Silymarin ameliorates peritoneal fibrosis by inhibiting the TGF-β/Smad signaling pathway

Bai, Yingwen; Wang, Lulu; TingYang,; Wang, Lingyun; Ge, Weihong

doi:10.1007/s00210-023-02450-4

Cited by 4 publications

(1 citation statement)

References 41 publications

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“…Peritoneal dialysis (PD) is a common alternative mode of renal replacement therapy for end-stage renal disease (ESRD) patients [ 1 , 2 ]. Long-term PD treatment can cause changes in peritoneal morphology and function, including the loss of the mesothelium, accumulation of extracellular matrix, vascular hyalinization, and angiogenesis, eventually leading to PF [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

MiR-132-3p suppresses peritoneal fibrosis induced by peritoneal dialysis via targeting TGF-β1/Smad2/3 signaling pathway

Yin,

Yang,

Zhang

et al. 2024

PLoS ONE

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Background Peritoneal fibrosis (PF) is the main complication of peritoneal dialysis (PD) and the most common cause of cessation from PD. There is still no effective therapeutic approach to reserve PF. We aimed to investigate the role of miR-132-3p and underlying potential mechanisms in PF. Methods A total of 18 Sprague-Dawley (SD) rats were divided randomly into three groups (n = 6): (i)Control group (ii)PF group (iii)PF+Losartan group; Rats in the PF group and PF+Losartan group received daily intraperitoneal injections of 3 mg/kg chlorhexidine for 14 days, and rats in the PF+Losartan group simultaneously received daily intraperitoneal injections of 2 mg/kg losartan for 14 days. The control group was injected with saline in the same volume. Met-5A cells were treated for 24h with TGF-β1 dissolved in recombinant buffered saline at a concentration of 10 ng/ml, meanwhile, PBS solution as a negative control. The human peritoneal solution was collected for the detection of miR-132-3p. Results In vivo, SD rats were infused with chlorhexidine to establish PF model, and we found that miR-132-3p significantly decreased and the expressions of transforming growth factor-β1 (TGF-β1), and Smad2/3 were up-regulated in PF. In vitro, miR-132-3p mimics suppressed TGF-β1/Smad2/3 activity, whereas miR-132-3p inhibition activated the pathway. In human peritoneal solution, we found that the expression of miR-132-3p decreased in a time-dependent model and its effect became more pronounced with longer PD duration. Conclusion MiR-132-3p ameliorated PF by suppressing TGF-β1/Smad2/3 activity, suggesting that miR-132-3p represented a potential therapeutic approach for PF.

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Section: Introductionmentioning

confidence: 99%

MiR-132-3p suppresses peritoneal fibrosis induced by peritoneal dialysis via targeting TGF-β1/Smad2/3 signaling pathway

Yin,

Yang,

Zhang

et al. 2024

PLoS ONE

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Nephroprotective effects of silymarin and its fabricated nanoparticles against aluminum‐induced oxidative stress, hyperlipidemia, and genotoxicity

El‐Demerdash,

Ahmed,

El‐Sayed

et al. 2024

Environmental Toxicology

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BackgroundAluminum (Al) is a ubiquitous element with proven nephrotoxicity. Silymarin (SM) is a mixture of polyphenolic components extracted from Silybum marianum and exhibited protective influences. However, SM bioactivity can be enhanced by its incorporation in chitosan (CS) through the use of nanotechnology. This work proposed to assess the protective influence of SM and its loaded chitosan nanoparticles (SM‐CS‐NPs) on aluminum chloride (AlCl3)‐induced nephrotoxicity.MethodsSix groups were created randomly from 42 male Wistar rats and each one contains 7 rats (n = 7). Group I, acted as a control and received water. Group II received SM (15 mg/kg/day) and group III administered with SM‐CS‐NPs (15 mg/kg/day). Group IV received AlCl3 (34 mg/kg) and groups V and VI were treated with SM and SM‐CS‐NPs with AlCl3 respectively for 30 days.ResultsAlCl3 administration significantly elevated TBARS, H2O2, and kidney function levels besides LDH activity. Whereas GSH, CAT, SOD, GPx, GST, and GR values were all substantially reduced along with protein content, and ALP activity. Additionally, significant alterations in lipid profile, hematological parameters, and renal architecture were observed. Moreover, TNF‐α, TGF‐β, and MMP9 gene expression were upregulated in kidney tissues. The administration of SM or its nanoparticles followed by AlCl3 intoxication attenuated renal dysfunction replenished the antioxidant system, and downregulated TNF‐α, TGF‐β, and MMP9 gene expression in renal tissues compared to the AlCl3 group.ConclusionSM‐CS‐NPs have more pronounced appreciated protective effects than SM and have the proficiency to balance oxidant/antioxidant systems in addition to their anti‐inflammatory effect against AlCl3 toxicity.

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Silymarin and MSC-exosomes ameliorate thioacetamide-evoked renal fibrosis by inhibiting TGF-β/SMAD pathway in rats

Mekawy,

Sabry,

Sabry

et al. 2024

Mol Biol Rep

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Background TGF-β1 and SMAD3 are particularly pathogenic in the progression of renal fibrosis. Aim This study aimed to evaluate the kidney protective potentials of silymarin (SM) and exosomes of mesenchymal stem cells against the nephrotoxin thioacetamide (TAA) in rats. Methods 32 female rats were randomly assigned into four groups: the control group, the TAA group, the TAA + SM group, and the TAA + Exosomes group. The kidney homogenates from all groups were examined for expression levels of TGF-β receptors I and II using real-time PCR, expression levels of collagen type I and CTGF proteins using ELISA, and the expression levels of nuclear SMAD2/3/4, cytoplasmic SMAD2/3, and cytoplasmic SMAD4 proteins using the western blot technique. Results Compared to the control group, the injection of TAA resulted in a significant increase in serum levels of urea and creatinine, gene expression levels of TβRI and TβRII, protein expression levels of both collagen I and CTGF proteins, cytoplasmic SMAD2/3 complex, and nuclear SMAD2/3/4 (p-value < 0.0001), with significantly decreased levels of the co-SMAD partner, SMAD4 (p-value < 0.0001). Those effects were reversed considerably in both treatment groups, with the superiority of the exosomal treatment regarding the SMAD proteins and the expression levels of the TβRI gene, collagen I, and CTGF proteins returning to near-control values (p-value > 0.05). Conclusion Using in vitro and in vivo experimental approaches, the research discovered a reno-protective role of silymarin and exosomes of BM-MSCs after thioacetamide-induced renal fibrosis in rats, with the advantage of exosomes.

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Silymarin ameliorates peritoneal fibrosis by inhibiting the TGF-β/Smad signaling pathway

Cited by 4 publications

References 41 publications

MiR-132-3p suppresses peritoneal fibrosis induced by peritoneal dialysis via targeting TGF-β1/Smad2/3 signaling pathway

MiR-132-3p suppresses peritoneal fibrosis induced by peritoneal dialysis via targeting TGF-β1/Smad2/3 signaling pathway

Nephroprotective effects of silymarin and its fabricated nanoparticles against aluminum‐induced oxidative stress, hyperlipidemia, and genotoxicity

Silymarin and MSC-exosomes ameliorate thioacetamide-evoked renal fibrosis by inhibiting TGF-β/SMAD pathway in rats

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