• Biomolecules & Therapeutics
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• v.23 no.6
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• pp.597-603
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• 2015

Synthetic cannabinoids JWH-018 and JWH-250 in 'herbal incense' also called 'spice' were first introduced in many countries. Numerous synthetic cannabinoids with similar chemical structures emerged simultaneously and suddenly. Currently there are not sufficient data on their adverse effects including neurotoxicity. There are only anecdotal reports that suggest their toxicity. In the present study, we evaluated the neurotoxicity of two synthetic cannabinoids (JWH-081 and JWH-210) through observation of various behavioral changes and analysis of histopathological changes using experimental mice with various doses (0.1, 1, 5 mg/kg). In functional observation battery (FOB) test, animals treated with 5 mg/kg of JWH-081 or JWH-210 showed traction and tremor. Their locomotor activities and rotarod retention time were significantly (p<0.05) decreased. However, no significant change was observed in learning or memory function. In histopathological analysis, neural cells of the animals treated with the high dose (5 mg/kg) of JWH-081 or JWH-210 showed distorted nuclei and nucleus membranes in the core shell of nucleus accumbens, suggesting neurotoxicity. Our results suggest that JWH-081 and JWH-210 may be neurotoxic substances through changing neuronal cell damages, especially in the core shell part of nucleus accumbens. To confirm our findings, further studies are needed in the future.

• Biomolecules & Therapeutics
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• v.25 no.5
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• pp.545-552
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• 2017

Increasing concern is being given to the association between risk of cancer and exposure to low-dose bisphenol A (BPA), especially in young-aged population. In this study, we investigated the effects of repeated oral treatment of low to high dose BPA in juvenile Sprague-Dawley rats. Exposing juvenile rats to BPA (0, 0.5, 5, 50, and 250 mg/kg oral gavage) from post-natal day 9 for 90 days resulted in higher food intakes and increased body weights in biphasic dose-effect relationship. Male mammary glands were atrophied at high dose, which coincided with sexual pre-maturation of females. Notably, proliferative changes with altered cell foci and focal inflammation were observed around bile ducts in the liver of all BPA-dosed groups in males, which achieved statistical significance from 0.5 mg/kg (ANOVA, Dunnett's test, p<0.05). Toxicokinetic analysis revealed that systemic exposure to BPA was greater at early age (e.g., 210-fold in $C_{max}$, and 26-fold in AUC at 50 mg/kg in male on day 1 over day 90) and in females (e.g., 4-fold in $C_{max}$ and 1.6-fold in AUC at 50 mg/kg vs. male on day 1), which might have stemmed from either age- or gender-dependent differences in metabolic capacity. These results may serve as evidence for the association between risk of cancer and exposure to low-dose BPA, especially in young children, as well as for varying toxicity of xenobiotics in different age and gender groups.

• The Journal of Internal Korean Medicine
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• v.31 no.3
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• pp.650-666
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• 2010

Objectives : In this study, the author tried to investigate whether wood vinegar produced from Morus alba (MA) significantly affects the increase in airway epithelial mucosubstances and hyperplasia of tracheal goblet cells of rats, and in vitro airway mucin secretion and PMA- or EGF- or TNF-alpha-induced MUC5AC mucin production / gene expression from human airway epithelial cells. Materials and Methods : For the in vivo experiment, the author induced hypersecretion of airway mucus and goblet cell hyperplasia by exposure of rats to SO2 over 3 weeks. Effect of orally-administered MA over 2 weeks on increase in airway epithelial mucosubstances from tracheal goblet cells of rats and hyperplasia of goblet cells were assessed using histopathological analysis after staining the epithelial tissue with alcian blue. For the in vitro experiment, confluent RTSE cells were chased for 30 min in the presence of MA to assess the effect of MA on mucin secretion by enzyme-linked immunosorbent assay (ELISA). Also, effects of MA on PMA- or EGF- or TNF-alpha-induced MUC5AC mucin production and gene expression from human airway epithelial cells (NCI-H292) were investigated. Confluent NCI-H292 cells were pretreated for 30 min in the presence of MA and treated with PMA (10 ng/ml), EGF (25 ng/ml) or TNF-alpha (0.2 nm) for 24 hrs, to assess both effects of MA on PMA- or EGF- or TNF-alpha-induced MUC5AC mucin production by enzyme-linked immunosorbent assay (ELISA) and gene expression by reverse transcription-polymerase chain reaction (RT-PCR). Possible cytotoxicities of MA in vitro were assessed by examining LDH release from RTSE cells and the rate of survival and proliferation of NCI-H292 cells. In vivo liver and kidney toxicities of MA were evaluated by measuring serum GOT/GPT activities and serum BUN/creatinine concentrations of rats after administering MA orally. Results : 1. MA decreased the amount of intraepithelial mucosubstances of rats exposed to sulfur dioxide inhalationally. 2. MA decreased in vitro mucin secretion from cultured RTSE cells. 3. MA significantly inhibited PMA-, EGF-, and TNF-alpha-induced MUC5AC mucin productions and the expression levels of MUC5AC mRNA from NCI-H292 cells. 4. MA did not show either in vitro or in vivo hepatic or renal toxicities. Conclusion : The results from this study suggests that MA can regulate the secretion, production and gene expression of airway mucin observed in diverse respiratory diseases accompanied by mucus hypersecretion and does not show in vivo toxicity to liver and kidney functions after oral administration. Effects of MA should be further studied using animal experimental models that simulate the diverse pathophysiology of respiratory diseases via future research.

• Biomolecules & Therapeutics
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• v.10 no.2
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• pp.71-77
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• 2002

Heme oxygenase-1 (HO-1) is the inducible from of the rate-limiting enzyme of heme degradation; it regulates the cellular contents of heme. HO-1 is up-regulated by various stimuli including oxidative stress so that it is thought to participate in general cellular defense mechanisms against oxidative stress in mammalian cells. To investigate the role of the cAMP-dependent protein kinase A (PKA) signaling pathway on nitrogen oxidative stress-induced HO-1 gene expression, RAW 264.7 cell cultures were treated with sodium nitroprusside (SNP). SNP increased the expression of HO-1 mRNA and protein, time- and concentration-dependently. Treatment with H89, PKA inhibitor, but not LY83583, guanylate cyclase inhibitor, significantly diminished the HO-1 expression by SNP, indicating that cAMP plays a crucial role in the induction of HO-1. Incubation with cAMP-elevating agents, such as forskolin or isoproterenol resulted in up-regulation of the expression of HO-1. Forskolin-induced expression of HO-1 was inhibited by H89. Furthermore, propranolol, $\beta$-adrenoceptor blocker, inhibited the isoproterenol-induced HO-1 expression, supporting the importance of cAMP in the induction of HO-1 expression. Higenamine-S, but not higenamineR, enhanced the HO-1 expression induced by SNP. Furthermore, cellular toxicity induced by hydrogen peroxide was attenuated by the presence of SNP, which was further increased by the presence of ZnPPIX, HO-1 inhibitor. Collectively, these results strongly suggest that up-regulation of HO-1 expression in RAW 264.7 cells involves PKA signal pathway.

• The Korean Journal of Pharmacology
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• v.31 no.3
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• pp.377-384
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• 1995

We examined the wound healing effect and toxicity of Forsythia suspensa extract to verify the therapeutic usefulness on wound treatment. Additionally, we examined its antibacterial effect. The wound healing effect of Forsythia suspensa extract was compared with the tetrachlorodecaoxygen anion complex (TCDO), protein free haemodialysate (Haemyl), and physiological saline. The wound areas on the 4th, 11th, 14th day of treatment with Forsythia suspensa extract, TCDO, and Haemyl were significantly smaller than with the saline treatment. The wounds on the 8th day of treatment with Forsythia suspensa extract were only siginificantly smaller than the saline treatment. On the 8th day of treatment with Forsythia suspensa extract, TCDO, and Haemyl accerlerlated the wound epithelization more than saline treatment. There was not a significant difference in liver enzyme activity (GOT, GPT) and blood cell count between the Fosythia suspensa extract and the saline treatment. In addition, the Forsythia suspensa extract did not inhibit bacterial proliferation. These results suggest that Forsythia suspensa extract has great possibility of being developed into new wound healing drugs. Its pharmacological effects seem to have no relation with antibacterial effect.

• Herbal Formula Science
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• v.15 no.2
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• pp.35-45
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• 2007

Objective : The purpose of this report was to provide the information activity and safety of Palmul-tang by analyzing domestic/international papers and theses about Palmul-tang, Methods: Domestic/international papers and theses related to Palmul-tang were reviewed and analyzed, These papers were then classified by year, experimental method and subject, Results: The following results were obtained in this study. 1. The study of Palmul-tang started from 1985 and was continuously increased. The study was mainly forcused on experimental model rather than clinical study. 2. As these studies were classified by subject, papers related to immune intensification were most abundant by 20 papers, Besides there were several papers related to cardiovascular activity, reproductive activity, anti-apoptotic activity and cerebral hemodynamics. 3. Among the papers related to immune intensification. the studies on recovery of fatigue were mostabundant by 10 papers and the studies of on immune cell and cytokine express were six. In addition to. several studies were associated with anti-cancer activity and anti-allergic activity. Recovery of fatigue was determined by measurement of fatigue markers in a living body such as lactate. CPK, pyruvate and triglyceride and assessment of exercise capability of animals such as swimming test. slopped plate test. Rota-rod test, and activity cage test after Palmul-tang treatment. 4. According to experimental data. it is supported that Palmul-tang has been used as Qi and Blood intensifier with immune intensification and recovery of fatigue. 5. The paper related to safety of Palmul-tang was only one paper which is studied on acute toxicity of Palmul-tang with experiment with ICR mouse. There was no study on evaluating safety by observing liver and kidney functions after Palmul-tang treatment Conclusion: Palmul-tang is being used in various ways associating with immune intensification. cardiovascular activity and reproductive activity. However. studies on efficacy and mechanism of Palmul-tang should be conducted at the molecular biology level and studies on safety of Palmul-tang need to be completed at the clinical level.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.3 no.1
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• pp.85-98
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• 1997

Oriental medicine as a candidate for effective cancer treatment recently gain positive concerns in fields of therapeutic oncology. that is why some herbal medicines have been empirically safer in toxicity than anticancer drugs used in western medicine, and to show excellent therapeutic efficacy in human trial. Thus, these effects by clinically applied-herbs have not yet fully demonstrated in experimental tumor model. This study was initiated to evaluate the antitumor effect of Insambaekhaptang as candidate of antitumor-herbal agent against B16 melanoma metastasized into C57BL/6 mice lung. In experiment to test whether Insambaekhaptang can directly kill cancer cells in vitro or not, Insambaekhaptang showed direct killing action in concentration or higher against B16 melanoma cells using MTT assay, and showed lower IC50. Another experiment to know whether Insambaekhaptang can inhibit growth and metastasis of cancer cell or not, Insambaekhaptang significantly inhibited Solid tumor by intraperiperal injected-melanoma and lung metastasis induced by intravenous injected-melanoma in inbred C57BL/6 mice. When quantitative survival time increasing, we could obtain results that increased 113% in treated by Insambaekhaptang. These results show that Insambaekhaptang can inhibit growth of B16 melanoma cells through various biological mechanisms.

• Journal of the Korean Applied Science and Technology
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• v.37 no.4
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• pp.820-829
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• 2020

This study was conducted to investigate the anti-oxydant and anti-winkle efficacy as cosmetics ingredient of Lysimachia christinae Hance. Recently, the study of wrinkle improvement of natural products has received continuous interest. so we looked at relationship between reactive oxygen species (ROS) generation and pro-collagen synthesis and matrix metalloproteinases (MMPs) through this study. L. christinae Hance were extracted with 70% ethanol (LcHE) and distilled water (LcHW), respectively, and the experiment was conducted. LcHE had better ROS inhibition effect than LcHW and showed no toxicity up to 250 ㎍/mL concentration as a result of MTT assay in HaCaT cells, so we selected LcHE and conducted the wrinkle improvement material study. We confirmed that the synthesis of type-1 pro-collagen reduced by UVB is activated through pro-collagen synthesis assay. we confirmed that LcHE inhibited the increase in MMP-1 -3 -9 of MMPs induced by UVB in skin cells through western blot and we also performed real-time PCR to confirm the effect of the extract with dependence of concentration at mRNA levels. Therefore, it is expected that Lysimachia christinae Hance is used as a natural material for cosmetics that can effectively prevent wrinkles and skin aging by UVB.

• Journal of Biomedical Engineering Research
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• v.38 no.1
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• pp.43-48
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• 2017

Chemotherapy, radiation therapy, and surgery are major methods to treat cancer. However, current cancer treatments report severe side effects and high recurrences. Recent studies about engineering nanoparticles as a drug carrier suggest possibilities in terms of specific targeting and spatiotemporal release of drugs. While many nanoparticles demonstrate lower toxicity and better targeting results than free drugs, they still need to improve their performance dramatically in terms of targeting accuracy, immune responses, and non-specific accumulation at organs. One possible way to overcome the challenges is to make precisely controlled nanoparticles with respect to size, shape, surface properties, and mechanical stiffness. Here, we demonstrate $500{\times}200nm$ discoidal polymeric nanoconstructs (DPNs) as a drug delivery carrier. DPNs were prepared by using a top-down fabrication method that we previously reported to control shape as well as size. Moreover, DPNs have multiple payloads, poly lactic-co-glycolic acid (PLGA), polyethylene glycol (PEG), lipid-Rhodamine B dye (RhB) and Salinomycin. In this study, we demonstrated a potential of DPNs as a drug carrier to treat cancer.

• Journal of Korean Ophthalmic Optics Society
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• v.12 no.2
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• pp.67-78
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• 2007

The eye irritant test of lens washing agent, CLIWELL$^{TM}$ was conducted using Draize methods according to KFDA Guidelines. In addition, to test the potential toxicity of test articles, the ratio of inflammatory cells and non-inflammatory epitheloid cells was also observed using smear cytology methods against ocular discharge. At sacrifice, the histopathological changes on Cornea, Iris, Retina and Sclera were also observed in all animals. Slight irritancy of cornea and conjunctiva was observed at 1, 2 and 3 days after dropping in non-washing group. The MIOI of these points are detected as 4.50, 1.67 and 0.67, respectively. In washing group, slight irritancy of cornea and conjunctiva were observed at 1 and 2 days after dropping with MIOI as 0.67, respectively. Therefore, CLIWELL$^{TM}$ was considered as non-irritating materials because the MIOI is detected below 5.00 throughout the whole experimental periods in both washing and non-washing groups and the IAOI was also detected as 4.50. Except for significant increase of the inflammatory cell ratios in ocular discharge at 1 day after dropping of non-washing group compared to that non-treated intact eyes, no meaningful changes on smear cytology of ocular discharges are observed in this study. In addition, no abnormal histopathological changes on the cornea, iris, retina and sclera were also detected in CLIWELL$^{TM}$ dropping group compared to that of non-treated intact eyes.