scholarly journals Effects of Curcuma comosa Roxb. Extract on the Expression of CYP450s in Immortalized Hepatocyte-like Cells (imHC)

2021 ◽  
Vol 18 (2) ◽  
Author(s):  
Petdao PETCHUAY ◽  
Yindee KITIYANANT ◽  
Patoomratana TUCHIDA ◽  
Suradej HONGENG ◽  
Khanit SA-NGIAMSUNTORN ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Hepg2 Cells ◽  
Inhibitory Effect ◽  
Detoxification Enzymes ◽  
Duration Of Treatment ◽  
Drug Induced ◽  
Curcuma Comosa ◽  
Expression Levels ◽  
Metabolism Enzymes ◽  
Mrna Expression Levels

Hepatocytes are the most abundant liver cells that produce biotransformation enzymes, including phase I metabolism enzymes and cytochrome P450s (CYP450s). These enzymes are induced or suppressed by several drugs and chemicals. Here, immortalized hepatocyte-like cells (imHC) were applied as a novel hepatocyte to study the CYP450 enzyme expression induced by a Thai folk herb, Curcuma comosa Roxb. (C. comosa). The results demonstrated that the mRNA expression levels were dependent on cell cultivation conditions, the extract's concentration, and the duration of treatment. In the 3-day cultivation, 1 µg/mL C. comosa extract upregulated the mRNA expression levels of CYP1A1, CYP1A2, CYP2B6, CYP2C9, CYP2D6, CYP2E1 and CYP3A4 in imHC, after treatment for 48 h, which was comparable to the expression levels of those genes in HepG2 cells. In addition, C. comosa increased CYP3A4 protein expression in both imHC and HepG2 cells. Furthermore, 1 µg/mLC. comosa could neutralize erythromycin's inhibitory effect, a specific CYP3A4 inhibitor, on CYP3A4 enzyme activity. In conclusion, imHC exhibited several detoxification enzymes, and this cell could be used to replace hepatic carcinoma cells in hepatotoxic studies. The function of C. comosa as a CYP enzyme-inducing agent indicates a promising treatment for the prevention of drug-induced hepatotoxicity by activating detoxification enzymes.

The fungicide difenoconazole alters mRNA expression levels of human CYP3A4 in HepG2 cells

2017 ◽  
Vol 15 (4) ◽  
pp. 673-678 ◽  
Author(s):  
Liumeng Pan ◽  
Liping Lu ◽  
Jingpeng Wang ◽  
Cunwu Zheng ◽  
Yujie Fu ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Hepg2 Cells ◽  
Expression Levels ◽  
Mrna Expression Levels

scholarly journals Commiphora Myrrha (Nees) Engl. Resin Extracts Induce Phase-I Cytochrome P450 2C8, 2C9, 2C19, and 3A4 Isoenzyme Expressions in Human Hepatocellular Carcinoma (HepG2) Cells

2020 ◽  
Author(s):  
Zeyad Alehaideb ◽  
Ghada Alatar ◽  
Atef Nehdi ◽  
Abeer Albaz ◽  
Hamad Al-Eidi ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Protein Expression ◽  
Phase I ◽  
Mrna Expression ◽  
Crude Extract ◽  
Hepg2 Cells ◽  
Aqueous Extracts ◽  
Expression Levels ◽  
Gene And Protein Expression ◽  
Mrna Expression Levels

Abstract Background: Commiphora myrrha (Nees) Engl. (C. myrrha) resin is one of the oldest Middle Eastern herbal medicine used for treatment and prevention of numerous diseases. This resin is prepared in different methods and widely consumed among Saudi Arabian patients. Despite its popularity, no studies have been done on potential modulation effects of C. myrrha resin extracts on human cytochrome P450 (CYP) drug-metabolizing enzyme expression.Methods: The C. myrrha extracts were prepared by two different methods of sonication and boiling resembling the most popular traditional preparations of maceration and decoction, respectively. Both extracts were fingerprinted using high-performance liquid chromatography equipped with ultra-violet detector (HPLC-UVD). The viability of HepG2 cells treated with aqueous extracts was determined using Promega CellTiter-Glo® assay in order to select the efficient and non-toxic resin extract concentrations for phase-I metabolic isoenzyme expression analysis. The isoenzyme gene and protein expression levels of CYP 2C8, 2C9, 2C19, and 3A4 were measured using reverse transcription-quantitative polymerase chain reaction and Western blot technologies, respectively. Results: The HPLC-UVD fingerprinting revealed different chromatograms for C. myrrha extracts indicating possible differences in their modulation effects on CYP expression. Both aqueous extracts were toxic to HepG2 cells when tested at concentrations exceeding 150 µg/ml of dry crude extract. The CYP 2C8, 2C9, and 2C19 mRNA expression levels increased up to 4.0-fold after cell treatment with concentrations ranging from 1 to 30 µg/ml C. myrrha extracts, as compared with the untreated cells. However, the modulation of CYP3A4 mRNA expression levels was only significant at 30 µg/ml of crude extract exceeding the 2.0-fold cutoff. The up-regulation of CYP mRNA expression levels induced by C. myrrha extracts was confirmed at the CYP protein expression levels as well. Conclusions: The C. myrrha aqueous extracts modulate CYP 2C8, 2C9, 2C19, and 3A4 gene expression at clinically-relevant concentrations regardless of preparation methods. Further in vitro and in vivo experiments are required for the establishment of herb-drug interaction profile for these traditional medicinal resin extracts.

scholarly journals The role of CXCR3 and its ligands expression in Brucellar spondylitis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Xin Hu ◽  
Xiaoqian Shang ◽  
Liang Wang ◽  
Jiahui Fan ◽  
Yue Wang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Healthy Controls ◽  
Inflammatory Infiltration ◽  
Peripheral Blood Mononuclear ◽  
Expression Levels ◽  
Inflammatory Damage ◽  
Ifn Γ ◽  
Mrna Expression Levels

Abstract Aim Brucellar spondylitis (BS) is one of the most serious complications of brucellosis. CXCR3 is closely related to the severity of disease infection. This research aimed to study the degree of BS inflammatory damage through analyzing the expression levels of CXCR3 and its ligands (CXCL9 and CXCL10) in patients with BS. Methods A total of 29 BS patients and 15 healthy controls were enrolled. Real-Time PCR was used to detect the mRNA expression levels of IFN-γ, CXCR3, CXCL9 and CXCL10 in peripheral blood mononuclear cells (PBMCs) of BS patients and healthy controls. Hematoxylin-Eosin staining was used to show the pathological changes in BS lesion tissues. Immunohistochemistry staining was used to show the protein expression levels of Brucella-Ab, IFN-γ, CXCR3, CXCL9 and CXCL10 in BS lesion tissues. At the same time, ELISA was used to detect the serum levels of IFN-γ, CXCL9 CXCL10 and autoantibodies against CXCR3 in patients with BS. Results In lesion tissue of BS patients, it showed necrosis of cartilage, acute or chronic inflammatory infiltration. Brucella-Ab protein was abundantly expressed in close lesion tissue. And the protein expression levels of IFN-γ, CXCR3 and CXCL10 were highly expressed in close lesion tissue and serum of BS patients. At the same time, the mRNA expression levels of IFN-γ, CXCR3 and CXCL10 in PBMCs of BS patients were significantly higher than those in controls. Conclusion In our research, the expression levels of IFN-γ, CXCR3 and its ligands were significantly higher than those in controls. It suggested that high expression levels of IFN-γ, CXCR3 and its ligands indicated a serious inflammatory damage in patients with BS.

Unilateral labyrinthectomy induced changes on GDNF receptor complex proteins in the rat medial vestibular nuclei

2007 ◽  
Vol 16 (4-5) ◽  
pp. 171-177
Author(s):  
Adrian Lozada ◽  
Kaj Karlstedt ◽  
Pertti Panula ◽  
Antti A. Aarnisalo
Keyword(s):  
Mrna Expression ◽  
Vestibular Nucleus ◽  
Medial Vestibular Nucleus ◽  
Receptor Complex ◽  
Trophic Effect ◽  
Expression Levels ◽  
Protein Levels ◽  
Unilateral Labyrinthectomy ◽  
Ganglion Neurons ◽  
Mrna Expression Levels

In the auditory periphery, GDNF has been shown to have a trophic effect to spiral ganglion neurons, both during development and in adult animals. We have studied the effect of unilateral labyrinthectomy (UL) on protein levels and expression of GDNF multicomponent receptor complex: the ret tyrosine kinase and coreceptor GFRα-1 in the medial vestibular nucleus of the adult rat. GFRα-1 protein levels display an increasing trend in ipsilateral medial vestibular nucleus culminating at 48 h post UL. On the other hand, GFRα-1 mRNA expression levels in ipsi- and contralateral medial vestibular nucleus show a steadily decreasing trend that is significant at 1 week post-lesion. Protein levels for c-Ret isoforms also show an initial bilateral decreasing trend that ceases at 48 h in ipsilateral medial vestibular nucleus but persists on the contralateral side. c-Ret mRNA expression levels show a significant decrease at 4 h post UL followed by another significant decrease 1 week post UL. Our data would suggest that neurotrophins belonging to the GDNF family are involved in this model of post-lesional CNS plasticity.

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