• 제목/요약/키워드: Reverse pharmacology

검색결과 198건 처리시간 0.023초

Identification of Differentially Expressed Genes by Gabapentin in Cultured Dorsal Root Ganglion in a Rat Neuropathic Pain Model

  • Heo, Ji Hye;Lee, Seung Ha;Chang, Kyung Ha;Han, Eun Hye;Lee, Seung Gwan;Choi, Dal Woong;Kim, Suhng Wook
    • Biomolecules & Therapeutics
    • /
    • 제21권2호
    • /
    • pp.126-131
    • /
    • 2013
  • Neuropathic pain is a chronic pain disorder caused by nervous system lesions as a direct consequence of a lesion or by disease of the portions of the nervous system that normally signal pain. The spinal nerve ligation (SNL) model in rats that reflect some components of clinical pain have played a crucial role in the understanding of neuropathic pain. To investigate the direct effects of gabapentin on differential gene expression in cultured dorsal root ganglion (DRG) cells of SNL model rats, we performed a differential display reverse transcription-polymerase chain reaction analysis with random priming approach using annealing control primer. Genes encoding metallothionein 1a, transforming growth factor-${\beta}1$ and palmitoyl-protein thioesterase-2 were up-regulated in gabapentin-treated DRG cells of SNL model rats. The functional roles of these differentially expressed genes were previously suggested as neuroprotective genes. Further study of these genes is expected to reveal potential targets of gabapentin.

Thiamine Eflects on Electroshock Seizure Threshold of Lead-exposed Rats

  • Cheong, Jae-Hoon;Kim, Yun-Tae;Ryu, Jae-Ryun;Park, Kyu-Hwan;Ko, Kwang-Ho
    • Biomolecules & Therapeutics
    • /
    • 제6권1호
    • /
    • pp.20-24
    • /
    • 1998
  • In the present study, we tested whether lead intoxication induces change of the thiamine content and the seizure threshold in rats and the changes of seizure threshold are related to the changes of thiamine status. It was also tested whether administration of excessive thiamine could reverse the toxic manifestation of lead in rats. Four groups of Wistar rats were prepared: 1) control group, 2) lead treated group, 3) lead plusthiamine treated group, and 4) thiamine deficient group. Each group of animals was divided into three subgroups based on age: 3, 7 and 16 weeks. In each group, thresholds of electroshock seizure and thiamine contents in brain regions including telencephalon, brain stem, cerebellum were measured. Thiamine contents in brain regions of the lead treated group were significantly lower than those of the control group and thiamine treatment reversed the decrease back to the control level. Thresholds of the electroshock seizure of the lead treated group in 3, 7 week old rats and those of thiamine deficient group in 3 week old rats were significantly lower than those of the control group. These observations were reversed by the supplementation with thiamine. These results from the present study suggest that increased seizure sensitivity induced by lead intoxication in rats may be mediated at least in part through the changes of thiamine status.

  • PDF

Photoprotective Effect of Topical EGb 761 and Korean Red Ginseng in C57BL/6 Mice

  • Choi, Wook-Hee;Han, Seon-Kyu;Yi, Seh-Yoon;Ann, Hyoung-Soo;Ahn, Ryoung-Me
    • 한국환경보건학회:학술대회논문집
    • /
    • 한국환경보건학회 2005년도 국제학술대회
    • /
    • pp.306-310
    • /
    • 2005
  • Exposure to UVB radiation can cause diverse biological photodamage to skin. Eeb 761 and Korean red ginseng are the major and most effective natural drug against a variety of oxidative damage. But, the protective effects against UVB radiation have not been clearly identified. In this study, we investigated the protective effect of topical EGb 761 and Korean red ginseng on pigmentation by UVB radiation. Pro-inflammatory cytokines($IL-l{\beta}$, IL-6 and $TNF-{\alpha}$) and melanogenesis proteins(tyrosinase, TRP-1 and TRP-2) mRNA were measured by reverse transcription-polymerase chain reaction(RT-PCR) analysis. The in vivo protection against pigmentation was calculated using chromameter. The mRNA level of IL-lf and TNF-a were increased by UVB irradiation in treated and non-treated group, while no significant changes were observed in IL-6 level. Topical treatment with EGb 761 and Korean red ginseng remarkably reduced expression of tyrosinase, TRP-1 and TRP-2 in the non-irradiated and irradiated skin. Application of EGb 761 and Korean red ginseng significantly protected the WB-induced skin pigmentation and Korean red ginseng was more effective. Our study suggests that topical ECb761 and Korean red ginseng can regulate melanogenic proteins and protect UVB radiation on skin pigmentation.

  • PDF

Lysophosphatidic Acid-Induced TWIST1 and Slug Expression in Oral Cancer Cell Invasion

  • Cho, Kyung Hwa
    • 치위생과학회지
    • /
    • 제17권5호
    • /
    • pp.433-438
    • /
    • 2017
  • Relative to its incidence, oral cancer has serious negative social effects. The exact causes of oral cancer have not been clarified, but many studies have implicated smoking and drinking. However, the fundamental mechanism of oral cancer causation has yet to be elucidated. Lysophosphatidic acid (LPA) augments epithelial mesenchymal transition (EMT) and development of various cancer cells. However, a detailed mechanistic explanation for LPA-induced EMT and the effects of EMT-promoting conditions on oral squamous cell carcinoma development remain elusive. In the present study, a quantitative reverse transcription polymerase chain reaction was used to analyze TWIST1, Slug, E-cadherin, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) transcript expression. Immunoblotting was used to analyze TWIST1, Slug, E-cadherin, and GAPDH protein expression. siRNAs were used to silence TWIST1 and Slug transcript expression. A matrigel-coated in vitro invasion insert was used to analyze oral cancer cell invasion. The results of the present study show that the expression levels of TWIST1 and Slug, which are EMT factors, were increased by LPA treatment in YD-10B oral squamous cell carcinoma. Conversely, E-cadherin expression was significantly reduced. In addition, transfection of the cells with TWIST1 and Slug siRNA strongly inhibited LPA-induced oral cancer cell invasion. The present study shows that TWIST1 and Slug mediate LPA-induced oral cancer cell EMT and invasiveness. The present study confirmed the mechanism by which LPA promotes oral cancer cell development, with TWIST1 and Slug providing novel biomarkers and promising therapeutic targets for oral cancer cell development.

The worldwide trend of using botanical drugs and strategies for developing global drugs

  • Ahn, Kyungseop
    • BMB Reports
    • /
    • 제50권3호
    • /
    • pp.111-116
    • /
    • 2017
  • Natural product drugs, or botanical drugs, are drugs composed of natural substances which have constituents with healthenhancing or medicinal activities. In Korea, government-led projects brought attention to botanical drugs invigorating domestic botanical drug industry. Foreign markets, as well, are growing bigger as the significance of botanical drugs stood out. To follow along with the tendency, Korea puts a lot of effort on developing botanical drugs suitable for global market. However, standards for approving drug sales vary by countries. And also, thorough standardization, certification, clinical studies and data of these will be required as well as data confirming safety and effectiveness. Meanwhile, as an international exchange in botanical drug market continues, the importance of plant resources was emphasized. Thus countries' ownership of domestic natural resources became vital. Not only establishing a systematic method to secure domestic plant resources, but also cooperation with other countries on sharing natural resources is essential to procure natural resources effectively. Korea started to show visible results with botanical drugs, and asthma/COPD treatment made out of speedwell is one example. Sufficient investment and government's active support for basic infrastructure for global botanical drugs will bring Korea to much higher level of botanical drug development.

경구 Corticosteroid계 약물 치료한 환자에 있어서 혈중 cortisol에 관한 연구 (Study on Blood Cortisol in Patients treated with Oral Corticosteroid Drugs)

  • 박정희;김기황;유형식;이종태;박창윤;유경자
    • 대한핵의학회지
    • /
    • 제14권1호
    • /
    • pp.23-28
    • /
    • 1980
  • This is an analysis of 32 patients who received long continuous corticosteroid drug due to some diseases. Patients were collected from June 1976 to March 1980. Blood cortisol level, variation of diurnal rhythm and side effects were studied. The Result as follows: 1. Side effects were observed in 24 patients(75%) and most common complaint was obesity. 2. Diurnal rhythm analysed by Doe's method shows abnormal diurnal rhythm is 21 out of 32(66%). 3. Mean durations or therapy of abnormal diurnal rhythm and normal diurnal rhythm were $55.7{\pm}4.4$ months and $43.9{\pm}7.0$ months respectively which shows statistically significant difference. 4. Mean cortisol value of steroid treated patients were lower than normal. 5. Reverse diurnal rhythm was 4 out of 21 patients. 6. 8 A.M. cortisol value is lower than 2 times of 8 P.M. in all patients who showed abnormal diurnal rhythm except one.

  • PDF

유향 추출물이 혈관내피세포 부착단백질 발현에 미치는 영향 (Effects of Olibanum Extracts on Vascular Cell Adhesion Molecules Expression)

  • 이숭인;권강범;한종현;류도곤
    • 동의생리병리학회지
    • /
    • 제25권3호
    • /
    • pp.445-450
    • /
    • 2011
  • In order to validate the use of Olibanum as an anti-inflammatory drug in the traditional Korean medicine, I have investigated the effect of water-soluble extract of Olibanum (EO) on the expression of pro-inflammatory vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) stimulated with tumor necrosis factor-${\alpha}$. The extract inhibited dose-dependently VCAM-1 expression without its cytotoxic effect on HUVECs, as measured by a flow cytometer using fluorescence-enhanced anti-VCAM-1 antibody, and significantly decreased mRNA levels of VCAM-1, as determined using reverse transcription polymerase chain reaction. These results suggest that Olibanum may have therapeutic potential in the control of endothelial disorders caused by inflammation.

Antioxidant activity and nitrite scavenging ability of each fractions from Phyllostachys bambusoides ethanolic extract

  • Lim, Jin-A;Oh, In-Kyo;Kim, Hyung-Min;Baek, Seung-Hwa
    • Advances in Traditional Medicine
    • /
    • 제5권3호
    • /
    • pp.209-215
    • /
    • 2005
  • This study was conducted to investigate the efficacy of antioxidative activity and nitrite scavenging ability of each fractions from Phyllostachys bambusoides S. et Z. (P. bambusoides) trunk ethanolic extract using reverse-phase flash chromatography. Among the each fractions, fraction 3 $(H_2O\;:\;MeOH\;=\;1:1)$ showed high DPPH free radical scavenging activity (81.33%) at $80\;{\mu}g/mL$ concentrations and strongly inhibited autooxidation of pyrogallol by superoxide dismutase-like activity (45.8 %) at 0.46 mg/mL concentrations compared with different fractions. The fraction 3 was also increased to 76.62% cell viability against hydrogen peroxide-mediated cytotoxicity. Nitrite scavenging ability was the most remarkable under pH 1.2 condition among various pH regions examined and effectively exhibited to 65.6% by treatment of the fraction 3 with a concentration of 0.2 mg/ml. In general, nitrite scavenging ability decreased with higher pH condition. These results suggest that fraction 3 from P. bambusoides ethanolic extract can be used for bioacitve and functional materials.

The Regulatory Effects of Trans-chalcone on Adipogenesis

  • Han, Younho
    • International Journal of Oral Biology
    • /
    • 제43권1호
    • /
    • pp.29-35
    • /
    • 2018
  • It is noted that chalcone derivatives have characteristic diverse pharmacological properties, and that precise evidence has been growing that they could regulate a tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) induced insulin resistance. The purpose of the present investigation is to elucidate the effects of the identified chalcone derivatives on adipogenesis, and to find the underlying mechanism of action in that case. Consequently, we first investigated whether the chalcone derivatives could affect the identified $PPAR{\gamma}$-induced transcriptional activity on the proliferator-activated receptor response elements (PPRE) at target promoters, and find that trans-chalcone most significantly increased the $PPAR{\gamma}$-induced transcriptional activity. Additionally, we confirmed that there were up-regulatory effects of trans-chalcone during the adipogenesis and lipid accumulation, and on the mRNA of adipogenic factors in 3T3-L1 cells. Next, we examined the effect of trans-chalcone on the inhibition induced by $TNF-{\alpha}$ on adipogenesis. To that end, we noted that the treatment with trans-chalcone attenuated the effect of $TNF-{\alpha}$ mediated secretion of various adipokines that are involved in insulin sensitivity. For this reason, we noted that this study clearly demonstrates that trans-chalcone enhanced adipogenesis, in part, by its potent effect on $PPAR{\gamma}$ activation and by its reverse effect on $TNF-{\alpha}$.

84-kDa의 폐렴구균 열충격단백질 ClpL의 Cloning 및 면역특성에 관한 연구 (Cloning and Immunological Characterization of the 84-kDa Heat Shock Protein, ClpL, in Streptococcus pneumoniae)

  • 권혁영;김용환;최혜진;박연진;표석능;이동권
    • Biomolecules & Therapeutics
    • /
    • 제9권2호
    • /
    • pp.79-87
    • /
    • 2001
  • Heat shock proteins serve as chaperone by preventing the aggregation of denatured proteins and promote survival of pathogens in harsh environments. In this study, heat shock gene encoding a 84-kDa (p84) protein, which is one of the three major heat shock proteins in S. pneumoniae, was cloned and characterized. PCR with a forward primer derived from N-terminal amino acid sequence of the p84 and a reverse primer derived from the conserved second ATP-binding region of Clp family was used for amplification of the gene encoding the p84 and subsequently the PCR product was used for sequence determination. Sequence analysis of the p84 gene demonstrated that it is a member of ClpL. The deduced amino acid sequence of pneumococcal ClpL shows homology with other members of the Clp family, and particularly, even in variable leader region, with bovine Clp-like protein and L. lactis ClpL. S. pneumoniae clpL is the smallest clop member (701 amono acids) containing the two conserved ATP-binding regions, and hydrophilic N-terminal variable region of pneu-mococcal Clp ATPase is much shorter than any known Clp ATPases. Histidine tagged ClpL was overexpressed and purified from E. coli. Immunoblot analysis employing antisera raised against pneumococcus p84 demonstrated no cross-reactivity with Clp analog in Eschericha coli, Staphylococcus aureus and human HeLa cells. Preimmunization of mice with ClpL extended mice life partially but did not protect them from death.

  • PDF