scholarly journals Inula britannica Inhibits Adipogenesis of 3T3-L1 Preadipocytes via Modulation of Mitotic Clonal Expansion Involving ERK 1/2 and Akt Signaling Pathways

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3037
Author(s):  
Hyung-Seok Yu ◽  
Won-Ju Kim ◽  
Won-Young Bae ◽  
Na-Kyoung Lee ◽  
Hyun-Dong Paik
Keyword(s):  
Transcription Factors ◽  
Phenolic Compounds ◽  
Signaling Pathways ◽  
Clonal Expansion ◽  
Akt Signaling ◽  
Inula Britannica ◽  
Mitotic Clonal Expansion ◽  
Underlying Mechanisms ◽  
Adipogenic Effect ◽  
Early Phases

The flower of Inula britannica contains various phenolic compounds with prophylactic properties. This study aimed to determine the anti-adipogenic effect of an I. britannica flower aqueous extract (IAE) and its underlying mechanisms in the 3T3-L1 preadipocytes and to identify the phenolic compounds in the extract. Treatment with IAE inhibited the adipogenesis of 3T3-L1 preadipocytes by showing a dose-dependently suppressed intracellular lipid accumulation and significantly mitigated expression levels of lipogenesis- and adipogenesis-associated biomarkers including transcription factors. IAE exerted an anti-adipogenic effect through the modulation of the early phases of adipogenesis including mitotic clonal expansion (MCE). Treatment with IAE inhibited MCE by arresting the cell cycle at the G0/G1 phase and suppressing the activation of MCE-related transcription factors. Furthermore, IAE inhibited adipogenesis by regulating the extracellular signal-regulated kinase 1/2 and Akt signaling pathways. Protocatechuic acid, chlorogenic acid, kaempferol-3-O-glucoside, and 6-methoxyluteolin, which are reported to exhibit anti-adipogenic properties, were detected in IAE. Therefore, modulation of early phases of adipogenesis, especially MCE, is a key mechanism underlying the anti-adipogenic activity of IAE. In summary, the anti-obesity effects of IAE can be attributed to its phenolic compounds, and hence, IAE can be used for the development of anti-obesity products.

scholarly journals RETRACTED ARTICLE: Chondro-protective effects of polydatin in osteoarthritis through its effect on restoring dysregulated autophagy via modulating MAPK, and PI3K/Akt signaling pathways

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Zhengyuan Wu ◽  
Zhiwei Luan ◽  
Xiaohan Zhang ◽  
Kai Zou ◽  
Shiting Ma ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Cartilage Degeneration ◽  
Cartilage Degradation ◽  
Akt Signaling ◽  
Protective Effects ◽  
Mediating Role ◽  
Retracted Article ◽  
Underlying Mechanisms

Abstract Osteoarthritis (OA) is a degenerative disease of the cartilage that is prevalent in the middle-aged and elderly demography. Polydatin (PD), a natural resveratrol glucoside, has shown significant anti-inflammatory and anti-arthritic potential in previous studies. This study was designed to evaluate the therapeutic properties of PD in vitro and in vivo, and elucidate their underlying mechanisms. The expression levels of all relevant factors were evaluated by qRT-PCR, western blotting, and immunohistochemistry (IHC) where suitable. Reactive oxygen species (ROS) and apoptosis were analyzed using the suitable probes and flow cytometry. The histological evidence of cartilage was assessed in rat models, moreover, the several serum cytokines levels and autophagy levels were evaluated. The result showed PD displayed significant chondro-protective effects, inferred in terms of reduced inflammation and cartilage degradation, apoptosis inhibition, and lower ROS production. The protective effects were attenuated by the autophagy inhibitor 3-MA, indicating a mediating role of autophagy in PD action. Mechanistically, PD exerted its effects by inhibiting the MAPK and PI3K/Akt signaling pathways which led to the down-regulation of mTOR. In conclusion, PD protects against cartilage degeneration by activating the autophagy flux in the chondrocytes via the MAPK and PI3K/Akt signaling pathways.

scholarly journals Cordycepin Reverses Cisplatin Resistance in Non-Small Cell Lung Cancer by Activating AMPK and Inhibiting the AKT Signaling Pathway

2020 ◽  
Author(s):  
Xiao-Zhong Liao ◽  
Ying Gao ◽  
Hong-Wei Zhao ◽  
Mi Zhou ◽  
Dan-Lei Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathways ◽  
Cell Lines ◽  
A549 Cells ◽  
Akt Signaling ◽  
Antineoplastic Effect ◽  
Proliferation And Apoptosis ◽  
Underlying Mechanisms

Abstract Background: Cisplatin (DDP) is the firs-line chemotherapeutic agent for the treatment of NSCLC. However, DDP resistance limits their usage to maximize the antineoplastic effect. The aims of this study were to investigate whether cordycepin (Cor) could reverse multidrug resistance (MDR) in NSCLC and to explore the underlying mechanisms.Methods: Cell proliferation and apoptosis were analyzed in NSCLC cell lines in vitro and in vivo, parental and DDP-resistant A549 cells, treated with DDP alone or combination with Cor. Proteins of different signaling pathways were investigated between DDP-sensistive and -insensitive A549 cell lines by GO terms and KEGG analysis, and perturbations of the MAPK and PI3K-AKT signaling pathways were evaluated by western blot. Results: Our data showed that Cor enhanced DDP inhibition of cell proliferation and promotion of apoptosis markedly compared to DDP alone group in both A549 and A549DDP. The synergic actions were associated with activation of AMPK and inhibition of AKT, mTOR and downstream P709S6K, S6 phosphorylation in the AKT pathway.Conclusion: Cor/DDP combination has synergistic effect on inhibiting proliferation and promoting apoptosis of NSCLC cells in the presence or absence of DDP resistance.

Biological role of AKT, and regulation of AKT signaling pathway by thymoquinone: perspectives in cancer therapeutics

2020 ◽  
Vol 20 ◽  
Author(s):  
Md. Junaid ◽  
Yeasmin Akter ◽  
Syeda Samira Afrose ◽  
Mousumi Tania ◽  
Md. Asaduzzaman Khan
Keyword(s):  
Clinical Trials ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Inhibitory Effect ◽  
Akt Signaling ◽  
Review Article ◽  
Therapeutic Drug ◽  
Akt Signaling Pathway ◽  
Anti Cancer

Background: AKT/PKB is an important enzyme with numerous biological functions, and its overexpression is related to the carcinogenesis. AKT stimulates different signaling pathways that are downstream of activated tyrosine kinases and phosphatidylinositol 3-kinase, hence functions as an important target for anti-cancer drugs. Objective: In this review article, we have interpreted the role of AKT signaling pathways in cancer and natural inhibitory effect of Thymoquinone (TQ) in AKT and its possible mechanism. Method: We have collected the updated information and data on AKT, their role in cancer and inhibitory effect of TQ in AKT signaling pathway from google scholar, PubMed, Web of Science, Elsevier, Scopus and many more. Results: There are many drugs already developed, which can target AKT, but very few among them have passed clinical trials. TQ is a natural compound, mainly found in black cumin, which has been found to have potential anti-cancer activities. TQ targets numerous signaling pathways, including AKT, in different cancers. In fact, many studies revealed that AKT is one of the major targets of TQ. The preclinical success of TQ suggests its clinical studies on cancer. Conclusion: This review article summarizes the role of AKT in carcinogenesis, its potent inhibitors in clinical trials, and how TQ acts as an inhibitor of AKT and TQ’s future as a cancer therapeutic drug.

scholarly journals Vitamin E beyond Its Antioxidant Label

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 634
Author(s):  
Anca Ungurianu ◽  
Anca Zanfirescu ◽  
Georgiana Nițulescu ◽  
Denisa Margină
Keyword(s):  
Vitamin E ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Protective Effects ◽  
Cellular Effects ◽  
Inflammatory Status ◽  
Anti Cancer ◽  
Key Factor ◽  
Exciting Potential ◽  
Underlying Mechanisms

Vitamin E, comprising tocopherols and tocotrienols, is mainly known as an antioxidant. The aim of this review is to summarize the molecular mechanisms and signaling pathways linked to inflammation and malignancy modulated by its vitamers. Preclinical reports highlighted a myriad of cellular effects like modulating the synthesis of pro-inflammatory molecules and oxidative stress response, inhibiting the NF-κB pathway, regulating cell cycle, and apoptosis. Furthermore, animal-based models have shown that these molecules affect the activity of various enzymes and signaling pathways, such as MAPK, PI3K/Akt/mTOR, JAK/STAT, and NF-κB, acting as the underlying mechanisms of their reported anti-inflammatory, neuroprotective, and anti-cancer effects. In clinical settings, not all of these were proven, with reports varying considerably. Nonetheless, vitamin E was shown to improve redox and inflammatory status in healthy, diabetic, and metabolic syndrome subjects. The anti-cancer effects were inconsistent, with both pro- and anti-malignant being reported. Regarding its neuroprotective properties, several studies have shown protective effects suggesting vitamin E as a potential prevention and therapeutic (as adjuvant) tool. However, source and dosage greatly influence the observed effects, with bioavailability seemingly a key factor in obtaining the preferred outcome. We conclude that this group of molecules presents exciting potential for the prevention and treatment of diseases with an inflammatory, redox, or malignant component.

scholarly journals Akt signaling is activated by TGFβ2 and impacts tenogenic induction of mesenchymal stem cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sophia K. Theodossiou ◽  
Jett B. Murray ◽  
LeeAnn A. Hold ◽  
Jeff M. Courtright ◽  
Anne M. Carper ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Akt Signaling ◽  
Cell Alignment ◽  
Limited Information ◽  
Akt Inhibitor ◽  
Tenogenic Differentiation

Abstract Background Tissue engineered and regenerative approaches for treating tendon injuries are challenged by the limited information on the cellular signaling pathways driving tenogenic differentiation of stem cells. Members of the transforming growth factor (TGF) β family, particularly TGFβ2, play a role in tenogenesis, which may proceed via Smad-mediated signaling. However, recent evidence suggests some aspects of tenogenesis may be independent of Smad signaling, and other pathways potentially involved in tenogenesis are understudied. Here, we examined the role of Akt/mTORC1/P70S6K signaling in early TGFβ2-induced tenogenesis of mesenchymal stem cells (MSCs) and evaluated TGFβ2-induced tenogenic differentiation when Smad3 is inhibited. Methods Mouse MSCs were treated with TGFβ2 to induce tenogenesis, and Akt or Smad3 signaling was chemically inhibited using the Akt inhibitor, MK-2206, or the Smad3 inhibitor, SIS3. Effects of TGFβ2 alone and in combination with these inhibitors on the activation of Akt signaling and its downstream targets mTOR and P70S6K were quantified using western blot analysis, and cell morphology was assessed using confocal microscopy. Levels of the tendon marker protein, tenomodulin, were also assessed. Results TGFβ2 alone activated Akt signaling during early tenogenic induction. Chemically inhibiting Akt prevented increases in tenomodulin and attenuated tenogenic morphology of the MSCs in response to TGFβ2. Chemically inhibiting Smad3 did not prevent tenogenesis, but appeared to accelerate it. MSCs treated with both TGFβ2 and SIS3 produced significantly higher levels of tenomodulin at 7 days and morphology appeared tenogenic, with localized cell alignment and elongation. Finally, inhibiting Smad3 did not appear to impact Akt signaling, suggesting that Akt may allow TGFβ2-induced tenogenesis to proceed during disruption of Smad3 signaling. Conclusions These findings show that Akt signaling plays a role in TGFβ2-induced tenogenesis and that tenogenesis of MSCs can be initiated by TGFβ2 during disruption of Smad3 signaling. These findings provide new insights into the signaling pathways that regulate tenogenic induction in stem cells.

scholarly journals Retraction Note: Chemopreventive Potential of Resveratrol in Mouse Skin Tumors Through Regulation of Mitochondrial and PI3K/AKT Signaling Pathways

2021 ◽  
Vol 38 (2) ◽  
pp. 375-375
Author(s):  
Preeti Roy ◽  
Neetu Kalra ◽  
Sahdeo Prasad ◽  
Jasmine George ◽  
Yogeshwer Shukla
Keyword(s):  
Signaling Pathways ◽  
Mouse Skin ◽  
Akt Signaling ◽  
Skin Tumors

Brown alga Ecklonia cava attenuates type 1 diabetes by activating AMPK and Akt signaling pathways

2010 ◽  
Vol 48 (2) ◽  
pp. 509-516 ◽  
Author(s):  
Changkeun Kang ◽  
Yeung Bae Jin ◽  
Hyunkyoung Lee ◽  
Mijin Cha ◽  
Eun-tae Sohn ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Signaling Pathways ◽  
Brown Alga ◽  
Akt Signaling ◽  
Ecklonia Cava

scholarly journals Role of Signal Transduction Pathways and Transcription Factors in Cartilage and Joint Diseases

2020 ◽  
Vol 21 (4) ◽  
pp. 1340 ◽  
Author(s):  
Riko Nishimura ◽  
Kenji Hata ◽  
Yoshifumi Takahata ◽  
Tomohiko Murakami ◽  
Eriko Nakamura ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Transcription Factors ◽  
Signaling Pathways ◽  
Genetic Disorder ◽  
Interleukin 1 ◽  
Genetic Diseases ◽  
Mtor Inhibitors ◽  
Joint Diseases ◽  
Ectopic Ossification ◽  
Parathyroid Hormone Related Protein

Osteoarthritis and rheumatoid arthritis are common cartilage and joint diseases that globally affect more than 200 million and 20 million people, respectively. Several transcription factors have been implicated in the onset and progression of osteoarthritis, including Runx2, C/EBPβ, HIF2α, Sox4, and Sox11. Interleukin-1 β (IL-1β) leads to osteoarthritis through NF-ĸB, IκBζ, and the Zn2+-ZIP8-MTF1 axis. IL-1, IL-6, and tumor necrosis factor α (TNFα) play a major pathological role in rheumatoid arthritis through NF-ĸB and JAK/STAT pathways. Indeed, inhibitory reagents for IL-1, IL-6, and TNFα provide clinical benefits for rheumatoid arthritis patients. Several growth factors, such as bone morphogenetic protein (BMP), fibroblast growth factor (FGF), parathyroid hormone-related protein (PTHrP), and Indian hedgehog, play roles in regulating chondrocyte proliferation and differentiation. Disruption and excess of these signaling pathways cause genetic disorders in cartilage and skeletal tissues. Fibrodysplasia ossificans progressive, an autosomal genetic disorder characterized by ectopic ossification, is induced by mutant ACVR1. Mechanistic target of rapamycin kinase (mTOR) inhibitors can prevent ectopic ossification induced by ACVR1 mutations. C-type natriuretic peptide is currently the most promising therapy for achondroplasia and related autosomal genetic diseases that manifest severe dwarfism. In these ways, investigation of cartilage and chondrocyte diseases at molecular and cellular levels has enlightened the development of effective therapies. Thus, identification of signaling pathways and transcription factors implicated in these diseases is important.

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