Oligo-Fucoidan Improves Diabetes-Induced Renal Fibrosis via Activation of Sirt-1, GLP-1R, and Nrf2/HO-1: An In Vitro and In Vivo Study

Yu, Wen-Chun; Huang, Ren‐Yeong; Chou, Tz-Chong

doi:10.3390/nu12103068

Cited by 46 publications

(29 citation statements)

References 44 publications

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“…Dietary flavone quercetin and genistein also show a benefit on endometriosis, by inhibiting the proliferation of endometriosis with the cell cycle arrest [ 32 ], and they can decrease ER-α expression and the antiangiogenics effect [ 41 ]. Fucoidan shows an anti-inflammatory effect in diabetes-induced renal fibrosis and hyperuricemia related renal damage [ 42 , 43 ] and has an anti-proliferation effect in gynecological cancer [ 29 ]. This indicates the potential effect of fucoidan on endometriosis progression.…”

Section: Discussionmentioning

confidence: 99%

The Potential Effect of Fucoidan on Inhibiting Epithelial-to-Mesenchymal Transition, Proliferation, and Increase in Apoptosis for Endometriosis Treatment: In Vivo and In Vitro Study

et al. 2020

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Endometriosis is common in reproductive-age women and its pathology is to increase proliferation and migration to enhance epithelial-to-mesenchymal transition progression (EMT). However, treatments are currently limited, so it is important to explore new therapeutic drugs. Hence, in this study, we investigate the therapeutic effect of fucoidan (FC) on the progression and mechanisms of endometriosis. The cell viability of endometrial cell lines End1/E6E7 and Vk2/E6E7 treated with different concentrations of FC were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell counting. Cell migration was evaluated using wound-healing assay. In an in vivo experiment, female Balb/c mice received surgically induced endometriosis followed by different concentrations of fucoidan for 6 weeks. High-frequency ultrasound imaging was applied to detect subsequent lesion growth. The results demonstrated that fucoidan inhibited the viability and migration ability of End1/E6E7 and Vk2/E6E7 cells. Additionally, the administration of fucoidan reduced the volume and weight of endometriotic lesions, decreased inflammatory cytokines and vascular endothelial growth factor (VEGF) of serum and lesions, and improved EMT proliferation and apoptosis-related protein expression. For the first time, fucoidan indicated anti-proliferative and anti-inflammatory effects as well as inhibited EMT progression and induced apoptosis, improving endometriosis.

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Section: Discussionmentioning

confidence: 99%

The Potential Effect of Fucoidan on Inhibiting Epithelial-to-Mesenchymal Transition, Proliferation, and Increase in Apoptosis for Endometriosis Treatment: In Vivo and In Vitro Study

et al. 2020

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“…GLP-1R (Glucagon-like peptide-1 receptor), which is present in various organs, such as the liver, brain and kidney, is an important pharmacological target for T2DM ( Aroda, 2018 ). A recent study showed that GLP-1R plays an important role in regulating non-diabetic and diabetic renal fibrosis Li et al (2018) , Yu et al (2020) , and Glp1r mRNA levels positively correlate with serum testosterone concentrations in normal male mice and in diabetic models ( Zhu et al, 2019 ). Research has demonstrated that miR-192 induces fibrosis in human renal tubular epithelial cells by targeting GLP-1R ( Jia et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Icariin Ameliorates Diabetic Renal Tubulointerstitial Fibrosis by Restoring Autophagy via Regulation of the miR-192-5p/GLP-1R Pathway

et al. 2021

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Tubulointerstitial fibrosis is one of the most common pathological features of diabetic nephropathy. Autophagy, an intracellular mechanism to remove damaged or dysfunctional cell parts and maintain metabolic homeostasis, is inhibited in diabetic neuropathy. Icariin is a traditional Chinese medicine extract known for nourishing the kidney and reinforcing Yang. In this study, we investigated the effects and mechanism of Icariin on renal function, autophagy, and fibrosis in type 2 diabetic nephropathic rats and in high-glucose-incubated human renal tubular epithelial cells and rat renal fibroblasts (in vitro). Icariin improved diabetes, renal function, restored autophagy, and alleviated fibrosis in type 2 diabetic neuropathic rats and in vitro. After we applied autophagy-related gene 5-small interfering RNA, we found that fibrosis improvement by Icariin was related to autophagy restoration. By detecting serum sex hormone levels, and using dihydrotestosterone, siRNA for androgen receptor, and the androgen receptor antagonist Apalutamide (ARN-509), we found that Icariin had an androgen-like effect and restored autophagy and reduced fibrosis by regulating the androgen receptor. In addition, miR-192-5p levels were increased under high glucose but reduced after dihydrotestosterone and Icariin treatment. Furthermore, dihydrotestosterone and Icariin inhibited miR-192-5p overexpression-induced fibrosis production and autophagy limitation. Glucagon-like peptide-1 receptor (GLP-1R) was downregulated by high glucose and overexpression of miR-192-5p and could be restored by dihydrotestosterone and Icariin. By using ARN-509, we found that Icariin increased GLP-1R expression by regulating the androgen receptor. GLP-1R-siRNA transfection weakened the effects of Icariin on autophagy and fibrosis. These findings indicate that Icariin alleviates tubulointerstitial fibrosis by restoring autophagy through the miR-192-5p/GLP-1R pathway and is a novel therapeutic option for diabetic fibrosis.

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“…The effects of the oligofucoidan on Nrf2 activation were inhibited, using a SIRT1 inhibitor, demonstrating that there is a crosstalk between the SIRT1 and Nrf2 cascade (Yu et al 2020). Shah et al (2017) corroborated this notion, since melatonin exerted antioxidant and anti-in ammatory activities through the Nrf2 activation, dependent on SIRT1, in the brain of immature rats and in BV2 cells.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of dimethyl fumarate against depression-like behaviors via astrocytes and microglia modulation in mice: possible involvement of the HCAR2/Nrf2 signaling pathway

Souza

Lopes

Filho

et al. 2022

Preprint

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We postulated that dimethyl fumarate (DMF), an activator of the Nuclear Factor Erythroid 2-related factor 2 (Nrf2) pathway, exerts neuroprotective effects against depression-like behaviors through astrocytes and microglia modulation. To ascertain our hypothesis and define the mechanistic pathways involved in effect of DMF on neuroinflammation, we used the depression model induced by Chronic Unpredictable Mild Stress (CUMS), in which, the mice were exposed to stressful events for 28 days and from the 14th day they received DMF in the doses of 50 and 100 mg / kg or fluoxetine 10 mg / kg or saline. On the 29th day, the animals were subjected to behavioral tests. Microglia (Iba1) and astrocytes (GFAP) markers expressions were evaluated by immunofluorescence analyzes and the cytokines TNF-α and IL-Iβ by immunoenzymatic assay. In addition, computational target prediction, 3D protein structure prediction and docking calculations were performed with monomethyl fumarate (DMF active metabolite) and the Kelch-like ECH associated protein-1 and hydroxycarboxylic acid receptor 2 (HCAR2), which suggested that these could be the probable targets related protective effects. CUMS induced anxiety- and depressive-like behaviors, cognitive deficit, decreased GFAP and increased Iba1, TNF-α and IL-Iβ expression in the hippocampus. These alterations were reversed by DMF. Thus, it is suggested that one of the mechanisms involved in the antidepressant effect of DMF is neuroinflammatory suppression, through the signaling pathway HCAR2 / Nrf2. However, more studies must be performed to better understand the molecular mechanisms of this drug.

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Oligo-Fucoidan Improves Diabetes-Induced Renal Fibrosis via Activation of Sirt-1, GLP-1R, and Nrf2/HO-1: An In Vitro and In Vivo Study

Cited by 46 publications

References 44 publications

The Potential Effect of Fucoidan on Inhibiting Epithelial-to-Mesenchymal Transition, Proliferation, and Increase in Apoptosis for Endometriosis Treatment: In Vivo and In Vitro Study

The Potential Effect of Fucoidan on Inhibiting Epithelial-to-Mesenchymal Transition, Proliferation, and Increase in Apoptosis for Endometriosis Treatment: In Vivo and In Vitro Study

Icariin Ameliorates Diabetic Renal Tubulointerstitial Fibrosis by Restoring Autophagy via Regulation of the miR-192-5p/GLP-1R Pathway

Neuroprotective effects of dimethyl fumarate against depression-like behaviors via astrocytes and microglia modulation in mice: possible involvement of the HCAR2/Nrf2 signaling pathway

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