Anti-adipogenic activity of maackiain and ononin is mediated via inhibition of PPARγ in human adipocytes

Mladenova, Saveta G.; Savova, Martina S.; Marchev, Andrey S.; Ferrante, Claudio; Orlando, Giustino; Wabitsch, Martin; Georgiev, Milen I.

doi:10.1016/j.biopha.2022.112908

Cited by 18 publications

(24 citation statements)

References 51 publications

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“…Following MDI induction of preadipocytes, which no longer grow owing to the formation of intercellular hyperjunctions, differentiation into mature adipocytes starts. During adipocyte differentiation and lipid deposition, SREBP-1c, PPAR-γ, and C/EBPα are the major adipogenic transcription factors, and these genes regulate the transcription of FAS and aP2, which are responsible for morphological changes and lipid accumulation in adipocytes [ 12 , 18 ]. SREBP-1c augments the expression of genes involved in adipogenesis, particularly fatty acid biosynthesis and triglyceride maturation.…”

Section: Resultsmentioning

confidence: 99%

“…Mature adipocytes are produced through preadipocyte differentiation, which is initiated by hormones and cell differentiation-inducing substances, such as 3-isobutyl-1-methylxanthine, dexamethasone, and insulin (MDI) [ 12 ]. Signal transduction through differentiation-inducing substances and insulin activates the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway in preadipocytes to induce their differentiation into mature adipocytes and produce adipogenesis signals, which further promotes adipogenic metabolism through the increase in cellular glucose uptake [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

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Characterization of Plocamium telfairiae Extract-Functionalized Au Nanostructures and Their Anti-Adipogenic Activity through PLD1

et al. 2022

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Here, Au nanostructure (AuNS) biosynthesis was mediated through ethanolic extract of Plocamium telfairiae (PT) without the use of stabilizers or surfactants. PT-functionalized AuNSs (PT-AuNSs) were analyzed using ultraviolet–visible spectroscopy, dynamic light scattering, high-resolution transmission electron microscopy, energy-dispersive spectroscopy, and Fourier-transform infrared spectroscopy. Stable monodisperse PT-AuNSs were synthesized, with a mean size of 15.36 ± 0.10 nm and zeta potential of −35.85 ± 1.36 mV. Moreover, biosynthetic AuNPs with a face-centered structure of PT-AuNS exhibited crystalline characteristics. In addition, many functional groups playing important roles in the biological reduction of PT extracts were adsorbed on the surface of PT-AuNSs. Furthermore, the effects of PT-AuNSs on adipogenesis in immature adipocytes were investigated. PT-AuNSs reduced morphological changes, lowered triglyceride content, and increased lipid accumulation by approximately 78.6% in immature adipocytes compared with the values in mature adipocytes (MDI-induced). PT-AuNS suppressed lipid accumulation by downregulating the transcript and protein expression of C/EBPα, PPARγ, SREBP 1, FAS, and aP2. Finally, PT-AuNS induced the transcript and protein expression of UCP1, PRDM16, and PGC1a, thereby increasing mitochondrial biogenesis in mature adipocytes and effectively inducing brown adipogenesis. In this study, the biosynthesized PT-AuNS was used as a potential therapeutic candidate because it conferred a potent anti-lipogenic effect. As a result, it can be used in various scientific fields such as medicine and the environment.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterization of Plocamium telfairiae Extract-Functionalized Au Nanostructures and Their Anti-Adipogenic Activity through PLD1

et al. 2022

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“…Various components identified through analysis are known to have various physiological activities including anti-obesity and related activities. In a previous study using an in vitro obesity model, ononin showed antiadipogenic capacity by upregulating SIRT1 and inhibiting PI3K, PPARc, and adiponectin [43]. In addition, astragaloside IV is known to prevent obesity in a high-fat diet mouse model [32] and is also known to have a positive effect on obesity-related nephropathy and hypertension [44,45].…”

Section: Discussionmentioning

confidence: 99%

Chemical Profiles and Antiobesity Effect of a Mixture of Astragalus membranaceus and Lithospermum erythrorhizon Extract in High Fat Diet Fed Mice

Choi

Lee

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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The present study aimed to evaluate the antiobesity potential and synergistic effects of ALM16, a mixture of Astragalus membranaceus (AM) and Lithospermum erythrorhizon (LE) extracts, in HFD-induced obese mice. C57BL/6 mice were fed a normal diet (ND), high-fat diet (HFD), HFD + AM, HFD + LE or HFD + ALM16 (50, 100, and 200 mg/kg) daily for 5 weeks. Compared to the ND group, HFD-fed mice showed significant increases in body weight, food efficiency ratio, weights of white adipose tissues, adipocytes size, liver weight, and hepatic steatosis grade. However, ALM16 significantly reduced those increases induced by HFD. Moreover, as compared to the HFD group, the ALM16 group significantly ameliorated serum levels of lipid profiles (TG, TC, HDL, and LDL), adipokines (leptin and adiponectin), and liver damage markers (AST and ALT levels). Notably, ALM16 was more effective than AM or LE alone and had a similar or more potent effect than Garcinia cambogia extracts, as a positive control, at the same dose. These results demonstrate that ALM16 synergistically exerts anti-obesity effects based on complementary interactions between each component. Also, metabolic profiling between each extract and the ALM16 was confirmed by UPLC-QTOF/MS, and the difference was confirmed by relative quantification.

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“…MK is isolated from the traditional Chinese herbal medicine Kushen (dried roots of Sophora flavescens Aiton) [ 80 ]. MK has been reported to have multiple pharmacologic properties, such as anti-allergic [ 81 , 82 ], anti-inflammatory [ 44 , 83 ], anti-oxidative [ 44 ], anti-obesity [ 84 ], and antibacterial [ 85 ] activity in addition to neuroprotection [ 86 , 87 ]. In cancer therapy, MK can hinder the proliferation, migration, invasion, and foci formation of triple-negative breast cancer cells and thus has a significant inhibitory effect on tumor growth.…”

Section: Discussionmentioning

confidence: 99%

A Novel Splice Variant of BCAS1 Inhibits β-Arrestin 2 to Promote the Proliferation and Migration of Glioblastoma Cells, and This Effect Was Blocked by Maackiain

Kuo

Hung

Tsai

et al. 2022

Cancers

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Brain-enriched myelin-associated protein 1 (BCAS1) is frequently highly expressed in human cancer, but its detailed function is unclear. Here, we identified a novel splice variant of the BCAS1 gene in glioblastoma multiforme (GBM) named BCAS1-SV1. The expression of BCAS1-SV1 was weak in heathy brain cells but high in GBM cell lines. The overexpression of BCAS1-SV1 significantly increased the proliferation and migration of GBM cells, whereas the RNA-interference-mediated knockdown of BCAS1-SV1 reduced proliferation and migration. Moreover, using a yeast-two hybrid assay, immunoprecipitation, and immunofluorescence staining, we confirmed that β-arrestin 2 is an interaction partner of BCAS1-SV1 but not BCAS1. The downregulation of β-arrestin 2 directly enhanced the malignancy of GBM and abrogated the effects of BCAS1-SV1 on GBM cells. Finally, we used a yeast two-hybrid-based growth assay to identify that maackiain (MK) is a potential inhibitor of the interaction between BCAS1-SV1 and β-arrestin 2. MK treatment lessened the proliferation and migration of GBM cells and prolonged the lifespan of tumor-bearing mice in subcutaneous xenograft and intracranial U87-luc xenograft models. This study provides the first evidence that the gain-of-function BCAS1-SV1 splice variant promotes the development of GBM by suppressing the β-arrestin 2 pathway and opens up a new therapeutic perspective in GBM.

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Anti-adipogenic activity of maackiain and ononin is mediated via inhibition of PPARγ in human adipocytes

Cited by 18 publications

References 51 publications

Characterization of Plocamium telfairiae Extract-Functionalized Au Nanostructures and Their Anti-Adipogenic Activity through PLD1

Characterization of Plocamium telfairiae Extract-Functionalized Au Nanostructures and Their Anti-Adipogenic Activity through PLD1

Chemical Profiles and Antiobesity Effect of a Mixture of Astragalus membranaceus and Lithospermum erythrorhizon Extract in High Fat Diet Fed Mice

A Novel Splice Variant of BCAS1 Inhibits β-Arrestin 2 to Promote the Proliferation and Migration of Glioblastoma Cells, and This Effect Was Blocked by Maackiain

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