• Korean Journal of Clinical Laboratory Science
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• v.43 no.4
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• pp.179-187
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• 2011

Animal models are important tools in thrombosis research and preclinical drug development. In recent studies, ferric chloride ($FeCl_3$) has been widely used to induce arterial thrombosis in a variety of species. The purpose of this study was to find an optimal concentration of $FeCl_3$ and validate this model suited better for thrombosis research. A small piece of filter paper, soaked in $FeCl_3$ solution (10, 20 or 35%, v/v, in distilled water) was topically applied on the carotid artery of SD rats to measure the time to occlusion (TTO) and thrombus weight (TW) to ascertain 35%, as an optimal $FeCl_3$ concentration ($8.63{\pm}0.92min$; p =0.000, $0.79{\pm}0.03mg/mm$; p =0.000, respectively). To validate this experimental model, Ginkgo biloba special extract EGb761 (5, 10 or 30 mg/kg) as a reference agent administered by peritoneal route for 1h prior to the induction of thrombosis, showed significantly delayed TTO in a dose dependent manner ($18.50{\pm}2.17$, $29.17{\pm}1.83$, and $38.00{\pm}1.79min$, respectively) and significantly reduced TW and repaired collagen fibre in the injured vessel compare to vehicle group. Our results provide a simple, reproducible and well controlled in vivo screening system to induce thrombosis in rats by the topical application of 35% $FeCl_3$ to assess the efficacy of the new anti-thrombotic agents.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.6
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• pp.353-358
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• 2010

This study demonstrates the ability of magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis, to inhibit LPS-induced expression of iNOS gene and activation of NF-${\kappa}B$/Rel in RAW 264.7 cells. Immunohisto-chemical staining of iNOS and Western blot analysis showed magnolol to inhibit iNOS gene expression. Reporter gene assay and electrophoretic mobility shift assay showed that magnolol inhibited NF-${\kappa}B$/Rel transcriptional activation and DNA binding, respectively. Since p38 is important in the regulation of iNOS gene expression, we investigated the possibility that magnolol to target p38 for its anti-inflammatory effects. A molecular modeling study proposed a binding position for magnolol that targets the ATP binding site of p38 kinase (3GC7). Direct interaction of magnolol and p38 was further confirmed by pull down assay using magnolol conjugated to Sepharose 4B beads. The specific p38 inhibitor SB203580 abrogated the LPS-induced NF-${\kappa}B$/Rel activation, whereas the selective MEK-1 inhibitor PD98059 did not affect the NF-${\kappa}B$/Rel. Collectively, the results of the series of experiments indicate that magnolol inhibits iNOS gene expression by blocking NF-${\kappa}B$/Rel and p38 kinase signaling.

• Journal of Pharmaceutical Investigation
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• v.40 no.1
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• pp.15-21
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• 2010

Sibutramine is an orally administered centrally-acting antiobesity agent and inhibits both noradrenaline(norephinephirine) and serotonin(5-HT) reuptake. These effects are contributed by its active metabolites, M1 and M2. However, as the free base form of sibutramine is an oil form in room temperature, it had the problem of handling and stability. Thus, this drug should be used in the form of acid salt form in the pharmaceutical application. Unfortunately, anhydrous sibutramine hydrochloride is highly hygroscopic and unstable. In order to solve the hygroscopicity of the anhydrous salt form, another sibutramine acid salt form must be developed as a hydrate form. In this study. to overcome these problems, various of sibutramine acid salt forms were prepared with the pharmaceutically available salts such as maleate, esylate, mandelate, camsylate, besylate, salicylate, tartrate, isethionate and malate forms, and their physicochemical properties were investigated. Sibutramine malate was selected for excellent solubility and stability among the listed salt forms above. Its pharmacokinetic parameters were evaluated in rats comparing with sibutramine HCl, resulting in similar parameters. In vitro dissolution study of sibutramine malate-loaded capsule was performed comparison with commercial product ($Reductil^{(R)}$) in pH 1.2, pH 4.0, pH 6.8 and water medium. Our results indicated that there were no significant differences in their dissolution profiles were similar in all tested medium. Thus, sibutramine malate-loaded capsule should be a potential candiate due to its excellent solubility, good stability and biosimilar absorption.

• Fisheries and Aquatic Sciences
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• v.17 no.2
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• pp.209-214
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• 2014

With the continuing demand for new solutions in the development of effective and safe candidiasis therapies, we investigated the efficacy of an antifungal agent from the marine brown alga Eisenia bicyclis. The methanolic extract of E. bicyclis evinced potential antifungal activity against Candida species. The ethyl acetate (EtOAc)-soluble extract from E. bicyclis demonstrated the strongest antifungal activity against Candida species among five solvent-soluble extracts. Indeed, the EtOAc-soluble extract showed minimum inhibitory concentrations (MICs) ranging from 4 to 8 mg/mL. Furthermore, the EtOAc-soluble extract considerably reversed high-level fluconazole resistance of Candida species. The MIC values of fluconazole against Candida species decreased substantially (from 64 to $4{\mu}g/mL$) in combination with the MIC of the EtOAc-soluble extract (4 mg/mL). The fractional inhibitory concentration indices of fluconazole ranged from 0.531 to 0.625 in combination with 4, 2, or 1 mg/mL of the EtOAc-soluble extract against Candida isolates, indicating that these combinations exert a marked synergistic effect against Candida isolates. These findings imply that compounds derived from E. bicyclis can be a potential source of natural antifungal agents against Candida species.

• Journal of Microbiology and Biotechnology
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• v.27 no.8
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• pp.1441-1448
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• 2017

Antibacterial compounds are widely used in the treatment of human and animal diseases. The overuse of antibiotics has led to a rapid rise in the prevalence of drug-resistant bacteria, making the development of new antibacterial compounds essential. This study focused on developing a fast and easy method for identifying marine bacteria that produce antibiotic compounds. Eight randomly selected marine target bacterial species (Agrococcus terreus, Bacillus algicola, Mesoflavibacter zeaxanthinifaciens, Pseudoalteromonas flavipulchra, P. peptidolytica, P. piscicida, P. rubra, and Zunongwangia atlantica) were tested for production of antibacterial compounds against four strains of test bacteria (B. cereus, B. subtilis, Halomonas smyrnensis, and Vibrio alginolyticus). Colony picking was used as the primary screening method. Clear zones were observed around colonies of P. flavipulchra, P. peptidolytica, P. piscicida, and P. rubra tested against B. cereus, B. subtilis, and H. smyrnensis. The efficiency of colony scraping and broth culture methods for antimicrobial compound extraction was also compared using a disk diffusion assay. P. peptidolytica, P. piscicida, and P. rubra showed antagonistic activity against H. smyrnensis, B. cereus, and B. subtilis, respectively, only in the colony scraping method. Our results show that colony picking and colony scraping are effective, quick, and easy methods of screening for antibacterial compound-producing bacteria.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.6
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• pp.447-456
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• 2014

Until now, a disease-modifying therapy (DMT) that has an ability to slow or arrest Alzheimer's disease (AD) progression has not been developed, and all clinical trials involving AD patients enrolled by clinical assessment alone also have not been successful. Given the growing consensus that the DMT is likely to require treatment initiation well before full-blown dementia emerges, the early detection of AD will provide opportunities to successfully identify new drugs that slow the course of AD pathology. Recent advances in early detection of AD and prediction of progression of the disease using various biomarkers, including cerebrospinal fluid (CSF) $A{\beta}_{1-42}$, total tau and p-tau181 levels, and imagining biomarkers, are now being actively integrated into the designs of AD clinical trials. In terms of therapeutic mechanisms, monitoring these markers may be helpful for go/no-go decision making as well as surrogate markers for disease severity or progression. Furthermore, CSF biomarkers can be used as a tool to enrich patients for clinical trials with prospect of increasing statistical power and reducing costs in drug development. However, the standardization of technical aspects of analysis of these biomarkers is an essential prerequisite to the clinical uses. To accomplish this, global efforts are underway to standardize CSF biomarker measurements and a quality control program supported by the Alzheimer's Association. The current review summarizes therapeutic targets of developing drugs in AD pathophysiology, and provides the most recent advances in the clinical utility of CSF biomarkers and the integration of CSF biomarkers in current clinical trials.

• Journal of Korean Biological Nursing Science
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• v.16 no.1
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• pp.41-51
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• 2014

Purpose: The purpose of this study was to identify clinical nurses' knowledge of pharmacology, their need on pharmacology education contents, and perceived connectivity between knowledge and clinical practice. Methods: Subjects consisted of 114 clinical nurses. They responded to self-administered questionnaires about knowledge of pharmacology and need in pharmacology, and perceived connectivity between the knowledge and clinical practice. Results: The mean score of knowledge of pharmacology was $5.2{\pm}1.7$. The mean score of need on pharmacology in clinical practice was $7.9{\pm}1.9$, and those of satisfaction, application, and confidence with clinical performance by applying the knowledge to clinical practice were $7.4{\pm}1.9$, $6.8{\pm}2.0$, and $7.5{\pm}2.1$ respectively. Knowledge of pharmacology was positively correlated with perceived connectivity between knowledge and clinical practice. Scores of need of dose calculations was the highest among 14 units of pharmacology education contents in undergraduate courses while that of development of new drugs was the lowest. Scores of need of coagulation modifier drugs and thrombolytic agents were the highest among 16 units of pharmacology education contents by system specific drug while those of dermatologic and ophthalmic drugs were the lowest. Conclusion: The results indicate that knowledge of pharmacology is important in promoting perceived connectivity with clinical practice by applying knowledge to clinical practice.

• BMB Reports
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• v.53 no.11
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• pp.594-599
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• 2020

Lin28a has diverse functions including regulation of cancer, reprogramming and regeneration, but whether it promotes injury or is a protective reaction to renal injury is unknown. We studied how Lin28a acts in unilateral ureteral obstruction (UUO)-induced renal fibrosis following unilateral ureteral obstruction, in a mouse model. We further defined the role of Lin28a in transforming growth factor (TGF)-signaling pathways in renal fibrosis through in vitro study using human tubular epithelium-like HK-2 cells. In the mouse unilateral ureteral obstruction model, obstruction markedly decreased the expression of Lin28a, increased the expression of renal fibrotic markers such as type I collagen, α-SMA, vimentin and fibronectin. In TGF-β-stimulated HK-2 cells, the expression of Lin28a was reduced and the expression of renal fibrotic markers such as type I collagen, α-SMA, vimentin and fibronectin was increased. Adenovirus-mediated overexpression of Lin28a inhibited the expression of TGF-β-stimulated type I collagen, α-SMA, vimentin and fibronectin. Lin28a inhibited TGF-β-stimulated SMAD3 activity, via inhibition of SMAD3 phosphorylation, but not the MAPK pathway ERK, JNK or p38. Lin28a attenuates renal fibrosis in obstructive nephropathy, making its mechanism a possible therapeutic target for chronic kidney disease.

• Parasites, Hosts and Diseases
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• v.54 no.4
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• pp.415-421
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• 2016

The drug-resistance of malaria parasites is the main problem in the disease control. The huge Brazilian biodiversity promotes the search for new compounds, where the animal kingdom is proving to be a promising source of bioactive compounds. The main objective of this study was to evaluate the antiplasmodial and cytotoxic activity of the compounds obtained from the toad venoms of Brazilian Amazon. Toad venoms were collected from the secretion of Rhinella marina and Rhaebo guttatus in Mato Grosso State, Brazil. The powder was extracted at room temperature, yielding 2 extracts (RG and RM) and a substance ('1') identified as a bufadienolide, named telocinobufagin. Growth inhibition, intraerythrocytic development, and parasite morphology were evaluated in culture by microscopic observations of Giemsa-stained thin blood films. Cytotoxicity was determined against HepG2 and BGM cells by MTT and neutral red assays. The 2 extracts and the pure substance ('1') tested were active against chloroquine-resistant Plasmodium falciparum strain, demonstrating lower $IC_{50}$ values. In cytotoxic tests, the 2 extracts and substance '1' showed pronounced lethal effects on chloroquine-resistant P. faciparum strain and low cytotoxic effect, highlighting toad parotoid gland secretions as a promising source of novel lead antiplasmodial compounds.

• Natural Product Sciences
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• v.26 no.2
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• pp.136-143
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• 2020

Psoriasis is one of the most common inflammatory skin disorders, with a global prevalence of 2% - 3%. It is an autoimmune skin disorder characterized by excessive generation of plaques on the skin with typical long-lasting red, itchy, and scaly lesions. In this study, we aimed to elucidate the anti-psoriatic effect of the methanolic extract of Persicaria senticosa (PS), a bioactive edible plant extract used in traditional medicine, using a mouse model of imiquimod (IMQ)-induced psoriasis. The daily topical application of IMQ could induce human psoriasis-like lesion. The extract ameliorated IMQ-induced psoriasis. Furthermore, hematoxylin and eosin staining and the Psoriasis Area and Severity Index (PASI) scores indicated that topical application of PS led to an improvement in erythema, scaling, and thickness scores of the mouse dorsal skin and a considerable decrease in the epidermal thickness of the ear and dorsal skin in the IMQ-induced psoriatic mouse model. We also studied the effect of PS on the proliferation of keratinocytes using HaCaT cells. The extract inhibited cell proliferation and IL-6 and pSTAT3 expression induced by M5 cocktail (comprising interleukin [IL]-1α, IL-17A, IL-22, oncostatin M, and tumor necrosis factor-α) in HaCaT cells. Thus, PS might serve as a potential therapeutic agent for the treatment of psoriasis.