scholarly journals Mycelium Polysaccharides from Termitomyces albuminosus Attenuate CCl4-Induced Chronic Liver Injury Via Inhibiting TGFβ1/Smad3 and NF-κB Signal Pathways

2019 ◽  
Vol 20 (19) ◽  
pp. 4872 ◽  
Author(s):  
Zhao ◽  
Li ◽  
Feng ◽  
Zhang ◽  
Yuan ◽  
...  
Keyword(s):  
Liver Injury ◽  
Chronic Liver ◽  
Molar Ratio ◽  
Gas Chromatography Mass Spectrometry ◽  
Signal Pathways ◽  
Chronic Liver Injury ◽  
Potential Health ◽  
Anti Inflammatory

A major fraction (MPT-W), eluted by deionized water, was extracted from mycelium polysaccharides of Termitomyces albuminosus (MPT), and its antioxidant, anti-fibrosis, and anti-inflammatory activities in CCl4-induced chronic liver injury mice, as well as preliminary characterizations, were evaluated. The results showed that MPT-W was a polysaccharide of α- and β-configurations containing xylose (Xyl), fucose (Fuc), mannose (Man), galactose (Gal), and glucose (Glc) with a molar ratio of 0.29:8.67:37.89:35.98:16.60 by gas chromatography-mass spectrometry (GC-MS), Fourier transform infrared (FT-IR) spectroscopy. Its molecular weight (Mw), obtained by high-performance gel permeation chromatography (HPGPC), was 1.30 × 105 Da. The antioxidant assays in vitro showed that MPT-W displayed scavenging free-radical abilities. Based on the data of in vivo experiments, MPT-W could inhibit TGFβ1/Smad3 and NF-κB pathways; decrease the level and activity of cytochrome P4502E1 (CYP2E1), malonaldehyde (MDA) and serum enzyme; activate the HO-1/Nrf2 pathway; and increase antioxidant enzymes to protect the liver in CCl4-induced chronic liver injury mice. Therefore, MPT-W could be a potentially natural and functional resource contributing to antioxidant, hepatoprotective, and anti-inflammatory effects with potential health benefits.

Liver 5-HT7 receptors: A novel regulator target of fibrosis and inflammation-induced chronic liver injury in vivo and in vitro

2017 ◽  
Vol 43 ◽  
pp. 227-235 ◽  
Author(s):  
Beyzagul Polat ◽  
Zekai Halici ◽  
Elif Cadirci ◽  
Emre Karakus ◽  
Yasin Bayir ◽  
...  
Keyword(s):  
Liver Injury ◽  
Chronic Liver ◽  
Chronic Liver Injury

scholarly journals Target prediction of anti-chronic liver injury of Kangxian pill based on network pharmacology

2021 ◽  
Author(s):  
Min Cao ◽  
Yiyang Wang ◽  
Haizhao Liu ◽  
Xueqian Dong ◽  
Mengxue Dong ◽  
...  
Keyword(s):  
Liver Injury ◽  
Protein Expression ◽  
Molecular Mechanisms ◽  
Target Prediction ◽  
Vital Role ◽  
Chronic Liver ◽  
Network Pharmacology ◽  
Chronic Liver Injury ◽  
Tnf Α

Abstract BackgroundThe present study aimed to validate the protect effect of Kangxian pill (KXP) on chronic hepatic injury (CHI) and investigate its potential mechanism by network pharmacology-based prediction and experimental verification in vivo . MethodsThe effect of KXP in the treatment of carbon tetrachloride (CCL 4 )-induced CHI is investigated by calculating liver index, measuring AST and ALT levels and performing HE staining. Targets of active ingredients of KXP were predicted in TCSMP and targets of chronic liver injury were searched in DisGeNET, OMIM and GeneCards databases. We obtain some pivotal targets of KXP for the treatment of CHI by intersecting the targets of KXP and CHI. Subsequently, we performed gene ontology (GO) functional and pathways enrichment analyses, as well as conducted networks based on potential targets to determine the core targets and representative pathways.We further validated expressions of IL-6, IL-1β, TNF-α, Bax, Bcl2, PI3K, Akt, and pAkt according to the potential molecular mechanisms analyzed based on network pharmacology analysis.ResultsThe results showed that the levels of AST and ALT in serum decreased after treatment with KXP. HE staining also revealed that KXP could improve hepatocyte abnormality in vivo . A total of 81 potential targets of KXP in the treatment of CHI were identified through network pharmacology analysis. After integrating potential targets, function enrichment, representative pathways and networks, we identified PI3K, AKT1,BCL2, TNF-α, IL-1β, and IL-6 as potential targets, which may play a vital role in the KXP treatment. The experimental results also showed that KXP could down-regulate the mRNA and protein expression of IL-1β, IL-6, TNF-α and Bax, and up-regulate the PI3K and p-Akt protein expression i n vivo .ConclusionsOur results suggest that KXP could alleviate CHI through regulating inflammation and apoptosis and provide deep insight into the hepato-protective mechanisms.

Formulation, Optimization, in Vitro and in Vivo Investigation of Ketoprofen - Fumaric Acid Co-crystal for the Solubility Enhancement of Ketoprofen

2021 ◽  
Author(s):  
Meenakshi Bhatia ◽  
Ashwani Kumar ◽  
Vikas Verma ◽  
Snehlata Yadav ◽  
SUNITA DEVI
Keyword(s):  
Fumaric Acid ◽  
Protein Denaturation ◽  
Research Work ◽  
Molar Ratio ◽  
Scanning Calorimetry ◽  
Standard Drug ◽  
Anti Inflammatory ◽  
Analgesic Activities

Abstract The present piece of research work is framed as improving the solubility of ketoprofen by forming co-crystal using fumaric acid as a coformer. Co-crystal of ketoprofen and fumaric acid were prepared by simple solvent assisted grinding. The independent variables i.e. drug and coformer were mixed in 1:1 molar ratio and dependent variables were assumed to be solubility and % drug release. Differential scanning calorimetry, fourier transform infrared spectroscopy, X-ray diffraction, nuclear magnetic resonance and scanning electron microscopy techniques were used to characterize the preparation of optimized batch of co-crystal and further, evaluated for in-vitro and in-vivo anti-inflammatory and analgesic activities. Based on results of solubility and dissolution rate studies the drug showed 4-5 fold improvement in both the properties on co-crystallisation. The values of Gibbs free energy are negative at all levels of carrier demonstrating spontaneity of drug solubilization process. The IC50 value of optimized batch of co-crystal formulation and pure drug was observed as 327.33 µg/ml and 556.11 µg/ml, respectively, demonstrating that co-crystal formulation possesses more percentage protection against protein denaturation than the drug ketoprofen. In-vivo (anti-inflammatory and analgesic) activities revealed that optimized batch of co-crystal formulation delivered a rapid pharmacological response in wistar rats and albino mice when compared with standard drug.

scholarly journals Raf Kinase Inhibitory Protein Down-Expression Exacerbates Hepatic Fibrosis In Vivo and In Vitro

2016 ◽  
Vol 40 (1-2) ◽  
pp. 49-61 ◽  
Author(s):  
Quanfang Huang ◽  
Chunhong Liang ◽  
Ling Wei ◽  
Jinlan Nie ◽  
Shengjuan Lu ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Liver Injury ◽  
Hepatic Fibrosis ◽  
Chronic Liver ◽  
Chronic Liver Injury ◽  
Inhibitory Protein ◽  
Raf Kinase ◽  
Raf Kinase Inhibitory Protein ◽  
Liver Tissues

Background/Aims: Raf kinase inhibitory protein (RKIP) is closely associated with numerous tumors and participates in their development through regulating the growth, apoptosis, invasion and metastasis of tumor cells. However, the role of RKIP in chronic liver injury and particularly in liver fibrosis is still unclear. Methods: In the present study, hepatic fibrosis was induced by porcine serum (PS) in rats and primary hepatic stellate cells (HSCs) were isolated from rat livers. Moreover, locostatin was used to interfere with RKIP expression. Results: RKIP expression was significantly inhibited by locostatin in both liver tissues of rats and primary HSCs. Down-regulating RKIP expression resulted in serious liver injury, extensive accumulation of collagen, and significant increase in the levels of ALT, AST and TNF-α during liver fibrosis in rats. Moreover, down-regulating RKIP significantly promoted HSCs proliferation and colony formation in vitro. Reduced RKIP significantly increased the production of collagen and the level of α-SMA as well as the expression of MMP-1 and MMP-2 in both liver tissues and primary HSCs. Furthermore, down-regulating RKIP promoted the activation of the ERK and TLR4 signaling pathways. Conclusion: Our findings clearly indicate an inverse correlation between RKIP level and the degree of the liver injury and fibrosis. The decrease in RKIP expression may exacerbate chronic liver injury and liver fibrosis.

Inhibition of monoacylglycerol lipase, an anti-inflammatory and antifibrogenic strategy in the liver

Gut ◽  
2018 ◽  
Vol 68 (3) ◽  
pp. 522-532 ◽  
Author(s):  
Aida Habib ◽  
Dina Chokr ◽  
JingHong Wan ◽  
Pushpa Hegde ◽  
Morgane Mabire ◽  
...  
Keyword(s):  
Liver Injury ◽  
Cannabinoid Receptor ◽  
Chronic Liver ◽  
Autophagic Flux ◽  
Monoacylglycerol Lipase ◽  
Chronic Liver Injury ◽  
Fibrosis Progression ◽  
Duct Ligation ◽  
Anti Inflammatory ◽  
The Impact

ObjectiveSustained inflammation originating from macrophages is a driving force of fibrosis progression and resolution. Monoacylglycerol lipase (MAGL) is the rate-limiting enzyme in the degradation of monoacylglycerols. It is a proinflammatory enzyme that metabolises 2-arachidonoylglycerol, an endocannabinoid receptor ligand, into arachidonic acid. Here, we investigated the impact of MAGL on inflammation and fibrosis during chronic liver injury.DesignC57BL/6J mice and mice with global invalidation of MAGL (MAGL-/-), or myeloid-specific deletion of either MAGL (MAGLMye-/-), ATG5 (ATGMye-/-) or CB2 (CB2Mye-/-), were used. Fibrosis was induced by repeated carbon tetrachloride (CCl4) injections or bile duct ligation (BDL). Studies were performed on peritoneal or bone marrow-derived macrophages and Kupffer cells.ResultsMAGL-/- or MAGLMye-/- mice exposed to CCl4 or subjected to BDL were more resistant to inflammation and fibrosis than wild-type counterparts. Therapeutic intervention with MJN110, an MAGL inhibitor, reduced hepatic macrophage number and inflammatory gene expression and slowed down fibrosis progression. MAGL inhibitors also accelerated fibrosis regression and increased Ly-6Clow macrophage number. Antifibrogenic effects exclusively relied on MAGL inhibition in macrophages, since MJN110 treatment of MAGLMye-/- BDL mice did not further decrease liver fibrosis. Cultured macrophages exposed to MJN110 or from MAGLMye-/- mice displayed reduced cytokine secretion. These effects were independent of the cannabinoid receptor 2, as they were preserved in CB2Mye-/- mice. They relied on macrophage autophagy, since anti-inflammatory and antifibrogenic effects of MJN110 were lost in ATG5Mye-/- BDL mice, and were associated with increased autophagic flux and autophagosome biosynthesis in macrophages when MAGL was pharmacologically or genetically inhibited.ConclusionMAGL is an immunometabolic target in the liver. MAGL inhibitors may show promising antifibrogenic effects during chronic liver injury.

scholarly journals Serratiopeptidase Niosomal Gel with Potential in Topical Delivery

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Ujwala A. Shinde ◽  
Shivkumar S. Kanojiya
Keyword(s):  
Ex Vivo ◽  
Skin Permeation ◽  
Entrapment Efficiency ◽  
Molar Ratio ◽  
Fourfold Increase ◽  
Surfactant Vesicles ◽  
Anti Inflammatory ◽  
Niosomal Gel

The objective of present study was to develop nonionic surfactant vesicles of proteolytic enzyme serratiopeptidase (SRP) by adapting reverse phase evaporation (REV) technique and to evaluate the viability of SRP niosomal gel in treating the topical inflammation. The feasibility of SRP niosomes by REV method using Span 40 and cholesterol has been successfully demonstrated in this investigation. The entrapment efficiency was found to be influenced by the molar ratio of Span 40 : cholesterol and concentration of SRP in noisome. The developed niosomes were characterized for morphology, particle size, and in vitro release. Niosomal gel was prepared by dispersing xanthan gum into optimized batch of SRP niosomes. Ex vivo permeation and in vivo anti-inflammatory efficacy of gel formulation were evaluated topically. SRP niosomes obtained were round in nanosize range. At Span 40 : cholesterol molar ratio 1 : 1 entrapment efficiency was maximum, that is, 54.82% ± 2.08, and showed consistent release pattern. Furthermore ex vivo skin permeation revealed that there was fourfold increase in a steady state flux when SRP was formulated in niosomes and a significant increase in the permeation of SRP, from SRP niosomal gel containing permeation enhancer. In vivo efficacy studies indicated that SRP niosomal gel had a comparable topical anti-inflammatory activity to that of dicolfenac gel.

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