scholarly journals The involvement of TGF-β1 /FAK/α-SMA pathway in the antifibrotic impact of rice bran oil on thioacetamide-induced liver fibrosis in rats

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260130
Author(s):  
Rehab F. Abdel-Rahman ◽  
Hany M. Fayed ◽  
Gihan F. Asaad ◽  
Hanan A. Ogaly ◽  
Alyaa F. Hessin ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Rice Bran ◽  
Rice Bran Oil ◽  
Stellate Cell ◽  
Biological Effects ◽  
Control Group ◽  
Blood Levels ◽  
Standard Group ◽  
Substantial Impact ◽  
Tgf Β1

The objective of the current study is to investigate the effect of rice bran oil (RBO) on hepatic fibrosis as a characteristic response to persistent liver injuries. Rats were randomly allocated into five groups: the negative control group, thioacetamide (TAA) group (thioacetamide 100 mg/kg thrice weekly for two successive weeks, ip), RBO 0.2 and 0.4 groups (RBO 0.2mL and 0.4 mL/rat/day, po) and standard group (silymarin 100 mg/kg/day, po) for two weeks after TAA injection. Blood and liver tissue samples were collected for biochemical, molecular, and histological analyses. Liver functions, oxidative stress, inflammation, liver fibrosis markers were assessed. The obtained results showed that RBO reduced TAA-induced liver fibrosis and suppressed the extracellular matrix formation. Compared to the positive control group, RBO dramatically reduced total bilirubin, AST, and ALT blood levels. Furthermore, RBO reduced MDA and increased GSH contents in the liver. Simultaneously RBO downregulated the NF-κβ signaling pathway, which in turn inhibited the expression of some inflammatory mediators, including Cox-2, IL-1β, and TNF-α. RBO attenuated liver fibrosis by suppressing the biological effects of TGF-β1, α-SMA, collagen I, hydroxyproline, CTGF, and focal adhesion kinase (FAK). RBO reduced liver fibrosis by inhibiting hepatic stellate cell activation and modulating the interplay among the TGF-β1 and FAK signal transduction. The greater dosage of 0.4 mL/kg has a more substantial impact. Hence, this investigation presents RBO as a promising antifibrotic agent in the TAA model through inhibition of TGF-β1 /FAK/α-SMA.

scholarly journals Effect and mechanism of vitamin D activation disorder on liver fibrosis in biliary atresia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Song Sun ◽  
Menghua Xu ◽  
Peijun Zhuang ◽  
Gong Chen ◽  
Kuiran Dong ◽  
...  
Keyword(s):  
Vitamin D ◽  
Liver Fibrosis ◽  
Biliary Atresia ◽  
Transforming Growth Factor ◽  
Serum Vitamin ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Control Group ◽  
Serum Vitamin D ◽  
Duct Ligation ◽  
Tgf Β1

AbstractTo investigate the mechanism of 25 hydroxyvitamin D (25(OH)D) deficiency in children with biliary atresia (BA) and its effect on liver fibrosis. The serum vitamin D and 25(OH)D, and expression of 25 hydroxylase (CYP2R1 and CYP27A1) in the liver of BA patients were detected and compared with those in the control group. We investigated the effect of differential expression of CYP2R1 in hepatocytes on the expression of genes related to liver fibrosis in primary hepatic stellate cells (HSCs) of BA and animal models of cholestasis. The ratio of 25(OH)D/vitamin D in the BA group was significantly lower than that in the control group. The mRNA and protein expression of CYP2R1 and CYP27A1 in liver tissue of the BA group was significantly lower than that in the control group. Exogenous active vitamin D (calcitriol) inhibited the proliferation and migration of primary HSCs isolated from BA patients, and reduced the expression of fibrosis-related genes in vitro. Downregulation of expression of CYP2R1 in hepatocytes increased expression of transforming growth factor (TGF)-β1, collagen (Col)-1α1 and tissue inhibitor of metalloproteinase (TIMP)-1, and decreased the expression of matrix metalloproteinase (MMP)-2 in cocultured primary HSCs of BA. Upregulation of expression of CYP2R1 in mice with bile duct ligation significantly increased the level of 25(OH)D, decreased the expression of TGF-β1, Col-1α1 and TIMP-1, and increased the expression of MMP-2. Children with BA have impaired vitamin D activation due to CYP2R1 deficiency. The dysactivation of vitamin D can promote the proliferation and activation of HSCs and participate in the development of hepatic fibrosis in BA.

Effects of Siniruangan Recipe on Proliferation, Apoptosis and Activation of Human Hepatic Stellate Cell Line LX-2

Pharmacology ◽  
2019 ◽  
Vol 104 (5-6) ◽  
pp. 342-351 ◽  
Author(s):  
Jinming Liu ◽  
Guorong Zhao ◽  
Bichen Ai ◽  
Yirong He ◽  
Ming Mei ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Liver Fibrosis ◽  
Cell Apoptosis ◽  
Transforming Growth Factor ◽  
Stellate Cell ◽  
Cell Activity ◽  
Relative Content ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Cell Counting ◽  
Tgf Β1

Background: Experimental and clinical evidence suggests that liver fibrosis is potentially reversible. Hepatic stellate cells (HSCs) play a key role in the development of hepatic fibrosis. Previous clinical applications and researches showed that Siniruangan recipe (SNRG) reversed liver fibrosis and even liver cirrhosis. This experimental study aimed to elucidate the effects of SNRG on the proliferation, apoptosis and activation of HSCs. Methods: The human HSCs line LX-2 was cultured with normal culture medium and multi-dose SNRG water decoction for 48 h. Cell Counting Kit-8 assay was used to detect the proliferation and cytotoxicity of LX-2 cells. Annexin V-FITC/PI double staining was performed to identify apoptotic cells. Immunofluorescence staining was used to determine the relative content of cleaved caspase-3, tissue inhibitor of metalloproteinase-1 (TIMP-1) and transforming growth factor-β1 (TGF-β1) in LX-2 cells. Western blot was used to detect the relative content of Bcl-2, Bax, α-smooth muscle actin, β-catenin and TIMP-1 protein expression in LX-2 cells. Results: The SNRG inhibited the proliferation of LX-2 and induced cell apoptosis through caspase-dependent and mitochondrial-dependent pathways. SNRG may inhibit the activation of LX-2 through the β-catenin pathway. The decrease in TIMP-1 and TGF-β1 protein induced by SNRG promoted the degradation of the extracellular matrix (ECM). Conclusions: SNRG induced LX-2 cell apoptosis, inhibited cell proliferation, decreased LX-2 cell activity and promoted the degradation of ECM in vitro, which may be important mechanisms for reversing liver fibrosis and liver cirrhosis.

scholarly journals Effects of Soybean and Rice Bran Oil Supplementation on Nutrient Utilization, Lactation Performance, Milk Fatty Acid Profile and Ruminal Fermentation in Surti Goats

2021 ◽  
Author(s):  
Ajay Prahladbhai Raval ◽  
Vipul R Patel ◽  
Lalitchandra M Sorathiya ◽  
Jignesh K Movalia
Keyword(s):  
Soybean Oil ◽  
Rice Bran ◽  
Nitrogen Balance ◽  
Milk Fat ◽  
Rice Bran Oil ◽  
Basal Diet ◽  
Nutrient Utilization ◽  
Control Group ◽  
Ruminal Fermentation ◽  
Lactation Performance

Abstract A study was conducted to observe the effect of soybean and rice bran oil supplementation onnutrient utilization, lactation performance and ruminal fermentation in Surti goats. Twentyfour multiparous lactating Surti does were distributed into four homogenous groups for entirelactation of 150 days. Control group (CON) was offered a basal diet consisting of compoundconcentrate mixture, green jowar and pigeon pea straws without any oil supplementation,while other treatment groups were additionally supplemented with soybean oil @ 3% of DMI(SBO), rice bran oil @ 3% of DMI (RBO) and equi-propotional blend of soybean oil and ricebran oil @ 3.0 % of DMI (SRBO). DM, CP, NDF and ADF intake (g/d) and digestibility (%)remained statistically (p>0.05) similar amongst dietary treatments groups. EE intake (g/d)and digestibility (%) was significantly (p<0.01) improved in all three oils supplementedgroups as compared to control but values between oils supplemented groups remained at par(p>0.05). Nitrogen balance of experimental groups remained unaffected (p>0.05) and all theanimals were under positive nitrogen balance. Milk yield (kg/d), milk fat, SNF, protein,lactose, FCM and ECM yields (g/d) were significantly (p<0.05) increased in oilssupplemented groups as compared to control. Feed efficiency in terms of MY/DMI andFCM/DMI significantly (p<0.05) improved in SBO, RBO and SRBO as compared to CON.Soybean and rice bran oil supplementation either alone or in combination significantlyreduced (p<0.05) SCFA, MCFA, SFA with increased LCFA and PUFA in milk. However,values between oils supplemented groups remained at par (p>0.05). Oil supplementationincreased (p<0.001) oleic acid (C18:1 n-9) and linoleic acid (C18:2 n-6) in SBO, RBO andSRBO as compared to CON while, linolenic acid (C18:3 n-9) remained non significantamongst treatments. Lipid quality indices (LQI) like atherogenicity index, thrombogenicityindex and hypocholesterolaemic/hypercholesterolaemic (h/H) index were significantlyimproved in all the oils supplemented groups as compared to control. Rumen pH, totalnitrogen and its fractions (ammonia N, TCA precipitable N and soluble N) remained similar(p>0.05) amongst treatment except TVFA. Thus, supplementation of soybean oil and ricebran oil either alone or in combination in lactating goat can be effectively used to improveboth nutritional quantity and quality of milk.

LEFTY2 alleviates hepatic stellate cell activation and liver fibrosis by regulating the TGF-β1/Smad3 pathway

2020 ◽  
Vol 126 ◽  
pp. 31-39
Author(s):  
Ya-ru Yang ◽  
Fang-tian Bu ◽  
Yang Yang ◽  
Hao Li ◽  
Cheng Huang ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Hepatic Stellate Cell ◽  
Cell Activation ◽  
Stellate Cell ◽  
Hepatic Stellate Cell Activation ◽  
Tgf Β1

scholarly journals Targeting Follistatin like 1 ameliorates liver fibrosis induced by carbon tetrachloride through TGF-β1-miR29a in mice

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Xin-Yi Xu ◽  
Yan Du ◽  
Xue Liu ◽  
Yilin Ren ◽  
Yingying Dong ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Cell Activation ◽  
Transforming Growth Factor ◽  
Stellate Cell ◽  
Neutralizing Antibody ◽  
Transforming Growth Factor Β1 ◽  
Chemokine Ligand ◽  
Tgf Β1

Abstract Background Hepatic fibrosis is a pathological response of the liver to a variety of chronic stimuli. Hepatic stellate cells (HSCs) are the major source of myofibroblasts in the liver. Follistatin like 1 (Fstl1) is a secreted glycoprotein induced by transforming growth factor-β1 (TGF-β1). However, the precise functions and regulation mechanisms of Fstl1 in liver fibrogenesis remains unclear. Methods Hepatic stellate cell (HSC) line LX-2 stimulated by TGF-β1, primary culture of mouse HSCs and a model of liver fibrosis induced by CCl4 in mice was used to assess the effect of Fstl1 in vitro and in vivo. Results Here, we found that Fstl1 was significantly up regulated in human and mouse fibrotic livers, as well as activated HSCs. Haplodeficiency of Fstl1 or blockage of Fstl1 with a neutralizing antibody 22B6 attenuated CCl4-induced liver fibrosis in vivo. Fstl1 modulates TGF-β1 classic Samd2 and non-classic JNK signaling pathways. Knockdown of Fstl1 in HSCs significantly ameliorated cell activation, cell migration, chemokines C-C Motif Chemokine Ligand 2 (CCL2) and C-X-C Motif Chemokine Ligand 8 (CXCL8) secretion and extracellular matrix (ECM) production, and also modulated microRNA-29a (miR29a) expression. Furthermore, we identified that Fstl1 was a target gene of miR29a. And TGF-β1 induction of Fstl1 expression was partially through down regulation of miR29a in HSCs. Conclusions Our data suggests TGF-β1-miR29a-Fstl1 regulatory circuit plays a key role in regulation the HSC activation and ECM production, and targeting Fstl1 may be a strategy for the treatment of liver fibrosis. Graphical abstract

scholarly journals Effects of soybean and rice bran oil on hemato-biochemical parameters in mice

2018 ◽  
Vol 5 (3) ◽  
pp. 365-372
Author(s):  
Nafis Islam ◽  
Md Shahidul Islam ◽  
Md Jahangir Alam ◽  
Md Kamrul Islam ◽  
Nazim Ahmad
Keyword(s):  
Soybean Oil ◽  
Rice Bran ◽  
Biochemical Parameters ◽  
Rice Bran Oil ◽  
Hemoglobin Concentration ◽  
Total Serum ◽  
Control Group ◽  
Total Serum Cholesterol ◽  
Group A ◽  
Group B

The study was conducted on “Swiss Albino” mice fed with additional supplementation of soybean oil and rice bran oil to observe the effects on hematological (total erythrocyte count and hemoglobin concentration) and biochemical parameters (total serum cholesterol, triglycerides, high density lipoproteins and uric acid). A total of 30, 6-8 weeks old mice were randomly divided into 3 equal groups (n=10) as A, B and C. Group A was considered as control (fed only commercial ration), group B was supplemented with rice bran oil and group C treated with soybean oil respectively in addition to commercial ration for 60 days. At the end of feeding trial the mice were sacrificed for analysis of hematobiochemical parameters. The total erythrocyte count and hemoglobin concentration were increased significantly (P<0.05) in group B and C compared to control group A and the highest values was recorded in soybean oil group C. The total serum cholesterol, triglycerides, HDL and uric acid were increased significantly (P<0.05) in both rice bran oil and soybean oil group compared to control group. It is concluded that some hemato-biochemical parameters of blood in the mice are affected by rice bran and soybean oil enriched diet. Though, oils and fats are detrimental to health but to evaluate the effects of rice bran and soybean oil, further studies with more animals and some other parameters like liver function, kidney function may be conducted. Res. Agric., Livest. Fish.5(3): 365-372, December 2018

scholarly journals Dioscin alleviates alcoholic liver fibrosis by attenuating hepatic stellate cell activation via the TLR4/MyD88/NF-κB signaling pathway

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Min Liu ◽  
Youwei Xu ◽  
Xu Han ◽  
Lianhong Yin ◽  
Lina Xu ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Signaling Pathway ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Stellate Cell ◽  
Pyrrolidine Dithiocarbamate ◽  
Type I ◽  
Tgf Β1

Abstract The present work aimed to investigate the activities and underlying mechanisms of dioscin against alcoholic liver fibrosis (ALF). In vivo liver fibrosis in mice was induced by an alcoholic liquid diet and in vitro studies were performed on activated HSC-T6 and LX2 cells treated with lipopolysaccharide. Our results showed that dioscin significantly attenuated hepatic stellate cells (HSCs) activation, improved collagen accumulation and attenuated inflammation through down-regulating the levels of myeloid differentiation factor 88 (MyD88), nuclear factor κB (NF-κB), interleukin (IL)-1, IL-6 and tumour necrosis factor-α by decreasing Toll-like receptor (TLR)4 expression both in vivo and in vitro. TLR4 overexpression was also decreased by dioscin, leading to the markedly down-regulated levels of MyD88, NF-κB, transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (α-SMA) and type I collagen (COL1A1) in cultured HSCs. Suppression of cellular MyD88 by ST2825 or abrogation of NF-κB by pyrrolidine dithiocarbamate eliminated the inhibitory effects of dioscin on the levels of TGF-β1, α-SMA and COL1A1. In a word, dioscin exhibited potent effects against ALF via altering TLR4/MyD88/NF-κB signaling pathway, which provided novel insights into the mechanisms of this compound as an antifibrogenic candidate for the treatment of ALF in the future.

scholarly journals Dihydromyricetin Reverses Thioacetamide-Induced Liver Fibrosis Through Inhibiting NF-κB-Mediated Inflammation and TGF-β1-Regulated of PI3K/Akt Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Yingchun Zhao ◽  
Xinglong Liu ◽  
Chuanbo Ding ◽  
Yan Gu ◽  
Wencong Liu
Keyword(s):  
Liver Fibrosis ◽  
Signaling Pathway ◽  
Cell Activation ◽  
Transforming Growth Factor ◽  
Histopathological Examination ◽  
Stellate Cell ◽  
Smooth Muscle Actin ◽  
Immunofluorescence Staining ◽  
Inflammatory Factors ◽  
Tgf Β1

As a natural active substance, dihydromyricetin (DHM) has been proven to have good hepatoprotective activity. However, the therapeutic effect of DHM on liver fibrosis, which has become a liver disease threatening the health of people around the world, has not been studied to date. The purpose of this study was to investigate the effect of DHM as a new nutritional supplement on thioacetamide (TAA)-induced liver fibrosis. The liver fibrosis model was established by intraperitoneal injection of TAA (200 mg/kg, every 3 days) for 8 weeks, and oral administration of DHM (20 mg/kg and 40 mg/kg, daily) after 4 weeks of TAA-induced liver fibrosis. The results showed that DHM treatment significantly inhibited the activities of alanine aminotransferase (ALT) (37.81 ± 7.62 U/L) and aspartate aminotransferase (AST) (55.18 ± 10.94 U/L) in serum of liver fibrosis mice, and increased the levels of superoxide dismutase (SOD) and glutathione (GSH) while reversed the level of malondialdehyde (MDA). In addition, histopathological examination illustrated that TAA induced the inflammatory infiltration, apoptosis and fibroatherosclerotic deposition in liver, which was further confirmed by western-blot and immunofluorescence staining. Moreover, DHM inhibited hepatocyte apoptosis by regulating the phosphorylation level of phosphatidylinositol 3-kinase (PI3K), protein kinase-B (AKT) and its downstream apoptotic protein family. Interestingly, immunofluorescence staining showed that DHM treatment significantly inhibited alpha smooth muscle actin (α-SMA), which was a marker of hepatic stellate cell activation, and regulated the expression of transforming growth factor (TGF-β1). Importantly, supplementation with DHM significantly inhibited the release of nuclear factor kappa-B (NF-κB) signaling pathway and pro-inflammatory factors in liver tissue induced by TAA, and improved liver fiber diseases, such as tumor necrosis factor alpha (TNF-α) and recombinant rat IL-1β (IL-1β). In conclusion, the evidence of this study revealed that DHM is a potential hepatoprotective and health factor, and which also provides the possibility for the treatment of liver fibrosis.

scholarly journals Orphan nuclear receptor NR4A2 inhibits hepatic stellate cell proliferation through MAPK pathway in liver fibrosis

PeerJ ◽  
2015 ◽  
Vol 3 ◽  
pp. e1518 ◽  
Author(s):  
Pengguo Chen ◽  
Jie Li ◽  
Yan Huo ◽  
Jin Lu ◽  
Lili Wan ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Liver Fibrosis ◽  
Nuclear Receptor ◽  
Mapk Pathway ◽  
Stellate Cell ◽  
Smooth Muscle Actin ◽  
Control Group ◽  
Orphan Nuclear Receptor ◽  
Fibrotic Liver

Hepatic stellate cells (HSCs) play a crucial role in liver fibrosis, which is a pathological process characterized by extracellular matrix accumulation. NR4A2 is a nuclear receptor belonging to the NR4A subfamily and vital in regulating cell growth, metabolism, inflammation and other biological functions. However, its role in HSCs is unclear. We analyzed NR4A2 expression in fibrotic liver and stimulated HSCs compared with control group and studied the influence on cell proliferation, cell cycle, cell apoptosis and MAPK pathway after NR4A2 knockdown. NR4A2 expression was examined by real-time polymerase chain reaction, Western blotting, immunohistochemistry and immunofluorescence analyses. NR4A2 expression was significantly lower in fibrotic liver tissues and PDGF BB or TGF-βstimulated HSCs compared with control group. After NR4A2 knockdownα-smooth muscle actin and Col1 expression increased. In addition, NR4A2 silencing led to the promotion of cell proliferation, increase of cell percentage in S phase and reduced phosphorylation of ERK1/2, P38 and JNK in HSCs. These results indicate that NR4A2 can inhibit HSC proliferation through MAPK pathway and decrease extracellular matrix in liver fibrogenesis. NR4A2 may be a promising therapeutic target for liver fibrosis.

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