• Journal of Life Science
• /
• v.33 no.3
• /
• pp.277-286
• /
• 2023

Sarcopenia is the age-related loss of muscle mass and function. It is a natural part of aging and can lead to decreased mobility and increased frailty. The ubiquitin-proteasome pathway, which is involved in muscle protein degradation, is closely linked to sarcopenia. Germinated Rhynchosia nulubilis hydrolysate (GRH) has been reported to have anti-inflammatory and antioxidant properties, but there have been no reports on its inhibitory effect on muscle reduction. However, no study has yet explored the relationship between GRH and muscle loss inhibition. In this study, we evaluated the effects of GRH on muscle atrophy inhibitory activity in dexamethasone (Dexa)-induced muscle atrophy C2C12 myotubes and mouse models. Moreover, we identified a molecular pathway underlying the effects of GRH on skeletal muscle. May Grunwald-Giemsa staining showed that the length and area of myotubes increased in the groups treated with GRH. In addition, the GRH-treated group significantly reduced the expression of muscle ring finger protein 1 and muscular atrophy F-box (MAFbx) in the Dexa-induced muscular atrophy C2C12 model. GRH also improved muscle strength in C57BL/6 mice with Dexa-induced muscle atrophy, resulting in prolonged running exhaustive time and increased grip strength. We found that muscle strengthening by GRH was correlated with a decreased expression of the MAFbx gene in mouse muscle tissue. In conclusion, GRH can attenuate Dexa-induced muscle atrophy by inhibiting the ubiquitin-proteasome pathway via downregulation of the MAFbx gene expression.

• Journal of the Society of Cosmetic Scientists of Korea
• /
• v.50 no.1
• /
• pp.37-48
• /
• 2024

Songla (Usnea diffracta Vain.) is one of the lichens belonging to the genus Usnea, and pharmacological activities such as antioxidant, antimicrobial, anti-inflammatory, anti-tumor and cardiovascular protection have been reported in previous studies, but its efficacy in skin and hair is not well known. In this study, the effect of Usnea diffracta extract (UDE) on anti-aging and dermal papilla cell proliferation was verified in vitro. As a result of the experiment, it was confirmed that the UDE significantly reduced the expression of MMP-1 and the activity of MAPKs (ERK, p38, JNK) and AP-1 (c-Fos, c-Jun), which were increased by UVA in HDFn. In addition, the UDE significantly increased the proliferation of HFDPC and significantly increased the mRNA expression of VEGF and KGF, which are hair growth factors. Accordingly, the phosphorylation of ERK/CREB involved in hair proliferation and expression of growth factors was increased in a concentration-dependent manner. The main component represented by the main peak was separated and purified using Prep LC by concentrating the UDE, which was confirmed as diffractaic acid through NMR and Mess analysis. Isolated diffractaic acid significantly reduced the expression of MMP-1 increased by UVA in HDFn and increased the proliferation of HFDPC in a concentration-dependent manner. The result suggest that UDE proved its usability as a natural cosmetic material with anti-aging and dermal papilla cell activation effects.

• Journal of the Society of Cosmetic Scientists of Korea
• /
• v.30 no.2
• /
• pp.263-278
• /
• 2004

Ursolic acid (UA) and Oleanolic acid (ONA), known as urson, micromerol and malol, are pentacyclic triterpenoid compounds which naturally occur in a large number of vegetarian foods, medicinal herbs, and plants. They may occur in their free acid form or as aglycones for triterpenoid saponins, which are comprised of a triterpenoid aglycone, linked to one or more sugar moieties. Therefore UA and ONA are similar in pharmacological activity. Lately scientific research, which led to the identification of UA and ONA, revealed that several pharmacological effects, such as antitumor, hepato-protective, anti-inflammatory, anticarcinogenic, antimicrobial, and anti-hyperlipidemic could be attributed to UA and ONA. Here, we introduced the effect of UA and ONA on acutely barrier disrupted and normal hairless mouse skin. To evaluate the effects of UA and ONA on epidermal permeability barrier recovery, both flanks of 8-12 week-old hairless mice were topically treated with either 0.01-0.1mg/mL UA or 0.1-1mg/mL ONA after tape stripping, and TEWL (transepidermal water loss) was measured. The recovery rate increased in those UA or ONA treated groups (0.1mg/mL UA and 0.5mg/mL ONA) at 6h more than 20% compared to vehicle treated group (p < 0.05). Here, we introduced the effects of UA and ONA on acute barrier disruption and normal epidermal permeability barrier function. For verifying the effects of UA and ONA on normal epidermal barrier, hydration and TEWL were measured for 1 and 3 weeks after UA and ONA applications (2mg/mL per day). We also investigated the features of epidermis and dermis using electron microscopy (EM) and light microscopy (LM). Both samples increased hydration compared to vehicle group from 1 week without TEWL alteration (p < 0.005). EM examination using RuO4 and OsO4 fixation revealed that secretion and numbers of lamellar bodies and complete formation of lipid bilayers were most prominent (ONA=UA > vehicle). LM finding showed that thickness of stratum corneum (SC) was slightly increased and especially epidermal thickening and flattening was observed (UA > ONA > vehicle). We also observed that UA and ONA stimulate epidermal keratinocyte differentiation via PPAR Protein expression of involucrin, loricrin, and filaggrin increased at least 2 and 3 fold in HaCaT cells treated with either ONA (10${\mu}$M) or UA (10${\mu}$M) for 24 h respectively. This result suggested that the UA and ONA can improve epidermal permeability barrier function and induce the epidermal keratinocyte differentiation via PPAR Using Masson-trichrome and elastic fiber staining, we observed collagen thickening and elastic fiber elongation by UA and ONA treatments. In vitro results of collagen and elastin synthesis and elastase inhibitory activity measurements were also confirmed in vivo findings. These data suggested that the effects of UA and ONA related to not only epidermal permeability barrier functions but also dermal collagen and elastic fiber synthesis. Taken together, UA and ONA can be relevant candidates to improve epidermal and dermal functions and pertinent agents for cosmeseutical applications.

• Tuberculosis and Respiratory Diseases
• /
• v.46 no.5
• /
• pp.685-696
• /
• 1999

Background : Idiopathic pulmonary fibrosis (IPF) is a diffuse inflammatory and fibrosing process that occurs within the interstitium and alveolus of the lung with invariably poor prognosis. The major problem in management of IPF results from the variable rate of disease progression and the difficulties in predicting the response to therapy. The purpose of this retrospective study was to evaluate the short-term efficacy of steroid and immunosuppressive therapy for IPF and to identify the pre-treatment determinants of favorable response. Method : Twenty patients of IPF were included. Diagnosis of IPF was proven by thoracoscopic lung biopsy and they were presumed to have active progressive disease. The baseline evaluation in these patients included clinical history, pulmonary function test, bronchoalveolar lavage (BAL), and chest high resolution computed tomography (HRCT). Fourteen patients received oral prednisolone treatment with initial dose of 1mg/kg/day for 8 to 12 weeks and then tapering to low-dose prednisolone (0.25mg/kg/day). Six patients who previously had experienced significant side effects to steroid received 2mg/kg/day of oral cyclophosphamide with or without low-dose prednisolone. Follow-up evaluation was performed after 6 months of therapy. If patients met more than one of followings, they were considered to be responders : (1) improvement of more than one grade in dyspnea index, (2) improvement in FVC or TLC more than 10% or improvement in DLco more than 20% (3) decreased extent of disease in chest HRCT findings. Result : One patient died of extrapulmonary cause after 3 month of therapy, and another patient gave up any further medical therapy due to side effect of steroid. Eventually medical records of 18 patients were analyzed. Nine of 18 patients were classified into responders and the other nine patients into nonresponders. The histopathologic diagnosis of the responders were all nonspecific interstitial pneumonia (NSIP) and that of nonresponders were all usual interstitial pneumonia (UIP) (p<0.001). The other significant differences between the two groups were female predominance (p<0.01), smoking history (p<0.001), severe grade of dyspnea (p<0.05), lymphocytosis in BAL fluid ($23.8{\pm}16.3%$ vs $7.8{\pm}3.6%$, p<0.05), and less honeycombing in chest HRCT findings (0% vs $9.2{\pm}2.3%$, p<0.001). Conclusion : Our results suggest that patients with histopathologic diagnosis of NSIP or lymphocytosis in BAL fluid are more likely to respond to steroid or immunosuppressive therapy. Clinical results in large numbers of IPF patients will be required to identify the independent variables.

• Biomedical Science Letters
• /
• v.2 no.2
• /
• pp.133-151
• /
• 1996

After cardiac surgery, it has been recognized that various complications were associated with injured humoral and cellular immunity by cardiopulmonary bypass(CPB). Especially, in postoperative pulmonary dysfunction, transpulmonary leukostasis followed complement activation and inflammatory responses are major pathogen. Some studies have showed that pretreated-corticosteroids before CPB protected postoperative pulmonary dysfunction. Corticosteroids may inhibit complement and leukocyte activation. On based previous studies, present investigator determined changes of leukocyte counts and transpulmonary leukostasis during cardiac surgery and postoperative periods. For the evaluation of postoperative pulmonary function and edema, $PaO_2$ and chest X-ray were compared between pre-CPB and post-CPB. Fever and other parameters were also observed postoperatively. The aim of this study was to define for the prophylactic effects of corticosteroid(Solu-Medrol: 30mg/kg) on all the researched parameters. This study was prospectively designed with randomized-blind fashion for 50 patients undergoing cardiac surgery. According to the purpose of study, all patients were divided into placebo and steroid group. : Placebo group was 25 patients received normal saline(not corticosteroid), and steroid group was 25patients received corticosteroid(Solu-Medrol: 30mg/kg) before initiation of CPB. The results of study were summarized as follows. 1. Total peripheral leukocyte counts decreased significantly at 5 minutes of CPB in all patients(P<0.01), and began to increase progressively at later periods of CPB with neutrophilia. The significant rise remained at postoperative 7th day(P<0.05). 2. During partial CPB, transpulmonary leukostasis occurred in placebo group(P<0.001), whereas it was prevented in steroid group. 3. In both groups, peripheral lymphocyte counts were stable during CPB, but began to reduce at time of intensive care unit(ICU) and the lymphocytopenia remained until postoperative 3rd day. The lymphocyte counts recovered on postoperative 7th day. 4. In both groups, peripheral counts of monocyte were relatively stable in the early peroid of CPB, and increased gradually in the later periods of CPB. This significant monocytosis remained throughout postoperlative periods(P<0.05). 5. The mean value of postoperative $paO)_2$ was lower than that of pre-CPB in placebo group(P=0.01) but didn't significant in steroid group(P=0.90). In the incidence of pulmonary edema signs and fever, placebo group was higher than steroid group(P=0.001, p=0.01, respectively). However mechanical respiratory supporting and care periods at intensive care unit were not significant difference between two groups(P>.0.05).With the above results, the investigator concluded that leukocyte activation and pulmonary sequestration were caused by cardiac surgery with CPB and demonstrated that high dose corticosteroid will provide prophylactic effect for pulmonary leukostasis and higher neutrophilia. These effects may ameliorate postoperative pulmonary dysfunction and contribute to postoperative less morbidity. However, further study should be performed because postoperative lymphocytopenia continued for 3 days in both groups, which may suspected damage or suppression of cell-mediated immunity with used corticosteroid.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.43 no.5
• /
• pp.631-640
• /
• 2014

The inhibitory effects of Boswellia serrata (BW) extracts on degenerative osteoarthritis were investigated in primary-cultured rat cartilage cells and a monosodium-iodoacetate (MIA)-induced osteoarthritis rat model. To identify the protective effects of BW extract against $H_2O_2$ ($800{\mu}M$, 2 hr) in vitro, cell survival was measured by MTT assay. Cell survival after $H_2O_2$ treatment was elevated by BW extract at a concentration of $20{\mu}g/mL$. In addition, BW extract treatment significantly reduced and normalized the productions of pro-inflammatory factors, nuclear transcription factor ${\kappa}B$, cyclooxygenase-2, tumor necrosis factor-${\alpha}$, and interleukin-6 at a concentration of $20{\mu}g/mL$. Treatment of chondrocytes with BW extract significantly reduced 5-lipoxygenase activity and production of prostaglandin E2, especially at a concentration of $10{\sim}20{\mu}g/mL$. For the in vivo animal study, osteoarthritis was induced by intra-articular injection of MIA into knee joints of rats. Consumption of a diet containing BW extract (100 and 200 mg/kg) for 35 days significantly inhibited the development and severity of osteoarthritis in rats. To determine the genetic expression of arthritic factors in articular cartilage, real-time PCR was applied to measure matrix metalloproteinases (MMP-3, MMP-9, and MMP-13), collagen type I, collagen type II, and aggrecan, and BW extract had protective effects at a concentration of 200 mg/kg. In conclusion, BW extract was able to inhibit articular cartilage degeneration by preventing extracellular matrix degradation and chondrocyte injury. One can consider that BW extract may be a potential therapeutic treatment for degenerative osteoarthritis.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.4
• /
• pp.823-834
• /
• 1998

Background: Chronic inhalation of silica induces the lung fiborsis. The alveolar macrophages ingest the inhaled silica; they liberate the pro-inflammatory cytokines such as IL-1$\beta$, IL-6, TNF-$\alpha$ and fibrogenic cytokines, TGF-$\beta$ and PDGF. Cytokines liberated from macrophage have pivotal role in pulmonary fibrosis. There is a complex cytokine network toward fibrosis. However, the exact roles and the interaction among the proinflammatory cytokines and TGF-$\beta$, a fibrogenic cytokine, have not been defined, yet. In this study, we investigated silica induced IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ production and the effect of IL-1$\beta$, IL-6, TNF-$\alpha$ on the production of TGF-$\beta$ from lung macrophages of Balb/C mice. Method: We extracted the lung of Balb/C mice and purified monocytes by Percoll gradient method. Macrphages were stimulated by silica ($SiO_2$) in the various concentration for 2, 4, 8, 12, and 24 hours. The supernatants were used for the measurement of protein levels by bioassay, and cells for the levels of mRNA by in situ hybridization. Results: The production of IL-6 was not observed till 4 hours, and reached the peak levels at 8 hours after stimulation of silica. The production of TNF-$\alpha$ increased from 2 hours and reached the peak levels at 4 hours after stimulation of silica. The spontaneous TGF-$\beta$ production reached the peak levels at 24 hours. TNF-$\alpha$ upregulated the silica induced TGF-$\beta$ production. Silica induced TGF-$\beta$ production was blocked by pretreated anti-TNF-$\alpha$ antibody. In situ hybridization revealed the increased positive signals at 4 hours in IL-6, at 4 hours TNF-$\alpha$ and 12 hours in TGF-$\beta$. Conclusion: The results above suggest that silica induced the sequential production of IL-6, 1NF-$\alpha$ and TGF-$\beta$ from macrophages and TNF-$\alpha$ upregultaes the production of TGF-$\beta$ from silica-induced macrophages.

• Tuberculosis and Respiratory Diseases
• /
• v.56 no.1
• /
• pp.51-66
• /
• 2004

Objectives : The matrix metalloproteinases (MMPs) that participate in the extracellular matrix metabolism play a important role in the progression of pulmonary fibrosis. The effects of the MMPs are regulated by several factors including Th-1 cytokines, $interferon-{\gamma}$ ($IFN-{\gamma}$). Up to now, $IFN-{\gamma}$ is known to inhibit pulmonary fibrosis, but little is known regarding the exact effect of $IFN-{\gamma}$ on the regulation of the MMPs. This study investigated the effects of $interferon-{\gamma}$ on the pulmonary fibrosis and the expression of the lung MMP-2,-9, TIMP-1,-2, and Th-2 cytokines in aa rat model of bleomycin induced pulmonary fibrosis. Materials and methods : Male, specific pathogen-free Sprague-Dawley rats were subjected to an intratracheal bleomycin instillation. The rats were randomized to a saline control, a bleomycin treated, and a bleomycin+$IFN-{\gamma}$ treated group. The bleomycin+$IFN-{\gamma}$ treated group was subjected to an intramuscular injection of $IFN-{\gamma}$ for 14 days. At 3, 7, 14, and 28 days after the bleomycin instillation, the rats were sacrificed and the lungs were harvested. In order to evaluate the effects of the $IFN-{\gamma}$ on lung fibrosis and inflammation, the lung hydroxyproline content, inflammation and fibrosis score were measured. Western blotting, zymography and reverse zymography were performed at 3, 7, 14, 28 days after bleomycin instillation in order to evaluate the MMP-2,-9, and TIMP-1,-2 expression level. ELISA was performed to determine the IL-4 and IL-13 level in a lung homogenate. Results : 1. 7 days after bleomycin instillation, inflammatory changes were more severe in the bleomycin+$IFN-{\gamma}$ group than the bleomycin group (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$2.08{\pm}0.15:2.74{\pm}0.29$, P<0.05), but 28 days after bleomycin instillation, lung fibrosis was significantly reduced as a result of the $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$3.94{\pm}0.43:2.64{\pm}0.13$, P<0.05). 2. 28 days after bleomycin instillation, the lung hydroxyproline content was significantly reduced as a result of $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$294.04{\pm}31.73{\mu}g/g:194.92{\pm}15.51{\mu}g/g$, P<0.05). 3. Western blotting showed that the MMP-2 level was increased as a result of the bleomycin instillation and highest in the 14 days after bleomycin instillation. 4. In zymography, the active forms of MMP-2 were significantly increased as a result of the $IFN-{\gamma}$ treatment 3 days after the bleomycin instillation, bleomycin+$IFN-{\gamma}$ group (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$209.63{\pm}7.60%:407.66{\pm}85.34%$, P<0.05), but 14 days after the bleomycin instillation, the active forms of MMP-2 were significantly reduced as a result of the $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$159.36{\pm}20.93%:97.23{\pm}12.50%$, P<0.05). 5. The IL-4 levels were lower in the bleomycin and bleomycin+$IFN-{\gamma}$ groups but this was not significant, and the IL-13 levels showed no difference between the experiment groups. Conclusion : The author found that lung inflammation was increased in the early period but the pulmonary fibrosis was inhibited in the late stage as a result of $IFN-{\gamma}$. The inhibition of pulmonary fibrosis by $IFN-{\gamma}$ appeared to be associated with the inhibition of MMP-2 activation by $IFN-{\gamma}$. Further studies on the mechanism of the regulation of MMP-2 activation and the effects of MMP-2 activation on pulmonary fibrosis is warranted in the future.