Stevioside attenuates isoproterenol-induced mouse myocardial fibrosis through inhibition of the myocardial NF-κB/TGF-β1/Smad signaling pathway

Wang, Jia; Shen, Wei; Zhang, Junyan; Jia, Chang-Hao; Xie, Ming

doi:10.1039/c8fo01663a

Cited by 37 publications

(16 citation statements)

References 28 publications

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“…Our result of decreased MDA content by STE supplementation was consistent with the previous finding that STE significantly reversed the lipid peroxidation in the liver of the LPS-challenged rat [49]. Increasing evidence has shown that STE exerts potent antioxidant properties in vivo and in vitro [11,49,51,52]. In agreement with these findings, we also demonstrated that STE markedly increased the total antioxidant capacity, and reduced oxidative stress in the intestinal mucosae of LPS-challenged broilers.…”

Section: Discussionsupporting

confidence: 92%

Dietary Stevioside Supplementation Alleviates Lipopolysaccharide-Induced Intestinal Mucosal Damage through Anti-Inflammatory and Antioxidant Effects in Broiler Chickens

Jiang

et al. 2019

Antioxidants

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The study was conducted to investigate the effects of dietary stevioside (STE) supplementation on the lipopolysaccharide (LPS)-induced intestinal mucosal damage of broiler chickens. A total of 192 one-day-old male Ross 308 broiler chicks were randomly divided into four treatments: (1) basal diet (CON); (2) basal diet supplemented with 250 mg/kg stevioside (STE);(3) basal diet + LPS-challenge (LPS); (4) basal diet supplemented with 250 mg/kg stevioside + LPS-challenge (LPS + STE). LPS-challenged groups received an intraperitoneal injection of LPS at 17, 19 and 21 d, whereas the CON and STE groups received a saline injection. The results showed that dietary STE supplementation normalized LPS-induced changes in protein expression of p-NF-κB and p-IκBα, mRNA expression of inflammatory genes (TLR4, NF-κB, and IFN-γ), tight junction-related genes (CLDN2, OCLN, and ZO-1), and antioxidant genes (Nrf2 and HO-1). LPS-induced decreases in serum diamine oxidase (DAO) level, villus height-to-crypt depth ratio, apoptotic index, and protein expression of proliferating cell nuclear antigen (PCNA) were reversed with dietary STE supplementation. Additionally, STE supplementation ameliorated the redox damage by reducing malondialdehyde (MDA) content and increasing total antioxidant capacity (T-AOC) and antioxidant enzyme activity. In conclusion, dietary stevioside supplementation could alleviate LPS-induced intestinal mucosal damage through anti-inflammatory and antioxidant effects in broiler chickens.Antioxidants 2019, 8, 575 2 of 20 and oxidative status of the intestine in broiler chickens [7][8][9]. Thus, LPS has been widely applied to establish a model of intestinal mucosal damage in broiler chickens [2,[7][8][9][10]. It is necessary to explore feed additives with therapeutic potential for disrupted intestinal homeostasis of LPS-challenged in broilers.Stevioside (STE) is a natural diterpenoid glycoside extracted from the Stevia rebaudiana (Bertoni), which has been proven to be safe in the food industry [11]. A previous study has suggested that STE exerts no harmful effects in the chicken diet with a dose of 667 mg/kg [12]. Despite STE being 250−300 times sweeter than sucrose, it has several nutritional and medical activities such as anti-hyperglycaemic [13], anti-hypertensive [14], and anti-tumor activities [15]. Furthermore, several studies have shown that STE exerts anti-inflammatory and antioxidant effects both in vivo and in vitro [11,14,16]. In rats, STE could prevent liver inflammation through antioxidant activity by activating Nrf2 and anti-inflammatory activity by suppressing NF-κB signaling [11]. In a human colonic cell line, steviol (a derivative of STE) suppressed the IL-8 release induced by TNF-α, and reduced the protein expression of NF-κB [17]. STE could also attenuate the LPS-induced synthesis of pro-inflammatory cytokines by regulating IκBα/NF-κB signaling pathway [16]. In mice, STE promoted macrophage function and increased humoral immune response [18]. STE treatment enhanced antioxidant defense in both the adi...

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Section: Discussionsupporting

confidence: 92%

Dietary Stevioside Supplementation Alleviates Lipopolysaccharide-Induced Intestinal Mucosal Damage through Anti-Inflammatory and Antioxidant Effects in Broiler Chickens

Jiang

et al. 2019

Antioxidants

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“…For example, NF-κB can promote the release of TGF-β1 in pulmonary fibrosis [45], whereas inhibition of the TLR4/MyD88/NF-κB pathway can downregulate the expression of TGF-β1 in glomerular mesangial cells [46]. A similar phenomenon was also observed in myocardia, where the activation of NF-κB can lead to an increase in the expression of its downstream target gene TGF-β1 [47]. Therefore, we may infer that PSAP promotes the secretion of TGF-β1 and/or increases the activity of this pathway through the NF-κB signaling pathway.…”

Section: Discussionmentioning

confidence: 74%

Prosaposin is a biomarker of mesenchymal glioblastoma and regulates mesenchymal transition through the TGF‐β1/Smad signaling pathway

Jiang

Zhou

Hou

et al. 2019

The Journal of Pathology

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Mesenchymal glioblastoma (GBM) is the most aggressive subtype of GBM. Our previous study found that neurotrophic factor prosaposin (PSAP) is highly expressed and secreted in glioma and can promote the growth of glioma. The role of PSAP in mesenchymal GBM is still unclear. In this study, bioinformatic analysis, western blotting and RT‐qPCR were used to detect the expression of PSAP in different GBM subtypes. Human glioma cell lines and patient‐derived glioma stem cells were studied in vitro and in vivo, revealing that mesenchymal GBM expressed and secreted the highest level of PSAP among four subtypes of GBM, and PSAP could promote GBM invasion and epithelial–mesenchymal transition (EMT)‐like processes in vivo and in vitro. Bioinformatic analysis and western blotting showed that PSAP mainly played a regulatory role in GBM invasion and EMT‐like processes via the TGF‐β1/Smad signaling pathway. In conclusion, the overexpression and secretion of PSAP may be an important factor causing the high invasiveness of mesenchymal GBM. PSAP is therefore a potential target for the treatment of mesenchymal GBM. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd

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“…Canonical TGF‐β signaling mobilizes Smad2 and Smad3 transcription factors that control fibrosis by promoting gene expression . TGF‐β1/Smad2/3 signaling has been shown to contribute to myocardial fibrosis . Overt expression of AP‐1 contributes to volume‐overload‐induced heart failure .…”

Section: Discussionmentioning

confidence: 99%

Induction of LOX by TGF‐β1/Smad/AP‐1 signaling aggravates rat myocardial fibrosis and heart failure

Qin

Yao

et al. 2019

IUBMB Life

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This study aims to evaluate the efficacy of lysyl oxidase (LOX) inhibition in regulating rat myocardial fibrosis and chronic heart failure (CHF) and to validate the regulation of LOX by TGF-β1/Smad2/3 signaling in this process. A rat model of CHF was established by abdominal aortic coarctation. The renin-angiotensinaldosterone system (RAAS) indexes (PRA, ACE2, Ang II, and ALD), cardiac function indicators (LVEF, LVFS, SAP, DAP, and LVEDP), ventricular remodeling-and fibrosis-related indicators (hydroxyproline, collagen deposition, and MMP-2/9), and morphological changes of myocardial tissues were examined. Rat cardiac fibroblasts (RCFs) were used in vitro assays. CHF patients showed increased LOX activity, accompanied by activated RAAS and TGF-β1. Furthermore, inhibition of LOX by β-aminopropionitrile (BAPN) mitigated the RAAS activation and attenuated cardiac dysfunction, ventricular remodeling, myocardial fibrosis, and collagen deposition in CHF rats. Moreover, TGF-β1 signaling diminished the LOX inhibition-mediated antiheart failure effect. Further assays showed that TGF-β1/ Smad2/3 signaling increased expression of c-jun (AP-1 transcription factor subunit), which transcriptionally induced LOX expression. Additionally, BAPN abrogated the TGF-β1-mediated increase in cell proliferation and levels of MMP-2/9 and collagen I/III in RCFs. In conclusion, LOX can be induced by TGF-β1/Smad/AP-1 signaling and LOX inhibition attenuates rat myocardial fibrosis and CHF. K E Y W O R D S chronic heart failure, c-Jun, LOXSmadTGF-β1

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Stevioside attenuates isoproterenol-induced mouse myocardial fibrosis through inhibition of the myocardial NF-κB/TGF-β1/Smad signaling pathway

Abstract: Stevioside attenuates isoproterenol-induced mouse myocardial fibrosis, and its mechanisms are associated with the increments of antioxidant ability, PPARγ activation, and Smad7 expression, which cause a synergistic inhibition of the NF-κB/TGF-β1/Smad signaling pathway.

Cited by 37 publications

References 28 publications

Dietary Stevioside Supplementation Alleviates Lipopolysaccharide-Induced Intestinal Mucosal Damage through Anti-Inflammatory and Antioxidant Effects in Broiler Chickens

Dietary Stevioside Supplementation Alleviates Lipopolysaccharide-Induced Intestinal Mucosal Damage through Anti-Inflammatory and Antioxidant Effects in Broiler Chickens

Prosaposin is a biomarker of mesenchymal glioblastoma and regulates mesenchymal transition through the TGF‐β1/Smad signaling pathway

Induction of LOX by TGF‐β1/Smad/AP‐1 signaling aggravates rat myocardial fibrosis and heart failure

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