WSF-7 Inhibits Obesity-Mediated PPARγ Phosphorylation and Improves Insulin Sensitivity in 3T3-L1 Adipocytes

Zhang, Yudian; Wang, Yunyun; Li, Xiaochuan; Gu, Kerui; Li, Mingxin; Zhang, Yan; Zhang, Zhijie; Wang, Shifa; Li, Zhen

doi:10.1248/bpb.b19-00986

Cited by 11 publications

(5 citation statements)

References 29 publications

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“…In previous studies, it was demonstrate that luteolin shows anti-inflammatory, anticancer, neuroprotective, and antiviral properties in vitro and in animal models [ 21 – 25 ]. Thus, luteolin has been investigated for potential use in the treatment of obesity [ 26 ] and obesity-related diseases and for antidiabetic [ 27 – 29 ] and neuroprotective therapies [ 30 , 31 ]. In ophthalmological research, luteolin protects against oxidative stress-related damage and decreases inflammation in ARPE-19 cells [ 32 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

Luteolin Attenuates IL-1β-Induced THP-1 Adhesion to ARPE-19 Cells via Suppression of NF-κB and MAPK Pathways

Huang

Liou

Shen

et al. 2020

Mediators of Inflammation

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Cytokine-induced endothelial dysfunction leads to inflammation and vascular adhesion molecule production in retinal pigment epithelium (RPE) cells. Inflammation is a critical mediator in retinal degeneration (RD) diseases, including age-related macular degeneration (AMD), and RD progression may be prevented through anti-inflammatory activity in RPE cells. The flavonoid polyphenol luteolin (LU) has anti-inflammatory and antidiabetes activities, but its effects regarding retinal protection remain unknown. Here, we examined the ability of luteolin to alleviate markers of inflammation related to RD in cytokine-primed APPE-19 cells. We found that luteolin decreased the levels of interleukin- (IL-) 6, IL-8, soluble intercellular adhesion molecule-1 (sICAM-1), and monocyte chemoattractant protein-1 (MCP-1) and attenuated adherence of the human monocytic leukemia cell line THP-1 to IL-1β-stimulated ARPE-19 cells. Luteolin also increased anti-inflammatory protein heme oxygenase-1 (HO-1) levels. Interestingly, luteolin induced protein kinase B (AKT) phosphorylation, thus inhibiting nuclear factor- (NF-) κB transfer from cytoplasm into the nucleus and suppressing mitogen-activated protein kinase (MAPK) inflammatory pathways. Furthermore, cotreatment with MAPK inhibitors and luteolin decreased inflammatory cytokine and chemokine levels, and further suppressed THP-1 adhesion. Overall, these results provide evidence that luteolin protects ARPE-19 cells from IL-1β-stimulated increases of IL-6, IL-8, sICAM-1, and MCP-1 production by blocking the activation of MAPK and NF-κB signaling pathways, thus ameliorating the inflammatory response.

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Section: Introductionmentioning

confidence: 99%

Luteolin Attenuates IL-1β-Induced THP-1 Adhesion to ARPE-19 Cells via Suppression of NF-κB and MAPK Pathways

Huang

Liou

Shen

et al. 2020

Mediators of Inflammation

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“…The choice of monoterpenoids for derivatization was also made based on the literature data on the hypoglycemic and hypolipidemic activity of the terpene derivatives. Derivatives of both bicyclic and acyclic monoterpenoids ( Figure 12 ) are known to be partial PPAR agonists and also have hypoglycemic and hepatoprotective activity [ 11 , 12 , 13 , 14 ].…”

Section: Discussionmentioning

confidence: 99%

Terpene-Containing Analogues of Glitazars as Potential Therapeutic Agents for Metabolic Syndrome

Blokhin

Kuranov

Хвостов

et al. 2023

CIMB

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Metabolic syndrome is a complex of abnormalities involving impaired glucose and lipid metabolism, which needs effective pharmacotherapy. One way to reduce lipid and glucose levels associated with this pathology is the simultaneous activation of nuclear PPAR-alpha and gamma. For this purpose, we synthesized a number of potential agonists based on the pharmacophore fragment of glitazars with the inclusion of mono- or diterpenic moiety in the molecular structure. The study of their pharmacological activity in mice with obesity and type 2 diabetes mellitus (C57Bl/6Ay) revealed one substance that was capable of reducing the triglyceride levels in the liver and adipose tissue of mice by enhancing their catabolism and expressing a hypoglycemic effect connected with the sensitization of mice tissue to insulin. It has also been shown to have no toxic effects on the liver.

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“…For example, S26948 reduced LDL and VLDL in the blood of ob/ob male C57BL/6 mice and reduced atherosclerotic lesions (Carmona et al, 2007). WSF‐7 upregulates PPARγ responsive genes, such as adiponectin and glucose transporter (Glut)4, inhibits obesity‐induced phosphorylation of PPARγ at Ser273, and enhances insulin sensitivity in 3T3‐L1 adipocytes (Zhang et al, 2020). Lobeglitazone inhibits VSMC proliferation and migration, reduces vascular cell adhesion, reduces NF‐κB p65 translocation, and improves circulating factors associated with atherosclerosis (Lim et al, 2015; Song et al, 2021).…”

Section: Pparγ Ligands and Atherosclerosismentioning

confidence: 99%

The role of peroxisome proliferator‐activated receptor γ in lipid metabolism and inflammation in atherosclerosis

Yang

Shang

2023

Cell Biology International

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Cardiovascular disease events are the result of functional and structural abnormalities in the arteries and heart. Atherosclerosis is the main cause and pathological basis of cardiovascular diseases. Atherosclerosis is a multifactorial disease associated with dyslipidemia, inflammation, and oxidative stress, among which dyslipidemia and chronic inflammation occur in all processes. Under the influence of lipoproteins, the arterial intima causes inflammation, necrosis, fibrosis, and calcification, leading to plaque formation in specific parts of the artery, which further develops into plaque rupture and secondary thrombosis. Foam cell formation from macrophages is an early event in the development of atherosclerosis. Lipid uptake causes a vascular inflammatory response, and persistent inflammatory infiltration in the lesion area further promotes the development of the disease. Inhibition of macrophage differentiation into foam cell and reduction of the level of proinflammatory factors in macrophages can effectively alleviate the occurrence and development of atherosclerosis. Peroxisome proliferator-activated receptor γ (PPARγ) is a ligandactivated nuclear receptor that plays an important antiatherosclerotic role by regulating triglyceride metabolism, lipid uptake, cholesterol efflux, macrophage polarity, and inhibiting inflammatory signaling pathways. In addition, PPARγ shifts its binding to ligands and co-activators or co-repressors of transcription of target genes through posttranslational modification, thereby affecting the regulation of its downstream target genes. Many ligand agonists have also been developed targeting PPARγ. In this review, we summarized the role of PPARγ in lipid metabolism and inflammation in development of atherosclerosis, the posttranslational regulatory mechanism of PPARγ, and further discusses the value of PPARγ as an antiatherosclerosis target.

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WSF-7 Inhibits Obesity-Mediated PPARγ Phosphorylation and Improves Insulin Sensitivity in 3T3-L1 Adipocytes

Cited by 11 publications

References 29 publications

Luteolin Attenuates IL-1β-Induced THP-1 Adhesion to ARPE-19 Cells via Suppression of NF-κB and MAPK Pathways

Luteolin Attenuates IL-1β-Induced THP-1 Adhesion to ARPE-19 Cells via Suppression of NF-κB and MAPK Pathways

Terpene-Containing Analogues of Glitazars as Potential Therapeutic Agents for Metabolic Syndrome

The role of peroxisome proliferator‐activated receptor γ in lipid metabolism and inflammation in atherosclerosis

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