• Archives of Pharmacal Research
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• 제4권1호
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• pp.9-17
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• 1981

A simple, accurate and specific NMR procedure is described for the determination of amplicilin and cloxacillin mixtures in injection dosage form and capsules. The solvent was dimethysulfoxde $d_{6}$ and maleic acid was the internal standard. By integrating the peak at 2.68 ppm and 4.57 ppm, cloxacillin and ampicillin could be determined respectively. The relative proton ratio of ampicillin trihydrate and cloxacillin were 1.038 and 0.950. The coefficents of variation of amplicillin trihydrate and cloxacillin in a few commerical preparation were 1.55 % (n =9), 2.69 % (n =15).

• Journal of Pharmaceutical Investigation
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• 제39권1호
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• pp.37-41
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• 2009

The purpose of this study was to compare the efficacy of Lorelin Depot $Injection^{(R)}$ (Dongkook Pharm. Co., LTD) with Lucrin Depot $Injection^{(R)}$ (Abbott) by measuring serum testosterone level in rats. Leuprorelin (leuprolide acetate), which is an active compound for the two formulations, is an LHRH analogue that is used for the treatment of a wide range of sex hormone-related disorders including advanced prostatic cancer, endometriosis and precocious puberty. Lorelin Depot $Injection^{(R)}$ is a micro-encapsulated formulation to suppress testosterone level by releasing leuprorelin continuously for four weeks with a single subcutaneous injection. The comparison study of the efficacy was performed during four weeks, and serum testosterone levels were monitored in the two formulations. The mean serum testosterone levels from the formulations were decreased to that of the castrate range (50 ng/dL or less) after three days after the initial depot injection, and the concentration were remained throughout four weeks' period. There were no significant differences in the $AUC_{0-3day}$ of testosterone and testosterone levels at 3, 7, 14, 21 and 28 days between the two formulations. These results indicate that the two formulations, Lorelin Depot $Injection^{(R)}$ and Lucrin Depot $Injection^{(R)}$, are bioequivalent in terms of the serum testosterone level in rats.

• Advances in Traditional Medicine
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• 제8권4호
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• pp.400-407
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• 2008

The aim of the present study is to investigate the anti-inflammatory and antimicrobial activity of petroleum ether and ethanol extracts of Scutia myrtina (Family: Rhamnaceae). In anti-inflammatory activity carrageenan and histamine induced paw oedema and cotton pellet induced granuloma for acute and chronic inflammatory models were studied in Wister albino rats. Based on the results of the present study it can be concluded that petroleum ether and ethanol extract of Scutia myrtina at 400 mg/kg has potential anti-inflammatory effect and they act in a dose dependent manner. Both extracts of Scutia myrtina showed antimicrobial activity against all bacterial and fungal strains tested at the concentration of $100\;{\mu}g$/ml. From the result, it can be concluded that the Scutia myrtina contain antibacterial and antifungal principle. Further more, besides the confirmation of the popular use; the obtained results demonstrate this herbal drug to represent a new source of antimicrobial and anti-inflammatory agent.

• BMB Reports
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• 제38권2호
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• pp.167-176
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• 2005

Nuclear factor-E2-related factor 2 (Nrf2) is known as a key regulator of ARE-mediated gene expression and the induction of Phase II detoxifying enzymes and antioxidant enzymes, which is also a common property of many chemopreventive agents. In the present study, we investigated the regulatory role of different chemopreventive agents including sulforaphane (SUL), allyl isothiocyanate (AITC), indole-3-carbinol (I3C), and parthenolide (PTL), in the expression and degradation of Nrf2 and the induction of the antioxidant enzyme HO-1. SUL strongly induced Nrf2 protein expression and ARE-mediated transcription activation, retarded degradation of Nrf2 through inhibiting Keap1, and thereby activating the transcriptional expression of HO-1. AITC was also a potent inducer of Nrf2 protein expression, ARE-reporter gene and HO-1 but had little effect on delaying the degradation of Nrf2 protein. Although PTL and I3C could induce ARE reporter gene expression and Nrf2 to some extent, they were not as potent as SUL and AITC. However, PTL dramatically induced the HO-1 expression, which was comparable to SUL, while I3C had no effect. In addition, when treated with SUL and PTL, inhibition of proteasome by MG132 did not cause additional accumulation of Nrf2, suggesting the involvement of other degradation mechanism(s) in the presence of these compounds such as SUL and PTL. In summary, the results of our current study indicated that different chemopreventive compounds have different regulatory properties on the accumulation and degradation of Nrf2 as well as the induction of cellular antioxidant enzyme HO-1.

• Advances in Traditional Medicine
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• 제8권2호
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• pp.154-163
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• 2008

The methanol extract of stem barks of Careya arborea Roxb. (MECA) (Family- Myrtaceae) was evaluated for antitumor activity and antioxidant status against Ehrlich's Ascites Carcinoma (EAC) bearing Swiss albino mice. After 24 h of tumor inoculation the MECA was administered at the doses of 50, 100 and 200 mg/kg body weight/mice/day for 14 days. After the last dose and 18 h fasting mice were sacrificed. The effect of MECA on the growth of transplantable murine tumor, life span of EAC bearing hosts, hematological profiles, serum and liver biochemical parameters were estimated. The MECA showed significant (P < 0.01) decrease in ascites volume, packed cell volume and viable cell count and prolonged the life span of EAC tumor bearing mice. Hematological profiles reverted to more or less normal levels in extract treated mice. The MECA also produced protective effect by decreasing the activity of serum enzymes, bilirubin and increase the protein and uric acid levels. MECA significantly (P < 0.05) decreased the levels of lipid peroxidation, while significantly (P < 0.05) increased the levels of glutathione content, vitamin C, vitamin E, superoxide dismutase and catalase CAT. The results indicate that MECA exhibited significant antitumor and antioxidant activity in EAC bearing mice.

• Archives of Pharmacal Research
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• 제29권10호
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• pp.911-920
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• 2006

Phenolic antioxidant butylated hydroxyanisole (BHA) is a commonly used food preservative with broad biological activities, including protection against chemical-induced carcinogenesis, acute toxicity of chemicals, modulation of macromolecule synthesis and immune response, induction of phase II detoxifying enzymes, as well as its undesirable potential tumor-promoting activities. Understanding the molecular basis underlying these diverse biological actions of BHA is thus of great importance. Here we studied the pharmacokinetics, activation of signaling kinases and induction of phase II/III drug metabolizing enzymes/transporter gene expression by BHA in the mice. The peak plasma concentration of BHA achieved in our current study after oral administration of 200 mg/kg BHA was around $10\;{\mu}M$. This in vivo concentration might offer some insights for the many in vitro cell culture studies on signal transduction and induction of phase II genes using similar concentrations. The oral bioavailability (F) of BHA was about 43% in the mice. In the mouse liver, BHA induced the expression of phase II genes including NQO-1, HO-1, ${\gamma}-GCS$, GST-pi and UGT 1A6, as well as some of the phase III transporter genes, such as MRP1 and Slco1b2. In addition, BHA activated distinct mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), as well as p38, suggesting that the MAPK pathways may play an important role in early signaling events leading to the regulation of gene expression including phase II drug metabolizing and some phase III drug transporter genes. This is the first study to demonstrate the in vivo pharmacokinetics of BHA, the in vivo activation of MAPK signaling proteins, as well as the in vivo induction of Phase II/III drug metabolizing enzymes/transporters in the mouse livers.

• Archives of Pharmacal Research
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• 제24권2호
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• pp.126-135
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• 2001

Quinacrine (QU), a phospholipase-A2 (PLA-2) inhibitor has been used clinically as a chemotherapeutic adjuvant. To understand the mechanisms leading to its chemotherapeutic effect, we have investigated QU-induced apoptotic signaling pathways in human cervical squamous carcinoma HeLa cells. In this study, we found that QU induced cytochrome c-dependent apoptotic signaling. The release of pro-apoptotic cytochrome c was QU concentration- and time-dependent, and preceded activation of caspase-9 and -3. Flow cytometric FACScan analysis using fluorescence intensities of $DiOC_6$/ demonstrated that QU-induced cytochrome c release was independent of mitochondrial permeability transition (MPT), since the concentrations of QU that induced cytochrome c release did not alter mitochondrial membrane potential (${\blacktriangle}{\Psi}_m$). Moreover, kinetic analysis of caspase activities showed that cytochrome c release led to the activation of caspase-9 and downstream death effector caspase-3, Caspase-3 inhibitor (Ac-DEVD-CHO) partially blocked QU-induced apoptosis, suggesting the importance of caspase-3 in this apoptotic signaling mechanism. Supplementation with arachidonic acid (AA) sustained caspase-3 activation induced by QU. Using inhibitors against cellular arachidonate metabolism of lipooxygenase (Nordihydroxyguaiaretic Acid, NDGA) and cyclooxygenase (5,8,11,14-Eicosatetraynoic Acid, ETYA) demonstrated that QU-induced apoptotic signaling may be dependent on its role as a PLA-2 inhibitor. Interestingly, NDCA attenuated QU-induced cytochrome c release, caspase activity as well as apoptotic cell death. The blockade of cytochrome c release by NDCA was much more effective than that attained with cyclosporin A (CsA), a MPT inhibitor. ETYA was not effective in blocking cytochrome c release, except under very high concentrations. Caspase inhibitor z-VAD blocked the release of cytochrome c suggesting that this signaling event is caspase dependent, and caspase-8 activation may be upstream of the mitochondrial events. In summary, we report that QU induced cytochrome c-dependent apoptotic signaling cascade, which may be dependent on its role as a PLA-2 inhibitor. This apoptotic mechanism induced by QU may contribute to its known chemotherapeutic effects.

• IMMUNE NETWORK
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• 제22권5호
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• pp.42.1-42.20
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• 2022

Vaccination with tumor peptide epitopes associated with MHC class I molecules is an attractive approach directed at inducing tumor-specific CTLs. However, challenges remain in improving the therapeutic efficacy of peptide epitope vaccines, including the low immunogenicity of peptide epitopes and insufficient stimulation of innate immune components in vivo. To overcome this, we aimed to develop and test an innovative strategy that elicits potent CTL responses against tumor epitopes. The essential feature of this strategy is vaccination using tumor epitope-loaded nanoparticles (NPs) in combination with polyinosinic-polycytidylic acid (poly-IC) and anti-PD1 mAb. Carboxylated NPs were prepared using poly(lactic-co-glycolic acid) and poly(ethylene/maleic anhydride), covalently conjugated with anti-H-2K^b mAbs, and then attached to H-2K^b molecules isolated from the tumor mass (H-2^b). Native peptides associated with the H-2K^b molecules of H-2K^b-attached NPs were exchanged with tumor peptide epitopes. Tumor peptide epitope-loaded NPs efficiently induced tumor-specific CTLs when used to immunize tumor-bearing mice as well as normal mice. This activity of the NPs significantly was increased when co-administered with poly-IC. Accordingly, the NPs exerted significant anti-tumor effects in mice implanted with EG7-OVA thymoma or B16-F10 melanoma, and the anti-tumor activity of the NPs was significantly increased when applied in combination with poly-IC. The most potent anti-tumor activity was observed when the NPs were co-administered with both poly-IC and anti-PD1 mAb. Immunization with tumor epitope-loaded NPs in combination with poly-IC and anti-PD1 mAb in tumor-bearing mice can be a powerful means to induce tumor-specific CTLs with therapeutic anti-tumor activity.

• Journal of Pharmaceutical Investigation
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• 제38권1호
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• pp.39-43
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• 2008

Cyclosporin A (CyA), a potent immunosuppressive drug used in allogeneic transplants and autoimmune disease, is a typical water-insoluble drug. Recently, nanoparticle carriers were investigated to improve the intestinal absorption of drugs. In this study, CyA-loaded nanostructured lipid carriers (NLCs) were prepared from a hot o/w emulsion using the high pressure homogenization method. The NLCs were consisted of cationic lipids, solid lipids, liquid lipids (oils), surfactant and stabilizer. Encapsulation efficiency of CyA in NLCs was approximately 71%. The average particle size and zeta potential of NLCs were below 250 nm and above +40 mV, respectively. The morphology of NLCs was confirmed by transmission electron microscopy (TEM) analysis. Compared to the CyA powder, higher in vitro release of CyA from NLCs was observed after burst release within 30 min. Thus, CyA-loaded NLCs could be applied not only for parenteral route but also for gastrointestinal administration, which needs further investigation.

• Journal of Microbiology and Biotechnology
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• 제34권7호
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• pp.1401-1409
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• 2024

Postbiotics have various functional effects, such as antioxidant, anti-inflammatory, and anti-obesity. Levilactobacillus brevis BK3, the subject of this study, was derived from lactic acid bacteria isolated from Kimchi, a traditional Korean fermented food. The antioxidant activity of BK3 was confirmed through the measurements of 2,2-diphenyl-1-picryl-hydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and total antioxidant capacity (TAC). The wrinkle improvement effect was validated by assessing elastase inhibitory activity and collagenase inhibitory activity. The intracellular activity was confirmed using human keratinocytes (HaCaT) and human fibroblasts (HFF-1). BK3 protects skin cells from oxidative stress induced by H₂O₂ and reduces intracellular reactive oxygen species (ROS) production. In addition, the expressions of the antioxidant genes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were upregulated. Meanwhile, matrix metalloproteinase-1 (MMP-1) and collagen type I alpha 1 (COL1A1), involved in collagen degradation and synthesis, were significantly regulated. These results suggest the possibility of utilizing BK3 as a functional ingredient with antioxidant and wrinkle-improving effects.