• Molecules and Cells
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• v.41 no.4
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• pp.290-300
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• 2018

Using an in vitro model of intestinal organoids derived from intestinal crypts, we examined effects of indole-3-carbinol (I3C), a phytochemical that has anticancer and aryl hydrocarbon receptor (AhR)-activating abilities and thus is sold as a dietary supplement, on the development of intestinal organoids and investigated the underlying mechanisms. I3C inhibited the in vitro development of mouse intestinal organoids. Addition of ${\alpha}$-naphthoflavone, an AhR antagonist or AhR siRNA transfection, suppressed I3C function, suggesting that I3C-mediated interference with organoid development is AhR-dependent. I3C increased the expression of Muc2 and lysozyme, lineage-specific genes for goblet cells and Paneth cells, respectively, but inhibits the expression of IAP, a marker gene for enterocytes. In the intestines of mice treated with I3C, the number of goblet cells was reduced, but the number of Paneth cells and the depth and length of crypts and villi were not changed. I3C increased the level of active nonphosphorylated ${\beta}$-catenin, but suppressed the Notch signal. As a result, expression of Hes1, a Notch target gene and a transcriptional repressor that plays a key role in enterocyte differentiation, was reduced, whereas expression of Math1, involved in the differentiation of secretory lineages, was increased. These results provide direct evidence for the role of AhR in the regulation of the development of intestinal stem cells and indicate that such regulation is likely mediated by regulation of Wnt and Notch signals.

• Journal of Animal Reproduction and Biotechnology
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• v.34 no.3
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• pp.148-156
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• 2019

The Transgenic livestock can be useful for the production of disease-resistant animals, pigs for xenotranplantation, animal bioreactor for therapeutic recombinant proteins and disease model animals. Previously, conventional methods without using artificial nuclease-dependent DNA cleavage system were used to produce such transgenic livestock, but their efficiency is known to be low. In the last decade, the development of artificial nucleases such as zinc-finger necleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regulatory interspaced short palindromic repeat (CRISPR)/Cas has led to more efficient production of knock-out and knock-in transgenic livestock. However, production of knock-in livestock is poor. In mouse, genetically modified mice are produced by coinjecting a pair of knock-in vector, which is a donor DNA, with a artificial nuclease in a pronuclear fertilized egg, but not in livestock. Gene targeting efficiency has been increased with the use of artificial nucleases, but the knock-in efficiency is still low in livestock. In many research now, somatic cell nuclear transfer (SCNT) methods used after selection of cell transfected with artificial nuclease for production of transgenic livestock. In particular, it is necessary to develop a system capable of producing transgenic livestock more efficiently by co-injection of artificial nuclease and knock-in vectors into fertilized eggs.

• Journal of Physiology & Pathology in Korean Medicine
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• v.33 no.6
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• pp.341-348
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• 2019

The purpose of this study was to investigate the efficacy of Torreyae semen extract against antimicrobial and allergic contact dermatitis to explore its utility as a herbal resource. To this end, the antibacterial effects of Torreyae Semend extracted with hot water and ethanol (30%, 60%, 90%) were investigated using Staphylococcus aureus, Staphylococcus epidermidis, pseudomonas aeruginosa, and Propionibacterium acnes. And observed the anti-atopic dermatitis efficacy with a mouse model that allergic contact dermatitis induced by DNCB. Experimental results showed that the antibacterial activity against S. epidermidis and P. aeruginosa was significantly higher in the hot water extract of Torreyae Semen. We observed that the extracts of 30% ethanol and hot water of Torreyae Semen inhibited growth in a concentration-dependent manner in P. acnes & S. epidermidis. We observed that the administration of hot water extracts and 30% ethanol extract of Torreyae Semen significantly reduce the thickness of ear & back and gross skin condition compared to the control group in the mice with allergic contact dermatitis. As a result of H & E histological staining, it was observed that the Torreyae Semen extraction group had markedly reduced epidermis and skin thickness, granules, and keratinization compared to the control group. The groups administrated with Torreyae Semen hot water extracts had decreased TNF-α and IL-10 contents compared with the control group. As a result, Torreyae Semen may be used as a useful herbal resource because it has a certain level of antibacterial and anti-atopic effects.

• Korean Journal of Pharmacognosy
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• v.37 no.4 s.147
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• pp.246-252
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• 2006

Processing of traditional herbal medicine is one of the pharmaceutical technique in oriental medicine. Most frequently used processing method in oriental medicine are roasting and steaming. In this studies, to elucidate the pharmacological transformation of traditional herbal medicine by means of processing them, Ginseng Radix (root of Panax ginseng, Araliaceae) was used as a sample. Processed ginseng radix (SGR, Sun Ginseng) was prepared by steaming of roots of white ginseng (GR) for 3 hours at $120^{\circ}C$. The biological activities of methanol extract of GR and SGR were investigated. According to DPPH radical scavenging effects, and inhibitory effects of xanthine oxidase and AAPH induced hemolysis, PGR exhibited more effective than those of GR in vitro. And, the antifatigue effect of GR and SGR were investigated using a weight-loading forced swimming test by monitoring swimming times and prolonged intensity exercise model rats by measuring blood biochemical parameters. GR and SGR were significantly prolonged swimming times in 8% body weight ratio loaded mice. Also, they had the inhibitory effects on the decrease of blood glucose levels, the elevation of serum creatinine, lactic acid and free fatty acid, and lactic dehydrogenase activities in forces swimming rats with 1% of the body weight attached to the neck for 3 hours. SGR was more excellent than GR on these effect. Also, these effects were transformed to the n-butanol fraction of methanol extract of SGR. From these results, it can be considered that SGR has antifatigue effect.

• Archives of Plastic Surgery
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• v.37 no.5
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• pp.526-530
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• 2010

Purpose: With the recent recognition of the importance of soft-tissue fillers, fat grafting has been assumed an increasingly important role as both an adjunctive and a primary procedure in aesthetic and reconstructive surgery. The main problem in achieving long-term soft-tissue augmentation is partial absorption of the injected fat and hence the need for overcorrection and re-injection. The purpose of this study is to improve the viability of the injected fat by the use of Lipo-PGE1. Methods: Human adipose tissue, obtained by suctionassisted lipectomy, was re -injected into the subcutaneous layer in the scalp of ICR mice. Lipo-PGE1 ($0.5{\mu}g$/kg) was injected intravenously in experimental group for 7 days from the operation day and saline was injected in control group. There were 5 animals in each group. The animals were euthanized 4 weeks after the procedure. Graft weight and volume were measured and histologic evaluation was performed. Result: Histologic analysis demonstrated significantly less cyst formation and less inflammatory reaction in the group treated with Lipo-PGE1. No significant difference was found between the groups regarding graft volume or the other histologic parameters investigated. Significant differences were demonstrated in microvascular density count. Conclusion: Less cyst formation, less inflammation, more angiogenesis indicating improved quality of the injected fat can be obtained by the addition of Lipo-PGE1. Further studies of various dosages of Lipo-PGE1 and their long-term effect are required before these encouraging results could be applied clinically.

• Biomolecules & Therapeutics
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• v.24 no.3
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• pp.283-290
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• 2016

Oroxylum indicum has long been used in Asian traditional medicine to prevent and treat respiratory diseases, diabetes, diarrhea and other conditions. Oroxylin A is a flavone that is present in Oroxylum indicum and in Scutellaria baicalensis. Because the root extracts of both plants have been shown to have anti-allergic effects, the authors investigated whether oroxylin A is likely to have beneficial effects on allergic asthma using female Balb/c mice and rat RBL-2H3 mast cells. Antigen-induced degranulation was measured in vitro by measuring b-hexosaminidase activity. A murine ovalbumin-induced allergic asthma model was used to test the in vivo efficacy of oroxylin A. Sensitization and challenge of ovalbumin induced allergic asthma responses, the accumulations of eosinophils and Th2 cytokine levels in bronchoalveolar lavage fluid and lung tissues. Oroxylin A administration decreased numbers of inflammatory cells, especially eosinophils, and reduced the expression and secretion of Th2 cytokines, including IL-4 and IL-13, in lung tissues and bronchoalveolar lavage fluid. Histologic studies showed oroxylin A reduced inflammatory signs and mucin production in lungs. These findings provide evidence that oroxylin A has potential use as an anti-allergic therapeutic.

• Biomolecules & Therapeutics
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• v.26 no.6
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• pp.576-583
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• 2018

Human rhinoviruses (HRV) are one of the major causes of common cold in humans and are also associated with acute asthma and bronchial illness. Heat-shock protein 90 (Hsp90), a molecular chaperone, is an important host factor for the replication of single-strand RNA viruses. In the current study, we examined the effect of the Hsp90 inhibitor pochonin D, in vitro and in vivo, using a murine model of human rhinovirus type 1B (HRV1B) infection. Our data suggested that Hsp90 inhibition significantly reduced the inflammatory cytokine production and lung damage caused by HRV1B infection. The viral titer was significantly lowered in HRV1B-infected lungs and in Hela cells upon treatment with pochonin D. Infiltration of innate immune cells including granulocytes and monocytes was also reduced in the bronchoalveolar lavage (BAL) by pochonin D treatment after HRV1B infection. Histological analysis of the lung and respiratory tract showed that pochonin D protected the mice from HRV1B infection. Collectively, our results suggest that the Hsp90 inhibitor, pochonin D, could be an attractive antiviral therapeutic for treating HRV infection.

• Biomolecules & Therapeutics
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• v.28 no.2
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• pp.152-162
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• 2020

Cerebral ischemia exhibits a multiplicity of pathophysiological mechanisms. During ischemic stroke, the reactive oxygen species (ROS) concentration rises to a peak during reperfusion, possibly underlying neuronal death. Recombinant human erythropoietin (EPO) supplementation is one method of treating neurodegenerative disease by reducing the generation of ROS. We investigated the therapeutic effect of PEGylated EPO (P-EPO) on ischemic stroke. Mice were administered P-EPO (5,000 U/kg) via intravenous injection, and middle cerebral artery occlusion (MCAO) followed by reperfusion was performed to induce in vivo ischemic stroke. P-EPO ameliorated MCAO-induced neurological deficit and reduced behavioral disorder and the infarct area. Moreover, lipid peroxidation, expression of inflammatory proteins (cyclooxygenase-2 and inducible nitric oxide synthase), and cytokine levels in blood were reduced by the P-EPO treatment. In addition, higher activation of nuclear factor kappa B (NF-κB) was found in the brain after MCAO, but NF-κB activation was reduced in the P-EPO-injected group. Treatment with the NF-κB inhibitor PS-1145 (5 mg/kg) abolished the P-EPO-induced reduction of infarct volume, neuronal death, neuroinflammation, and oxidative stress. Moreover, P-EPO was more effective than EPO (5,000 U/kg) and similar to a tissue plasminogen activator (10 mg/kg). An in vitro study revealed that P-EPO (25, 50, and 100 U/mL) treatment protected against rotenone (100 nM)-induced neuronal loss, neuroinflammation, oxidative stress, and NF-κB activity. These results indicate that the administration of P-EPO exerted neuroprotective effects on cerebral ischemia damage through anti-oxidant and anti-inflammatory properties by inhibiting NF-κB activation.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.14 no.1
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• pp.117-128
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• 2001

Gamiseunggal-tang(G-tang) has long been used for the treatment of acute and chronic allergic diseases(especially, urticaria) in oriental medicine. But, It's mechanism of action is not well investigated. Anal therapy is another way of taking medicine, which is not used in common situation but available for the treatment of colon and anal diseases. It is also used in GI tract diseases, Gynecological diseases, and pediatric diseases and so on. It is especially benefitable for patients who are in such situations as coma, severe vomiting, and swallowing difficulty. In this study, the author investigated the effects of G-tang by anal therapy on acute and chronic allergic reactions in murine model. The results obtained are as follows: 1. G-tang(0.01, 0.1 g/kg) inhibited the compound 48/80-induced ear swelling response in mice. Inhibitory effects of G-tang was significant (P<0.05) at the dose of 0.01 g/kg. 2. G-tang(0.001-0.1 g/kg) inhibited the cutaneous allergic reaction activated by anti-dinitrophenyl(DNP) IgE in rats. Especially, G-tang 0.01, 0.1 g/kg inhibited the cutaneous allergic reaction significantly. 3. G-tang(0.01-1 g/L) dose-dependently inhibited the compound 48/80-induced histamine release from the peritoneal mast cells. 4. G-tang(0.001-0.1 g/L) had a inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-${\alpha}$ production. Above results indicate that anal therapy of G-tang may be beneficial in the treatment of acute and chronic allergic diseases.

• The Journal of Internal Korean Medicine
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• v.38 no.6
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• pp.877-890
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• 2017

Objectives: Lonicerae flos (LF), a dried flower part of Lonicera japonica Thunb., has been widely used in Korean medicine as anti-inflammatory and antioxidative agent. The purpose of this study was to determine the cardioprotective effects of LF, through potential antioxidant effects, on the pressure overload (PO)-induced heart failure (HF) in C57BL/6 mice after transverse aortic constriction (TAC) surgery. Methods: Resveratrol (10 mg/kg body weight) or LF (125, 250 or 500 mg/kg body weight) was orally administered, once daily for 14 days, starting 14 days after TAC surgery. Changes in the mortality, body weights, heart weights, histopathology of the heart, and antioxidant defense systems of the heart were analyzed. Results: Marked and noticeable increases of heart weights, mortalities, and hypertrophic, focal, and lytic fibrotic histological changes in the LVs were observed, with destruction of heart antioxidant defense systems after surgery. However, HF signs, induced by TAC surgery through PO, and destruction of heart antioxidant defense systems were significantly and dose-dependently inhibited by 14 days of maintained oral treatment with LF 500, 250 or 125 mg/kg. Treatment with 250 mg/kg LF was comparable to treatment with 10 mg/kg resveratrol. Conclusions: The results in this study suggest that oral administration of LF favorably relieves PO-induced HF following TAC, through increase of heart antioxidant defense systems. The overall effects of 250 mg/kg LF were similar to those of 10 mg/kg resveratrol. More detailed mechanistic studies should be conducted in the future, with screening of the biologically active compounds in LF.