• Journal of Veterinary Science
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• v.22 no.5
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• pp.61.1-61.13
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• 2021

Background: Hepatocellular carcinoma is the most common primary hepatic malignancy in humans and dogs. Several differentially expressed molecules have been studied and reported in human hepatocellular carcinoma and non-neoplastic liver lesions. However, studies on the features of canine hepatocellular carcinoma are limited, especially related to the differential characteristics of neoplastic and non-neoplastic lesions. Objectives: The study's objective was 1) to examine and evaluate the expression of arginase-1, P-glycoprotein, and cytokeratin 19 in canine liver tissues and 2) to investigate the differential features of hepatocellular carcinomas, liver tissue with non-neoplastic lesions, and paracancerous liver tissues in dogs. Methods: The expression levels of three markers underwent immunohistochemical analysis in 40 non-neoplastic liver tissues, 32 hepatocellular carcinoma tissues, and 11 paracancerous liver tissues. Scoring of each marker was performed semi-quantitatively. Results: Arginase-1 and P-glycoprotein were significantly downregulated in hepatocellular carcinoma, compared with hepatic tissues with non-neoplastic diseases (p < 0.001). Expression levels of arginase-1 and P-glycoprotein were also significantly lower in hepatocellular carcinoma than in paracancerous liver tissues (arginase-1, p = 0.0195; P-glycoprotein, p = 0.047). Few cytokeratin 19-positive hepatocytes were detected and only in one hepatocellular carcinoma and one cirrhotic liver sample. Conclusions: The results of this study suggest that downregulation of arginase-1 and P-glycoprotein is a feature of canine hepatocellular carcinoma; thus, those markers are potential candidates for use in differentiating hepatocellular carcinomas from non-neoplastic liver lesions in dogs.

• Journal of Environmental Science International
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• v.28 no.2
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• pp.249-257
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• 2019

Ulmus davidiana Nakai (UDN) has been traditionally used as a herbal medicine to treat inflammatory diseases in Korea. In the present study, we investigated the anti-ecotoxic potential of a 116 kDa glycoprotein isolated from UDN (UDN glycoprotein) in human intestinal epithelial INT-407 cells. We demonstrated that UDN glycoprotein ($20{\mu}g/mL$) could inhibit the production of lactate dehydrogenase (LDH) induced by toluene, an ecotoxic substance. Additionally, we found that the toluene-induced intestinal cytotoxicity was mediated by the phosphorylation of p38 Mitogen-Activated Protein Kinase (MAPK) via the production of intracellular Reactive Oxygen Species (ROS). The UDN glycoprotein significantly decreased the levels of ROS production and p38 MAPK activation in toluene-stimulated INT-407 cells. Moreover, the UDN glycoprotein inhibits the phosphorylation of nuclear factor-kappa B ($NF-{\kappa}B$), which is responsible for the production of LDH, in toluene-stimulated INT-407 cells. Collectively, our data indicate that UDN glycoprotein is a natural antioxidant and a modulator of ecotoxicity signaling pathways in human intestinal epithelial cells.

• Journal of the Korean Wood Science and Technology
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• v.32 no.5
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• pp.51-58
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• 2004

This study was performed to investigate compositions of inorganic elements, amino acids and glycoprotein fractions as biological substances in fruit body of Sarcodon aspratus. The fruit body of Sarcodon aspratus contained Ca, Mg, Zn, Mn, Fe, Cu, and Pb, in particular high Ca and Na. Hot water extracts consisted of 54% of polysaccharide fraction and 32.6% of protein. In amino acids composition, fourteen free amino acids were detected, mainly glutamic acid, alanine and arginine. Fifteen kinds of total amino acids were contained with major components of glutamic acid, aspartic acid, serine and threonine. Concerned to glycoprotein extraction, 95% ethyl alcohol concentration gave the highest yields with 70.6% sugar fraction, 332% glycoprotein. Different ethyl alcohol concentration resulted in different protein precipitations, and lower concentration ethyl alcohol in the range of 30 to 70% gave more than 92% of higher sugar fraction. Crude glycoprotein (GP) was fractionated by P fraction of more than MW 300,000, P-1 fraction unadsorbed by DEAE-Sephadex, P-2 fractionated from P-1 by Sepharose 2B gel chromatography and P-3 fraction adsorbed by DEAE-Sephadex. Total sugars were increased and protein contents decreased during fractionation. GP and P-3 contained glucose, galactose, mannose and fucose. GP had high glucose with high contents of glutamic acid, serine, alanine and glycine. P-3 fraction contained high mannose with aspartic acid, glutamic acid, and glycine. P-2 fraction was 700,000 MW with high glucose and fucose, and low protein of 1.1%, high amounts of aspartic acid, glutamic acid and alanine, but no mannose and no cysteine.

• Natural Product Sciences
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• v.20 no.1
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• pp.1-6
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• 2014

P-glycoprotein (P-gp) is a permeability glycoprotein also known as multidrug resistance protein 1 (MDR1). P-gp is an ATP-binding cassette (ABC) transporter that pumps various types of drugs out of cells. These transporters reduce the intracellular concentrations of drugs and disturb drug absorption. The Caco-2 cell permeability assay system is an effective in vitro system that predicts the intestinal absorption of drugs and the functions of enzymes and transporters. Rhodamine-123 (R-123) and digoxin are well-known P-gp substrates that have been used to determine the function of P-gp. Efflux of P-gp substrates by P-gp has been routinely evaluated. To date, a number of herbal medicines have been tested with Caco-2 cell permeability assay system to assess bioavailability. There are growing efforts to find phytochemicals that potentially regulate P-gp function. The Caco-2 cell permeability assay system is a primary strategy to search for candidates of P-gp inhibitors. In this mini review, we have summarized the P-gp modulation by herbal extracts, decoctions or single components from natural products using Caco-2 cell permeability assays. Many natural products are known to regulate P-gp and herbal medicines could be used in combination with conventional drugs to enhance bioavailability.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1639-1642
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• 2014

The multidrug resistance phenotype is one of the major problems in development of cancer cell resistance to chemotherapy. Some natural compounds from medicinal plants have demonstrated promising capacity in enhancing anticancer effects in drug resistant cancer cells. We aimed to investigate whether mangiferin might have an ability to re-sensitize MCF-7 breast cancer cells previously treated with short-term doxorubicin in vitro, through the modulation of efflux transporters, P-glycoprotein (P-gp), MRP1 and BCRP. We exposed MCF-7 breast cancer cells pretreated with doxorubicin for 10 days to mangiferin (10, 25 or 50 ${\mu}M$) for 96 hours. Afterwards, we evaluated influence on cell viability and level of mRNA expression of P-gp, MRP1 and BCRP. Doxorubicin given in combination with mangiferin at low concentrations (10 and 25 ${\mu}M$) failed to give significant reduction in cell viability, while at the highest concentrations, the combination significantly reduced cell viability. The mRNA expression analysis of P-gp, MRP1 and BCRP showed that mangiferin had inhibitory effects on P-gp but no effects on MRP1 and BCRP. In conclusion, we suggest that mangiferin at high concentrations can be used as chemosensitizer for doxorubicin therapy. This effect might be attributed by inhibitory effects of mangiferin on P-glycoprotein expression.

• Journal of Integrative Natural Science
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• v.4 no.1
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• pp.23-30
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• 2011

Multidrug resistance (MDR) is one of the main obstacles in the chemotherapy of cancer. MDR is associated with the over expression of P-glycoprotein (P-gp), resulting in increased efflux of chemotherapy from cancer cells. Inhibiting P-gp as a method to reverse MDR in cancer patients has been studied extensively, but the results have generally been disappointing. First-generation agents were limited by unacceptable toxicity, whereas second-generation agents had better tolerability but were confounded by unpredictable pharmacokinetic interactions and interactions with other transporter proteins. Third-generation inhibitors have high potency and specificity for P-gp. Furthermore, pharmacokinetic studies to date have shown no appreciable impact on drug metabolism and no clinically significant drug interactions with common chemotherapy agents. Third-generation P-gp inhibitors have shown promise in clinical trials. The continued development of these agents may establish the true therapeutic potential of P-gp-mediated MDR reversal.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.6831-6839
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• 2015

Multidrug resistance is a principal mechanism by which tumors become resistant to structurally and functionally unrelated anticancer drugs. Resistance to chemotherapy has been correlated with overexpression of p-glycoprotein (p-gp), a member of the ATP-binding cassette (ABC) superfamily of membrane transporters. P-gp mediates resistance to a broad-spectrum of anticancer drugs including doxorubicin, taxol, and vinca alkaloids by actively expelling the drugs from cells. Use of specific inhibitors/blocker of p-gp in combination with clinically important anticancer drugs has emerged as a new paradigm for overcoming multidrug resistance. The aim of this paper is to review p-gp regulation by dietary nutraceuticals and to correlate this dietary nutraceutical induced-modulation of p-gp with activity of anticancer drugs.

• Journal of Microbiology
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• v.34 no.1
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• pp.7-14
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• 1996

Teh baculovirus gp64 glycoprotein is a major component of the envelope of budded virus (BV) and has been shown that it plays an essential role in the infection process, especially virus-cell membrane fusion. We have cloned Autographa californica Nuclear Polyhedrosis Virus (AcNPV) gp64 protein were examined for membrane fusion activity by using a synchtium formation assay under various conditions. The optimal conditions required for inducing membrane fusion are 1) form pH 4.0 to 4.8 2) 15 min exposure of cells to acidic pH 3) at least 1 .mu.g of gp64 cloned plasmid DNA per 3 * 10$^{6}$ cells 4) and an exposure of cells to acidic pH at 72 h post-transfection. In order to investigate the role of hydrophobicity of the gp64 glycoprotein for the membrane fusion, the two leucine residues (amino acid position at 229 and 230) within hydrophobic region I were substituted to alanine by PCR-derived site-directed mutagenisis and the membrane fusion activity of the mutant was anlaysed. The gp64 glycoprotein carrying double alamine substitution mutation showed no significant difference in fusion activity. This result suggested that minor changes in hydrophobicity at the amino acid position 229 and 230 does not affect the acid-induced membrane fusion activity of the gp64 glycoprotein.

• Advances in Traditional Medicine
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• v.8 no.3
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• pp.207-214
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• 2008

In recent years, the combined use of Herbal medicines and Western drugs has been increasing. Though certain problems may occur when both types of medicines are taken together, they havenot been adequately analyzed. It was reported that anticoagulation was enhanced in addition tobleeding when patients took long-term warfarin therapy in combination with Salvia miltiorrhiza(danshen), and laxative herbs accelerate intestinal transit and interfere with the absorption. Herbal constituents, curcumin, ginsenosides, piperine, catechins and silymarin were found to beinhibitors of P-glycoprotein. St John's wort induces the intestinal expression of P-glycoprotein. Anthraquinone, quercetin and coumarins were found to be a potent inhibitor of P-450. Glycyrrhizin or liquorice extracts, Garlic and St John's wort are a potent inducer of CYP3A4. This review provides a critical overview of interactions between herbal medicines and other drugs. Hence, it is necessary to study the pharmacodynamic and pharmacokinetic interactions of many herbal medicines between western drugs.

• Korean Journal of Food Science and Technology
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• v.37 no.4
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• pp.624-630
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• 2005

Glycoprotein (60 kDa) isolated from Ficus Carica Linnoeus (FCL glycoprotein) was examined by evaluating its hypolipidemic effects on plasma cholesterol levels and hepatic detoxicant enzyme activities in ICR mice. FCL glycoprotein $(100{\mu}g/mL)$ had strong scavenging activities (38%) against lipid peroxyl radicals. When mice were treated with Triton WR-1339 (400 mg/kg), levels of total cholesterol (TC) and low-density lipoprotein (LDL)-cholesterol in plasma significantly increased by 53.9 and 47.5 mg/dL, respectively, compared to the control, whereas, when pretreated with FCL glycoprotein $(100{\mu}g/mL)$, decreased remarkably by 55.4, and 47,0 mg/dL, compared to Triton WR-1339 treatment alone. Interestingly, high-density lipoprotein (HDL)-cholesterol level did not change. Body and liver weights did not change significantly after Triton WR-1339 treatment in presence of FCL glycoprotein. FCL glycoprotein $(100{\mu}g/mL)$ stimulated activities of antioxidative detoxicant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), whereas GPx activity significantly increased compared to the control. These results suggest FCL glycoprotein has abilities to scavenge lipid peroxyl radicals, lower plasma lipid levels, and stimulate detoxicant enzyme activity in mouse liver.