• Title/Summary/Keyword: Reverse pharmacology

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Residual determination of Ceftiofur in Raw Bovine Milk by Liquid Chromatography-Electrospray Mass Spectrometry

  • Lim, Jong-hwan;Park, Byung-kwon;Kim, Myoung-seok;Jang, Beom-Su;Kim, Doo;Yun, Hyo-in
    • Korean Journal of Veterinary Research
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    • v.44 no.3
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    • pp.367-371
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    • 2004
  • This report describes the determination of ceftiofur residues in milk from treatment of lactating dairy cattle by intramuscular injection of three consecutive daily doses of about 1 mg /kg BW, the recommended label dosing. The separation of ceftiofur was achieved on $C_1_8$ reverse phase column. The mobile phase consisted of 0.1% trifluoracetic acid in water (A) and 0.05% acetic acid in acetonitrile (B) and grediently flowed at the flow rate of 0.4 mL/min. As a result of analysis of blank raw bovine milk samples, matrix interference was not shown. Limit of detection and limit of quantitaion was 0.5 ng/mL and 1 ng/mL, respectively. The values of precision and recovery satisfied the guideline of National Veterinary Research and Quarantine Service (NVRQS, Korea). The mean residual concentration of ceftiofur in milk did not exceed 3.71 ng/mL when ceftiofur was administered intramuscularly to lactating dairy cattle for 3 consecutive days at 1 mg/kg of BW per day. It is much lower than the proposed MRL (100 ng/mL) of ceftiofur in milk.

AMP-activated protein kinase: An emerging target for ginseng

  • Jeong, Kyong Ju;Kim, Go Woon;Chung, Sung Hyun
    • Journal of Ginseng Research
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    • v.38 no.2
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    • pp.83-88
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    • 2014
  • The adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a key sensor of cellular energy. Once activated, it switches on catabolic pathways generating adenosine triphosphate (ATP), while switching off biosynthetic pathways consuming ATP. Pharmacological activation of AMPK by metformin holds a therapeutic potential to reverse metabolic abnormalities such as type 2 diabetes and nonalcoholic fatty liver disease. In addition, altered metabolism of tumor cells is widely recognized and AMPK is a potential target for cancer prevention and/or treatment. Panax ginseng is known to be useful for treatment and/or prevention of cancer and metabolic diseases including diabetes, hyperlipidemia, and obesity. In this review, we discuss the ginseng extracts and ginsenosides that activate AMPK, we clarify the various mechanisms by which they achieve this, and we discuss the evidence that shows that ginseng or ginsenosides might be useful in the treatment and/or prevention of metabolic diseases and cancer.

Effect of Chrysin on Gene Expression and Production of MUC5AC Mucin from Cultured Airway Epithelial Cells

  • Shin, Hyun-Dae;Lee, Hyun Jae;Sikder, Asaduzzaman Md.;Park, Su Hyun;Ryu, Jiho;Hong, Jang-Hee;Kim, Ju-Ock;Seok, Jeong Ho;Lee, Choong Jae
    • Tuberculosis and Respiratory Diseases
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    • v.73 no.4
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    • pp.204-209
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    • 2012
  • Background: We investigated whether chrysin affected MUC5AC mucin production and gene expression induced by phorbol ester (phorbol 12-myristate 13-acetate, PMA) or epidermal growth factor (EGF) from human airway epithelial cells. Methods: Confluent NCI-H292 cells were pretreated with varying concentrations of chrysin for 30 minutes, and were then stimulated with PMA and EGF for 24 hours, respectively. MUC5AC mucin gene expression and mucin protein production were measured by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Results: Concentrations of $10{\mu}M$ and $100{\mu}M$ chrysin were found to inhibit the production of MUC5AC mucin protein induced by PMA; A concentration of $100{\mu}M$ chrysin also inhibited the production of MUC5AC mucin protein induced by EGF; $100{\mu}M$ chrysin inhibited the expression of MUC5AC mucin gene induced by PMA or EGF. The cytotoxicity of chrysin was checked by lactate dehydrogenase assay, and there was no cytotoxic effect observed for chrysin. Conclusion: These results suggest that chrysin can inhibit mucin gene expression and the production of mucin protein by directly acting on airway epithelial cells.

The effect of Korean Red Ginseng extract on rosiglitazone-induced improvement of glucose regulation in diet-induced obese mice

  • Oh, Mi-Jeong;Kim, Hyun-Ju;Park, Eun-Young;Ha, Na-Hee;Song, Mun-Gyu;Choi, Sang-Hyun;Chun, Boe-Gwun;Kim, Dong-Hoon
    • Journal of Ginseng Research
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    • v.41 no.1
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    • pp.52-59
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    • 2017
  • Background: Korean Red Ginseng extract (KRG, Panax ginseng Meyer) and its constituents have been used for treating diabetes. However, in diet-induced obese mice, it is unclear whether KRG can enhance the glucose-lowering action of rosiglitazone (ROSI), a peroxisome proliferator-activated receptor gamma synthetic activator. Methods: Oral glucose tolerance tests (oGTTs) were performed after 4 days of treatment with a vehicle (CON), KRG [500 mg/kg body weight (b.w.)], ROSI (3.75 mg/kg b.w, 7.5 mg/kg b.w, and 15 mg/kg b.w.), or ROSI and KRG (RK) in obese mice on a high-fat diet. Adipose tissue morphology, crown-like structures (CLSs), and inflammation were compared by hematoxylin-eosin staining or quantitative reverse transcription polymerase chain reaction. Results: The area under the glucose curve (AUC) was significantly lower in the RK group (15 mg/kg b.w. and 500 mg/kg b.w. for ROSI and KRG, respectively) than in the CON group. There was no significant difference in the AUC between the CON and the other groups. Furthermore, the AUC was significantly lower in the RK group than in the ROSI group. The expression of the Ccl2 gene and the number of CLSs were significantly reduced in the RK group than in the CON group. Conclusion: Our results show a potential enhancement of ROSI-induced improvement of glucose regulation by the combined treatment with KRG.

Computational analysis of the electromechanical performance of mitral valve cerclage annuloplasty using a patient-specific ventricular model

  • Lee, Kyung Eun;Kim, Ki Tae;Lee, Jong Ho;Jung, Sujin;Kim, June-Hong;Shim, Eun Bo
    • The Korean Journal of Physiology and Pharmacology
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    • v.23 no.1
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    • pp.63-70
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    • 2019
  • We aimed to propose a novel computational approach to predict the electromechanical performance of pre- and post-mitral valve cerclage annuloplasty (MVCA). Furthermore, we tested a virtual estimation method to optimize the left ventricular basement tightening scheme using a pre-MVCA computer model. The present model combines the three-dimensional (3D) electromechanics of the ventricles with the vascular hemodynamics implemented in a lumped parameter model. 3D models of pre- and post-MVCA were reconstructed from the computed tomography (CT) images of two patients and simulated by solving the electromechanical-governing equations with the finite element method. Computed results indicate that reduction of the dilated heart chambers volume (reverse remodeling) appears to be dependent on ventricular stress distribution. Reduced ventricular stresses in the basement after MVCA treatment were observed in the patients who showed reverse remodeling of heart during follow up over 6 months. In the case who failed to show reverse remodeling after MVCA, more virtual tightening of the ventricular basement diameter than the actual model can induce stress unloading, aiding in heart recovery. The simulation result that virtual tightening of the ventricular basement resulted in a marked increase of myocardial stress unloading provides in silico evidence for a functional impact of MVCA treatment on cardiac mechanics and post-operative heart recovery. This technique contributes to establishing a pre-operative virtual rehearsal procedure before MVCA treatment by using patient-specific cardiac electromechanical modeling of pre-MVCA.

Anti-inflammatory and antinociceptive effects of sitagliptin in animal models and possible mechanisms involved in the antinociceptive activity

  • Valiollah Hajhashemi;Hossein Sadeghi;Fatemeh Karimi Madab
    • The Korean Journal of Pain
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    • v.37 no.1
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    • pp.26-33
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    • 2024
  • Background: Sitagliptin is an antidiabetic drug that inhibits dipeptidyl peptidase-4 enzyme. This study aimed to investigate the antinociceptive and anti-inflammatory effects of sitagliptin in formalin and carrageenan tests and determine the possible mechanism(s) of its antinociceptive activity. Methods: Male Swiss mice (25-30 g) and male Wistar rats (180-220 g) were used for formalin and carrageenan tests, respectively. In the formalin test, paw licking time and in the carrageenan test, paw thickness were considered as indexes of pain behavior and inflammation respectively. Three doses of sitagliptin (2.5, 5, and 10 mg/kg) were used in these tests. Also, several antagonists and enzyme inhibitors were used to evaluate the role of adrenergic, serotonergic, dopaminergic, and opioid receptors as well as the NO/cGMP/KATP pathway in the antinociceptive effect of sitagliptin (5 mg/kg). Results: Sitagliptin showed significant antinociceptive and anti-inflammatory effects in the formalin and carrageenan tests respectively. In the carrageenan test, all three doses of sitagliptin significantly (P < 0.001) reduced paw thickness. Pretreatment with yohimbine, prazosin, propranolol, naloxone, and cyproheptadine could not reverse the antinociceptive effect of sitagliptin (5 mg/Kg), which indicates that adrenergic, opioid, and serotonin receptors (5HT2) are not involved in the antinociceptive effects. L-NAME, methylene blue, glibenclamide, ondansetron, and sulpiride were able to reverse this effect. Conclusions: NO/cGMP/KATP, 5HT3 and D2 pathways play an important role in the antinociceptive effect of sitagliptin. Additionally significant anti-inflammatory effects observed in the carrageenan test might contribute in reduction of pain response in the second phase of the formalin test.

Effects of PCB Congeners in Rodent Neuronal Cells in Culture

  • Kim, Sun-Young;Yang, Jae-Ho
    • The Korean Journal of Physiology and Pharmacology
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    • v.9 no.1
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    • pp.9-15
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    • 2005
  • We attempted to analyze the mechanism of polychlorinated biphenyl (PCB)-induced neurotoxicity and identify the target molecules in the neuronal cells for PCBs.Since the developing neuron is particularly sensitive to PCB-induced neurotoxicity, we isolated cerebellar granule cells derived from 7-day old Sprague Dawley (SD) rats and grew cells in culture for additional 7 days to mimic PND-14 conditions. Only non-coplanar PCBs at a high dose showed a significant increase of total protein kinase C (PKC) activity at phobol 12,13-dibutyrate ([$^3M$]PDBu) binding assay, indicating that non-coplanar PCBs are more neuroactive than coplanar PCBs in neuronal cells. PKC isozymes were immunoblotted with the selected monoclonal antibodies. PKC-${\alpha}$, ${\delta}$, and ε were activated with non-coplanar PCB exposure. Receptor for activated C kinase-1 (RACK-1), anchoring protein for activated PKC, was more induced with exposure to coplanar PCBs than non-coplanar PCBs. Reverse transcription PCR (RT-PCR) analysis showed induction of neurogranin (RC-3) and growth associated protein-43 (GAP-43) mRNA with non-coplanar PCBs. The results indicate that these factors may be useful biomarkers for differentiating non-coplanar PCBs from coplanar PCBs. The present study demonstrated that non-coplanar PCBs are more neuroactive congeners than coplanar PCBs.

Regulation of Tumor Necrosis Factor-${\alpha}$-induced Airway Mucin Production and Gene Expression by Carbenoxolone, Prunetin, and Silibinin

  • Lee, Hyun-Jae;Lee, Su-Yel;Jeon, Byeong-Kyou;Lee, Jae-Woo;Lee, Mi-Nam;Kim, Ju-Ock;Lee, Choong-Jae
    • Tuberculosis and Respiratory Diseases
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    • v.69 no.5
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    • pp.348-353
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    • 2010
  • Background: In this study, we tried to investigate whether carbenoxolone, prunetin, and silibinin affect tumor necrosis factor (TNF)-${\alpha}$-induced MUC5AC mucin production and gene expression from human airway epithelial cells. Methods: Confluent NCI-H292 cells were pretreated with each agent (carbenoxolone, prunetin, and silibinin) for 30 min and then stimulated with TNF-${\alpha}$ for 24 hours. The MUC5AC mucin gene expression and mucin protein production were measured by reverse transcription-polymerase chain reaction and enzyme linked immunosorbent assay, respectively. Results: Carbenoxolone, prunetin and silibinin inhibited the production of MUC5AC mucin protein induced by TNF-${\alpha}$; the 3 compounds also inhibited the expression of MUC5AC mucin gene induced by TNF-${\alpha}$. Conclusion: This result suggests that carbenoxolone, prunetin and silibinin can inhibit mucin gene expression and production of mucin protein induced by TNF-${\alpha}$, by directly acting on airway epithelial cells.

Protective Effects of Verapamil against H2O2-Induced Apoptosis in Human Lens Epithelial Cells

  • Wang, Zhuo;Wang, Dan;Li, Yan;Zhang, Xiuli
    • Biomolecules & Therapeutics
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    • v.22 no.6
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    • pp.553-557
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    • 2014
  • Verapamil is used in the treatment of hypertension, angina pectoris, and atrial fibrillation. Recently, several studies have demonstrated that verapamil increased the optic nerve head blood flow and improved the retrobulbar circulation. All these show that verapamil is potentially useful for ophthalmic treatment. Thus, the aim of this study is to investigate whether verapamil could protect human lens epithelial cell (HLEC) from oxidative stress induced by $H_2O_2$ and the cellular mechanism underlying this protective function. The viability of HLEC was determined by the MTT assay and apoptotic cell death was analyzed by Hoechst 33258 staining. Moreover, Caspase-3 expression was detected by immunocytochemistry and flow cytometry analysis. We also detected Caspase-3 mRNA expression by reverse-transcription-polymerase chain reaction and the GSH content in cell culture. The results showed that oxidative stress produced significant cell apoptotic death and it was reduced by previous treatment with the verapamil. Verapamil was effective in reducing HLEC death mainly through reducing the expression level of apoptosis-related proteins, caspase-3, and increasing glutathione content. Therefore, it was suggested that verapamil was effective in reducing HLEC apoptosis induced by $H_2O_2$.

Effects of Lobetyolin, Lobetyol and Methyl linoleate on Secretion, Production and Gene Expression of MUC5AC Mucin from Airway Epithelial Cells

  • Yoon, Yong Pill;Ryu, Jiho;Park, Su Hyun;Lee, Hyun Jae;Lee, Seungho;Lee, Sang Kook;Kim, Ju-Ock;Hong, Jang-Hee;Seok, Jeong Ho;Lee, Choong Jae
    • Tuberculosis and Respiratory Diseases
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    • v.77 no.5
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    • pp.203-208
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    • 2014
  • Background: In this study, we investigated whether lobetyolin, lobetyol, and methyl linoleate derived from Codonopsis pilosula affect MUC5AC mucin secretion, production, and gene expression from airway epithelial cells. Methods: Confluent NCI-H292 cells were pretreated with lobetyolin, lobetyol, or methyl linoleate for 30 minutes and then stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 hours. The MUC5AC mucin gene expression, and mucin protein production and secretion were measured by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Results: Lobetyolin, lobetyol, and methyl linoleate inhibited the gene expression of MUC5AC mucin induced by PMA; lobetyolin did not affect PMA-induced MUC5AC mucin production. However, lobetyol and methyl linoleate inhibited the production of MUC5AC mucin; lobetyolin and lobetyol did not significantly affect PMA-induced MUC5AC mucin secretion from NCI-H292 cells. However, methyl linoleate decreased the MUC5AC mucin secretion. Conclusion: These results suggest that among the three compounds, methyl linoleate can regulate gene expression, production, and secretion of MUC5AC mucin by directly acting on the airway epithelial cells.