Therapeutic Effect of Curcumin, a Plant Polyphenol Extracted From <i>Curcuma longae</i>, in Fibroblasts From Patients With Graves' Orbitopathy

Lee, Jihei Sara; Kim, Jinjoo; Lee, Mi Kyung; Yoon, Jin Sook

doi:10.1167/iovs.19-27376

Cited by 19 publications

(11 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CUR also significantly reduced H 2 O 2 -induced ROS synthesis in fibroblasts. 188 The acute pharmacokinetics and pharmacodynamics of commercially marketed CUR capsules (4 g) in 12 normal, healthy volunteers with a standard breakfast were evaluated and plasma levels of CUR were detected by HPLC-ITMS/MS/MS. The major metabolite of CUR, curcumin-O-glucuronide, was detected at 30 min.…”

Section: Antioxidant Effects Of Curcumin Clinical Studiesmentioning

confidence: 99%

Experimental and clinical reports on anti‐inflammatory, antioxidant, and immunomodulatory effects ofCurcuma longaand curcumin, an updated and comprehensive review

et al. 2021

View full text Add to dashboard Cite

Curcuma longa (C. longa) or turmeric is a plant with a long history of use in traditional medicine, especially for treating inflammatory conditions C. longa and its main constituent, curcumin (CUR), showed various pharmacological effects such as antioxidant and anti-microbial properties. The updated knowledge of anti-inflammatory, antioxidant, and immunomodulatory effects of C. longa and CUR is provided in this review article. Pharmacological effects of C. longa, and CUR, including anti-inflammatory, antioxidant, and immunomodulatory properties, were searched using various databases and appropriate keywords until September 2020. Various studies showed anti-inflammatory effects of C. longa and CUR, including decreased white blood cell, neutrophil, and eosinophil numbers, and its protective effects on serum levels of inflammatory mediators such as phospholipase A2 and total protein in different inflammatory disorders. The antioxidant effects of C. longa and CUR were also reported in several studies. The plant extracts and CUR decreased

show abstract

Section: Antioxidant Effects Of Curcumin Clinical Studiesmentioning

confidence: 99%

Experimental and clinical reports on anti‐inflammatory, antioxidant, and immunomodulatory effects ofCurcuma longaand curcumin, an updated and comprehensive review

et al. 2021

View full text Add to dashboard Cite

show abstract

“…40,41 As such, evidence regarding the importance of Wnt signaling pathways in the patho-genesis of GO is mounting; recently, we found that suppression of the adipogenesis of GO fibroblasts by curcumin involved activation of the canonical Wnt signaling pathway, as well. 42 The changes in the phosphorylation of multiple transcription factors upon the addition of GSK-3β inhibitor in our GO fibroblasts indicate that a more complex network of signaling pathways may exist than once believed. Kumar et al 28 discovered that an auto-antibody against thyroid-stimulating hormone receptor stimulated the PI3K/Akt pathway downstream and induced adipogenesis of orbital preadipocytes in GO.…”

Section: Discussionmentioning

confidence: 82%

“… 40 , 41 As such, evidence regarding the importance of Wnt signaling pathways in the pathogenesis of GO is mounting; recently, we found that suppression of the adipogenesis of GO fibroblasts by curcumin involved activation of the canonical Wnt signaling pathway, as well. 42 …”

Section: Discussionmentioning

confidence: 99%

Glycogen Synthase Kinase-3β Mediates Proinflammatory Cytokine Secretion and Adipogenesis in Orbital Fibroblasts from Patients with Graves’ Orbitopathy

Lee

Chae

Kikkawa

et al. 2020

Invest. Ophthalmol. Vis. Sci.

Self Cite

View full text Add to dashboard Cite

Purpose We sought to determine the role of glycogen synthase kinase-3β (GSK-3β) in the pathogenesis of Graves’ orbitopathy(GO). Methods Expression of the GSK-3β gene in whole orbital tissue explants was compared between GO and non-GO donors using quantitative real-time PCR (RT-PCR). The expression of proinflammatory molecules in the presence of the GSK-3β inhibitor CHIR 99021 was analyzed using RT-PCR, western blot, and ELISA. Adipogenic differentiation was identified using Oil Red O staining, and the levels of peroxisome proliferator activator gamma (PPARγ) and CCAAT-enhancer-binding proteins (C/EBPs) α and β were determined by western blot. Results The expression of GSK-3β was significantly higher in GO tissues than in control tissues. The addition of CHIR 99021 led to a decrease in the active form of the kinase in which the Y216 residue is phosphorylated. When GO and non-GO fibroblasts were stimulated with IL-1β or TNF-α, IL-6, IL-8, intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-1 (COX-1), and monocyte chemoattractant protein 1 (MCP-1) showed increased production, which was blunted when CHIR 99021 was added. The activation of Akt, PI3K, nuclear factor (NF)-κB, Erk, Jnk, and p38 kinase by IL-1β and TNF-α was diminished with CHIR 99021 in GO cells. A decrease in lipid droplets and expression of PPARγ and c/EBPα and -β was noted in fibroblasts treated with CHIR 99021 during adipocyte differentiation. The inhibition of Wnt and β-catenin in adipogenesis was reversed by CHIR 99021. Conclusions GSK-3β plays a significant role in GO pathogenesis. The inhibition of the kinase attenuated the proinflammatory cytokines production and fibroblast differentiation into adipocytes. GSK-3β may be a potential target for anti-inflammatory and anti-adipogenic treatment of GO.

show abstract

“…Previously, we have found that quercetin inhibits cigarette smoke extract-induced adipogenesis in GO fibroblasts by reducing ROS ( 48 ). Additionally, we have reported several molecules with anti-oxidative properties such as resveratrol, caffeine, and curcumin suppress adipogenesis in GO fibroblasts ( 49 – 51 ). Given that oxidative stress contributes to the proliferation of orbital fibroblasts ( 52 ), the impeded proliferation of GO fibroblasts by PCSK9 inhibition demonstrated in this study may be attributed to the anti-oxidative property of the PCSK9 inhibitor.…”

Section: Discussionmentioning

confidence: 99%

Role of Proprotein Convertase Subtilisin/Kexin Type 9 in the Pathogenesis of Graves’ Orbitopathy in Orbital Fibroblasts

et al. 2021

Self Cite

View full text Add to dashboard Cite

BackgroundThe proprotein convertase subtilisin/kexin type 9 (PCSK9) has been implicated in the pathogenesis of inflammatory diseases. We sought to investigate the role of PCSK9 in the pathogenesis of Graves’ orbitopathy (GO) and whether it may be a legitimate target for treatment.MethodsThe PCSK9 was compared between GO (n=11) and normal subjects (n=7) in orbital tissue explants using quantitative real-time PCR, and in cultured interleukin-1β (IL-1β)-treated fibroblasts using western blot. Western blot was used to identify the effects of PCSK9 inhibition on IL-1β-induced pro-inflammatory cytokines production and signaling molecules expression as well as levels of adipogenic markers and oxidative stress-related proteins. Adipogenic differentiation was identified using Oil Red O staining. The plasma PCSK9 concentrations were compared between patients with GO (n=44) and healthy subjects (n=26) by ELISA.ResultsThe PCSK9 transcript level was higher in GO tissues. The depletion of PCSK9 blunted IL-1β-induced expression of intercellular adhesion molecule 1 (ICAM-1), IL-6, IL-8, and cyclooxygenase-2 (COX-2) in GO and non-GO fibroblasts. The levels of activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and phosphorylated forms of Akt and p38 were diminished when PCSK9 was suppressed in GO fibroblasts. Decreases in lipid droplets and attenuated levels of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein β (C/EBPβ), and leptin as well as hypoxia-inducible factor 1α (HIF-1α), manganese superoxide dismutase (MnSOD), thioredoxin (Trx), and heme oxygenase-1 (HO-1) were noted when PCSK9 was suppressed during adipocyte differentiation. The plasma PCSK9 level was significantly higher in GO patients and correlated with level of thyrotropin binding inhibitory immunoglobulin (TBII) and the clinical activity score (CAS).ConclusionsPCSK9 plays a significant role in GO. The PCSK9 inhibition attenuated the pro-inflammatory cytokines production, oxidative stress, and fibroblast differentiation into adipocytes. PCSK9 may serve as a therapeutic target and biomarker for GO.

show abstract

Therapeutic Effect of Curcumin, a Plant Polyphenol Extracted From Curcuma longae, in Fibroblasts From Patients With Graves' Orbitopathy

Cited by 19 publications

References 47 publications

Experimental and clinical reports on anti‐inflammatory, antioxidant, and immunomodulatory effects ofCurcuma longaand curcumin, an updated and comprehensive review

Experimental and clinical reports on anti‐inflammatory, antioxidant, and immunomodulatory effects ofCurcuma longaand curcumin, an updated and comprehensive review

Glycogen Synthase Kinase-3β Mediates Proinflammatory Cytokine Secretion and Adipogenesis in Orbital Fibroblasts from Patients with Graves’ Orbitopathy

Role of Proprotein Convertase Subtilisin/Kexin Type 9 in the Pathogenesis of Graves’ Orbitopathy in Orbital Fibroblasts

Contact Info

Product

Resources

About