Effects and Mechanisms of Acremoniumterricola milleretal mycelium on Liver Fibrosis Induced by Carbon Tetrachloride in Rats

2011 ◽  
Vol 39 (03) ◽  
pp. 537-550 ◽  
Author(s):  
Xiao-Peng Tian ◽  
Yan-Yan Yin ◽  
Xia Li

Acremoniumterricola milleretal mycelium (AMM) is one of the most precious traditional Chinese medicines. It has numerous protective effects on organs, and has been used in Chinese herb prescription to treat refractory diseases. Our preliminary studies demonstrated that AMM had hepatoprotective activity in acute liver injury. We further investigated the effects of AMM on liver fibrosis in rats induced by carbon tetrachloride ( CCl 4) and explore its possible mechanisms. The animal model was established by injection with 50% CCl 4 subcutaneously in male Sprague-Dawley rats twice a week for eight weeks. Meanwhile, AMM (175, 350 and 700 mg/kg) was administered intragastrically per day until sacrifice. We found that treatment with AMM (175, 350 and 700 mg/kg) decreased CCl 4-induced elevation of serum transaminase activities, hyaluronic acid, laminin and procollagen type III levels, and contents of hydroxyproline in liver tissues. It also restored the decreased SOD and GSH-Px activities and inhibited the formation of lipid peroxidative products during CCl 4 treatment. Moreover, AMM (350 and 700 mg/kg) decreased the elevation of TGF-β1 by 19.6% and 34.3%, respectively. In the pathological study, liver injury and the formation of liver fibrosis in rates treated by AMM were improved significantly. Immunoblot analysis showed that AMM (175, 350 and 700 mg/kg) inhibited Smad 2/3 phosphorylation, and elevated inhibitor Smad 7 expression. These results suggested that AMM could protect liver damage and inhibit the progression of hepatic fibrosis induced by CCl 4, and its mechanisms might be associated with its ability to scavenge free radicals, decrease the level of TGF-β1 and block TGF-β/Smad signaling pathway.

1989 ◽  
Vol 17 (1_part_1) ◽  
pp. 38-45 ◽  
Author(s):  
Frej Stenbäck ◽  
Hannu U. Saarni ◽  
Arja Rautio ◽  
Jari Stengård ◽  
Eero A. Sotaniemi

The possible effects of a synthetic progesterone, medroxyprogesterone acetate (MPA), on carbon tetrachloride/phenobarbital (CCl4/PB)-induced rat liver injury were studied by morphological methods. CCl4/PB-treated rats showed extensive liver fibrosis consisting of procollagen type III aminoterminal propeptide-positive strands and fibres with concomitant extensive basement membrane deposits and fibronectin synthesis. MPA treatment after CCl4/PB-induced liver damage reduced alterations in cytoplasmic organelles, inflammation and hemorrhages and reversed the fibrosis, mostly around individual liver cells, possibly due to the normalization of cellular structure and function with a decrease in fibronectin deposits.


2017 ◽  
Vol 41 (6) ◽  
pp. 2242-2254 ◽  
Author(s):  
Tao Wu ◽  
Jingjing Li ◽  
Yong Li ◽  
Hongping Song

Background/Aims: Swertiamarin (STM), the main bioactive component in Swertia mussotii Franch (Gentianaceae), has been shown to exert hepatoprotective effects on experimental liver injury. However, the effects and exact mechanisms of STM on carbon tetrachloride (CCl4) causing hepatotoxicity are still unknown. This study investigated the potential protective effects and mechanisms of STM on CCl4-induced liver injury in rats. Methods: Adult male Sprague-Dawley (SD) rats were exposed to CCl4 with or without STM co-administration for consecutive eight weeks. Results: STM significantly ameliorated CCl4-induced increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels and histopathological changes in the liver. Hepatic oxidative stress was repressed by STM, as evidenced by the decrease in malondialdehyde (MDA), with concomitant increase in antioxidase activity (e.g. superoxide dismutase (SOD); glutathione peroxidase (GPx)), glutathione (GSH) level. STM also obviously attenuated inflammatory response in CCl4-lesioned livers as evidenced by the decrease in inflammatory cytokines/ chemokines (e.g. inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β)). Additionally, STM significantly induced the expression of CYPs, efflux transporters and PDZK1 as compared with the CCl4 group. Moreover, co-administration of STM with CCl4 remarkably up-regulated the expression of Nrf2, HO-1 and NQO1 compared with the CCl4 group. Conclusions: The present study demonstrates that STM exerts a protective effect against CCl4-induced liver injury and inflammation with its antioxidant effects and induction of hepatic detoxification enzymes and efflux transporters expression, at least in part, via the Nrf2/HO-1 pathway in rats.


2021 ◽  
Vol 11 (1) ◽  
pp. 390
Author(s):  
Beom-Rak Choi ◽  
Il-Je Cho ◽  
Su-Jin Jung ◽  
Jae-Kwang Kim ◽  
Dae-Geon Lee ◽  
...  

Lemon balm and dandelion are commonly used medicinal herbs exhibiting numerous pharmacological activities that are beneficial for human health. In this study, we explored the protective effects of a 2:1 (w/w) mixture of lemon balm and dandelion extracts (MLD) on carbon tetrachloride (CCl4)-induced acute liver injury in mice. CCl4 (0.5 mL/kg; i.p.) injection inhibited body weight gain and increased relative liver weight. Pre-administration of MLD (50–200 mg/kg) for 7 days prevented these CCl4-mediated changes. In addition, histopathological analysis revealed that MLD synergistically alleviated CCl4-mediated hepatocyte degeneration and infiltration of inflammatory cells. MLD decreased serum aspartate aminotransferase and alanine transferase activities and reduced the number of liver cells that stained positive for cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase, suggesting that MLD protects against CCl4-induced hepatic damage via the inhibition of apoptosis. Moreover, MLD attenuated CCl4-mediated lipid peroxidation and protein nitrosylation by restoring impaired hepatic nuclear factor erythroid 2-related factor 2 mRNA levels and its dependent antioxidant activities. Furthermore, MLD synergistically decreased mRNA and protein levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the liver. Together, these results suggest that MLD has potential for preventing acute liver injury by inhibiting apoptosis, oxidative stress, and inflammation.


2017 ◽  
Vol 8 (9) ◽  
pp. 3276-3287 ◽  
Author(s):  
Wei-Lun Hung ◽  
Guliang Yang ◽  
Yu-Chuan Wang ◽  
Yi-Shiou Chiou ◽  
Yen-Chen Tung ◽  
...  

TSA markedly reduced the CCl4-induced liver injury in mice.


2007 ◽  
Vol 37 (11) ◽  
pp. 948-956 ◽  
Author(s):  
Li Zhang ◽  
Jingyuan Wan ◽  
Hongzhong Li ◽  
Ping Wu ◽  
Shengwei Jin ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Farkaad A. Kadir ◽  
Normadiah M. Kassim ◽  
Mahmood Ameen Abdulla ◽  
Behnam Kamalidehghan ◽  
Fatemeh Ahmadipour ◽  
...  

The antifibrotic effects of traditional medicinal herbCaesalpinia sappan(CS) extract on liver fibrosis induced by thioacetamide (TAA) and the expression of transforming growth factorβ1 (TGF-β1),α-smooth muscle actin (αSMA), and proliferating cell nuclear antigen (PCNA) in rats were studied. A computer-aided prediction of antioxidant and hepatoprotective activities was primarily performed with the Prediction Activity Spectra of the Substance (PASS) Program. Liver fibrosis was induced in male Sprague Dawley rats by TAA administration (0.03% w/v) in drinking water for a period of 12 weeks. Rats were divided into seven groups: control, TAA, Silymarin (SY), and CS 300 mg/kg body weight and 100 mg/kg groups. The effect of CS on liver fibrogenesis was determined by Masson’s trichrome staining, immunohistochemical analysis, and western blotting.In vivodetermination of hepatic antioxidant activities, cytochrome P450 2E1 (CYP2E1), and matrix metalloproteinases (MPPS) was employed. CS treatment had significantly increased hepatic antioxidant enzymes activity in the TAA-treated rats. Liver fibrosis was greatly alleviated in rats when treated with CS extract. CS treatment was noted to normalize the expression of TGF-β1,αSMA, PCNA, MMPs, and TIMP1 proteins. PASS-predicted plant activity could efficiently guide in selecting a promising pharmaceutical lead with high accuracy and required antioxidant and hepatoprotective properties.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Peng-chun Yang ◽  
Wei-zhe Bai ◽  
Jing Wang ◽  
Cai-hua Yan ◽  
Wei-feng Huang ◽  
...  

Objectives. Schistosomiasis is a parasitic disease that affects over 142 million people worldwide. The main causes of death of schistosomiasis include liver granuloma and secondary hepatic cirrhosis resulting from severe fibrosis. Despite intensive research, controlling liver fibrosis associated with schistosomiasis remains challenging. Sedum sarmentosum total flavonoid (SSTF) is a promising agent to reduce liver fibrosis with an unknown mechanism. Thus, the objectives of this study are to validate its effect on the liver fibrosis caused by schistosomiasis and to explore the underlying molecular mechanism. Methods. Sixty male Sprague-Dawley rats were randomly divided into six groups: one group of normal control and five groups of liver fibrosis induced by schistosomiasis japonica with or without SSTF or colchicine treatment, the latter serving as the positive control. Liver tissues from each animal were harvested to observe the degree and grade of hepatic fibrosis. We also measured the expression of transforming growth factor-beta 1 (TGF-β1) and Smad7 using RT-qPCR, Western blot, and immunohistochemistry. Results. Compared with the untreated model group, groups treated with SSTF at all three tested doses had significantly reduced hepatic fibrosis ( P < 0.05 ). Each dose of SSTF also significantly reduced TGF-β1 protein expression and mRNA levels in the liver tissues ( P < 0.05 ). In contrast, the middle and high doses of SSTF significantly increased Smad7 protein expression and mRNA levels ( P < 0.05 ). Immunohistochemistry showed that each dose of SSTF reduced TGF-β1 protein expression ( P < 0.05 ). Conclusion. Our results demonstrated that SSTF alleviated schistosomiasis japonica-induced hepatic fibrosis by inhibiting the TGF-β1/Smad7 pathway.


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