Forskolin Inhibits Lipopolysaccharide-Induced Modulation of MCP-1 and GPR120 in 3T3-L1 Adipocytes through an Inhibition of NF<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:mtext mathvariant="bold">κ</mml:mtext></mml:mrow></mml:math>B

Chiadak, Jeanne Durendale; Arsenijević, Tatjana; Verstrepen, Kevin J.; Grégoire, Françoise; Bolaky, Nargis; Delforge, Valérie; Flamand, Véronique; Perret, Jason; Delporte, Christine

doi:10.1155/2016/1431789

Cited by 12 publications

(13 citation statements)

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“…lead to insulin resistance. Moreover, previous studies have demonstrated that excessive circulating levels of FFAs are released from ectopic fat deposits, which activate TNF-α, protein kinase C, c-Jun NH2-terminal kinase, JNK1, and IL-6 expression (28)(29)(30) in the state of obesity. The concentrations of FFAs in vivo range from 0.1 to 1 mM (31,32).…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rb1 inhibits free fatty acids-induced oxidative stress and inflammation in 3T3-L1 adipocytes

Wang

Chen

Xiong

et al. 2017

Molecular Medicine Reports

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Free fatty acids (FFAs) increase in visceral fat and are inferred to be one of the underlying inducers of adipose tissue inflammation. In our previous study, it was demonstrated that ginsenoside Rb1 stimulates endothelial nitric oxide synthase (eNOS) and Sirtuin 1 to protect against endothelial cell senescence. In the present study, 3T3‑L1 adipocytes were exposed to 0.5 mM FFAs with or without Rb1 (10‑40 µM). Monocyte chemotactic protein‑1 (MCP‑1) and interleukin‑6 (IL‑6) secretion was measured using ELISA. Tumor necrosis factor‑α (TNF‑α) expression and nuclear factor‑κB (NF‑κB) p65 phosphorylation were detected using western blot analysis. Oxidative stress was determined via measuring intracellular reactive oxygen species (ROS) and nitric oxide (NO) production. The results demonstrated that MCP‑1 and IL‑6 secretion, as well as TNF‑α expression, were significantly increased following FFA treatment, which was attenuated by Rb1 in a dose‑dependent manner. Furthermore, Rb1 attenuated FFA‑induced NF‑κB phosphorylation, suggesting that the inhibitory effect of Rb1 on inflammatory cytokines was partially mediated through blockade of NF‑κB phosphorylation. Further experiments demonstrated that Rb1 ameliorated FFA‑induced ROS generation and NO reduction through upregulation of superoxide dismutase 2 and eNOS expression. Taken together, these results demonstrate proinflammatory and pro‑oxidant effects of FFA on 3T3‑L1 adipocytes, which are effectively ameliorated by Rb1. Suppression of inflammatory responses and oxidative stress may be a novel mechanism for attenuating the effect of Rb1 on adipocyte dysfunction.

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Section: Discussionmentioning

confidence: 99%

Ginsenoside Rb1 inhibits free fatty acids-induced oxidative stress and inflammation in 3T3-L1 adipocytes

Wang

Chen

Xiong

et al. 2017

Molecular Medicine Reports

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“…Forskolin ( coleonol) belongs to the labdane diterpene family and is an extract from the Indian coleus plant ( Coleus forskohli ). Although not many reports exist regarding its anti-inflammatory properties, it has been recently reported to strongly inhibit the LPS-induced increases in MCP-1, TLR-4, and NF κ B1 mRNA levels in adipocytes [ 109 ].…”

Section: Natural Pharmacological Modulatorsmentioning

confidence: 99%

Phytochemicals as modulators of M1-M2 macrophages in inflammation

Sarkar²,

et al. 2018

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Macrophages are critical mediators of the innate immune response against foreign pathogens, including bacteria, physical stress, and injury. Therefore, these cells play a key role in the “inflammatory pathway” which in turn can lead to an array of diseases and disorders such as autoimmune neuropathies and myocarditis, inflammatory bowel disease, atherosclerosis, sepsis, arthritis, diabetes, and angiogenesis. Recently, more studies have focused on the macrophages inflammatory diseases since the discovery of the two subtypes of macrophages, which are differentiated on the basis of their phenotype and distinct gene expression pattern. Of these, M1 macrophages are pro-inflammatory and responsible for inflammatory signaling, while M2 are anti-inflammatory macrophages that participate in the resolution of the inflammatory process, M2 macrophages produce anti-inflammatory cytokines, thereby contributing to tissue healing. Many studies have shown the role of these two subtypes in the inflammatory pathway, and their emergence appears to decide the fate of inflammatory signaling and disease progression. As a next step in directing the pro-inflammatory response toward the anti-inflammatory type after an insult by a foreign pathogen (e. g., bacterial lipopolysaccharide), investigators have identified many natural compounds that have the potential to modulate M1 to M2 macrophages. In this review, we provide a focused discussion of advances in the identification of natural therapeutic molecules with anti-inflammatory properties that modulate the phenotype of macrophages from M1 to M2.

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“…Also, ALX is demonstrated to inhibit inflammatory responses activated via GRK5 (Patial et al, 2011;Quan et al, 2019). The stimulation of ACs by FSK facilitates the bioavailability of cAMP (Huang and Wong, 1989;Chiadak et al, 2016), which might ensure the modulation of cardiac and inflammatory functions during CCS. Therefore, by inhibiting GRK5 and stimulating ACs, we attenuated the hyperactive proinflammatory responses observed in vitro.…”

Section: Introductionmentioning

confidence: 99%

Amlexanox and Forskolin Prevents Isoproterenol-Induced Cardiomyopathy by Subduing Cardiomyocyte Hypertrophy and Maladaptive Inflammatory Responses

Adzika

Hou

Adekunle

et al. 2021

Front. Cell Dev. Biol.

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Chronic catecholamine stress (CCS) induces the occurrence of cardiomyopathy—pathological cardiac hypertrophy (PCH), which is characterized by left ventricular systolic dysfunction (LVSD). Recently, mounting evidence has implicated myocardial inflammation in the exacerbation of pathological cardiac remodeling. However, there are currently no well-defined treatment interventions or regimes targeted at both the attenuation of maladaptive myocardial hypertrophy and inflammation during CCS to prevent PCH. G protein-coupled receptor kinase 5 (GRK5) and adenylyl cyclases (ACs)-cAMP mediates both cardiac and inflammatory responses. Also, GRK5 and ACs are implicated in stress-induced LVSD. Herein, we aimed at preventing PCH during CCS via modulating adaptive cardiac and inflammatory responses by inhibiting GRK5 and/or stimulating ACs. Isoproterenol-induced cardiomyopathy (ICM) was modeled using 0.5 mg/100 g/day isoproterenol injections for 40 days. Alterations in cardiac and inflammatory responses were assessed from the myocardia. Similarities in the immunogenicity of cardiac troponin I (cTnI) and lipopolysaccharide under CCS were assessed, and Amlexanox (35 μM/ml) and/or Forskolin (10 μM/ml) were then employed in vitro to modulate adaptive inflammatory responses by inhibiting GRK5 or activating ACs-cAMP, respectively. Subsequently, Amlexanox (2.5 mg/100 g/day) and/or Forskolin (0.5 mg/100 g/day) were then translated into in vivo during CCS to modulate adaptive cardiac and inflammatory responses. The effects of Amlexanox and Forskolin on regulating myocardial systolic functions and inflammatory responses during CCS were ascertained afterward. PCH mice had excessive myocardial hypertrophy, fibrosis, and aggravated LVSD, which were accompanied by massive CD68+ inflammatory cell infiltrations. In vitro, Forskolin-AC/cAMP was effective than Amlexanox-GRK5 at downregulating proinflammatory responses during stress; nonetheless, Amlexanox and Forskolin combination demonstrated the most efficacy in modulating adaptive inflammatory responses. Individually, the translated Amlexanox and Forskolin treatment interventions were ineffective at subduing the pathological remodeling and sustaining cardiac function during CCS. However, their combination was potent at preventing LVSD during CCS by attenuating maladaptive myocardial hypertrophy, fibrosis, and inflammatory responses. The treatment intervention attained its potency mainly via Forskolin-ACs/cAMP-mediated modulation of cardiac and inflammatory responses, coupled with Amlexanox inhibition of GRK5 mediated maladaptive cascades. Taken together, our findings highlight the Amlexanox and Forskolin combination as a potential therapeutic intervention for preventing the occurrence of pathological cardiac hypertrophy during chronic stress.

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Forskolin Inhibits Lipopolysaccharide-Induced Modulation of MCP-1 and GPR120 in 3T3-L1 Adipocytes through an Inhibition of NFκB

Cited by 12 publications

References 50 publications

Ginsenoside Rb1 inhibits free fatty acids-induced oxidative stress and inflammation in 3T3-L1 adipocytes

Ginsenoside Rb1 inhibits free fatty acids-induced oxidative stress and inflammation in 3T3-L1 adipocytes

Phytochemicals as modulators of M1-M2 macrophages in inflammation

Amlexanox and Forskolin Prevents Isoproterenol-Induced Cardiomyopathy by Subduing Cardiomyocyte Hypertrophy and Maladaptive Inflammatory Responses

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