The role of oxymatrine in regulating TGF-β1 in rats with hepatic fibrosis

Wu, Jing; Lin, Pei; Jin, Xin; Li, Weihua; Li, Hongbing; Chen, Jianmao; Yang, Wen

doi:10.1590/s0102-865020180030000002

Cited by 13 publications

(10 citation statements)

References 23 publications

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“…Increasing reports suggest that TGF-β1/TAK1 signalling plays critical roles in extracellular matrix production and the pathogenesis of fibrosis. 30,38 TAK1 mediates fibrosis by increasing the expression of type I collagen and fibronectin. 39,40 In this study, we found that fibrosis was accompanied by TAK1 activation in mdx mice.…”

Section: Discussionmentioning

confidence: 99%

A potential therapeutic effect of catalpol in Duchenne muscular dystrophy revealed by binding with TAK1

Zhao

Jiang

et al. 2020

J cachexia sarcopenia muscle

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Background Duchenne muscular dystrophy (DMD) is a progressive muscle disease caused by the loss of dystrophin, which results in inflammation, fibrosis, and the inhibition of myoblast differentiation in skeletal muscle. Catalpol, an iridoid glycoside, improves skeletal muscle function by enhancing myogenesis; it has potential to treat DMD. We demonstrate the positive effects of catalpol in dystrophic skeletal muscle. Methods mdx (loss of dystrophin) mice (n = 18 per group) were treated with catalpol (200 mg/kg) for six consecutive weeks. Serum analysis, skeletal muscle performance and histology, muscle contractile function, and gene and protein expression were performed. Molecular docking and ligand-target interactions, RNA interference, immunofluorescence, and plasmids transfection were utilized to explore the protective mechanism in DMD by which catalpol binding with transforming growth factor-βactivated kinase 1 (TAK1) in skeletal muscle. Results Six weeks of catalpol treatment improved whole-body muscle health in mdx mice, which was characterized by reduced plasma creatine kinase (n = 18, À35.1%, P < 0.05) and lactic dehydrogenase (n = 18, À10.3%, P < 0.05) activity. These effects were accompanied by enhanced grip strength (n = 18, +25.4%, P < 0.05) and reduced fibrosis (n = 18, À29.0% for hydroxyproline content, P < 0.05). Moreover, catalpol treatment protected against muscle fatigue and promoted muscle recovery in the tibialis anterior (TA) and diaphragm (DIA) muscles (n = 6, +69.8%, P < 0.05 and + 74.8%, P < 0.001, respectively), which was accompanied by enhanced differentiation in primary myoblasts from DMD patients (n = 6, male, mean age: 4.7 ± 1.9 years) and mdx mice. In addition, catalpol eliminated p-TAK1 overexpression in mdx mice (n = 12, À21.3%, P < 0.05) and primary myoblasts. The catalpol-induced reduction in fibrosis and increased myoblast differentiation resulted from the inhibition of TAK1 phosphorylation, leading to reduced myoblast trans-differentiation into myofibroblasts. Catalpol inhibited the phosphorylation of TAK1 by binding to TAK1, possibly at Asp-206, Thr-208, Asn-211, Glu-297, Lys-294, and Tyr-293. Conclusions Our findings show that catalpol and TAK1 inhibitors substantially improve whole-body muscle health and the function of dystrophic skeletal muscles and may provide a novel therapy for DMD.

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Section: Discussionmentioning

confidence: 99%

A potential therapeutic effect of catalpol in Duchenne muscular dystrophy revealed by binding with TAK1

Zhao

Jiang

et al. 2020

J cachexia sarcopenia muscle

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“…It is well known that TAA induced marked hepatotoxicity and is predominantly used to develop hepatofibrosis in several experimental studies [10,11] . In agreement with the reported data, TAA (200 mg/kg, ip) produced hepatic damage and elevated levels of ALT and AST in serum.…”

Section: Fig 1: Effect Of Ate In Cell Viability Assay On Chang Livermentioning

confidence: 99%

“…Inhibiting ECM secretion by activated HSCs and targeting HSCs apoptotic pathways, which are involved in the pathogenesis of liver fibrosis has great significance in ameliorating chronic liver diseases [9] . Several studies on thioacetamide (TAA) in experimental animals revealed similar mechanism of liver fibrogenesis both metabolic and histological when compared with the fibrotic livers of humans including virus-induced cirrhosis [10,11] . Therefore, TAAinduced liver fibrosis in rodents could be a classical model to evaluate therapeutic efficacy of various agents for studying liver damage and liver fibrosis [11] .…”

mentioning

confidence: 99%

“…Several studies on thioacetamide (TAA) in experimental animals revealed similar mechanism of liver fibrogenesis both metabolic and histological when compared with the fibrotic livers of humans including virus-induced cirrhosis [10,11] . Therefore, TAAinduced liver fibrosis in rodents could be a classical model to evaluate therapeutic efficacy of various agents for studying liver damage and liver fibrosis [11] . Use of natural products derived from plants in aiding liver capacity and preventing liver damage such as Ampelopsis brevipedunculata, Orostachys japonicus, Artemisia, Chrysanthemum, Plantago seed, Gardenia jasminoides and Paeonialactiflora have been practiced in Asian countries since centuries [12] .…”

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confidence: 99%

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Aster tataricus Linn., Suppresses Hepatic Stellate Cell Activation and Protects Against Thioacetamide-induced Liver Fibrosis in Rats

Kim¹,

Koppula²,

Yum³

et al. 2020

ijps

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Kim et al.: Antihepatofibrotic Effect of Aster tataricusAster tataricus Linn., (Asteraceae), an oriental and nutrient-potential herb is used in Asian countries for various health benefits. The present study focused on the protective effects of Aster tataricus against liver fibrosis in cellular and an experimental rat model. Cell cytotoxicity, cell cycle and apoptosis functions were analyzed using hepatic stellate cell lines following MTT assay, flow cytometry, and Annexin V-FITC/PI staining methods. For in vivo evaluation, thioacetamide-induced hepatofibrosis rat model was established. Sprague Dawley rats were divided into 5 groups of 10 each (control, thioacetamide, thioacetamide with Aster tataricus extract 100 and 500 mg/kg and silymarin 50 mg/kg groups, respectively). Fibrosis was induced by thioacetamide treatment (200 mg/kg, ip) 3 times per week for 13 weeks except for the control group. Aster tataricus extract (100 and 500 mg/kg), and silymarin was administrated orally to each group 6 times a week from week 7 to 13 and various fibrosis-related parameters were estimated using real-time polymerase chain reaction using TRIzol Plus RNA purification Kit and a spectrophotometer. Results indicated that hepatic stellate cells treated with Aster tataricus extract (0.5 mg/ml) and silymarin (0.05 mg/ml) significantly (p<0.05) induced apoptosis (19.04 and 24.82 %, respectively) compared to the control group (9.78 %). Moreover, rat primary hepatic stellate cells showed morphological changes and degradation of collagen and fibronectin when treated with 0.5 mg/kg of Aster tataricus extract. In vivo evaluation Aster tataricus extract at concentrations of 100 and 500 mg/mlattenuated the increased serum levels of alanine transaminase, aspartate transaminase and hydroxyproline and restored the decreased glutathione levels significantly in thioacetamide induced fibrotic rats (p<0.05). The altered histopathology in thioacetamide-induced liver tissues and changes in fibrosis-related gene expression (TGF-β, α-SMA and Col1α1) were also restored by Aster tataricus extract treatment. In conclusion, Aster tataricus can be developed as a potential therapeutic agent in the treatment of liver fibrosis.

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“… 12 Oxymatrine may also inhibit the secretion of transforming growth factor (TGF)-β1 and TGF-α1 to degrade the ECM. 13 , 14 Based on the aforementioned studies, models of HF were established and treated with oxymatrine in the present study to investigate the anti-fibrotic effects and mechanism of the agent.…”

Section: Introductionmentioning

confidence: 99%

Oxymatrine exerts anti-fibrotic effects in a rat model of hepatic fibrosis by suppressing endoplasmic reticulum stress

et al. 2020

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Objective This study evaluated the anti-fibrotic effects of oxymatrine and the role of endoplasmic reticulum (ER) stress in hepatic fibrosis (HF) in animal models. Methods The HF rat model was established by exposure to NaAsO2, followed by treatment with oxymatrine. Biomarkers of HF and ER stress were measured. The difference in protein expression between groups was evaluated using isobaric tag for relative and absolute quantification (iTRAQ) analysis. The mechanism by which oxymatrine modulated ER stress to alleviate arsenic-induced HF was evaluated using LX2 hepatic stellate cells in vitro. Results The rat model mimicked the pathological and physical phenotypes of HF including ER stress, oxidative stress, impaired liver function, and fibrosis. Treatment with oxymatrine suppressed these responses. Moreover, apoptosis, inflammation, and hepatic stellate cell activation were also inhibited by oxymatrine treatment. The differentially expressed proteins and pathways related to ER stress were identified in the HF and oxymatrine-treated groups via iTRAQ analysis combined with liquid chromatography–mass spectrometry. LX2 cells were activated by NaAsO2 in vitro. Meanwhile, oxymatrine suppressed the activation of LX2 cells by alleviating ER stress and regulating cellular calcium homeostasis. Conclusions Oxymatrine could reverse NaAsO2-induced HF by alleviating ER stress.

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The role of oxymatrine in regulating TGF-β1 in rats with hepatic fibrosis

Abstract: Oxymatrine is effective in protecting rats from thioacetamide-induced hepatic fibrosis by regulating TGF-β1 expression.

Cited by 13 publications

References 23 publications

A potential therapeutic effect of catalpol in Duchenne muscular dystrophy revealed by binding with TAK1

A potential therapeutic effect of catalpol in Duchenne muscular dystrophy revealed by binding with TAK1

Aster tataricus Linn., Suppresses Hepatic Stellate Cell Activation and Protects Against Thioacetamide-induced Liver Fibrosis in Rats

Oxymatrine exerts anti-fibrotic effects in a rat model of hepatic fibrosis by suppressing endoplasmic reticulum stress

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