• The Korean Journal of Physiology and Pharmacology
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• v.18 no.2
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• pp.129-134
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• 2014

It has been suggested that transition metal ions such as iron can produce an oxidative injuries to nigrostriatal dopaminergic neurons, like Parkinson's disease (PD) and subsequent compensative increase of tetrahydrobiopterin ($BH_4$) during the disease progression induces the aggravation of dopaminergic neurodegeneration in striatum. It had been established that the direct administration of $BH_4$ into neuron would induce the neuronal toxicity in vitro. To elucidate a role of $BH_4$ in pathogenesis in the PD in vivo, we assessed the changes of dopamine (DA) and $BH_4$ at striatum in unilateral intranigral iron infused PD rat model. The ipsistriatal DA and $BH_4$ levels were significantly increased at 0.5 to 1 d and were continually depleting during 2 to 7 d after intranigral iron infusion. The turnover rate of $BH_4$ was higher than that of DA in early phase. However, the expression level of GTP-cyclohydrolase I mRNA in striatum was steadily increased after iron administration. These results suggest that the accumulation of intranigral iron leads to generation of oxidative stress which damage to dopaminergic neurons and causes increased release of $BH_4$ in the dopaminergic neuron. The degenerating dopaminergic neurons decrease the synthesis and release of both $BH_4$ and DA in vivo that are relevance to the progression of PD. Based on these data, we propose that the increase of $BH_4$ can deteriorate the disease progression in early phase of PD, and the inhibition of $BH_4$ increase could be a strategy for PD treatment.

• Biomolecules & Therapeutics
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• v.25 no.5
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• pp.528-534
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• 2017

Placenta is a special organ that contains many nutrients such as growth factors, minerals, and bioactive peptides. Dipeptides of glycine and leucine are major components of porcine placenta extracts (PPE) that has been used as an alternative of human placenta extracts. In this study, we investigated whether major peptides of PPE, Glycyl-L-Leucine (Gly-Leu), L-Leucyl-Glycine (Leu-Gly), and L-Leucyl-L-Leucine (Leu-Leu), affect skin hydration and elasticity in vitro and in vivo. We found that Gly-Leu and Leu-Gly dipeptides induced the expression of transglutaminase 1 in normal human epidermal keratinocytes (NHEKs) whereas Leu-Leu dipeptides did not. Treatment with Gly-Leu or Leu-Gly significantly increased hyaluronan (HA) synthesis in NHEKs and the upregulation of hyaluronan synthase 2 (HAS2) mRNA level was confirmed. In addition, elastase activity was inhibited in NHEKs treated with Gly-Leu or Leu-Gly dipeptides. Oral administration of Gly-Leu or Leu-Gly dipeptides increased skin hydration and elasticity in UVB-irradiated hairless mice. The significant upregulation of HA in UVB-irradiated hairless mice was observed in response to oral administration of Gly-Leu or Leu-Gly. These results suggest that the major dipeptides of porcine placenta, Gly-Leu and Leu-Gly, are potentially active ingredients for skin moisturization formulations.

• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.57-61
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• 2012

The matrix metalloproteinase (MMP) family is involved in the breakdown of the extracellular matrix during normal physiological processes such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes such as pathological aging, arthritis, and metastasis. Oxidative conditions generate reactive oxygen species (ROS) (e.g., hydrogen peroxide [$H_2O_2$]) in cells, which subsequently induce the synthesis of matrix metalloproteinase-1 (MMP-1). MMP-1, an interstitial collagenase, in turn stimulates an aging phenomenon. In this study, baicalein (5,6,7-trihydroxyfl avone) was investigated for its in vitro activity against $H_2O_2$-induced damage using a human skin keratinocyte model. Baicalein pretreatment signifi cantly inhibited $H_2O_2$-induced up-regulation of MMP-1 mRNA, MMP-1 protein expression and MMP-1 activity in cultured HaCaT keratinocytes. In addition, baicalein decreased the transcriptional activity of activator protein-1 (AP-1) and the expression of c-Fos and c-Jun, both components of the heterodimeric AP-1 transcription factor. Furthermore, baicalein reduced phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinase (JNK), which are upstream of the AP-1 transcription factor. The results of this study suggest that baicalein is involved in the inhibition of oxidative stress-induced expression of MMP-1 via inactivation of the ERK/JNK/AP-1 signaling pathway.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.2
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• pp.131-138
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• 2009

The binding of interleukin-6 (IL-6) cytokine family ligands to the gp130 receptor complex activates the Janus kinase (JAK)/ signal transducer and activator of transcription 3 (STAT3) signal transduction pathway, where STA T3 plays an important role in cell survival and tumorigenesis. Constitutive activation of STAT3 has been frequently observed in many cancer tissues, and thus, blocking of the gp130 signaling pathway, at the JAK level, might be a useful therapeutic approach for the suppression of STAT3 activity, as anticancer therapy. AG490 is a tyrphostin tyrosine kinase inhibitor that has been extensively used for inhibiting JAK2 in vitro and in vivo. In this study, we demonstrate a novel mechanism associated with AG490 that inhibits the JAK/STAT3 pathway. AG490 induced downregulation of gp130, a common receptor for the IL-6 cytokine family compounds, but not JAK2 or STAT3, within three hours of exposure. The downregulation of gp130 was not caused by enhanced degradation of gp130 or by inhibition of mRNA transcription. It most likely occurred by translation inhibition of gp130 in association with phosphorylation of the eukaryotic initiation factor-2 a. The inhibition of protein synthesis of gp130 by AG490 led to immediate loss of mature gp130 in cell membranes, due to its short half-life, thereby resulting in reduction in the STAT3 response to IL-6. Taken together, these results suggest that AG490 blocks the STAT3 activation pathway via a novel pathway.

• Proceedings of the Korean Society of Sericultural Science Conference
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• 1997.06a
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• pp.51-72
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• 1997

Diapause hormone (DH) is a neuropeptide hormone which is secreted from the suboesophageal ganglion (SG) and is responsible for induction of embryonic diapause of the silkworm, Bombyx mori. DH is isolated from SGs and determined to be a 24 amino acid peptide amide. The cDNA encodes the polyprotein precursor from which DH, pheromone biosynthesis activating neuropeptide (PBAN) and three other neuropeptides are released and become matured. The C-terminal FXPRL-NH2 sequence of DH is essential but not sufficient for expression of full activity. Recently, we have isolated a unique hydrohobic peptide (VAP peptide) with a slight diapause egg induceing activity from organic solvent extracts of the male adult heads of the silkworm. The VAP peptide itself has no diapause inducing activity, but enhances DH activity through reducing ED50 value and the threshold concentration of DH. The DH-PBAN gene is composed of 6 exons interrupted by 5 introns and is expressed in 12 neurosecretory cells of the SG. The incubation of eggs at 25$^{\circ}C$, which induces embryonic diapause in the progeny, caused DH-PBAN mRNA content to increase at 5 different stages in the life cycle. By contrast, a 15$^{\circ}C$ incubation only induced expression of the gene at the late phrase adult stage. The temperature-controlled expression of DH-PBAN gene is closely correlated to the incidence of diapause, indicating that DH-PBAN gene expression is the initial event leading to diapause induction. DH acts to stimulate trehalase activity in developing ovary to bring about hyprglycogenism in mature eggs, a prerequisite metabolism for diapause initiation. Using in vivo and in vitro systems, DH is clearly shown to induce trehalase gene expression in developing ovaries. New protein synthesis is not needed for this process, but a Ca2+-dependent proteinkinase seems to be involved. Quite recently, we have sucessfully applied a new and potent trehalase inhibitor (Trehazoline) to reudce glycogen content in developing ovaries. The eggs deficient in glycogen were also able to enter diapause as the natural eggs do, so that we could provide the new egg system to reconsider the diapause associated metabolism other than the glycogen-sorbitol metabolic system.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.20 no.2 s.33
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• pp.10-35
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• 2007

Objectives : To investigate the effects of Ohbaesangami (OBSGM) on mucosa and skin diseases, anti-microbial and anti-inflammatory tests were performed using several in vitro test models. Results : In anti-microbial test, OBSGM showed the slight inhibitory effect against Propionibacterium acnes (P. acnes) and Staphylococcus aureus (S. aureus). In anti-oxidant test, OBSGM showed the potent radical scavenging activity. In anti-inflammatory test, OBSGM weakly inhibited the lipopolysaccharide (LPS)-induced nitric oxide(NO) release from the RAW 264.7 macrophage cells. OBSGM also inhibited the LPS-induced $interleukin-1{\beta}(IL-1{\beta})$ and cyclooxygenase-2 (COX-2) expressions. The inhibitory effects of OBSGM on macrophage activation was via the inhibition of $NF-{\kappa}B$, evidenced by transient transfection assay. Furthermore, OBSGM markedly inhibited the activation of Jun-N-terminal kinase (JNK) and p38 MAP kinase in RAW 264.7 cells. In skin wrinkle formation assay, OBSGM strongly inhibited collagnease and elastase, whose activities are tightly related with the wrinkle formation. In addition, OBSGM inhibited the activities of MMP-1, MMP-2 on the mRNA levels in RAW 264.7 cells. However, OBSGM did not show an inhibitory potential on tyrosinase activity and melanin synthesis, indicating that it could not be applicable for skin whitening. Conclusion : These results suggest that the anti-inflammatory effect of OBSGM may be due to its inhibitory potentials on the macrophage activation. And, the anti-wrinkle effects of OBSGM may be due to its inhibitory potential on the collagnease and elastase activities. Therefore, OBSGM could be applicable for the treatment of mucosa and skin diseases.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.28 no.1
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• pp.135-149
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• 2002

To date, research on the regulation of melanogenesis has focused on factors which affect tyrosinase, the rate-limiting enzyme in the melanogenic pathway, by searching for chemicals which competitively inhibit tyrosinase function. Many types of tyrosinase inhibitors have been developed, but no satisfactory results have been made clinically until now, To find a new whitening agent, which effectively inhibits melanogenesis, we synthesized several compounds and selected compounds by cell-based assay system. Finally, 3, 4, 5-trimethoxy cinnamaie thymol ester(TCTE, Melasolv) was selected and the effects of TCTE on melanogenesis were investigated. Treatment of mouse-derived melanocyte melan-a cells with TCTE results in a marked down-regulation of tyrosinase activity. 80% decrease of tyrosinase activity occurs with 30uM TCTE treatment for 72 hours without affecting cell growth. The inhibition of tyrosinase activity is dose-dependent and melanin content was also decreased to 40%. From the in vitro tyrosinase assay using cell extract, TCTE does not act as a direct inhibitor of the enzyme. Treatment of melan-a cultures with TCTE blocks the increase in tyrosinase activity by either forskolin, 3-isobutyl-1-methtyl-xanthine. TCTE decreased the expression of tyrosinase, TRP-1 without effects on TRP-2 protein expression through the down regulation of tyrosinase and TRP-1 mRNA. From the results of cAMP immunoassays, intracellular levels of the cyclin nucleotide are unaffected in cells treated with TCTE. The inhibitory effects of melanin synthesis were also shown in reconstitute human epidermis model by topical application. These findings suggest that TCTE can be used for studying the regulation of melanogenesis and depigmenting agent.

• Journal of Periodontal and Implant Science
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• v.53 no.1
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• pp.20-37
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• 2023

Purpose: Our pilot study showed that a 3-dimensional dual drug delivery scaffold (DDDS) loaded with Chinese herbs significantly increased the regenerated bone volume fraction. This study aimed to confirm the synergistic anti-inflammatory and osteogenic preclinical effects of this system. Methods: The targets and pathways of parthenolide and naringin were predicted. Three cell models were used to assess the anti-inflammatory effects of parthenolide and the osteogenic effects of naringin. First, the distance between the cementoenamel junction and alveolar bone crest (CEJ-ABC) and the bone mineral density (BMD) of surgical defects were measured in a rat model of periodontitis with periodontal fenestration defects. Additionally, the mRNA expression levels of matrix metallopeptidase 9 (MMP9) and alkaline phosphatase (ALP) were measured. Furthermore, the number of inflammatory cells and osteoclasts, as well as the protein expression levels of tumor necrosis factor-alpha (TNF-α) and levels of ALP were determined. Results: Target prediction suggested prostaglandin peroxidase synthase (PTGS2) as a potential target of parthenolide, while cytochrome P450 family 19 subfamily A1 (CYP19A1) and taste 2 receptor member 31 (TAS2R31) were potential targets of naringin. Parthenolide mainly targeted inflammation-related pathways, while naringin participated in steroid hormone synthesis and taste transduction. In vitro experiments revealed significant antiinflammatory effects of parthenolide on RAW264.7 cells, and significant osteogenic effects of naringin on bone marrow mesenchymal stem cells and MC3T3-E1 cells. DDDS loaded with parthenolide and naringin decreased the CEJ-ABC distance and increased BMD and ALP levels in a time-dependent manner. Inflammation was significantly alleviated after 14 days of DDDS treatment. Additionally, after 56 days, the DDDS group exhibited the highest BMD and ALP levels. Conclusions: DDDS loaded with parthenolide and naringin in a rat model achieved significant synergistic anti-inflammatory and osteogenic effects, providing powerful preclinical evidence.

• The Journal of Internal Korean Medicine
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• v.19 no.1
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• pp.3-21
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• 1998

This study was to investigate the effects of Gibangganbang on the liver injury induced dimethylnitrosamine, CCl4, ethanol and partial hepatectomy. Hydroxyproline, hepatic fibrosis, hepatic inflammatory cell infiltration, fatty value, lipidoperoxide levels, glutathione levels, mitotic index, contents of protein in the serum and liver tissues were measured and observed. The results obtained were as follows. 1. The increasing level of hydroxyproline volume induced by dimethylnitrosamine in mice was decreased by the oral administration of Gibangganbang. 2. The degree of hitological fibrosis and hepatic inflammatory cell infiltration induced by $CCl_4$ was decreased by the oral administration of Gibangganbang. 3. The degree of fatty value and the increasing level of lipidoperoxide in liver tissues was decreased by the oral administration of Gibangganbang. 4. The level of glutathione in liver tissues was increasing by the oral administration of Gibangganbang. 5. The increasing level of microsomal lipidoperoxide in vitro assay was decreasing by the oral administration of Gibangganbang. 6. The increasing level of the mitotic index, weight of liver, contents of protein, RNA and DNA synthesis of the liver tissues after partial hepatectomy was activated by the oral administration of Gibangganbang. These results suggest that Gibangganbang not only inhibits liver cirrhotic change and ethanol-induced fatty change but also activates antioxidant enzymes and regeneration ability ocf liver.

• International Journal of Oral Biology
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• v.34 no.1
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• pp.43-48
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• 2009

Thrombin-induced platelet microbicidal protein (tPMP) is a small cationic peptide that exerts potent in vitro microbicidal activity against a broad spectrum of human pathogens, including Staphylococcus aureus and Streptococcus rattus BHT. Earlier evidence has suggested that tPMP targets and disrupts the bacterial membrane. However, it is not yet clear whether membrane disruption itself is sufficient to kill the bacteria or whether subsequent, presumably intracellular, events are also involved in this process. In this study, we investigated the microbicidal activity of rabbit tPMP toward S. rattus BHT cells in the presence or absence of a pretreatment with antibiotics that differ in their mechanisms of action. The streptocidal effects of tPMP on control cells (no antibiotic pretreatment) were rapid and concentration-dependent. Pretreatment of S. rattus BHT cells with either penicillin or amoxicillin (inhibitors of bacterial cell wall synthesis) significantly enhanced the anti-S. rattus BHT effects of tPMP compared with the effects against the respective control cells over most tPMP concentration ranges tested. On the other hand, pretreatment of S. rattus BHT cells with tetracycline or doxycycline (30S ribosomal subunit inhibitors) significantly decreased the streptocidal effects of tPMP over a wide peptide concentration range. Furthermore, pretreatment with rifampin (an inhibitor of DNA-dependent RNA polymerase) essentially blocked the killing of S. rattus BHT by tPMP at most concentrations compared with the respective control cells. These results suggest that tPMP exerts anti-S. rattus BHT activity through mechanisms involving both the cell membrane and intracellular targets.