBM-MSCs). CDK5 inhibitors exhibit insulin-sensitizing activities by suppressing the phosphorylation of peroxisome proliferator-activated receptor γ (PPARγ). However, the adiponectin production-enhancing activities of butyrolactone I have not been correlated with the potency of CDK5 inhibitor activities. In a target identification study, butyrolactone I was found to directly bind to PPARγ. In the crystal structure of the human PPARγ, the ligand-binding domain (LBD) in complex with butyrolactone I interacted with the amino acid residues located in the hydrophobic binding pockets of the PPARγ LBD, which is a typical binding mode of the PPARγ partial agonists. Therefore, the adiponectin production-enhancing effect of butyrolactone I was mediated by its polypharmacological dual modulator activities as both a CDK5 inhibitor and a PPARγ partial agonist.

show abstract

Recent Advances on the Role of Nitrogen‐Based Heterocyclic Scaffolds in Targeting HIV through Reverse Transcriptase Inhibition

Kumar¹,

Wahan²,

Virendra³

et al. 2022

ChemistrySelect

View full text Add to dashboard Cite

Acquired immune deficiency syndrome (AIDS) caused by human immunodeficiency virus continues to scavenge lives of millions around the world. Reverse transcriptase (RT) also known as the RNA-directed DNA polymerase enzyme is responsible for converting RNA into viral DNA through process known as reverse transcription. Investigations on the pathogenic aspects of the RT enzyme, its associated elements such as gag (group-specific antigen gene), pol (polymerase gene), and env (environmental gene) (envelope gene) reveals its contribution towards emergence of resistance to all various anti-HIV drugs. Therefore, research into the control and blockage of the RT pathway has been a prominent focus in the quest for novel targets for HIV treatment. A slew of heterocyclics has been claimed to play a significant part in the fight against doomy HIV, saving the lives of millions of people throughout the world and providing hope for HIV treatment. Due to their improved potency and selectivity, as well as the fact that they have fewer off-target effects against the several targets implicated in RT inhibition, heterocyclics are becoming more and more useful. The RT inhibition pathway, the function of numerous heterocyclic scaffolds, and their ability to inhibit the RT enzyme pathway have all been the main topics of this paper. Recent advances in RT inhibitors in the last eight years (2014-2022) including mechanisms of action, preclinical and clinical investigations, structural activity relationships, and docking studies, to investigate mechanistic studies that would eventually aid in the design and development of powerful RT inhibitors have also discussed.

show abstract

2-Formyl-komarovicine promotes adiponectin production in human mesenchymal stem cells through PPARγ partial agonism

Cited by 19 publications

References 31 publications

Diallyl Biphenyl-Type Neolignans Have a Pharmacophore of PPARα/γ Dual Modulators

Diallyl Biphenyl-Type Neolignans Have a Pharmacophore of PPARα/γ Dual Modulators

Cyclin-Dependent Kinase 5 Inhibitor Butyrolactone I Elicits a Partial Agonist Activity of Peroxisome Proliferator-Activated Receptor γ

Recent Advances on the Role of Nitrogen‐Based Heterocyclic Scaffolds in Targeting HIV through Reverse Transcriptase Inhibition

Contact Info

Product

Resources

About