scholarly journals Therapeutic Effect of Biejiaxiaozheng Pills on Carbon Tetrachloride-Induced Hepatic Fibrosis in Rats through the NF-κB/Nrf2 Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Weibin Wu ◽  
Liqiang Li ◽  
Jian Yang ◽  
Pinyu Li ◽  
Yuying Hu ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Function ◽  
Hepatic Fibrosis ◽  
Inflammatory Cytokine ◽  
Nrf2 Pathway ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Commercial Kits ◽  
Plasma Antioxidant ◽  
Masson Staining

Aims. To explore the effects of Biejiaxiaozheng pills on carbon tetrachloride-induced hepatic fibrosis in rats through the NF-κB/Nrf2 pathway and to explore the possible antifibrotic mechanisms of the drug. Material and Method. A rat model of hepatic fibrosis was established via CCl4 induction. Liver function and antioxidant indices were detected using commercial kits. Hematoxylin-eosin and Masson staining were used to detect pathological changes in hepatic tissues. ELISA was used to measure plasma TNF-α, IL-β, and IL-6 levels. RT-PCR was used to measure changes in TNF-α, IL-β, and IL-6 levels in hepatic tissues. Changes in p65, P-p65, Nrf2, and HO-1 protein expression were detected using western blotting. Results. In rats with hepatic fibrosis, Biejiaxiaozheng pills effectively improved liver function, alleviated fibrosis in hepatic tissues, and significantly reduced collagen accumulation. The pills significantly downregulated inflammatory cytokine expression in hepatic tissues by suppressing p65 phosphorylation and reduced plasma inflammatory cytokine levels to some extent. The pills upregulated Nrf2 and HO-1 expression in hepatic tissues, enhanced antioxidant potential, and upregulated plasma antioxidant levels. Conclusion. Biejiaxiaozheng pills improved hepatic fibrosis symptoms and lesions in rats, likely by inhibiting the NF-κB pathway and promoting the Nrf2 pathway.

scholarly journals TheBDKRB2 +9/-9 Polymorphisms Influence Pro-Inflammatory Cytokine Levels in Knee Osteoarthritis by Altering TLR-2 Expression: Clinical and in Vitro Studies

2016 ◽  
Vol 38 (3) ◽  
pp. 1245-1256 ◽  
Author(s):  
Shuo Chen ◽  
Lei Zhang ◽  
Ruonan Xu ◽  
Yunfan Ti ◽  
Yunlong Zhao ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Inflammatory Cytokine ◽  
Molecular Mechanisms ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Knee Oa ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Underlying Mechanisms

Background/Aims: The bradykinin B2 receptor (BDKRB2) +9/-9 gene polymorphisms have been shown to be associated with the susceptibility and severity of osteoarthritis (OA); however, the underlying mechanisms are unclear. In this study, we investigated the correlation between the BDKRB2 +9/-9 polymorphisms and pro-inflammatory cytokine levels in OA and the molecular mechanisms involved. Methods: A total of 156 patients with primary knee OA and 121 healthy controls were enrolled. The BDKRB2 +9/-9 polymorphisms were genotyped. The tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 levels were determined using Enzyme-linked immunosorbent assay (ELISA). The toll-like receptor (TLR)-2 and TLR-4 mRNA levels were determined by quantitative real-time PCR. The basal and bradykinin-stimulated pro-inflammatory cytokine secretion in human OA synoviocytes and the involvement of TLR-2 and mitogen-activated protein kinases (MAPKs) were investigated. Results: The presence of -9 bp genotype is associated with higher TNF-α, IL-6, and IL-8 levels and higher TLR-2 expression in OA patients. The basal and bradykinin-induced TLR-2 expressions in human OA synoviocytes were significantly reduced by specific inhibitors of p38, JNK1/2, and ERK1/2. Both the B2 receptor antagonist MEN16132 and TLR-2 silencing inhibited IL-6 and IL-8 secretion in human OA synoviocytes. Conclusion: The data suggested that the BDKRB2 +9/-9 polymorphisms influence pro-inflammatory cytokine levels in knee osteoarthritis by altering TLR-2 expression.

Hepatoprotective Effects of Saponins from Rhizoma panacis majoris on Hepatic Fibrosis Induced by Carbon Tetrachloride in Rats

2014 ◽  
Vol 568-570 ◽  
pp. 1915-1920
Author(s):  
Ji Hong Zhang ◽  
Meng Qiong Shi ◽  
Hai Bo He ◽  
Cai Hong Bai ◽  
Jun Zhi Wang ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Function ◽  
Antioxidant Capacity ◽  
Hepatic Fibrosis ◽  
Separation And Purification ◽  
Sprague Dawley ◽  
Gene Expressions ◽  
Total Antioxidant ◽  
Hepatoprotective Effects ◽  
Underlying Mechanisms

Saponins from Rhizoma Panacis Majoris (SRPM), the bioactive component in Rhizoma Panacis Majoris, have been used extensively as a remedy for liver injury diseases and achieved good clinical efficacy, but the underlying mechanisms remain poorly understood. The goal of our present study was to further confirm SRPM hepatoprotective effect, and evaluate that whether SRPM attenuate oxidative stress and fibrosis in carbon tetrachloride (CCl4)-induced hepatic injury, based on these results, investigate the probable mechanisms involved. At first, the separation and purification of SRPM were studied. And then, in the animal experiment, the male Sprague-Dawley rats were randomly divided into control, model, l-SRPM and h-SRPM group. Hepatic fibrosis model were made according to our previous studies reported. At the same time, the experimental rats were treated respectively with relative drugs, once a day for 8 weeks. Hepatoprotective effects of SRPM were evaluated by liver function, total antioxidant capacity and total-superoxide dismutase, histopathological observations and the hepatic fibrosis relative gene expressions. In the study, we found that SRPM significantly improved liver function, serum antioxidation level, reversed the upregulated α-SMA and TIMP1 mRNA expressions, and further increased the MMP1 mRNA expression. Our studies indicated that SRPM exerted beneficially hepatoprotective effects on the CCl4 induced hepatic fibrosis, mainly enhancing liver tissue antioxidant capacity, reducing the lipid peroxidation of hepatocyte membranes, and then alleviating hepatic fibrosis and hepatic cell death.

scholarly journals Synergistic Inhibitory Effect of the Gut Microbiome and Lithocholic Acid on Liver Fibrosis

2021 ◽  
Author(s):  
Junwei Shao ◽  
Tiantian Ge ◽  
Senzhong Chen ◽  
Zhi Chen
Keyword(s):  
Liver Fibrosis ◽  
Liver Function ◽  
Gut Microbiome ◽  
Lithocholic Acid ◽  
Inhibitory Effect ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Serum Biochemical ◽  
The Relationship

Abstract Background: Lithocholic acid are essential signaling molecules that mediate the relationship between the gut microbiome and liver function by regulating inflammation. The purpose of this study is to investigate the role of lithocholic acid in liver fibrosis. Methods: A liver fibrosis mouse model was induced by carbon tetrachloride followed by gavage of lithocholic acid, and the effects of lithocholic acid were evaluated by serum biochemical analysis and liver histology. Plasma cytokine levels and the number of immune cells were determined by cytometric bead array and flow cytometry, respectively. Results: Lithocholic acid treatment increased the recruitment of NK cells and reduced the activation of NKT cells, and reduced M1 macrophages differentiation and increased M2 macrophages differentiation. Furthermore, the lithocholic acid prevented inflammatory liver disease by reducing TNF-α and IL-22 secretion. However, the effect of lithocholic acid disappeared when the host gut microbiome was treated with antibiotics. Conclusions: It showed that the activation of lithocholic acid-mediated signaling was linked to the inhibition of inflammation and improvement of liver fibrosis. The role of lithocholic acid in liver fibrosis is mediated by the gut microbiome. The association between the gut microbiome, lithocholic acid, and liver function can serve as a therapeutic target for liver fibrosis.

Triterpenoid CDDO-IM protects against lipopolysaccharide-induced inflammatory response and cytotoxicity in macrophages: The involvement of the NF-κB signaling pathway

2022 ◽  
pp. 153537022110669
Author(s):  
Hassan Ahmed ◽  
Urooj Amin ◽  
Xiaolun Sun ◽  
Demetrius R Pitts ◽  
Yunbo Li ◽  
...  
Keyword(s):  
Septic Shock ◽  
Inflammatory Cytokine ◽  
Interleukin 1 ◽  
Severe Form ◽  
Necrosis Factor Alpha ◽  
Monocyte Chemoattractant Protein 1 ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Factor Alpha ◽  
Gene Expression Levels

Lipopolysaccharide (LPS), also known as endotoxin, can trigger septic shock, a severe form of inflammation-mediated sepsis with a very high mortality rate. However, the precise mechanisms underlying this endotoxin remain to be defined and detoxification of LPS is yet to be established. Macrophages, a type of immune cells, initiate a key response responsible for the cascade of events leading to the surge in inflammatory cytokines and immunopathology of septic shock. This study was undertaken to determine whether the LPS-induced inflammation in macrophage cells could be ameliorated via CDDO-IM (2-cyano-3,12 dioxooleana-1,9 dien-28-oyl imidazoline), a novel triterpenoid compound. Data from this study show that gene expression levels of inflammatory cytokine genes such as interleukin-1 beta (IL-1β), interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) were considerably increased by treatment with LPS in macrophages differentiated from ML-1 monocytes. Interestingly, LPS-induced increase in expression of pro-inflammatory cytokine levels is reduced by CDDO-IM. In addition, endogenous upregulation of a series of antioxidant molecules by CDDO-IM provided protection against LPS-induced cytotoxicity in macrophages. LPS-mediated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) transcriptional activity was also noted to decrease upon treatment with CDDO-IM in macrophages suggesting the involvement of the NF-κB signaling. This study would contribute to improve our understanding of the detoxification of endotoxin LPS by the triterpenoid CDDO-IM.

scholarly journals Thymoquinone Rescues T Lymphocytes from Gamma Irradiation-Induced Apoptosis and Exhaustion by Modulating Pro-Inflammatory Cytokine Levels and PD-1, Bax, and Bcl-2 Signaling

2016 ◽  
Vol 38 (2) ◽  
pp. 786-800 ◽  
Author(s):  
Mona Samy Guida ◽  
Ali Abd El-Aal ◽  
Yehya Kafafy ◽  
Safwat Farid Salama ◽  
Badr Mohamed Badr ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cell ◽  
Gamma Radiation ◽  
Inflammatory Cytokine ◽  
Caspase 3 ◽  
Flow Cytometry Analysis ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Radiation Induced ◽  
Gamma Irradiated

Background/Aims: Recent studies have shown that thymoquinone (TQ) exerts protective effects against ionizing radiation-induced cataracts in lens after total cranium irradiation of rats. Nevertheless, there is no published work investigated the effects of TQ on T cell development and biology in animal models exposed to gamma radiation. Therefore, in the present study we focused on determining the effects of TQ on radiation damage in the thymus, radiation-induced T cell imbalance, and on immune dysfunction induced by gamma-rays. Methods: Three groups of rats were used: a control group, a gamma-irradiated group, and a gamma-irradiated group that was orally supplemented with TQ. Serum lipid profiles, malondialdehyde (MDA) levels, and pro-inflammatory cytokine levels were measured to assess gamma irradiation-induced oxidative stress and inflammatory capacity. T cell apoptosis was evaluated by annexin V/propidium iodide staining followed by flow cytometry analysis. The expression of pro-apoptotic proteins such as Bax and caspase-3, the anti-apoptotic protein Bcl-2, and an exhaustion marker of T cells (PD-1) in CD4+ and CD8+ T cell populations was evaluated using flow cytometry analysis. The T cell architecture of the thymus gland was evaluated by histological analysis. Results: Exposure to gamma radiation increased triglyceride, cholesterol, LDL-C, MDA, TNF-α and IL-6 levels and decreased HDL-C levels. The altered lipid profile and MDA and pro-inflammatory cytokine (TNF-α and IL-6) levels induced by exposure to gamma radiation were significantly restored in TQ-treated gamma-irradiated rats. Rats exposed to gamma radiation exhibited increased exhaustion of T lymphocytes via down-regulation of Bcl-2 expression and upregulation of PD-1, Bax, and caspase-3 expression, which sensitized these cells to apoptosis. Interestingly, treatment of gamma-irradiated rats with TQ decreased T cell exhaustion and apoptosis by modulating the expression of Bcl-2, PD-1, Bax, and caspase-3. Conclusions: Our results provide evidence for the beneficial effects of TQ as an effective radioprotective candidate that enhances cellular immunity.

scholarly journals Cytokine profiles in highly active antiretroviral treatment non-adherent, adherent and naive HIV-1 infected patients in Western Kenya

2021 ◽  
Vol 21 (4) ◽  
pp. 1584-92
Author(s):  
Fauzia Musa ◽  
Nathan Shaviya ◽  
Fidelis Mambo ◽  
Collins Abonyo ◽  
Erick Barasa ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Antiretroviral Treatment ◽  
Healthy Controls ◽  
Highly Active ◽  
Cytokine Balance ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine ◽  
Hiv 1

Background: Cytokines play an important role in signaling the immune system to build an adequate immune responseagainst HIV. HIV distorts the balance between pro and anti-inflammatory cytokines causing viral replication. Highly active antiretroviral treatment (HAART) acts by trying to restore pro and anti-inflammatory cytokine balance. It is not clear how HAART non-adherence influences circulating cytokine levels. This study therefore determined cytokine levels in HAART non-adherent individuals. Methods: This cross-sectional study recruited 163 participants (51 controls, 23 HIV-1+ HAART naive, 28 HAART-adherent6 months, 19 HAART-adherent 12 months and 42 HAART non-adherent). Cytokines were analyzed by ELISA while CD4 T cells determined in 3.0 μl of whole blood using BD FACSCaliburTM and viral load in 0.2ml plasma sample using Abbott Molecular m2000sp sample preparation and m2000rt real-time amplification and detection systems (Abbott MolecularInc., Illinois, USA) according to the manufacturer’s methods. Results: IL-4, IL-6, IL-10, TNF-α and TGF-β were significantly elevated in HIV-1 HAART non-adherent compared withHIV-1 HAART adherent and healthy controls P<0.01. IFN- γ was significantly decreased in HIV-1 HAART non-adherentcompared with HIV-1 HAART adherent and healthy controls P<0.01. TNF-α and TGF-β were significantly reduced in HIV-1 HAART adherent patients at 12 months compared to those at 6 months P<0.01. IL-4 and IL-10 correlated positively withviral load. IL-4, IL-6, IL-10, TNF-α and TGF- β associated inversely with CD4 T cell counts and body mass index (BMI). Conclusion: This study established that HAART adherence is immunologically beneficial to the pro and anti-inflammatory cytokine balance milieu while non-adherence appears to cause alterations in pro and anti-inflammatory cytokines warping the balance in this dichotomy. Keywords: Cytokines; non-adherence; HAART.

Allicin Improves Hepatic Fibrosis by Regulating Notch 1 Pathway

2021 ◽  
Vol 11 (11) ◽  
pp. 2153-2161
Author(s):  
Wenxiang Li ◽  
Yajing Sun ◽  
Zaixing Wang
Keyword(s):  
Liver Function ◽  
Protein Expression ◽  
Hepatic Fibrosis ◽  
Volume Fraction ◽  
Mtor Pathway ◽  
Elisa Assay ◽  
Notch 1 ◽  
Collagen Volume Fraction ◽  
Mtor Protein ◽  
Masson Staining

Aim: To discuss effects and mechanisms of allicin in hepatic fibrosis by vivo study. Materials and methods: Dividing 45 rats into 5 groups. Evaluating pathology and fibrosis by HE and Masson staining, measuring α-SMA, Collage III, Notch 1, p-AKT and p-mTOR protein expression by IHC assay and WB assay; LC 3B protein expression were evaluated by Immunofluorescence. Liver function were measured by Elisa assay. Results: With Allicin supplement, rats’ liver function, pathological and Collagen volume fraction were significantly improved with doses-dependent in liver tissues (P < 0.05, respectively); α-SMA, Collage III, Notch 1, p-AKT and p-mTOR protein expression were significantly suppressed with doses-dependent (P < 0.05, respectively); LC 3B protein expression was significantly increased with doses-dependent (P < 0.05, respectively). Conclusion: Allicin improved hepatic fibrosis by authophagy up regulation via regulation Notrch1/AKT/mTOR pathway by vivo study.

scholarly journals Low IL-6, IL-10, and TNF-α and High IL-13 Cytokine Levels Are Associated with Severe Hepatic Fibrosis in Schistosoma mansoni Chronically Exposed Individuals

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Mable M. Mutengo ◽  
Takafira Mduluza ◽  
Paul Kelly ◽  
James C. L. Mwansa ◽  
Geoffrey Kwenda ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Hepatic Fibrosis ◽  
Endemic Region ◽  
Necrosis Factor Alpha ◽  
Group Iii ◽  
Group I ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Th17 Cytokines ◽  
Factor Alpha

Several studies have attributed the etiopathogenesis of chronic Schistosoma mansoni related hepatic fibrosis to unregulated immune responses against trapped parasite ova in the host. However, there is limited data on immune profiles associated with varying degrees of the disease in a population under chronic exposure to the parasite. We therefore investigated the role of selected T-helper (Th)1, Th2, and Th17 cytokines in relation to hepatic fibrosis severity among individuals resident in a hyper-Schistosoma mansoni endemic region of Western Zambia. Two hundred and forty-four S. mansoni infected individuals with and without fibrosis were analysed for cytokine profiles. Based on hepatic fibrosis stage as determined by ultrasound, participants were categorized into Group 0, Group I, Group II, and Group III. Cytokines were measured in S. mansoni egg stimulated whole blood culture supernatants using the BD Cytometric Bead Array kits. Compared to the nonfibrotic group, participants in the severe hepatic fibrotic group produced less interleukin- (IL-) 6, IL-10, and tumour necrosis factor-alpha (TNF-α). On the other hand, IL-13 was significantly elevated in this group compared to the nonfibrotic group (p<0.001). Our results suggest that low IL-6, IL-10, and TNF-α and high IL-13 levels may influence S. mansoni disease progression.

scholarly journals Neurotrophins, cytokines, oxidative parameters and funcionality in Progressive Muscular Dystrophies

2015 ◽  
Vol 87 (3) ◽  
pp. 1809-1818 ◽  
Author(s):  
CLARISSA M. COMIM ◽  
GISIANE B. MATHIA ◽  
ANDREZA HOEPERS ◽  
LISIANE TUON ◽  
FLÁVIO KAPCZINSKI ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Muscular Dystrophy ◽  
Inflammatory Cytokine ◽  
Serum Levels ◽  
Superoxide Dismutase Activity ◽  
Age And Gender ◽  
Tnf Α ◽  
Cytokine Levels ◽  
And Gender ◽  
Anti Inflammatory Cytokine

We investigated the levels of brain derived-neurotrophic factor (BDNF), cytokines and oxidative parameters in serum and tried to correlate them with the age and functionality of patients with Progressive Muscle Dystrophies (PMD). The patients were separated into six groups (case and controls pared by age and gender), as follows: Duchenne Muscular Dystrophy (DMD); Steinert Myotonic Dystrophy (SMD); and Limb-girdle Muscular Dystrophy type-2A (LGMD2A). DMD patients (±17.9 years old) had a decrease of functionality, an increase in the IL-1β and TNF-α levels and a decrease of IL-10 levels and superoxide dismutase activity in serum. SMD patients (±25.8 years old) had a decrease of BDNF and IL-10 levels and superoxide dismutase activity and an increase of IL-1β levels in serum. LGMD2A patients (±27.7 years old) had an decrease only in serum levels of IL-10. This research showed the first evidence of BDNF involvement in the SMD patients and a possible unbalance between pro-inflammatory and anti-inflammatory cytokine levels, along with decreased superoxide dismutase activity in serum of DMD and SMD patients.

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