• Journal of Ginseng Research
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• 제47권1호
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• pp.89-96
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• 2023

Background and aim: Panax ginseng, a key herbal medicine of replenishing Qi and tonifying Spleen, is widely used in the treatment of gastrointestinal diseases in East Asia. In this study, we aim to investigate the potential effects and mechanisms of polysaccharides from P. ginseng (PGP) on intestinal mucosal restitution which is one of the crucial repair modalities during the recovery of mucosal injury controlled by the Ca²⁺ signaling. Methods: Rat model of intestinal mucosal injury was induced by indomethacin. The fractional cell migration was carried out by immunohistochemistry staining with BrdU. The morphological observations on intestinal mucosal injury were also performed. Intestinal epithelial cell (IEC-6) migration in vitro was conducted by scratch method. Western-blot was adopted to determine the expressions of PLC-𝛾1, Rac1, TRPC1, RhoA and Cav-1. Immunoprecipitation was used to evaluate the levels of Rac1/PLC-𝛾1, RhoA/TRPC1 and Cav-1/TRPC1. Results: The results showed that PGP effectively reduced the assessment of intestinal mucosal injury, reversed the inhibition of epithelial cell migration induced by Indomethacin, and increased the level of Ca²⁺ in intestinal mucosa in vivo. Moreover, PGP dramatically promoted IEC-6 cell migration, the expression of Ca²⁺ regulators (PLC-𝛾1, Rac1, TRPC1, Cav-1 and RhoA) as well as protein complexes (Rac1/PLC-𝛾1, Cav-1/TRPC1 and RhoA/TRPC1) in vitro. Conclusion: PGP increases the Ca²⁺ content in intestinal mucosa partly through controlling the regulators of Ca²⁺ mobilization, subsequently promotes intestinal epithelial cell migration, and then prevents intestinal mucosal injury induced by indomethacin.

• 대한약리학회지
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• 제27권2호
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• pp.109-118
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• 1991

허혈심근의 재관류시 arachidonic acid가 반응성 산소대사물의 발생원으로서 심근 손상에 미치는 영향을 검토하였다. Langendorff 관류장치를 이용하여 흰쥐 적출심장을 0.5ml/min의 저용량으로 관류 (45분)한 후 정상관류 (7 ml/min)로 복귀 시키므로써 실험적인 허혈-재관류 심장을 만들었다. 재관류시 Na arachidonate $(10^{-7}{\sim}10^{-2}{\mu}g/ml)$를 투여한 후 superoxide anion 생성을 관찰하고, 심근 손상의 지표로 lactic dehydrogenase(LDH)유리를 측정 하였으며 이들에 대한 각종 arachidonic acid 대사 억제 약물의 영향을 비교 검토하였다. Superoxide anion 생성은 SOD-억제성 ferricytochrorme C 환원 반응을 이용하였다. 연구성적은 다음과 같다. 1) 저용량 관류후 재관류시 ferricytochrorme C환원은 superoxide dismutase (SOD, 300 U/ml) 및 indomethacin (60 nmole/ml), ibuprofen $(30\;{\mu}g/ml)$에 의하여 억제되었다. 2) Na arachidonate는 용량의존적으로 ferricytochrorme C 환원을 증가 시켰으며 반응성 산소대사물 제거효소인 superoxide dismutase (SOD, 300 U/ml)에 의하여 현저히 억제되었다. 3) Na arachidonate $(10^{-3}\;{\mu}g/ml)$에 의한 superoxide anion 생성은 cyclooxygenase 억제약물인 indomethacin (60 nmol/ml), lipooxygenase 억제약물인 nordihydroguaiaretic acid$(NDGA,\;0.1\;{\mu}mole/ml)$, arachidonic acid의 substrate inhibitor인 eicosatetraynoic acid $(ETYA,\;1\;{\mu}g/ml)$에 의하여 현저히 억제되었다. 4) Na arachidonate는 LDH 유리를 증가시켰으며 SOD에 의하여 유의하게 억제 되었다. 5) Na archidonate에 의한 LDH 유리증가는 indomethacin, NDGA, ETYA에 의하여 유의하게 억제 되었다. 이상의 결과로 흰쥐의 허혈-재관류심근에서 arachidonic acid는 그 대사 과정에서 반응성 산소대사물을 발생하고 이는 심근세포손상에 부분적으로 기여할 수 있을 것으로 여겨졌다.

• Tuberculosis and Respiratory Diseases
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• 제39권6호
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• pp.474-483
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• 1992

연구배경 : 급성 폐손상은 원인에 상관없이 병태생리학적으로 폐동맥압의 증가와 폐부종을 특징으로 하는데 산소기를 포함한 여러 종류의 염증매개성 물질들이 급성 폐손상의 발병기전에 관여할 것으로 생각되고 있다. 그러나 산소기에 의한 급성 폐손상에서 폐모세혈관압의 변화는 확실하게 알려져 있지 않다. 또한 폐부종의 형성에는 폐포-모세혈관투과성과 함께 폐모세혈관과 폐포사이의 수압차도 중요한 역할을 하는 것으로 알려져 있으나 산소기에 의한 급성 폐손상에서 폐포모세혈관압의 역할에 관해서는 별로 알려져 있지 않은 실정이다. 방법 : Sprague-Dawley 백서를 정상 대조군(n=5), xanthine/xanthine oxidase 처치군(n=7), catalase 전치치군(n=5), papaverine 전처치군(n=7)과 indomethacin 전처치군(n=5)으로 나누어 격리순환폐모델에서 시간경과 따른 폐동맥압, 폐모세혈관압을 측정하고 폐의 무게 변화를 관찰하여 폐부종의 지표로 사용하였다. 폐모세혈관압은 micropuncture에 의한 방법과 일치도가 높은 것으로 알려져 있는 double occlusion법을 이용하였다. 즉, 폐동맥으로의 관류와 좌심방으로부터의 관류를 동시에 2초간 차단하여 폐동맥압과 좌심방압이 비슷한 압력에서 평형상태를 유지할 때의 압력을 폐모세혈관압으로 사용하였다. 결과 : 1) 폐동맥압과 폐모세혈관압은 각각 xanthine/xanthine oxidase 처치군에서 대조군에 비해 유의하게 높았다. 이들은 catalase와 papaverine 전처치로 각각 유의하게 완화되었으나 indomethacin 전처치로는 유의하게 완화되지 않았다. 2) xanthine/xanthine oxidase 처치군에서 관찰된 폐부종은 catalase 천처치와 papaverine 전처치로 유의하게 완화되었으나 indomethacin 전처치로는 완화되지 않았다. 결론 : 격리순환폐모델에서 산소기에 의한 백서의 급성 폐손상시 폐모세혈관압이 증가하고 이는 폐포-모세혈관투과성이 증가된 상태하에서 폐부종을 악화시키며 산소기에 의한 폐모세혈관압의 증가와 폐부종에 cyclooxygenase 대사물은 큰 역할을 하지 않을 것으로 생각된다.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제11권1호
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• pp.171-186
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• 1989

This study was undertaken to investigate the effects of indomethacin on 4-nitroquinoline 1-oxide (4NQO) induced palatal carcinoma of albino rats. Sixty albino rats about 100 gms of body weight, 6 weeks old-were used classifying as 1) six albino rats of normal group received no treatment, 2) six albino rats of control group treated with propane 1, 2-diol 3 times a week, 3) twenty four albino rats of experimental group I treated with 0.5% 4NQO in propane 1, 2-diol 3 times a week, 4) twenty four albino rats of experimental group II treated with 0.5% of 4NQO in propane 1, 2-diol 3 times a week and administrated 20${\mu}g/ml$ indomethacin in drinking water ad lib. The animals of normal and control groups were sacrificed 7th, 11th, 15th, 19th, 23rd and 27th week, while those of experimental group I and II were sacrificed 7th, 9th, 11th, 13th, 15th, 17th, 19th, 21st, 23rd, 25th, 27th and 29th week after the experiment. The palatal mucosa was excised and examined grossly, light-microscopically and electron-microscopically. Following results were obtained. 1. In control group, there was no specific difference from normal tissue histopathologically. 2. In group I, hyperkeratosis mild acantosis and dyskeratosis in in 7th week, dysplasia in 11th week and severe acantosis in 19th week were observed, but squamous cell carcinoma not observed until 29th week on light-microscope. 3. In group II, hyperkeratosis, mild acantosis in 9th week, dyskeratosis and dysplasia in 21st week, severe acantosis in 27th week and squamous cell carcinoma in 29th week were observed on light-microscope. 4. In group I, widening of intercellular space in 7th week, increasing of desmosome, giant desmosome and tonofilament in cytoplasm in 9th week, severe widening of intercellular space, increasing of mitochondria and vascular degeneration in 11th week, irregular pattern of cell feature and nucleus and prominent nucleoli in 19th week, and continuity of basal lamina in 29th week were observed on electron-microscope. 5. In group II, mild widening of intercellular space in 9th week, increasing of mitochondria, vascular degeneration and tonofilament in cytoplasm in 13th week, increasing of desmosome and giant desmosome in 15th week, irregular pattern of cell surface and nucleus and prominent nucleoli, and in 21st week continuity of basal lamina were observed on electron-microscope which phenomenon occurred little later than group I. After 21st week, however, severe widening of intercellular space, vascular degeneration and continuity of basal lamina were observed as in group I.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제11권1호
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• pp.187-202
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• 1989

This study was undertaken to investigate the effect of indomethacin on prostaglandins in 4-Nitroquinoline-N-Oxide (4-NQO) induced palatal carcinoma of albino rats. 128 Sprague-Dawley strain albino rats-about 100g in body weight-were used in this study, divided into as belows; 1. Normal group (16-albino rats) with no treatment, 2. Control group (16-albino rats) treated with prophylene application onto palatal mucosa 3 times a week. 3. Experimental group I (48-albino rats) treated with 0.5% 4-NQO in prophylene application onto palatal mucosa 3 times a week. 4. Experimental group II (48-albino rats) treated with 0.5% 4-NQO in prophylene application with administered $20{\mu}g/ml$ of indomethacin in drinking water ad. lib. Four animals were sacrificed 7th, 13th, 19th, and 25th week respectively in normal and control group, and 7th, 9th, 11th, 13th, 15th, 17th, 19th, 21st, 23rd, 25th, 27th and 29th week respectively in experimental group I and II at each time. The palatal and lingual tissues were excised and kept frozen at $-70^{\circ}C$. Densitometer scan and Beta-counting counter were used for the thin layer chromatography of the arachidonic acid metabolites. The obtained results were as belows; 1. In normal and control group, there was little change of the arachidonic acid metabolites during experiment period, and the tissue homogenates included prostaglandin $D_2$, 6-keto-prostaglandin $F_{1{\alpha}}$, prostaglandin $E_2$, thromboxane $B_2$, prostaglandin $F_{2{\alpha}}$ in that order of relative abundances. 2. In experimental group I, prostaglandin $D_2$, and prostaglandin $E_2$ were increased, while 6-keto-prostaglandin $F_{1{\alpha}}$ and thromboxane $B_2$ were decreased in relative abundances of arachidonic acid metabolites. And there was little change in prostaglandin $F_{1{\alpha}}$ 3. In experimental group II, prostaglandin $D_2$, and prostaglandin $E_2$ were increased, while 6-keto-prostaglandin $F_{1{\alpha}}$ and thromboxane $B_2$ were decreased in relative abundances of arachidonic acid metabolites. And there was little change in prostaglandin $F_{2{\alpha}}$ also. 4. In the range of increase in prostaglandin $D_2$, and prostaglandin $E_2$, and that of decrease in 6-keto-prostaglandin $F_{1{\alpha}}$ and thromboxane $B_2$, in relative abundances, there was wider in experimental group I than in group II. 5. In the range of increase in prostaglandin $D_2$, and prostaglandin $E_2$, and that of decrease in 6-keto-prostaglandin $F_{1{\alpha}}$ and thromboxane $B_2$, in relative abundances, there was wider in palatal mucosa than in lingual mucosa in experimental group I and II.

• International Journal of Oral Biology
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• 제30권2호
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• pp.47-57
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• 2005

Leptin, the product of the obese gene, is a circulating hormone secreted primarily from adipocytes. Several results suggest that leptin is important mediators of bone metabolism. The present study was undertaken to determine the effects of leptin on anti-osteoclastogenesis using murine precursors cultured on Ca-P coated plates and on the production of osteoprotegerin (OPG) in osteoblastic cells. Additionally, this study examined the possible involvement of prostaglandin $E_2\;(PGE_2)$/protein kinase C (PKC)-mediated signals on the effect of leptin on anti-osteoclastogenesis to various culture systems of osteoclast precursors. Osteoclast generation was determined by counting tartrate-resistant acid phosphatase positive [TRAP (+)] multinucleated cells (MNCs). Osteoclastic activity was determined by measuring area of resorption pits formed by osteoclasts on Ca-P coated plate. The number of 1,25-dihydroxycholecalciferol $(1,25[OH]_2D_3)$- or $PGE_2$-induced TRAP (+) MNCs in the mouse bone marrow cell culture decreased significantly after treatment with leptin. The number of receptor activator of NF-kB ligand (RANKL)-induced TRAP (+) MNCs in M-CSF dependent bone marrow macrophage (MDBM) cell or RAW264.7 cell culture decreased significantly with leptin treatment. Indomethacin inhibited osteoclast generation induced by $1,25[OH]_2D_3$ and dexamethasone, however, no significant differences were found in the leptin treated group when compared to the corresponding indomethacin group. Phorbol 12-myristate 13-acetate (PMA), a PKC activator, inhibited osteoclast generation induced by $1,25[OH]_2D_3$. The number of TRAP (+) MNCs decreased significantly with treatment by PMA at concentrations of 0.01 and $0.1{\mu}M$ in culture. Leptin inhibited PMA-mediated osteoclast generation. Isoquinoline-5-sulfonic 2-methyl-1-piperazide dihydrochloride (H7) had no effect on osteoclast generation induced by $1,25[OH]_2D_3$. Cell culture treatment with leptin resulted in no significant differences in osteoclast generation compared to the corresponding H7 group. Indomethacin showed no significant effect on TRAP (+) MNCs formation from the RAW264.7 cell line. PMA inhibited TRAP (+) MNCs formation induced by RANKL in the RAW264.7 cell culture. H7 had no effect on osteoclast generation from the RAW264.7 cell line. There was no difference compared with the corresponding control group after treatment with leptin. $1,25[OH]_2D_3$- or $PGE_2$-induced osteoclastic activity decreased significantly with leptin treatment at a concentration of 100 ng/ml in mouse bone marrow cell culture. Indomethacin, PMA, and H7 significantly inhibited osteoclastic activity induced by $1,25[OH]_2D_3$ in mouse bone marrow cell culture. No significant differences were found between the leptin treated group and the corresponding control group. The secretion of OPG, a substance known to inhibit osteoclast formation, was detected from the osteoblasts. Treatment by leptin resulted in significant increases in OPG secretion by osteoblastic cells. Taken these results, leptin may be an important regulatory cytokines within the bone marrow microenvironment.

• The Korean Journal of Physiology and Pharmacology
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• 제2권1호
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• pp.77-84
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• 1998

Ureteral obstruction causes increase in renal blood flow (RBF) and partial impairment of the autoregulation of RBF. Although increased renal prostaglandin production is responsible for the former, it is not clear whether or not it is also responsible for the latter. Therefore, we investigated the role which prostaglandins play in the autoregulation of RBF during an ureteral pressure elevation (40 $cmH_2O$). Since the major mechanism of RBF autoregulation is the tubuloglomerular feedback, studying the interaction between ureteral pressure and RBF autoregulation may reveal the role of prostaglandin in tubuloglomerular feedback. To pursue the purpose, six anesthetized dogs were prepared for the measurements of RBF, mean sytemic and renal arterial pressure (RAP) and the manipulation of ureteral pressure. The autoregulation curves were determined during both control and elevation of the ureteral pressure, before and after the pretreatment with indomethacin, a cyclooxygenase inhibitor. The desired ureteral pressure was achieved by vertically elevating the water-filled reservoir connected to the ureteral catheter to 40 cm above the kidney level. In response to the elevation of the ureteral pressure, RBF increased from $170{\pm}8 ml{\cdot}min^{-1}\;to\;189{\pm}8$, and the systemic arterial pressure didn't change significantly. During spontaneous urine flow, RBF autoregulation was abolished when RAP was reduced to $59{\pm}3$ mmHg. On the other hand, during the ureteral pressure elevation, the autoregulation curves shifted upward and rightward from control, and the pressure when RBF autoregulation was abolished was $74{\pm}3$ mmHg. The pretreatment of the dogs with indomethacin failed to affect the lower limit of RBF autoregulaion during both control ($63{\pm}5$ mmHg) and the elevated ureteral pressure ($77{\pm}5$ mmHg). Since RBF failed to increase in response to the elevated ureteral pressure, RBF autoregulation curves obtained during the elevated ureteral pressure shifted only rightward from indomethacin control. The results indicate that the increased intrarenal level of prostaglandin or prostaglandin-induced vasodilation does not appear to bear any relation to the reduction in the autoregulatory capacity during partial ureteral obstruction. It seems that the partial impairment of the autoregulation during acute ureteral obstruction is due to the consumption of tubuloglomerular feedback mechanism at spontaneous RAP and that prostaglandin is neither mediator nor effector of tubuloglomerular feedback mechanism.

• 한국식품영양과학회지
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• 제33권1호
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• pp.34-40
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• 2004

본 연구는 기능성 식품으로의 활용을 위한 한약자원에 관한 연구의 일환으로 계획되었고 선행연구와 문헌상의 기록을 바탕으로 한 오미자의 여러 기능 중 혈류개선효과에 중점을 두고 그 기능을 과학적으로 확인하여 보고자 하였다. 백서를 대상으로 LDF를 이용하여 오미자의 국소 뇌혈류량과 혈압에 대한 효능을 관찰한 결과는 다음과 같다. 오미자를 여러 농도로 투여시 국소 뇌혈류량은 증가되었다 오미자가 국소 뇌혈류량을 증가시키는 기전을 확인하기 위해 propranolol, atropine, L-NNA, indomethacin을 전처리한 후 오미자를 투여 했을 때는 국소 뇌혈류량에 유의한 변화를 관찰할 수 없었으나 methylene blue를 전처리한 후 오미자를 1.0 mg/kg 농도 이상으로 투여했을 때는 국소 뇌혈류량이 유의적으로 증가함을 관찰할 수 있었다. 오미자를 여러 농도로 투여시 혈압은 하강되었다. 오미자가 어떤 기전으로 혈압의 변화를 초래하는지를 확인하기 위해 propranolol, atropine, L-NNA, indomethacin을 전처리한 후 오미자를 투여했을 때는 혈압하강에 유의한 변화를 관찰할 수 없었으나 methylene blue를 전처리한 후 오미자를 1.0 mg/kg 농도이상으로 투여했을 때에는 혈압이 유의적으로 하강하는 변화가 나타났다. 이상의 결과에서 오미자는 뇌혈류량을 증가시키고 혈압을 강하시키는 작용이 있음을 확인하였고 그 기전은 guanylyl cyclase의 활성을 변화시킴으로써 나타나는 결과로 판단된다. 따라서 연구의 목적인 기능성 식품으로의 활용에 있어 원재료로 사용이 가능하다고 판단되며 향후 오미자를 이용한 기능성 식품의 제조 및 완제품에 대한 기능성을 평가하여 기능성 식품시장이 올바르게 정립되는데 기여하고자 한다.

• 동의생리병리학회지
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• 제17권2호
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• pp.493-498
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• 2003

Paeoniae Radix, Glycyrrhizae Radix and Jakyakgamchotang have been used in Oriental Medicine for many centuries as a treatment for various disease. The purpose of the present study is to determine the effect of Paeoniae Radix, Glycyrrhizae Radix and Jakyakgamchotang on narepinephrine(NE) induced contraction of isolated rabbit femoral artery. Rabbits (2.0kg, female) were killed by CO₂ exposure and a segment (8-10mm) of the aortic ring from each rabbit was cut into equal segments and mounted 'in pairs' in a tissue bath. Contractile force was measured with force displacement transducers under 1.5g loading tension. The dose of NE which evoked 50% of maximal response (ED/sub 50/) was obtained from cumulative dose response curves for NE (10/sup -7/～10/sup -4/M). Contractions evoked by NE (ED/sub 50/) were inhibited significantly by Paeoniae Radix, Glycyrrhizae Radix and Jakyakgamcho-tang. The mean percent inhibition of NE induced contraction was 83.9% (p<0.01) after 150㎕/㎖ Paeoniae Radix, 101.1 %(p<0.01) after 150 ㎕/㎖, Glycyrrhizae Radix and 107.3%(p<0.01) after 150㎕/㎖ Jakyakgamcho-tang, Indomethacin slightly but significantly attenuated the inhibitory effects of Paeoniae Radix. Following treatment with indomethacin, the mean percent inhibition caused by 150㎕/㎖ Paeoniae Radix fell to 16.4% in femoral artery induced by NE contraction. Propranolol, ODQ, and L-NNA did not significantly alter the inhibitory effect of Paeoniae Radix. ODQ slightly but significantly attenuated the inhibitory effects of Glycyrrhizae Radix. Following treatment with ODQ, the mean percent inhibition caused by 150㎕/㎖ Glycyrrhizae Radix fell to 13.0% in femoral artery induced by NE contraction. Propranolol, indomethacin and L-NNA did not significantly alter the inhibitory effect of Glycyrrhizae Radix. L-NNA slightly but significantly attenuated the inhibitory effects of Jakyakgamchotang. Following treatment with L-NNA, the mean percent inhibition caused by 150㎕/㎖ Jakyakgamchotang fell to 13.8% in femoral artery induced by NE contraction. Propranolol, ODQ and indomethacin did not significantly alter the inhibitory effect of Jakyakgamcho-tang. These results indicate that Paeoniae Radix, Glycyrrhizae Radix and Jakyakgamcho-tang can relax NE induced contraction of the isolated rabbit femoral artery, and that this inhibition related to nitric oxide.

• 한국식품위생안전성학회지
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• 제31권4호
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• pp.286-293
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• 2016

본 연구에서는 ursolic acid의 위의 보호효과를 위한 실험을 실시하였다. 위장 질병에 대한 ursolic acid의 효과를 확인하기 위해서 급성, 만성위염은 각각의 HCl ethanol과 indomethacin에 의해 유도된 위염 동물 모델을 사용하여 관찰하였다. 대표적인 공격인자인 위산에 관해서는 PPI activity를 통해서 확인하였고, 위의 손상에 대한 보호인자에 관해서는, $PGE_2$를 정량적으로 분석하였다. 항균활성 실험은 만성위염, 위궤양, 위암에 원인인자로 잘 알려진 H. pylori로 실험하였다. AGS cell를 이용하여 DAPI 염색, Flow cytometry assay를 통하여 ursolic acid가 위암세포의 apoptosis에 관여하는지를 확인하였다. 그 결과 ursolic acid는 HCl ethanol과 indomethacin에 의해 유도된 급성, 만성에 대한 위손상을 억제하였다. Ursolic acid는 위산분비의 마지막 단계인 위염분비효소인 proton pump를 억제시킴으로써 산의 분비를 억제하였다. 그리고 ursolic acid는 위 점막의 보호인자인 $PGE_2$의 농도가 증가함으로써 위 점막 보호 효과를 확인하였다. 또한 ursolic acid는 공격인자인 H. pylori colonization을 억제하였다. DAPI를 이용한 핵 염색에서, 대조군과는 달리, 핵 형상의 변형과 함께 수축 된 세포 또는 염색질의 응축현상이 관찰되었다. Flow cytometry assay에서 ursolic acid에 의해 apoptosis가 증가하는 것을 확인 하였다. 이를 통하여 ursolic acid는 위 손상에 대한 방어 효과가 있음을 확인할 수 있었다.