• Mass Spectrometry Letters
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• v.14 no.3
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• pp.116-119
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• 2023

Gynostemma pentaphyllum (Thunb.) Makino extract, a natural product with a history of traditional use, has gained attention for its potential health benefits. This study aimed to investigate its effects on key cytochrome P450 (CYP) enzymes using LC-MS/MS. Human liver microsomes and cDNA-expressed CYP2C8, CYP2C9, CYP2C19, and CYP3A4 supersomes were employed. Enzyme activity was assessed based on the formation of CYP-specific marker metabolites. The resulting data showed that the extract exhibited inhibitory effects on CYP2C8, CYP2C9, CYP2C19, and CYP3A4. Thus, G. pentaphyllum extract may influence the pharmacokinetics of drugs metabolized by CYP2C8, CYP2C9, CYP2C19, and CYP3A4. These findings emphasize the importance of considering potential herb-drug interactions when incorporating this extract into therapeutic regimens or dietary supplements.

• Environmental Analysis Health and Toxicology
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• v.31
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• pp.16.1-16.9
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• 2016

Objectives Banha-sasim-tang (BST), which consists of seven different herbs, is one of the most popular herbal formulae for treating gastrointestinal disorders in Eastern Asia. The commonly used herbal medicine is often co-administered with other therapeutic drugs, which raises the possibility of herb-drug interactions and may modify the clinical safety profile of therapeutic drugs. Methods We investigated the potential herb-drug interactions between BST extract and midazolam (MDZ) in mice. The area under the plasma concentration-time curve (AUC) of MDZ and 1'-hydroxymidazolam (1'-OH-MDZ) was evaluated for both oral and intraperitoneal administration of MDZ, following oral administration of BST (0.5 and 1 g/kg). Results It was found that the AUC of MDZ and 1'-OH-MDZ was lower in case of oral administration of MDZ. Administration of BST extract was not associated with hepatic cytochrome P450 activity. BST extract induced a strong reduction in pH and it has been reported that oral mucosal absorption of MDZ is lower at low pH. The decreased absorption rate of MDZ might be caused by the ingredients of BST and may not be related to other factors such as increased excretion of MDZ by P-glycoprotein. Conclusions The altered pharmacokinetics of midazolam caused by co-administration with BST in vivo could be attributed to a decrease in pH and subsequent reduction of MDZ absorption rate.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.278-278
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• 1996

Judging from hydrocortisone concentration in dosing area, the extent of absorption was reduced in the liposome-gel formulation. However, higher and sustained skin concentrations of hydrocortisone were achieved for the liposome-gel as compared to the ointment. Drug concentration in both viable and deep skin reached its maximum within 0.5 h after application of both formulations to both skin types. Drug concentrations in both skins from the ointment declined with time, while those from the liposome-gel were greatly sustained. The sustainment by the liposome-gel was more remarkable in the viable skin than in the deep skin. Drug concentration in the viable skin could be maintained at a nearly constant level for over 8 h by applying the liposome-gel. As a result, a 5-fold higher viable skin drug concentration was obtained from the liposome-gel than from the ointment at 8 h after the application to the SC-removed skin. However, the plasma concentration of hydrocortisone at 4 h from the liposome-gel was only one-fourth (p<0.01) the value from the ointment when the drug was applied to the SC-removed skin, consistent with. the lower urinary (one-third, p<0.05) and fecal (one-half, p＜0.05) excretion. Conclusions : Retarded diffusion of the drug from the skin to the systemic blood stream appears to be a potential factor in the sustained skin concentration of hydrocortisone from the liposome-gel, Interaction of hydrocortisone in the skin with phosphatidylcholine, a component of the liposomes and skin, may well be a factor in retarding the diffusion of the drug in the skin.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.3
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• pp.225-234
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• 2018

Adenosine is a naturally occurring breakdown product of adenosine triphosphate and plays an important role in different physiological and pathological conditions. Adenosine also serves as an important trigger in ischemic and remote preconditioning and its release may impart cardioprotection. Exogenous administration of adenosine in the form of adenosine preconditioning may also protect heart from ischemia-reperfusion injury. Endogenous release of adenosine during ischemic/remote preconditioning or exogenous adenosine during pharmacological preconditioning activates adenosine receptors to activate plethora of mechanisms, which either independently or in association with one another may confer cardioprotection during ischemia-reperfusion injury. These mechanisms include activation of $K_{ATP}$ channels, an increase in the levels of antioxidant enzymes, functional interaction with opioid receptors; increase in nitric oxide production; decrease in inflammation; activation of transient receptor potential vanilloid (TRPV) channels; activation of kinases such as protein kinase B (Akt), protein kinase C, tyrosine kinase, mitogen activated protein (MAP) kinases such as ERK 1/2, p38 MAP kinases and MAP kinase kinase (MEK 1) MMP. The present review discusses the role and mechanisms involved in adenosine preconditioning-induced cardioprotection.

• Journal of Integrative Natural Science
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• v.5 no.1
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• pp.22-26
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• 2012

Chemokine receptor antagonists have potential applications in field of drug discovery. Although the chemokine receptors are G-protein-coupled receptors, their cognate ligands are small proteins (8 to 12 kDa), and so inhibiting the ligand/receptor interaction has been challenging. In particular, CCR2 and CCR5 and their ligands have been implicated in the pathophysiology of a number of diseases, including rheumatoid arthritis and multiple sclerosis. Based on their roles in disease, they have been attractive targets for the pharmaceutical industry, targeting both CCR2 and CCR5 could be a useful strategy. Because of the importance of these receptors, providing information regarding the binding site is of prime importance. Herein, we report the comparison of CCR2 of CCR5 binding sites both sequentially as well as structurally. We also urged the importance of crucial residues in the binding site, to facilitate the development of dual antagonists targeting both the receptors. These results could also be useful for the design of novel and potent dual CCR2 and CCR5 antagonists using structure based drug design.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.1
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• pp.95-103
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• 2023

Rosiglitazone is a thiazolidinedione-class antidiabetic drug that reduces blood glucose and glycated hemoglobin levels. We here investigated the interaction of rosiglitazone with Kv3.1 expressed in Chinese hamster ovary cells using the wholecell patch-clamp technique. Rosiglitazone rapidly and reversibly inhibited Kv3.1 currents in a concentration-dependent manner (IC₅₀ = 29.8 µM) and accelerated the decay of Kv3.1 currents without modifying the activation kinetics. The rosiglitazonemediated inhibition of Kv3.1 channels increased steeply in a sigmoidal pattern over the voltage range of -20 to +30 mV, whereas it was voltage-independent in the voltage range above +30 mV, where the channels were fully activated. The deactivation of Kv3.1 current, measured along with tail currents, was also slowed by the drug. In addition, the steady-state inactivation curve of Kv3.1 by rosiglitazone shifts to a negative potential without significant change in the slope value. All the results with the use dependence of the rosiglitazone-mediated blockade suggest that rosiglitazone acts on Kv3.1 channels as an open channel blocker.

• YAKHAK HOEJI
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• v.58 no.4
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• pp.255-261
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• 2014

Poly-pharmacy has been on the rise because of aging of population and chronic disease. Most of drug metabolism happens in the liver by CYP isozymes and the metabolism by CYP450 enzymes. The Cytochrome P450 (CYP) is a superfamily of enzymes that catalyzes the oxidations of many endogenous and exogenous compounds. Primary human Hepatocytes (HH) are considered as the gold standard model for In vitro drug interaction studies. However, there are several limitations (cost, limited life span) for using HH cells. HepaRG cells are being used as a possible alternative. HepaRG cells were cultured in William E medium containing the positive control inducers (1A2: 10, 25, 50 ${\mu}M$ omeprazole, 2C9 and 2C19: 10 ${\mu}M$ rifampin, 3A4: 10, 25, 50 ${\mu}M$ rifampin) at $37^{\circ}C$, 5 % $CO_2$ in a humidified atmosphere. This study was to evaluate the induction of CYP isozymes (1A2, 2C9, 2C19 and 3A4) using LC-MS/MS. We evaluated the potential induction ability of Bosentan, as a drug of pulmonary artery hypertension, in HepaRG cells. For reference, dose of the Bosentan is determined to the basis of the $C_{max}$ (835 mg/ml) value. The enzyme activity demonstrated that CYP2C9 and 3A4 were induced up to 20 times by Bosentan. Like as In vivo, the enzyme activity of CYP2C9 and CYP3A4 is significantly induced in a dose-dependent by Bosentan.

• Toxicological Research
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• v.32 no.3
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• pp.207-213
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• 2016

Although propolis is one of the most popular functional foods for human health, there have been no comprehensive studies of herb-drug interactions through cytochrome P450 (CYP) inhibition. The purpose of this study was to determine the inhibitory effects of propolis on the activities of CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1 and 3A4 using pooled human liver microsomes (HLMs). Propolis inhibited CYP1A2, CYP2E1 and CYP2C19 with an $IC_{50}$ value of 6.9, 16.8, and $43.1{\mu}g/mL$, respectively, whereas CYP2A6, 2B6, 2C9, 2D6, and 3A4 were unaffected. Based on half-maximal inhibitory concentration shifts between microsomes incubated with and without nicotinamide adenine dinucleotide phosphate, propolis-induced CYP1A2, CYP2C19, and CYP2E1 inhibition was metabolism-independent. To evaluate the interaction potential between propolis and therapeutic drugs, the effects of propolis on metabolism of duloxetine, a serotonin-norepinephrine reuptake inhibitor, were determined in HLMs. CYP1A2 and CYP2D6 are involved in hydroxylation of duloxetine to 4-hydroxy duloxetine, the major metabolite, which was decreased following propolis addition in HLMs. These results raise the possibility of interactions between propolis and therapeutic drugs metabolized by CYP1A2.

• Korean Journal of Clinical Pharmacy
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• v.23 no.1
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• pp.42-48
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• 2013

Background: Patients diagnosed with cancer tend to have multiple risk factors for drug related problems such as old age, comorbid conditions, self-medication, additional medications for supportive therapy, and the cancer treatment itself. Objective: The aim of this study was to investigate notable polypharmacy and related problems in oncology patients during hospitalization or following clinic visit. Method: The electronic medical records of patients who were discharged from oncology division at Seoul National University Hospital (SNUH) from June $1^{st}$ to June $30^{th}$, 2011 were retrospectively reviewed. Results: A total of 334 discharged patients were included in this study. Among them, 221 patients had pre-admission medications. Forty percent of the patients, including 60.3% of elderly patients (over 65 years of age) were prescribed more than 5 kinds of medications. Twenty percent of the patients were prescribed to take medications more than 7 times a day. Medication duplications were observed in 2.4% of patients. In 10.5% of the reviewed patients, 47 cases of potential drug-drug interaction including 3 cases of contraindication and 17 cases of major clinical implication according to Micromedex were detected. Medication changes were made in 88% of patients during hospitalization and in 94.7% of patients at their first visit after discharge. Antidiarrheal agent (loperamide) was prescribed along with laxatives in 18.5% of the prescriptions and inadequate instructions on how to take it were observed in 63% of the prescriptions. Conclusion: This study identified the prevalence of polypharmacy and related problems in cancer patients, which presents the need for an active role of pharmacists in pharmaceutical care in oncology wards.

• Journal of Microbiology and Biotechnology
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• v.25 no.5
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• pp.612-619
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• 2015

We have synthesized gold nanoparticles (GNPs) using chicken feathers (poultry waste) and Bacillus subtilis RSE163. Disulfide reductase and keratinase produced by Bacillus subtilis during the degradation of chicken feather has been used to reduce Au³⁺ from HAuCl₄ precursor to produce gold nanoparticles. The synthesized biogenic GNPs were characterized by UV-visible spectroscopy, transmission electron microscopy (TEM), and zeta potential measurements. Fourier transform infrared (FTIR) spectroscopy indicated the presence of protein capping on synthesized GNPs, imparting multifunctionality to the GNP surface. Furthermore, the nontoxic nature of biogenic GNPs was insured by interaction with Escherichia coli (ATCC11103), where TEM images and enhancement of growth rate of E. coli in log phase signified their nontoxic nature. The results indicate that the synthesis of biocompatible GNPs using poultry waste may find potential applications in drug delivery and sensing.