• 대한본초학회지
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• 제31권3호
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• pp.59-69
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• 2016

Objectives： Presently Mume Fructus (MF) undergoes fumigation, which produces benzo[a]pyrene. As a primary analysis with the aims to minimize the production of benzo[a]pyrene and to suggest standards for processing the MF, the steaming method was chosen among the various processing methods, and reviewed through a series of experiments.Methods： Methods：Pitted and un-pitted MF were steamed and processed into samples. After testing level of benzo[a]pyrene, the samples were analyzed for amount of polyphenol and flavonoids. Scavenging activities of the samples for the DPPH and ABTS radicals were tested. In order to measure anti-inflammatory effects of the samples, cell survival rate was investigated using CCK-8 Assay. Also, water extracts of dried and steamed MF were administered to the RAW 264.7 cells to compare expressions of NO, PGE₂, IL-1β, and TNF-α. In addition, anti-diarrhea effects of the herbal medicine were tested on animal models with diarrhea induced by MgSO₄ and Castor oil.Results： Regardless of pitting, processed MF contained no benzo[a]pyrene. Anti-oxidation effect increased in relation to the frequency of steaming process. However, extracts of dried and steamed MF suppressed different kinds of inflammation factors, and extract of dried MF showed superior anti-diarrhea effect than extract of steamed MF.Conclusions： It is suggested that steaming method of MF is recommended for processing the herbal medicine without the production of benzo[a]pyrene. But regarding that dried and steamed MF showed differences in their anti-oxidative, anti-inflammatory, and anti-diarrhea effects, it is recommended to perform further researches on different efficacies of MF according to their processing methods.

• IMMUNE NETWORK
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• 제3권3호
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• pp.248-254
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• 2003

Oral administration of antigen has long been used in the induction of immune tolerance in various animal models of autoimmune diseases including rheumatoid arthritis (RA). Alleveation of arthritogenic symptoms has been reported from RA patients who received oral administration of type II collagen (CII) without side effects, however its rather inconsistent therapeutic efficacy and variation among patients calls for more detailed investigation on the mechanism of oral tolerance to be settled as regular treatment for RA. In an attempt to understand the immunogenic processes underpinning tolerance induction by orally administered CII, we analyzed changes in the expression of costimulatory molecules and STAT/SOCS signaling messengers in the mouse model of collagen induced arthritis (CIA). We found thatin the spleen of CIA mice, that has been undergone repeated oral feeding of CII prior to the induction of arthritis, showed increased promortion of CTLA4 expressing lymphocytes than in the spleen of PBS fed control. On the other hand, cells expressing CD28 or ICOS were decreased in the spleen of tolerized mice. Tolerance induction by oral CII administration also enhanced the expression of STAT6 in both RNA and protein level, while not affecting the expression of STAT3. The expression of SOCS3, which hasbeen known to transmit STAT-mediated signals from Th2 type cytokines, remained unchanged in the spleen of tolerized mice. Interestingly transcript of SOCS1, which has been associated with Th1 related pathways, was only visible in the spleen of tolerized but not of control mice, suggesting that as in the case of IL-6 signaling, it may exert a feed back inhibition toward the Th1 type stimulation.

• 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.

• Tuberculosis and Respiratory Diseases
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• 제78권3호
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• pp.239-245
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• 2015

Background: Chronic obstructive pulmonary disease is characterized by emphysema, chronic bronchitis, and small airway remodeling. The alveolar destruction associated with emphysema cannot be repaired by current clinical practices. Stem cell therapy has been successfully used in animal models of cigarette smoke- and elastase-induced emphysema. However, the optimal dose of mesenchymal stem cells (MSCs) for the most effective therapy has not yet been determined. It is vital to determine the optimal dose of MSCs for clinical application in emphysema cases. Methods: In the present study, we evaluated the therapeutic effects of various doses of MSCs on elastase-induced emphysema in mice. When 3 different doses of MSCs were intravenously injected into mice treated with elastase, only $5{\times}10^4$ MSCs showed a significant effect on the emphysematous mouse lung. We also identified action mechanisms of MSCs based on apoptosis, lung regeneration, and protease/antiprotease imbalance. Results: The MSCs were not related with caspase-3/7 dependent apoptosis. But activity of matrix metalloproteinase 9 increased by emphysematous lung was decreased by intravenously injected MSCs. Vascular endothelial growth factor were also increased in lung from MSC injected mice, as compared to un-injected mice. Conclusion: This is the first study on the optimal dose of MSCs as a therapeutic candidate. This data may provide important basic data for determining dosage in clinical application of MSCs in emphysema patients.

• Tuberculosis and Respiratory Diseases
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• 제80권3호
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• pp.265-269
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• 2017

Background: The first line of anti-tuberculosis (TB) drugs are the most effective standard of drugs for TB. However, the use of these drugs is associated with hepatotoxicity. Silymarin has protective effects against hepatotoxicity of anti-TB drugs in animal models. This study aims to investigate the protective effect of silymarin on hepatotoxicity caused by anti-TB drugs. Methods: This is a prospective, randomized, double-blind and placebo-controlled study. Patients were eligible if they were 20 years of age or order and started the first-line anti-tuberculosis drugs. Eligible patients were randomized for receiving silymarin or a placebo for the first 4 weeks. The primary outcome was the proportion of patients who showed elevated serum liver enzymes more than 3 times the upper normal limit (UNL) or total bilirubin (TBil) > $2{\times}UNL$ within the first 8 weeks of anti-TB treatment. Results: We enrolled a total of 121 patients who silymarin or a placebo to start their anti-TB treatment, for the first 8 weeks. The proportions of elevated serum liver enzymes more than 3 times of UNL at week 2, week 4, and week 8 did not show any significant difference between the silymarin and placebo groups, at 0% versus 3.6% (p>0.999); 4.4% versus 3.6% (p>0.999); and 8.7% versus 10.8% (p=0.630), respectively. However, patients with TBil >$2{\times}UNL$ at week 8 were significantly low in the silymarin group (0% versus 8.7%, p=0.043). Conclusion: Our findings did not show silymarin had any significant preventive effect on the hepatotoxicity of anti-TB drugs.

• Molecules and Cells
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• 제40권12호
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• pp.906-915
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• 2017

Impairment of wound healing is a common problem in individuals with diabetes. Adiponectin, an adipocyte-derived cytokine, has many beneficial effects on metabolic disorders such as diabetes, obesity, hypertension, and dyslipidemia. C1q/TNF-Related Protein 9 (CTRP9), the closest paralog of adiponectin, has been reported to have beneficial effects on wound healing. In the current study, we demonstrate that CTRP9 regulates growth, differentiation, and apoptosis of HaCaT human keratinocytes. We found that CTRP9 augmented expression of transforming growth factor beta 1 ($TGF{\beta}1$) by transcription factor activator protein 1 (AP-1) binding activity and phosphorylation of p38 in a dose-dependent manner. Furthermore, siRNA-mediated suppression of $TGF{\beta}1$ reversed the increase in p38 phosphorylation induced by CTRP9. siRNA-mediated suppression of $TGF{\beta}1$ or p38 significantly abrogated the effects of CTRP9 on cell proliferation and differentiation while inducing apoptosis, implying that CTRP9 stimulates wound recovery through a $TGF{\beta}1$-dependent pathway in keratinocytes. Furthermore, intravenous injection of CTRP9 via tail vein suppressed mRNA expression of Ki67 and involucrin whereas it augmented $TGF{\beta}1$ mRNA expression and caspase 3 activity in skin of type 1 diabetes animal models. In conclusion, our results suggest that CTRP9 has suppressive effects on hyperkeratosis, providing a potentially effective therapeutic strategy for diabetic wounds.

• 대한한방내과학회지
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• 제37권3호
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• pp.467-483
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• 2016

Objective: This study was performed to investigate the effect of IUS (Inulsan, an extract of Artemisiae capillaris (茵蔯), Curcumae longae (鬱金), and Crataegi fructus (山査)) on anti-hyperlipidemia, anti-oxidation, and anti-inflammation.Method: We administered water extracts of Artemisiae capillaris, Curcumae longae, and Crataegi fructus for three weeks to db/db mice (C57BL/Ks), animal models induced with type 2 diabetes mellitus. Mice were divided into three groups: normal (C57BL/6J mice group), control group (db/db mice without administration of IUS) and IUS group (db/db mice treated with IUS). Then we measured total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride in the serum after the oral administration of IUS.Results: 1. IUS did not show any cytotoxicity in RAW 264.7 cells. 2. IUS decreased AST, ALP, and creatinine levelsand did not show any liver or renal toxicity in the db/db mice. 3. IUS increased DPPH and ABTS radical scavenging activity and decreased ROS production in RAW 264.7 cells. 4. IUS significantly decreased IL-1β, IL-6, and TNF-α production in RAW 264.7 cells. 5. IUS increased HDL cholesterol and significantly decreased total cholesterol and triglyceride in db/db mice. 6. IUS significantly decreased the atherogenic index and cardiac risk factor. 7. In contrast with the control group, fat infiltration in the liver and aorta decreased in IUS treated mice. The cell nucleus was located in the central area in H&E staining of liver. And endomembranes also were more thinner than the control group in H&E staining of aorta.Conclusions: These results suggest that IUS might be effective in the prevention and treatment of dyslipidemia.

• Biomolecules & Therapeutics
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• 제24권5호
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• pp.536-542
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• 2016

Shuangdan oral liquid (SDO) containing radix Salviae miltiorrhizae (Chinese name Danshen) and cortex moutan (Chinese name Mudanpi) is a traditional Chinese medicine using for treating vascular diseases. Danshensu (DSS) is a main effective monomer composition derived from radix Salviae miltiorrhizae and paeonol (Pae) from cortex moutan. Although the two herbs are widely used in traditional Chinese medicine, the pharmacological functions of their active compositions were not reported. Therefore, the research of DSS and Pae in mechanisms and pharmacodynamics interaction can provide scientific evidence to support clinical application. The diabetic nephropathy (DN) rats which were induced by streptozotocin (STZ) were treated with SDO, DSS, Pae, and DSS+Pae for eight weeks. The positive effects on DN animal models were investigated by detection of physiological and biochemical indexes and oxidative stress markers, within five treatments: SDO, DSS, Pae, DSS+Pae and insulin group. Compared with the model group, the DSS+Pae group improved the renal function, blood lipid metabolism and blood viscosity, increased the vitality of T-SOD or T-AOC and decreased the level of MDA or NO after the treatment. The study was successfully showed that the DSS+Pae group could delay the process of DN, especially in the renal injury part of histopathology changes. Our results suggest that the co-administration of DSS and Pae significantly may play a protective role in DN rats through decreasing the oxidative stress and improving the blood lipid metabolism mechanisms.

• Biomolecules & Therapeutics
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• 제26권3호
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• pp.242-254
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• 2018

Defensins are antimicrobial peptides that participate in the innate immunity of hosts. Humans constitutively and/or inducibly express ${\alpha}$- and ${\beta}$-defensins, which are known for their antiviral and antibacterial activities. This review describes the application of human defensins. We discuss the extant experimental results, limited though they are, to consider the potential applicability of human defensins as antiviral agents. Given their antiviral effects, we propose that basic research be conducted on human defensins that focuses on RNA viruses, such as human immunodeficiency virus (HIV), influenza A virus (IAV), respiratory syncytial virus (RSV), and dengue virus (DENV), which are considered serious human pathogens but have posed huge challenges for vaccine development for different reasons. Concerning the prophylactic and therapeutic applications of defensins, we then discuss the applicability of human defensins as antivirals that has been demonstrated in reports using animal models. Finally, we discuss the potential adjuvant-like activity of human defensins and propose an exploration of the 'defensin vaccine' concept to prime the body with a controlled supply of human defensins. In sum, we suggest a conceptual framework to achieve the practical application of human defensins to combat viral infections.

• Nuclear Medicine and Molecular Imaging
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• 제42권2호
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• pp.98-111
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• 2008

This review introduces advances in clinical and pre-clinical single photon emission computed tomography (SPECT) and positron emission tomography (PET) providing noninvasive functional images of biological processes. Development of new collimation techniques such as multi-pinhole and slit-slat collimators permits the improvement of system spatial resolution and sensitivity of SPECT. Application specific SPECT systems using smaller and compact solid-state detector have been customized for myocardial perfusion imaging with higher performance. Combined SPECT/CT providing improved diagnostic and functional capabilities has been introduced. Advances in PET and CT instrumentation have been incorporated in the PET/CT design that provide the metabolic information from PET superimposed on the anatomic information from CT. Improvements in the sensitivity of PET have achieved by the fully 3D acquisition with no septa and the extension of axial field-of-view. With the development of faster scintillation crystals and electronics, time-of-flight (TOF) PET is now commercially available allowing the increase in the signal-to-noise ratio by incorporation of TOF information into the PET reconstruction process. Hybrid PET/SPECT/CT systems has become commercially available for molecular imaging in small animal models. The pre-clinical systems have improved spatial resolution using depth-of-interaction measurement and new collimators. The recent works on solid state detector and dual modality nuclear medicine instrumentations incorporating MRI and optical imagers will also be discussed.