• Tuberculosis and Respiratory Diseases
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• v.48 no.4
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• pp.487-499
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• 2000

Background : Acute lung injury is an hypoxic respiratory failure resulting from damage to the alveolar-capillary membrane, which can be developed by a variety of systemic inflammatory diseases. In this study the therapeutic effects of intra-tracheal pulmonary surfactant instillation was evaluated in the intratracheal endotoxin induced acute lung injury model of a rat. Methods : Twenty Sprague-Dawley rats were divided into 4 groups, and normal saline (2 ml/kg, for group 1) or LPS (5 mg/kg, for group 2, 3, and 4) was instilled into the trachea respectively. Either normal saline (2 ml/kg, for group 1 & 2, 30 min later) or bovine surfactant (15 mg/kg, 30 min later for group 3, 5 hr later for group 5) was instilled into the trachea. The therapeutic effect of intratracheal surfactant therapy was evaluated with one chamber body plethysmography (respiratory frequency, tidal volume and enhanced pause), ABGA, BAL fluid analysis (cell count with differential, protein concentration) and pathologic examination of the lung. Results : Intratracheal endotoxin instillation increased the respiration rate decreased the tidal volume and int creased the Penh in all group of rats. Intratracheal instillation of surfactant decreased Penh, increased arterial oxygen tension, decreased protein concentration of BAL fluid and decreased lung inflammation at both times of administration (30 minute and 5 hour after endotoxin instillation). Conclusion : Intratracheal instillation of surfactant can be a beneficial therapeutic modality as discovered in the acute lung injury model of rats induced by intratracheal LPS intillation. It deserves to be evaluated for treatment of human acute lung injury.

• Proceedings of the KOR-BRONCHOESO Conference
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• 1979.05a
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• pp.3.2-3
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• 1979

Bone conduction loss is one of the most common complication in chronic otitis media, and is mostly high frequency loss. Of 233 tympanomastoidectomy ears, 187 ears were considered eligible for this study. A histopathological change was examined in the natural otitis media of guinea pigs. It is our intention to analyze the pattern of bone conduction loss in chronic otitis media, and to correlate this findings with clinical and pathological changes in human and animal otitis media. l) In unilateral cases, a significant difference in bone conduction threshold was observed between normal and diseased ears, and between each frequency with significant interaction between 2KHz and 4KHz (p 0.01). 2) Using one way analysis of variance, mean bone conduction was compared with the duration of disease. We observed a significant difference (p 0.05) between each group of duration, except between 11-15 and 15-20 years group. 3) A comparison of bone conduction between stapes loss group and intact stapes group revealed significant t ratio (p 0.01) at each frequency. The effect of stapes loss on each frequency was evaluated, using one way analysis of variance. there were significant difference(p 0.05) between 250Hz and 500Hz. and between 2KHz and 4KHz. 4) A comparison of bone conduction between round window obliteration and nonobliteration group revealed significant t ratio (p 0.01) at each frequency. Using one way analysis of variance. the effect of round window obliteration was evaluated in each frequency. We observed significant difference (p 0.05) between 250Hz and 500Hz. and between 2KHz and 4KHz. 5) A comparison of bone conduction between cholesteatoma and non -cholesteatoma group revealed significant t ratio (p 0.01) only in 2KHz and 4KHz. No significant differency was observed in mean bone conduction. 6) In a histopathological study of natural otitis media in guinea pig, we observed inflammatory infiltration of the round window membrane, serofibrinous precipitate in the scala tympani, and degeneration of the organ of Corti most significant near the basal turn. These changes would explain high tone bone conduction loss in the process of chronic otitis media.

• Journal of Life Science
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• v.19 no.11
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• pp.1637-1643
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• 2009

Shikonin, a component of Lithospermum erythrorhizon Sieb. et Zucc, exerts various characteristics such as anti-inflammatory, anti-cancer and anti-obesity functions. To elucidate the molecular mechanism of shikonin-induced inhibition of adipogenesis, we analyzed the mRNA expression level of various adipogenesis-related factors including C/EBPs (CCAAT/enhancerbinding proteins) and $PPAR{\gamma}$ (peroxisome proliferator-activated receptor $\gamma$). The data showed that mRNA expressions of C/$EBP{\beta}$ and C/$EPB{\delta}$ were only slightly changed by shikonin treatment, but mRNA expressions of $PPAR{\gamma}$ and C/$EPB{\alpha}$ were significantly down-regulated. Then, we tested whether upstream regulators of C/$EBP{\beta}$ and $PPAR{\gamma}$ were involved in anti-adipogenesis of shikonin. C/$EBP{\gamma}$ and CHOP (C/EBP homologous protein), which are upstream regulators of C/$EBP{\beta}$, were not affected by shikonin treatment. On the contrary, the mRNA level of KROX20 was markedly down-regulated by shikonin treatment. These results suggest that KROX20 might regulate downstream factors of adipogenesis through C/$EBP{\beta}$-independent pathway. The expression of KLF15 (Kruppel-like factor15), which is a member of KLF family and is a upstream regulator of $PPAR{\gamma}$, was dramatically decreased by shikonin treatment, but KLF2 was not changed. Shikonin had no impact on the expression of KLF5 in the early stage of adipogenesis, but shikonin increased expression of KLF5 in the late stage of adipogenesis. Even though mRNA expression of KLF5 was moderately changed by shikonin treatment, its effect may be small compared with the effect of KLF15, which was markedly inhibited. Taken together, these results suggest that shikonin inhibits adipogenesis through the down-regulation of $PPAR{\gamma}$ and C/$EPB{\alpha}$, which is mediated by the down-regulation of two pro-adipogenic factors, KROX20 and KLF15.

• Journal of Life Science
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• v.23 no.3
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• pp.389-398
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• 2013

Platycodin D is a major constituent of triterpene saponins, which is found in the root of Platycodon grandiflorum, Platycodi Radix, which is widely used in traditional Oriental medicine for the treatment of many chronic inflammatory diseases. Several pharmacological effects of this compound have been reported recently, such as anti-inflammation, immunogenicity, anti-adipogenesis, lowered cholesterol, and anti-cancer activity. However, the mechanism by which this action occurs is poorly understood. In this study, we found that platycodin D greatly increased the potential of the anti-proliferative effect in various cancer cell lines. Our data revealed that platycodin D treatment resulted in a time- and concentration-response growth inhibition of U937 cells by inducing apoptosis, as evidenced by the formation of apoptotic bodies, chromatin condensation, and the accumulation of cells in the sub-G1 phase. Apoptosis induction of U937 cells by platycodin D correlated with an increase in the Bax/Bcl-2 ratio and caused the down-regulation of IAP family members. In addition, platycodin D treatment resulted in proteolytic activation of caspase-3, the concomitant degradation of poly(ADP-ribose) polymerases, and the collapse of the mitochondria membrane potential (${\Delta}{\Psi}_m$). However, the cytotoxic effects induced by platycodin D treatment were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrated the important role that caspase-3 played in the observed cytotoxic effect. These findings suggest that platycodin D may be a potential chemotherapeutic agent for use in the control of human leukemia U937 cells. These findings also provided important new insights into possible molecular mechanisms of the anti-cancer activity of platycodin D.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.1
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• pp.8-15
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• 2008

Saussurea lappa (SL) has been used to reduce abdominal pain and tenesmus in traditional oriental medicine. SL and major compounds of SL, sesquiterpene lactones, have been suggested to possess various biological effects, including anti-tumor, anti-ulcer, anti-inflammatory, anti-viral and cardiotonic activities. Recently, it has been reported that ethanol extracts from roots of SL have antiproliferative effects on gastric cancer cells. To explore the possibility that SL has chemopreventive effects on prostate cancer, we examined whether the hexane extract of SL (HESL) inhibits the growth of LNCaP human prostate cancer cells. Cells were incubated with various concentrations ($0{\sim}4$ mg/L) of HESL in DMEM/F12 containing 5% charcoal stripped fetal bovine serum. HESL substantially decreased viable cell numbers and induced apoptosis of LNCaP cells in dose-dependent manners. HESL increased the levels of cleaved caspase-8, -9, -7 and -3, and poly (ADP-ribose) polymerase. HESL increased the levels of the pro-apoptotic Bak and truncated-Bid proteins whereas it had no effect on the anti-apoptotic Bcl-2, Bcl-xL, or Mcl-1. The present results indicate that HESL inhibits the growth of human prostate cancer cells by inducing apoptosis, which involves the activation of the caspase cascades.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.29 no.2 s.43
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• pp.205-232
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• 2003

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 0.01-0.1 mg/ml UA or 0.1-1 mg/ml ONA after tape stripping, and TEWL (Transepidermal water loss) was measured . The recovery rate increased in those UA or ONA treated groups (0.1 mg/ml UA and 0.5 mg/ml ONA) at 6 h 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 f 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 $(ONA{\geq}UA>Vehicle)$. LM finding showed that thickness of stratum corneum (SC) was slightly increased and especially epidermal thickening and flattening was observed (UA>ONA>Veh). We also observed that UA and ONA stimulate epidermal keratinocyte differentiation via $PPAR\;\alpha$. 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 24h respectively. This result suggested that the UA and ONA can improve epidermal permeability barrier function and induce the epidermal keratinocyte differentiation via $PPAR\;{\alpha}$. 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
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• v.42 no.6
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• pp.888-899
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• 1995

Background: Topical inhaled steroids, budesonide(Bu) and beclomethasone dipropionate (BOP), are now established as effective drugs in the management of chronic asthma. These drugs have high topical anti-inflammatory effect with low systemic activity. This study was performed to determine the effects of two inhaled corticosteroids, Bu and BOP, on the adrenocortical supression in 44 patients with bronchial asthma or chronic obstructive pulmonary disease. Methods: The adrenocortical function was assessed by measurement of serum cortisol concentration at 8 o'clock in morning and free cortisol in 24-hour urine collection at interval in 44 patients. No steroid was administered during the pretreatment period of 10 days and the final 6 days of the study. Each subject inhaled BOP or Bu, in daily doses of 800 or 1,600 micrograms for 12 days. The dose was delivered by metered dose inhaler (MDI) or diskhaler or large spacing device attached to MDI. Results: The levels of serum cortisol and 24-hour urinary free cortisol were decreased during the treatment period in patients inhaled Bu delivered by MDI in daily doses of 800 and 1,600 micrograms. In contrast, serum cortisol level was decreased on 6 and 12th day of treatment period in patients with BDP diskhaler in daily doses of 800 micrograms. In daily doses of 1,600 micrograms, the serum cortisol and 24hour urine free cortisol levels were decreased on 6, 9 and 12th day of treatment period in patients with BDP disk haler. The serum cortisol and 24-hour urinary free cortisol levels were not significantly decreased during the treatment period in patients inhaled Bu delivered by large spacing device attached to a MDI. Conclusion: These results showed that 1) the endogenous cortisol secretion was suppressed after inhalation of BDP and Bu in daily doses of 800 and 1,600micrograms, 2) Bu with MDI suppressed the adrenocortical function more than BDP with diskhaler, in daily doses of 1600 micrograms. and 3)large spacing device attached to a MDI might decrease the risk of suppression in the hypothalamic -pituitary- adrenal axis.

• Journal of Life Science
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• v.24 no.6
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• pp.595-602
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• 2014

Styela Clava tunic (SCT) has found some applications in many areas of medical treatment including as an anti-inflammatory compound, a wound healing film, in guided bone regeneration, and as a food additive. The protective effect of SCT aqueous extract (AE-SCT) on cell death induced by $H_2O_2$ treatment was investigated by measuring the changes in cell viability in HepG2 cells after AE-SCT treatment. High concentrations of antioxidant compounds including flavonoids (3.3 mg/g) and phenolics (32.3 mg/g) were detected in AE-SCT but no significant cytotoxicity was observed in HepG2 cells treated with AE-SCT. The viability of HepG2 cells was also not changed by treatment with different concentrations of AE-SCT after $H_2O_2$ treatment. However, cell viability was significantly increased in cells treated with three different concentrations of AE-SCT before $H_2O_2$ treatment. The greatest increase in cell viability was observed in the group treated with $50{\mu}g/ml$ AE-SCT, when compared with vehicle-treated group. FACS and DAPI staining analysis indicated that the decrease in number of dead cells was dependent on the concentration of AE-SCT. Alterations in the Bax/Bcl-2 ratio after $H_2O_2$ treatment were significantly restored by treatment with different concentrations of AE-SCT. These results indicate that AE-SCT, which contains high levels of antioxidants, may protect cells against death induced by $H_2O_2$ treatment.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.6
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• pp.908-914
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• 2012

To investigate the difference and change of ingredient and efficacy of Galgeun-tang (GGT) according to extraction solvent, water and 70% EtOH, the quantities of index components and the several in vitro activities of two kinds of GGT extract were compared. The contents of extracts were analyzed with HPLC. The biological activities such as anti-inflammatory and anti-obesity effects were measured through cell line-based in vitro assay. The cytotoxicity was measured by CCK-8 assay in RAW 264.7 cell, BEAS-2B cell, HaCaT cell and 3T3-L1 cell. We compared effects of two kinds of extract by measuring NO, PGE2, IL-6 and TNF-${\alpha}$ in RAW264.7 cell, RANTES in BEAS-2B cell, MDC and RANTES in HaCaT cell and GPDH activity and leptin level in differentiated 3T3-L1. 70% EtOH extract of GGT contained more compositions than water extract. The inhibitory effect of water extract of GGT on NO in RAW 264.7 cell and GPDH activity in 3T3-L1 was stronger than that of 70% EtOH. 70% EtOH has a stronger inhibitory effect on PGE2 in RAW264.7 cell, RANTES in BEAS-2B cell, MDC, RANTES in HaCaT cell, leptin in 3T3-L1 cell than water extraction. These results suggest that the ingredient and efficacy from 70% EtOH extract of GGT are more effective than water extract.

• Korean Journal of Food Science and Technology
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• v.40 no.2
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• pp.207-214
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• 2008

In Asia Saussurea lappa (SL) has been used as a traditional herbal medicine to treat abdominal pain and tenesmus. Recently, in vitro cell culture studies have shown that SL has anti-ulcer, anti-inflammatory, and anti-tumor properties. To explore its potential chemopreventive and chemotherapeutic effects in colon cancer, we examined whether the hexane extract of SL (HESL) could inhibit the growth of HT-29 human colon cancer cells, and investigated the mechanisms for this effect. The cells were cultured with various concentrations (0-5 ${\mu}g/mL$) of HESL. The results indicated that HESL markedly decreased the numbers of viable HT-29 cells; whereas at the concentration of 5 ${\mu}g/mL$, HESL slightly decreased the viable cell numbers of CCD 1108Sk human skin normal fibroblasts at 72 hr. HESL substantially increased the numbers of cells in the sub G1 phase, and dose-dependently increased apoptotic cell numbers. Western blot analysis of the total cell lysates revealed that HESL increased Bax protein levels, but did not affect Bcl-2 levels. HESL induced the cleavage of poly (ADP-ribose) polymerase and caspases 8, 9, 7, and 3. This study demonstrated that HESL inhibits cell growth and induces apoptosis in HT-29 cells, which may be mediated by its ability to increase Bax levels and activate the caspase pathway. These findings may lead to the development of new therapeutic strategies for colon cancer treatment.