• The Korean Journal of Physiology and Pharmacology
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• 제19권4호
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• pp.365-372
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• 2015

Aripiprazole (ARI) is a commonly prescribed medication used to treat schizophrenia and bipolar disorder. To date, there have been no studies regarding the molecular pathological and immunotoxicological profiling of aripiprazole. Thus, in the present study, we prepared two different formulas of aripiprazole [Free base crystal of aripiprazole (ARPGCB) and cocrystal of aripiprazole (GCB3004)], and explored their effects on the patterns of survival and apoptosis-regulatory proteins under acute toxicity and cytotoxicity test conditions. Furthermore, we also evaluated the modulatory activity of the different formulations on the immunological responses in macrophages primed by various stimulators such as lipopolysaccharide (LPS), pam3CSK, and poly(I:C) via toll-like receptor 4 (TLR4), TLR2, and TLR3 pathways, respectively. In liver, both ARPGCB and GCB3004 produced similar toxicity profiles. In particular, these two formulas exhibited similar phospho-protein profiling of p65/nuclear factor $(NF)-{\kappa}B$, c-Jun/activator protein (AP)-1, ERK, JNK, p38, caspase 3, and bcl-2 in brain. In contrast, the patterns of these phospho-proteins were variable in other tissues. Moreover, these two formulas did not exhibit any cytotoxicity in C6 glioma cells. Finally, the two formulations at available in vivo concentrations did not block nitric oxide (NO) production from activated macrophage-like RAW264.7 cells stimulated with LPS, pam3CSK, or poly(I:C), nor did they alter the morphological changes of the activated macrophages. Taken together, our present work, as a comparative study of two different formulas of aripiprazole, suggests that these two formulas can be used to achieve similar functional activation of brain proteins related to cell survival and apoptosis and immunotoxicological activities of macrophages.

• Journal of Ginseng Research
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• 제47권3호
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• pp.376-384
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• 2023

Background: Hepatic lipid disorder impaired mitochondrial homeostasis and intracellular redox balance, triggering development of non-alcohol fatty liver disease (NAFLD), while effective therapeutic approach remains inadequate. Ginsenosides Rc has been reported to maintain glucose balance in adipose tissue, while its role in regulating lipid metabolism remain vacant. Thus, we investigated the function and mechanism of ginsenosides Rc in defending high fat diet (HFD)-induced NAFLD. Methods: Mice primary hepatocytes (MPHs) challenged with oleic acid & palmitic acid were used to test the effects of ginsenosides Rc on intracellular lipid metabolism. RNAseq and molecular docking study were performed to explore potential targets of ginsenosides Rc in defending lipid deposition. Wild type and liver specific sirtuin 6 (SIRT6, 50721) deficient mice on HFD for 12 weeks were subjected to different dose of ginsenosides Rc to determine the function and detailed mechanism in vivo. Results: We identified ginsenosides Rc as a novel SIRT6 activator via increasing its expression and deacetylase activity. Ginsenosides Rc defends OA&PA-induced lipid deposition in MPHs and protects mice against HFD-induced metabolic disorder in dosage dependent manner. Ginsenosides Rc (20mg/kg) injection improved glucose intolerance, insulin resistance, oxidative stress and inflammation response in HFD mice. Ginsenosides Rc treatment accelerates peroxisome proliferator activated receptor alpha (PPAR-α, 19013)-mediated fatty acid oxidation in vivo and in vitro. Hepatic specific SIRT6 deletion abolished ginsenoside Rc-derived protective effects against HFD-induced NAFLD. Conclusion: Ginsenosides Rc protects mice against HFD-induced hepatosteatosis by improving PPAR-α-mediated fatty acid oxidation and antioxidant capacity in a SIRT6 dependent manner, and providing a promising strategy for NAFLD.

• 대한화장품학회지
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• 제30권2호
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• pp.227-233
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• 2004

자외선이 피부에 지속적으로 조사되면 썬번, 염증, 광노화와 같은 다양한 부작용이 생기게 된다. 따라서 광손상에 대한 보호작용은 점점 중요성이 인식되고 있으며, 천연 식물추출물에서 자외선에 대한 광보호효과가 있는 안전하고 효과적인 물질개발에 대한 연구가 진행되고 있다. 본 연구는 자외선에 의해 유도된 피부손상에 대한 보호효과가 우수한 천연식물추출물에 대한 것이다. 향나무, 능소화, 비자추출물에서 자외선에 의해 생성되는 라디칼에 대한 항산화효과, MMP 발현 및 활성 저해, 염증관련 사이토카인인 인터루킨 1알파, 6, 프로스타글란딘 E$_2$ 생성저해효과 등으로 피부세포보호 효과를 연구하였다. 실험결과 천연추출물 중 향나무추출물과 능소화추출물이 프리라디칼 및 슈퍼옥사이드 라디칼 소거효과가 우수하게 나타났으며 피부 콜라겐과 같은 메트릭스를 분해하는 효소인 MMP-1의 활성 및 발현 저해효과는 섬유아세포에서 UVA 조사에 의한 실험에서 우수하게 나타났으며, 피부세포 배양액에 대해 zymography를 실시하여 활성이 감소됨을 확인하였다. 피부 각질형성세포에서 자외선에 의해 유도된 염증관련 사이토카인인 인터루킨 6의 발현량 실험에서도 무처리군에 비해 향나무추출물이 인터루킨 6을 30% 정도 저해효과가 나타났으며, 염증반응 중 cyclooxygenase(COX)에 의한 경로에서 생성되는 프로스타글란딘 E$_2$의 생성량도 감소시켰다. 사람피부에서 SLS (0.5%) 첩포로 유발된 자극성 피부염의 항염증 효과 평가 시 SLS에 의해 유발되는 자극정도가 피검자의 피부상태에 따라 다양하게 나타났으며, 향나무 추출물 함유 에멀젼 제품 도포 실험에서는 피부 홍반 완화 효과와 피부장벽 회복효과가 우수하게 나타났다. 이상의 결과로 향나무추출물은 자외선 조사 및 SLS에 의한 피부손상에 대한 피부세포보호작용이 우수하여 광노화에 대응하는 자극완화 소재로서의 화장품 응용 가능성을 확인하였다.

• Journal of Periodontal and Implant Science
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• 제31권4호
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• pp.833-846
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• 2001

Recently, use of natural medicine is getting more attention, and some of them are believed to be effective in　the treatment of periodontitis. Among them, the seeds of safflower(Carthamus tinctrorius L.) have been proven to be effective through its use in bone diseases such as fracture and osteoporosis. During the last few years, studies using the seeds of safflower gown in Korea have been active, and it has been reported that safflower seed extract increase the proliferation and the alkaline phosphatase(ALP) activity of human periodontal ligament fibroblast(hPDLF), osteoblast, and that they promote the mineralization process. In animal studies, when safflower seed extract were administered orally new bone formation was promoted. Recently, in an effort to find out the most effective osteogenic components, among many components of the safflower seed, various safflower seed fraction extracts were obtained by multistep extraction of the safflower components using various solvents. Among these, saf-M-W fraction extracted by methanol and water was most effective in increasing osteogenic potential of osteoblasts. In this study, the effect of safflower seed fraction extract, saf-M-W, on the growth and differentiation of hPDLF and MC3T3-E1 cell was investigated. The toxicity of saf-M-W on both cells was measured using M'IT(3-(4,5dimethylthiazol-2-y1)-2,5-diphenyl tetrazolium bromide) test, and ALP activity was measured using the colorimetric assay of hPDLF. In addition, in MC3T3-El cells, the expression of ALP, bone sialoprotein(BSP) mRNA was observed using Northern blot, and the mineralized nodule formation Was observed using von Kossa stain and phase-contrast microscope. 1. In concentrations below $10{\mu}g/ml$, saf-M-W didn't show any toxicity on hPDLF and MC3T3-El cell. 2. The change in saf-M-W concentration had no effect on the ALP activity of hPDLF. 3. In MC3T-E1 cells, mRNA expressions of ALP and BSP were greater in the experimental group treated with $10{\mu}g/ml$ concentration of saf-M-W compared with the control group. 4. In MC3T3-El cells, abundance of mineralized nodules were formed in the experimental group treated with $10{\mu}g/ml$ Concentration of saf-M-W, while no mineralized nodule was formed in the control group. These results suggest that safflower seed fraction extract, saf-M-W. didn't show any toxicity on hPDLF and MC3T3-E1 cell at concentrations below $10{\mu}g/ml$ and effectively enhanced the differentiation and osteogenic potential of MC3T3-El cell.

• 한국식품저장유통학회지
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• 제16권2호
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• pp.238-245
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• 2009

본 연구에서는 천일염의 아직 밝혀지지 않은 기능성과 청국장의 효과를 감안하여 천일염으로 제조된 청국장의 기능적 우수성을 평가하기 위하여 Bacillus subtilis DJI 균주를 접종하여 발효시킨 무염청국장, 3% 천일염 첨가 청국장, 3% 정제염 첨가 청국장과 3% 정제염이 첨가되어진 시판청국장의 에탄올, 물 및 헥산 추출물의 항산화력을 비교 검토하였다. 청국장 에탄올, 헥산 및 물 추출 수율은 각각 $10.9{\sim}11.8%$, $15.7{\sim}16.9%$, $18.6{\sim}19.4%$ 범위로 청국장 용매별 간에는 서로 유사한 경향이었으며, 물 추출 수율이 가장 높게 나타났다. 추출물의 DPPH에 대한 전자소거능, 아질산염 소거능, linoleic acid에 대한 과산화물가 및 항산화지수 측정에 의한 항산화효과는 에탄올 추출 시료군이 물 추출 시료군에 비하여 높았다. 청국장 추출물의 전자소거능과 아질산염 소거능은 무염청국장과 3% 천일염 첨가 청국장 추출물이 가장 우수하였으나, 합성항산화제에 비해서는 낮은 효능을 보였다. 청국장 추출물 중 항산화지수는 3% 천일염 첨가 청국장 추출물이 가장 우수하였다. Bacillus subtilis DJI 균주를 접종하여 발효시킨 청국장인 무염청국장, 3% 천일염 첨가 청국장 및 3% 정제염 첨가 청국장이 시판청국장에 비하여 항산화효과가 우수하였으며, 균주를 접종하여 발효시킨 청국장 중 무염청국장과 3% 천일염 첨가 청국장이 3% 정제염 첨가 청국장에 비하여 항산화효과가 다소 우수하였다.

• 아시안잔디학회지
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• 제21권2호
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• pp.147-154
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• 2007

2004년 3월에 전라북도에 위치한 한 골프장의 켄터키 블루그래스와 퍼레니얼 라이그래스에 설부병이 발병되었다. 감염된 잔디잎들은 서로 엉켜저 매트화 되고, 흰색에서 회백색의 균사체들로 덮여있었다. 균핵들은 잔디의 엽신, 엽초 및 관부 위에 형성되어 있었다. 이병 잎으로부터 분리된 곰팡이는 직경이 1.4 mm 미만의 밝은 핑크에서 갈색의 불규칙한 모양의 균핵과 꺽쇠연결체, 흰색의 균사체 등을 형성하여 Typhula incarnata와 같은 특징을 보였다. 분리된 T. incarnata의 균사생육 적온은 $5{\sim}15^{\circ}C$이었다. 원인균의 ribosomal RNA IST1의 부분 염기서열은 GeneBank database에 등록된 T. incarnata의 부분 염기서열과 91%로의 상동성을 보여 T. incarnata로 동정되었다. 실내 약제방제 시험결과 14개 살균제 중 iprodione, tebuconazole, polyoxin D, flutolanil, hexaconazole, tolclofos-methyl, fosetyl-Al, mepronil, pencycuron+ tebuconazole 및 fenarimol 살균제들은 추천농도에서 완전하게 균생장을 억제하였다. 포장시험에서, 이들 살균제와 thifluzamide와 thiram과 같은 살균제들은 다소 방제효능의 정도 차이는 있지만 효과적으로 잔디 설부병을 방제하였다.

• Journal of Pharmaceutical Investigation
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• 제32권3호
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• pp.215-221
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• 2002

Cephradine is a first generation cephalosporin and has broad spectrum antibacterial activity against gram-positive and gram-negative microorganisms, through inhibition of bacterial cell wall synthesis. Cephradine is useful for treatment of infections of the urinary and respiratory tract, skin and soft tissues. The purpose of the present study was to evaluate the bioequivalence of two cephradine capsules, Cefradine Yuhan (YuHan Corporation) and Broadcef (Ilsung Pharmaceuticals Co. Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The cephradine release from the two cephradine capsules in vitro was tested using KP VII Apparatus II method with various different kinds of dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty normal male volunteers, $23.10{\pm}2.90$ years in age and $67.69{\pm}8.04\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one capsule containing 500 mg as cephradine was orally administered, blood was taken at predetermined time intervals and the concentrations of cephradine in serum were determined using HPLC method with UV detector. The dissolution profiles of two cephradine capsules were very similar at all dissolution media. Besides, the pharmacokinetic parameters such as $AVC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AVC_t\;and\;C_{max}$ and untransformed $T_{max}$. The results showed that the differences in $AVC_t,\;C_{max}\;and\;T_{max}$ between two capsules based on the Cefradine Yuhan were -2.87%, -0.96% and -4.85%, respectively. There were no sequence effects between two capsules in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of 1og(0.8) to log(1.25) $(e.g.,\;log(0.93){\sim}log(1.02)\;and\;log(0.88){\sim}log(1.13)\;for \;AVC_t\;and\;C_{max},\;respectively)$. The 90% confidence interval using untransformed data was within ${\pm}20%$ $(e.g., \;-17.54{\sim}7.78\;for\;T_{max})$. All parameters met the criteria of KFDA guideline for bioequivalence, indicating that Broadcef capsule is bioequivalent to Cefradine Yuhan capsule.

• Journal of Animal Science and Technology
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• 제45권3호
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• pp.473-482
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• 2003

Lactobacillus spp. 급여에 의하여 Salmonella enteritidis 감염에 의한 치사율의 저하 성향, 시험관내 억제활성, 장액 내의 총 IgA 농도변화와 Lactobacillus casei.의 16S-23S rRNA intergenic spacer region의 sequence를 측정 비교한 결과는 다음과 같다. Lactobacillus spp. 5균주는 시험관내 Salmo- nella enteritidis 억제활성 측정 결과 모든 시험균주가 억제활성을 나타내었고 그 억제활성의 차이가 통계적인 유의성을 보였으며, 억제활성의 차이는 L. helveticus CU 631 > L. rhamnosus GG ATCC 53103 > L. johnsonii C-4 > L. acidophilus ATCC 4356 > L. casei YIT 9018 인 것으로 나타났다. Lactobacillus spp. 급여에 의하여 Salmonella enteritidis challenge에 의한 치사율 저하효과는 Lb. helveticus CU 631은 대조구의 생존률 62%에 대하여 100%로서 가장 높은 치사율 저하효과를 나타내었고, L casei YIT 9018, L johnsonii C-4의 생존률이 70%와 50%를 나타내었다. Lactobacillus spp.의 16S-23S rRNA intergenic spacer region의 sequence를 측정하고 gene bank에 등록된 균주의 sequence와 비교한 결과 homology의 차이를 나타내었다.

• Journal of Pharmaceutical Investigation
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• 제38권6호
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• pp.413-419
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• 2008

Carvedilol, is a nonselective $\beta$-blocking agent and it also has vasodilating properties that are attributed mainly to its blocking activity at ${\alpha}_1$-receptors. The purpose of the present study was to evaluate the bioequivalence of two carvedilol tablets, $Dilatrend^{(R)}$ tablet 12.5 mg (Chong Kun Dang Pharmaceutical Co., Ltd.) and Cadilan tablet 12.5 mg (KyungDong Pharmaceutical. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of carvedilol from the two carvedilol formulations in vitro was tested using KP VIII Apparatus II method with pH 4.5 dissolution medium. Thirty two healthy male subjects, $25.00{\pm}3.09$ years in age and $70.71{\pm}11.35\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single tablet containing 12.5 mg as carvedilol was orally administered, blood samples were taken at predetermined time intervals and the concentrations of carvedilol in serum were determined using HPLC with fluorescence detector. The dissolution profiles of two formulations were similar in the tested dissolution medium. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Dilatrend^{(R)}$ tablet 12.5 mg, were 4.66%, 8.33% and -7.45% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., $\log\;0.9823{\sim}\log\;1.1042$ and $\log\;1.0132{\sim}\log\;1.1875$ for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Cadilan tablet 12.5 mg was bioequivalent to $Dilatrend^{(R)}$ tablet 12.5 mg.

• 환경생물
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• 제35권2호
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• pp.116-122
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• 2017

말라카이트 그린과 메틸렌 블루 같은 기본 염료는 1930년대부터 물 곰팡이 감염을 통제하는 소독제로 사용되었다. 하지만 이 염료의 발암성 및 생체 내부 축적이 보고된 후 공중보건을 위해 이 염료의 사용이 금지되었다. 본 연구에서는 천연유황수의 Saprolegnia parasitica의 감염에 대한 치료 효과와 어류에서의 안전성을 평가하고자 하였다. 천연유황수의 항진균성 시험에서 S. parasitica 균사체의 성장이 50 ppm 또는 그 이상의 농도에서 억제되었다. 미꾸라지의 치어와 미성어에 대한 천연유황수의 급성 독성 시험에서 무 영향농도(NOEC)는 100 ppm, 최저 영향농도(LOEC)는 125 ppm 그리고 반수치사농도($LC_{50}$)는 치어에서 125 ppm, 미성어에서 250 ppm으로 측정되었다. 또한, 물벼룩을 이용한 천연유황수의 생태 독성 시험에서는 100 ppm 이하의 농도에서 물벼룩의 유영저해가 나타나지 않았다. 결론적으로, 천연유황수는 50 ppm 농도에서 미꾸라지에 대한 S. parasitica의 감염을 방지하였을 뿐만 아니라 100 ppm 농도까지 미꾸라지에 급성독성 그리고 물벼룩에 생태독성을 나타내지 않았다. 그러므로 미꾸라지 양식에서 많은 문제를 일으키는 수생균을 제거하기 위하여 말라카이트 그린 및 메틸렌 블루 같은 발암성 소독제를 대신하여 천연유황수를 유용하게 사용할 수 있으며 잠재적으로 다른 어종 양식에서도 천연유황수를 친환경 소독제로 사용할 수 있을 것으로 기대된다.