• 생약학회지
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• 제41권2호
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• pp.73-88
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• 2010

Traditionally, the root of Lithospermum erythrorhizon Sieb. et Zucc(L.E) has been used as efficacious therapy for inflammation, burns, frostbite and skin ailments (e.g eczema and psoriasis). It contains isohexenylnaphthoquinone derivatives (shikonin and its esters) and furylhydroquinones (shikonofurans) in lipophilic fractions and caffeic acid oligomers (rosmarinic acid, lithospermic acid B) in polar fractions. Recently, new preparative isolation and analysis procedures of shikonin along with its oligomers from the extract of L. erythrorhizon by the combination of high-speed counter-current chromatography with high-performance liquid chromatography-diode array detection have also been introduced. Although there have been many reports on the wound healing, antiinflammatory, and anticancer effects, the research on the effects of anti-atopic dermatitis of the root of L. erythrorhizon were relatively scarce. However, in recent years, new information gathered from research efforts, on the anti-atopic dermatitis properties of the extract or constituents of L. erythrorhizon has been accumulated. In this paper, the findings and advance on the in vitro and in vivo activities of L. erythrorhizon and its constituents especially focused on antiinflammatory and anti-atopic dermatitis effects are summarized. The phytochemical constituents of L. erythrorhizon or its tissue cultures are also presented. Although there are few to verify or refute its activity in human, one result of clinical study of the extract of L. erythrorhizon on the atopic dermatitis patients was introduced to assess the possibility of its clinical use. The reported mechanisms of action and in vivo pharmacological studies in different animal models for the various types of extracts or constituents of L. erythrorhizon are supportive of its therapeutic potential or dietary supplement, however, more evidence from clinically relevant models, as well as systemic studies on the active constituents or the various types of standardized extracts at the cellular and molecular level, are required.

• 대한한의학방제학회지
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• 제28권4호
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• pp.313-325
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• 2020

Objectives : To explore the associated potential pathways and molecular targets of Hwangryunhaedok-tang(HHT) by the approaches of network pharmacology and bioinformatics in traditional chinese medicine(TCM). Methods : Hwangryunhaedok-tang constituent drugs(Coptidis Rhizoma, CR; Scutellariae Radix, SR; Phellodendri Cortex, PC; Gardeniae Fructus, GF) and their processing types were searched from TCM systems pharmacology(TCMSP). The databases of TCMSP, Kyoto Encyclopedia of Genes and Genomes(KEGG), MCODE and STRING were used to gather information. The network of bioactive ingredients and target gene was constructed by Cytoscape software(version 3.8). Results : A total of 94 HHT active compounds(CR, 12; SR, 35; PC, 33; GF, 14, respectively) were found, and HHT were identified by TCMSP. Applications of KEGG and MCODE analysis indicates that total of 6 bioactive ingredients in the top 10% ranking were obtained and 32 diseases of HHT were screened. The molecular pathway analysis revealed that HHT exerts cancer, inflammation and cerebrovascular diseases effects by acting on several signaling pathway. In addition, HHT found that three genes(e.g. SPIN1, TRIM25, and APP) correlate with the aforementioned diseases. Conclusions : This study showed that network pharmacology analysis is useful to elucidate the complex mechanisms of action of HHT.

• 대한한의학회지
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• 제25권2호
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• pp.138-150
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• 2004

Objectives : Alzheimer's disease (AD) is a geriatric dementia that is widespread in old age. In the near future AD will be the biggest problem in public health service. Although a variety of oriental prescriptions, including Sesim-tang, have been traditionally utilized for the treatment of AD, their pharmacological effects and action mechanisms have not yet been fully elucidated. The present study investigated the effects of Sesim-tang on apoptotic cell death induced by CT105 (carboxy terminal 105 amino acid peptide fragment of APP) overexpression in SK-N-SH neuroblastoma cell lines. Methods: We studied the regenerative and inhibitory effects on Alzheimer's disease in CT105-induced SK-N-SH cell lines by Sesim-tang water extract. We examined for cell morphological pattern, DNA fragmentation, LDH activity assay, zymography assay, and immunohistochemistric analysis. Additionally, we investigated the association between the CT105 and neurite degeneration caused by CT105-induced apoptotic response in neurone cells. Results: Findings from our experiments have shown that Sesim-tang inhibits the synthesis or activities of CT105, which has neurotoxicities and apoptotic activities in the cell line. In addition, pretreatment with Sesim-tang ($>50\mu\textrm{g}/ml$ for 12 hours) partially prevented CT105-induced cytotoxicity in SK-N-SH cell lines. SK-N-SH cell lines overexpressed with CT105 exhibited remarkable apoptotic cell damage. Based on morphological observations by phase-contrast microscope and LDH activity measurements in the culture media, the CT105-induced cell death was significantly inhibited by Sesim-tang water extract. Sesim-tang was found to reduce the expression of APP and caspase-3 induced by CT105 in SK-N-SH cell lines and in rat hippocampus. Conclusions: As the result of this study, in the Sesim-tang group, apoptosis in the nervous system is inhibited, the repair against the degeneration of SK-N-SH cell lines by CT105 expression is promoted. Hence, Sesim-tang may be beneficial for the treatment of AD.

• 대한약리학회지
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• 제8권2호
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• pp.35-39
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• 1972

Previous studies on the effect of the visible lights on the organism have shown the possible influences on the nervous system. It was reported that the illumination of blue beam increased the sympathetic tone and that of red beam increased the parasympathetic tone. The pharmacological actions of the sympathomimetics were also known to be altered by various visible lights. But their modes and mechanisms of actions on the nervous system have not been clarified and is obscure. To elucidate the precise mechanism of action of the visible lights on the nervous system, present study was made to observe the survival time of the mole living in the dark environment, under the illumination of the various visible lights and influences of several drugs. The results are summerized as follows: 1. The illumination of the natural sun light caused the survival time of the mole to be shortened and visible monochromatic beams (red, blue and green) even more markedly shortened the survival time. No significant difference was noted depending on the wave length of the chromatic beam. 2. The shortened survival time caused by the visible monochromatic lights was prolonged by strychnine but not affected by morphine. 3. The survival time under the illumination of the visible monochromatic lights was prolonged by acetylcholine and physostigmine. 4. The shortened survival time under the illumination of the monochromatic visible lights was not affected by adrenaline but prolonged by priscoline. It is suggested that the shortened survival time of the mole by the illumination of the visible lights can be prolonged by the stimulation of central and parasympathetic nervous system and blocking of the sympathetic nervous system.

• 대한한의학방제학회지
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• 제8권1호
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• pp.147-167
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• 2000

Reactive oxygen species (ROS) play an important role in the pathogenesis of a variety of life threatening conditions such as atherosclerosis, myocardial infarction and cerebral stroke. In this study, the effect of Sunghyangchungisan (SHCS) as a cytoproctant against ROS-induced cell injury was studied by investigating its effect on $H_{2}O_2-induced$ cell injury in cultured endothelial cells derived from the human umbilical vein. SHCS effectively proteced the cells against $H_{2}O_2-induced$ injury determined by trypan blue exclusion ability and lactate dehydrogenase (LDH) release. The effect of SHCS was concentration-dependent and the concentrations to inhibit by 50% the cell death and LDH release were $0.9{\pm}0.1$ and $1.2{\pm}0.1\;mg/ml$, respectively. In addition, SHCS effectively protected the cells against t-butylhydroperoside- and menadione-Induced injury as well. SHCS inhibited lipid peroxidation determined by malondialdehyde production. SHCS exerted as an effective scavenger of ROS produced by exposing the cells to $H_{2}O_2$ The activities of the intracellular ROS scavenging enzymes such as superoxide dismutase, catalase and glutathione peroxidase were not Influenced by SHCS.These results indicate that SHCS might exert as an effective cytoprotectant against ROS-induced cell injury. Further intensive studies would provide us insights into mechanisms of the pharmacological actions of SHCS.

• The Korean Journal of Pain
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• 제26권4호
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• pp.336-346
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• 2013

Intrathecal drug delivery is an effective and safe option for the treatment of chronic pathology refractory to conventional pain therapies. Typical intrathecal administered drugs are opioids, baclofen, local anesthetics and adjuvant medications. Although knowledge about mechanisms of action of intrathecal drugs are every day more clear many doubt remain respect the correct location of intrathecal catheter in order to achieve the best therapeutic result. We analyze the factors that can affect drug distribution within the cerebrospinal fluid. Three categories of variables were identified: drug features, cerebrospinal fluid (CSF) dynamics and patients features. First category includes physicochemical properties and pharmacological features of intrathecal administered drugs with special attention to drug lipophilicity. In the second category, the variables in CSF flow, are considered that can modify the drug distribution within the CSF with special attention to the new theories of liquoral circulation. Last category try to explain inter-individual difference in baclofen response with difference that are specific for each patients such as the anatomical area to treat, patient posture or reaction to inflammatory stimulus. We conclude that a comprehensive evaluation of the patients, including imaging techniques to study the anatomy and physiology of intrathecal environment and CSF dynamics, could become essential in the future to the purpose of optimize the clinical outcome of intrathecal therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2453-2459
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• 2014

Ginsenoside Rg1 is one effective anticancer and antioxidant constituent of total saponins of Panax ginseng (TSPG), which has been shown to have various pharmacological effects. Our previous study demonstrated that Rg1 had anti-tumor activity in K562 leukemia cells. The aim of this study was designed to investigate whether Rg1 could induce apoptosis in TF-1/Epo cells and further to explore the underlying molecular mechanisms. Here we found that Rg1 could inhibit TF-1/Epo cell proliferation and induce cell apoptosis in vitro in a concentration and time dependent manner. It also suppressed the expression of EpoR on the surface membrane and inhibited JAK2/STAT5 pathway activity. Rg1 induced up-regulation of Bax, cleaved caspase-3 and C-PAPR protein and down-regulation of Bcl-2 and AG490, a JAK2 specific inhibitor, could enhance the effects of Rg1. Our studies showed that EpoR-mediated JAK2/STAT5 signaling played a key role in Rg1-induced apoptosis in TF-1/Epo cells. These results may provide new insights of Rg1 protective roles in the prevention a nd treatment of leukemia.

• 한국미생물·생명공학회지
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• 제48권3호
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• pp.383-388
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• 2020

부추 속에 속하는 코끼리마늘(Allium ampeloprasum L.)에 대한 몇 가지 약리효과는 보고된 바 있으나, 이의 항비만 및 작용기전에 대한 보고 전무한 실정이다. 이에 따라, 본 연구에서는 코끼리마늘 추출물이 3T3-L1 지방세포의 분화에 미치는 영향을 조사하여 이의 지방세포 분화 억제 효능을 규명하였다. 본 연구에서는 생코끼리마늘(Raw Elephant Rarlic, REG) 및 흑코끼리마늘(Steam Elephant Garlic, SEG) 추출물이 지방세포의 분화 및 지질축적을 억제한다는 것을 보여주었다. 주목할 만한 점은, REG의 경우 지방세포에 독성을 나타낸 반면, SEG는 독성을 나타내지 않았다는 점이다. 추가적으로, SEG는 PPARγ, C/EBPα, Adiponectin, Ap2 및 LPL와 같은 지방세포 분화 관련 유전자의 발현을 통계적으로 유의하게 억제하였다. 본 연구는 두 종류의 코끼리 마늘이 3T3-L1지방세포의 분화를 억제함을 보고한 최초의 연구이다.

• The Korean Journal of Physiology and Pharmacology
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• 제19권6호
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• pp.549-555
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• 2015

We attempted to investigate molecular mechanisms underlying phenotypic change of vascular smooth muscle cells (VSMCs) by determining signaling molecules involved in chemokine production. Treatment of human aortic smooth muscle cells (HAoSMCs) with thrombin resulted not only in elevated transcription of the (C-C motif) ligand 11 (CCL11) gene but also in enhanced secretion of CCL11 protein. Co-treatment of HAoSMCs with GF109230X, an inhibitor of protein kinase C, or GW5074, an inhibitor of Raf-1 kinase, caused inhibition of ERK1/2 phosphorylation and significantly attenuated expression of CCL11 at transcriptional and protein levels induced by thrombin. Both Akt phosphorylation and CCL11 expression induced by thrombin were attenuated in the presence of pertussis toxin (PTX), an inhibitor of Gi protein-coupled receptor, or LY294002, a PI3K inhibitor. In addition, thrombin-induced production of CCL11 was significantly attenuated by pharmacological inhibition of Akt or MEK which phosphorylates ERK1/2. These results indicate that thrombin is likely to promote expression of CCL11 via PKC/Raf-1/ERK1/2 and PTX-sensitive protease-activated receptors /PI3K/Akt pathways in HAoSMCs. We propose that multiple signaling pathways are involved in change of VSMCs to a secretory phenotype.

• The Korean Journal of Physiology and Pharmacology
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• 제18권6호
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• pp.475-480
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• 2014

We investigated the question of whether cholesterol catabolite can influence expression of inflammatory cytokines via Toll-like receptors (TLR) in monocytic cells. Treatment of THP-1 monocytic cells with 27-hydroxycholesterol (27OHChol) resulted in induction of gene transcription of TLR6 and elevated level of cell surface TLR6. Addition of FSL-1, a TLR6 agonist, to 27OHChol-treated cells resulted in transcription of the $IL-1{\alpha}$ gene and enhanced secretion of the corresponding gene product. However, cholesterol did not affect TLR6 expression, and addition of FSL-1 to cholesterol-treated cells did not induce expression of $IL-1{\alpha}$. Using pharmacological inhibitors, we investigated molecular mechanisms underlying the expression of TLR6 and $IL-1{\alpha}$. Treatment with Akt inhibitor IV or U0126 resulted in significantly attenuated expression of TLR6 and $IL-1{\alpha}$ induced by 27OHChol and 27OHChol plus FSL-1, respectively. In addition, treatment with LY294002, SB202190, or SP600125 resulted in significantly attenuated secretion of $IL-1{\alpha}$. These results indicate that 27OHChol can induce inflammation by augmentation of TLR6-mediated production of $IL-1{\alpha}$ in monocytic cells via multiple signaling pathways.