• Asian-Australasian Journal of Animal Sciences
• /
• 제27권9호
• /
• pp.1303-1310
• /
• 2014

A 12 week growth study was carried out to investigate the supplemental effects of dietary garlic powder (GP) on growth, feed utilization and whole body composition changes of fingerling sterlet sturgeon Acipenser ruthenus (averaging weight, 5.5 g). Following a 24-h fasting, 540 fish were randomly distributed to each of 18 tanks (30 fish/tank) under a semi-recirculation freshwater system. The GP of 0.5% (GP0.5), 1% (GP1), 1.5% (GP1.5), 2% (GP2) and 3% (GP3) was added to the control diet (GP0) containing 43% protein and 16% lipid. After the feeding trial, weight gain (WG) of fish fed GP1.5, GP2 and GP3 were significantly higher (p<0.05) than those of fish fed GP0, GP0.5 and GP1. Feed efficiency and specific growth rate (SGR) showed a similar trend to WG. Protein efficiency ratio of fish fed GP1.5, GP2, and GP3 were significantly higher (p<0.05) than those of fish groups fed the other diets. A significant difference (p<0.05) was found in whole body composition (moisture, crude protein, crude lipid, ash, and fiber) of fish at the end of the experiment. Significantly higher (p<0.05) protein and lipid retention efficiencies (PRE and LRE) were also found in GP1.5, GP2, and GP3 groups. Broken-line regression model analysis and second order polynomial regression model analysis relation on the basis of SGR and WG indicated that the dietary optimal GP level could be greater than 1.77% and 1.79%, but less than 2.95% and 3.18% in fingerling sterlet sturgeon. The present study suggested that dietary GP for fingerling sterlet sturgeon could positively affect growth performance and protein retention.

• Journal of Pharmaceutical Investigation
• /
• 제41권6호
• /
• pp.381-386
• /
• 2011

Multi-drug resistance (MDR) has been known as a major hurdle in cancer chemotherapy. One of the most clinically significant causes of MDR was the efflux of anticancer agents mediated by p-glycoprotein (p-gp) over-expressed in MDR cancer cells. To overcome MDR, there have been several strategies such as co-administration with p-gp inhibitors and encapsulation of anticancer drugs into drug delivery systems. In the present study, curcumin was evaluated for its potential as p-gp inhibitor and MDR reversal activity when combined with paclitaxel incorporated into lipid nanoparticles (PTX/LN). Western blot assay showed curcumin did not modulate the level of p-gp expression in MCF-7/ADR which is a MDR variant of human breast cancer cell line, MCF-7, and over-expresses p-gp. However, curcumin inhibited p-gp-mediated efflux of calcein in a dose-dependent manner even though it showed lower activity compared to verapamil, a well-known p-gp inhibitor. Incorporation of paclitaxel into lipid nanoparticles partially recovered the anticancer activity of paclitaxel in MCF-7/ADR. The combined use of curcumin and PTX/LN exhibited further full reversal of MDR, suggesting susceptibility of PTX/LN to the efflux system. In conclusion, combined approach of using p-gp inhibitors and incorporation of the anticancer agents into nano-delivery systems would be an efficient strategy to overcome MDR.

• Archives of Pharmacal Research
• /
• 제26권9호
• /
• pp.768-772
• /
• 2003

Tween 80 (Polysorbate 80) is a hydrophilic nonionic surfactant commonly used as an ingredient in dosing vehicles for pre-clinical in vivo studies (e.g., pharmacokinetic studies, etc.). Tween 80 increased apical to basolateral permeability of digoxin in Caco-2 cells suggesting that Tween 80 is an in vitro inhibitor of P-gp. The overall objective of the present study was to investigate whether an inhibition of P-gp by Tween 80 can potentially influence in vivo absorption of P-gp substrates by evaluating the effect of Tween 80 on the disposition of digoxin (a model P-gp substrate with minimum metabolism) after oral administration in rats. Rats were dosed orally with digoxin (0.2 mg/kg) formulated in ethanol (40％, v/v) and saline mixture with and without Tween 80 (1 or 10％, v/v). Digoxin oral AUC increased 30 and 61％ when dosed in 1 ％ and 10％ Tween 80, respectively, compared to control (P＜0.05). To further examine whether the increase in digoxin AUC after oral administration of Tween 80 is due, in part, to a systemic inhibition of digoxin excretion in addition to an inhibition of P-gp in the GI tract, a separate group of rats received digoxin intravenously (0.2 mg/kg) and Tween 80 (10％ v/v) orally. No significant changes in digoxin IV AUC was noted when Tween 80 was administered orally. In conclusion, Tween 80 significantly increased digoxin AUC and Cmax after oral administration, and the increased AUC is likely to be due to an inhibition of P-gp in the gut (i.e., improved absorption). Therefore, Tween 80 is likely to improve systemic exposure of P-gp substrates after oral administration. Comparing AUC after oral administration with and without Tween 80 may be a viable strategy in evaluating whether oral absorption of P-gp substrates is potentially limited by P-gp in the gut.

• 통합자연과학논문집
• /
• 제4권1호
• /
• pp.23-30
• /
• 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.

• Bulletin of the Korean Chemical Society
• /
• 제35권8호
• /
• pp.2317-2325
• /
• 2014

P-glycoprotein (P-gp) is a member of the ATP-Binding Cassette transporter superfamily and mediates transmembrane efflux of many drugs. Since it is involved in multi-drug resistance activity in various cancer cells, the development of P-gp inhibitor is one of the major concerns in anticancer therapy. Human P-gp protein has at least two "functional" drug binding sites that are called "H" site and "R" site, hence it has multi-binding-specificities. Though the amino acid residues that constitute in drug binding pockets have been proposed by previous experimental evidences, the shapes and the binding poses are not revealed clearly yet. In this study, human P-gp structure was built by homology modeling with available crystal structure of mouse P-gp as a template and docking simulations were performed with inhibitors such as verapamil, hoechst33342, and rhodamine123 to construct the interaction between human P-gp and its inhibitors. The docking simulations were performed 500 times for each inhibitor, and then the interaction frequency of the amino acids at the binding poses was analyzed. With the analysis results, we proposed highly contributing residues that constitute binding pockets of the human P-gp for the inhibitors. Using the highly contributing residues, we proposed the locations and the shapes of verapamil binding site and "R" site, and suggested the possible position of "H" site.

• 통합자연과학논문집
• /
• 제6권4호
• /
• pp.205-210
• /
• 2013

Human P-gp is a protein responsible for the multidrug resistance (MDR) and causes failure of cancer chemotherapy. Till date no X-ray crystal structure is reported for this membrane protein, which hampers active research in the field. We performed homology modeling to develop three dimensional (3D) model of P-gp, and docking studies of the verapamil and curcumin have been performed to gain insight into the interaction mechanism between inhibitors and P-gp. It was identified that the inhibitors docked into the upper part of P-gp and interacted through the hydrophobic interactions.

• Journal of Pharmaceutical Investigation
• /
• 제40권5호
• /
• pp.269-275
• /
• 2010

P-gp plays a critical role in drug disposition and represents a mechanism for the development of multidrug resistance. Flavonoids, a major class of natural compounds widely present in foods and herbal products, have been shown to inhibit P-gp. Therefore, the aim of this study was to identify new candidate chemosensitizers by screening various plant extracts. The ability of natural plant extracts to inhibit P-gp activity was assessed by measuring cellular accumulation of calcein AM, daunorubicin and vincristine in P-gp overexpressing MDCKII-MDR1 cells. Among more than 800 plant extracts, eight were found to inhibit P-gp activity. Curcuma aromatica extract produced greatest inhibition, followed by Curcuma longa and Dalbergia odorifera extracts. Extracts of Aloe ferox, Curcuma zedoariae rhizome, Zanthoxylum planispinum, and Ageratum conyzoides showed moderate inhibitory effects. Curcumin and quercetin exhibited similar inhibition of P-gpmediated efflux of daunorubicin and vincristine, and flavones had a lesser effect. When chemosensitizing effect was evaluated by measuring daunorubicin sensitivity to MDCKII-MDR1 cells in the presence of natural plant extracts, Curcuma aromatica showed the most potent chemosensitizing effect based on daunorubicin cytotoxicity. In conclusion, natural plant extracts such as Curcuma aromatica can potently inhibit P-gp activity and may have potential as a novel chemosensitizers.

• Current Research on Agriculture and Life Sciences
• /
• 제11권
• /
• pp.1-9
• /
• 1993

신문 용지용(用) 지료(紙料)의 조성조건(調成條件)에 따른 보류(保留)의 변화를 연구(硏究)한 결과 다음과 같은 사실을 알수가 있었다. 1. 온도(溫度)의 상승(上昇)에 따라 보류(保留)는 지료(紙料)의 종류 및 배합비(配合比)에 관계없이 감소(減少)하였으며 GP보다 DIP가 온도(溫度)변화에 민감(敏感)하였다. 2. pH변화에 따른 보류(保留)의 변화는 GP와 DIP 및 GP/DIP=50/50 모두 pH5에서 보류(保留)가 가장 높았으며 pH 5보다 높거나 낮으면 감소(減少)하였고 DIP가 GP보다 감소(減少)가 적었다. 3. Alum첨가(添加)에 따른 보류(保留)의 변화는 GP와 GP/DIP=50/50의 경우 2% 첨가(添加)에서 보류(保留)가 가장 높았고 DIP는 3% 첨가(添加)에서 가장 높았다. 4. 보류(保留)는 지료(紙料)의 응집작용(凝集作用)과 밀접한 관련이 있었다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권5호
• /
• pp.2379-2383
• /
• 2012

Objective: To investigate possible signal pathway involvement in multi-drug resistant P-glycoprotein (P-gp) expression induced by cyclooxygenase-2 (COX-2) in a human gastric adenocarcinoma cell line stimulated with pacliaxel (TAX). Methods: The effects of TAX on SGC7901 cell growth with different doses was assessed by MTT assay, along with the effects of the COX-2 selective inhibitor NS-398 and the nuclear factor-KB (NF-KB) pathway inhibitor pyrrolidine dithiocarbamate (PDTC). Influence on COX-2, NF-KB p65 and P-gp expression was determined by Western blotting. Results: TAX, NS-398 and PDTC all reduced SGC7901 growth, with dosedependence. With increasing dose of TAX, the expression of COX-2, p65 and P-gp showed rising trends, this being reversed by NS-398. PDTC also caused decrease in expression of p65 and P-gp over time. Conclusion: COX-2 may induce the expression of P-gp in SGC7901 cell line via the NF-kappa B pathway with pacliaxel stimulation.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권16호
• /
• pp.6831-6839
• /
• 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.