• Toxicological Research
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• 제33권4호
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• pp.273-282
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• 2017

Chemoprevention entails the use of synthetic agents or naturally occurring dietary phytochemicals to prevent cancer development and progression. One promising chemopreventive agent, procyanidin, is a naturally occurring polyphenol that exhibits beneficial health effects including anti-inflammatory, antiproliferative, and antitumor activities. Currently, many preclinical reports suggest procyanidin as a promising lead compound for cancer prevention and treatment. As a potential anticancer agent, procyanidin has been shown to inhibit the proliferation of various cancer cells in "in vitro and in vivo". Procyanidin has numerous targets, many of which are components of intracellular signaling pathways, including proinflammatory mediators, regulators of cell survival and apoptosis, and angiogenic and metastatic mediators, and modulates a set of upstream kinases, transcription factors, and their regulators. Although remarkable progress characterizing the molecular mechanisms and targets underlying the anticancer properties of procyanidin has been made in the past decade, the chemopreventive targets or biomarkers of procyanidin action have not been completely elucidated. This review focuses on the apoptosis and tumor inhibitory effects of procyanidin with respect to its bioavailability.

• Archives of Pharmacal Research
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• 제16권2호
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• pp.83-88
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• 1993

opioid pure agonists, morphine, meperidine and methadone, were used to investigate the effect on the opioid receptor of fron sciatic nerve fibers using sucrose gap apparatus. When applied extracellularly by perfusion, morphine, methadone and meperidine significantly depressed the amplitude of the action potential in frog sciatic nerve fibers as a dose-dependent $(10^{-10}\;M-10^{-2}\;M)$ manner. The depression with morphine or methadone was partially antagonized by the simultaueous treatment with a lower $(10^{-10}\;M-10^{-8}\;M)$ concentration of naloxone, but that of meperidine was not blocked. When the three opioid agonists were applied intracellularly by placing it in a compartment with a cut end of the sciatic nerve fibers, all of themn depressed the amplitude of the action potentials by similar potency, and these reductions significantly blocked by pretreatment of lower concentration $(10^{-10}\;M-10^{-8}M)$ of naloxone. These results support the previous findings by other workers that the stereospecific opioid receptors of this preparation are located on or near the intracellular opening of the sodium channels which are sensitive to naloxone.

• Biomolecules & Therapeutics
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• 제28권4호
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• pp.344-353
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• 2020

This study aims to develop new potential therapeutic moracin M prodrugs acting on lung inflammatory disorders. Potential moracin M prodrugs (KW01-KW07) were chemically synthesized to obtain potent orally active derivatives, and their pharmacological activities against lung inflammation were, for the first time, examined in vivo using lipopolysaccharide (LPS)-induced acute lung injury model. In addition, the metabolism of KW02 was also investigated using microsomal stability test and pharmacokinetic study in rats. When orally administered, some of these compounds (30 mg/kg) showed higher inhibitory action against LPS-induced lung inflammation in mice compared to moracin M. Of them, 2-(3,5-bis((dimethylcarbamoyl)oxy)phenyl)benzofuran-6-yl acetate (KW02) showed potent and dose-dependent inhibitory effect on the same animal model of lung inflammation at 1, 3, and 10 mg/kg. This compound at 10 mg/kg also significantly reduced IL-1β concentration in the bronchoalveolar lavage fluid of the inflamed-lungs. KW02 was rapidly metabolized to 5-(6-hydroxybenzofuran-2-yl)-1,3-phenylene bis(dimethylcarbamate) (KW06) and moracin M when it was incubated with rat serum and liver microsome as expected. When KW02 was administered to rats via intravenous or oral route, KW06 was detected in the serum as a metabolite. Thus, it is concluded that KW02 has potent inhibitory action against LPS-induced lung inflammation. It could behave as a potential prodrug of moracin M to effectively treat lung inflammatory disorders.

• 한국응용과학기술학회지
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• 제38권6호
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• pp.1466-1475
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• 2021

Compound K (20-O-β-(_D-glucopyranosyl)-20(S)-protopanaxadiol)는 진세노사이드의 활성성분이다. Compound K는 경구 투여 후 Rb₁, Rb₂ 및 Rc가 사람의 장내 미생물의 β-glucosidase에 의해 생물전환 과정을 거쳐 생성된다고 알려져 있다. 본 연구는 생물전환된 인삼농축액에서 얻은 compound K를 이용해 항염증 및 독성을 조사하였다. 세포독성평가 결과, compound K는 0.001~1 ㎍/mL의 농도범위에서 유의적인 세포독성은 나타나지 않았으며, LPS로 염증이 유발된 RAW 264.7 세포에서 TNF-α, MCP-1, IL-6 및 NO의 생성을 억제하는 것으로 확인되었다. 동일 농도범위에서 TNF-α 및 IFN-γ로 염증이 유발된 HaCaT 세포는 compound K의 처리로 인해 IL-8의 생성을 감소시키는 것으로 나타났지만, IL-6의 경우 일부 농도에서 생성을 감소시켰으나, 통계적인 유의성은 나타나지 않았다. Brine shrimp를 이용한 치사율 검정법에서 compound K의 LC₅₀는 0.37mg/mL로 다소의 독성을 함유하고 있는 것으로 나타났으나 compound K가 35% 고함유된 생물전환물은 LC₅₀가 0.87mg/mL로 나타나 상대적으로 낮은 독성을 보였다. 따라서 이 생성물은 향후 여드름 완화용 화장품 개발에 사용할 수 있는 매우 우수한 기능성 소재가 될 수 있을 것으로 기대된다.

• 사상체질의학회지
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• 제35권4호
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• pp.10-22
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• 2023

Objectives The aim of this study is to explore the mechanism of action and target diseases of Sasang constitutional prescriptions using a multiscale interactome approach. Methods The compound and target information of Sasang constitutional prescriptions were retrieved from various databases such as the TM-MC, STITCH, and TTD. Key targets for Sasang constitutional prescriptions were identified by selecting the top 100 targets based on the number of simple paths within the constructed network. Diffusion profiles for Sasang constitutional prescriptions and diseases were calculated based on a biased random walk algorithm. Potential diseases and key mechanisms of Sasang constitutional prescriptions were identified by analyzing diffusion profiles. Results We identified 144 Sasang constitutional prescriptions and their targets, finding 80 herbs with effective biological targets. A cluster analysis based on selecting up to 100 key targets for each prescription revealed a more cohesive grouping of prescriptions according to Sasang constitution. We then predicted potential diseases for 62 Sasang constitutional prescriptions using diffusion profiles calculated on a multiscale interactome. Finally, our analysis of diffusion profiles revealed key targets and biological functions of prescriptions in obesity and diabetes. Conclusions This study demonstrates the effectiveness of a multiscale interactome approach in elucidating the complex mechanisms and potential therapeutic applications of prescriptions in Sasang constitutional medicine.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9049-9058
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• 2014

Casticin (3', 5-dihydroxy-3, 4', 6, 7-tetramethoxyflavone) is an active compound isolated from roots, stems, leaves, fruits and seeds of a variety of plants. It is well known for its pharmacological properties and has been utilized as an anti-hyperprolactinemia, anti-tumor, anti-inflammatory, neuroprotetective, analgesic and immunomodulatory agent. Recently, the anticancer activity of casticin has been extensively investigated. The resulkts showed that it exerts protective potential by targeting apoptosis, considered important for cancer therapies. In this article, our aim was to review the pharmacological and therapeutic applications of casticin with specific emphasis on its anticancer functions and related molecular mechanisms. Chemotherapeutic effects are dependent on multiple molecular pathways, which may provide a new perspective of casticin as a candidate anti-neoplastic drug. This review suggests that additional studies and preclinical trials are required to determine specific intracellular sites of action and derivative targets in order to fully understand the mechanisms of its antitumor activity and validate this compound as a medicinal agent for the prevention and treatment of various cancers.

• 한국환경과학회지
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• 제21권2호
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• pp.165-179
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• 2012

Indirect $CO_2$ effect due to non-methane volatile organic compound (NMVOC) emissions from solvent and product use and fugitive NMVOC emissions from fuels in the Republic of Korea and 13 Annex I countries under United Nations Framework on Climate Change were estimated and the proportions of them to total greenhouse gas (GHG) emissions ranged from 0.092% to 0.45% in 2006. Indirect greenhouse effect ($CO_2$, $CH_4$, and $O_3$) were estimated at 13 photochemical assessment monitoring sites in the Republic of Korea using concentrations of 8 NMVOCs of which indirect global warming potential (GWP) were available. The contribution of toluene to mixing ratio was highest at 11 sites and however, the contribution of toluene to indirect greenhouse effect was highest at nine sites. In contrast to toluene, the contributions of ethane, butane, and ethylene were enhanced. The indirect greenhouse effects of ethane and propane, of which ozone formation potentials are the lowest and the third lowest respectively among targeted 10 NMVOCs, ranked first and fourth highest respectively. Acetaldehyde has relatively higher maximum incremental reactivity and is classified as probable human carcinogen however, its indirect GWP ranked second lowest.

• Journal of Microbiology and Biotechnology
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• 제23권2호
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• pp.225-236
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• 2013

Among several bacteria examined, an antibacterial-producing Lactobacillus strain with probiotic characteristics was selected and identified based on 16S rRNA gene sequencing. Subsequent purification and mode of action of the antibacterial compounds on target cells including E. coli were investigated. Maximum production of the antibacterial compound was recorded at 18 h incubation at $30^{\circ}C$. Interestingly, antibacterial activity remained unchanged after heating at $121^{\circ}C$ for 45 min, 24 h storage in temperature range of $70^{\circ}C$ to room temperature, and 15 min exposure to UV light, and it was stable in the pH of range 2-10. The active compounds were inactivated by proteolytic enzymes, indicating their proteinaceous nature, and, therefore, referred to as bacteriocin-like inhibitory substances. Isolation and partial purification of the effective agent was done by performing ammonium sulfate precipitation and gel filtration chromatography. The molecular mass of the GFC-purified active compound (~3 kDa) was determined by Tris-Tricine SDS-PAGE. To predict the mechanisms of action, transmission electron microscopy (TEM) analysis of ultrathin sections of E. coli before and after antibacterial treatment was carried out. TEM analysis of antibacterial compounds-treated E. coli demonstrated that the completely altered bacteria appear much darker compared with the less altered bacteria, suggesting a change in the cytoplasmic composition. There were also some membrane-bound convoluted structures visible within the completely altered bacteria, which could be attributed to the response of the E. coli to the treatment with the antibacterial compound. According to the in vivo experiments oral administration of L. plantarum HKN01 resulted in recovery of infected BALB/c mice with Salmonella enterica ser. Typhimurium.

• Biotechnology and Bioprocess Engineering:BBE
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• 제5권3호
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• pp.191-195
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• 2000

Quantitation of N7-methyldeoxyguanosine (N7-MedG) produced in the in vitro N-methly-N-nitrosuourea (NMU) action on thymus DNA has been achieved by enzymatic degradation, liquid chromatoraphic separaphic separation and desorption chemical ionization tandem mass spectrometry. In conjunction with the resolving power HPLC in the separation of isomers, desorprion chemical ionization tandem mass spectrometry has utilized in determining modified nucleosides at low levels using a stable-isotope labled compound as an internal reforence. The quantitative estimation of N7-methyldeoxyguanosine was previously established by an independent HPLC analysis of methylated calf thymus DNA. A sensitive and specific methodogy for the quantitation of N7-MedG at the picomole level using HPLC combined with tandem mass spectrometry without radioisotope labeling process is presented. The potential of the liquid chromatoraphic tandem mass exposure to methlation agents in vitro.

• Natural Product Sciences
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• 제23권4호
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• pp.281-285
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• 2017

The purpose of this study was to confirm the anti-tumor activity of an ethanol extract of Saussurea laniceps against pancreatic tumor and to isolate the active compound from S. laniceps extract. Treatment with S. laniceps extract and hispidulin inhibited proliferation of pancreatic cell lines, such as Capan-1, Capan-2, Panc-1 and S2-013 in a dose-dependent manner using the hollow fiber assay. Hispidulin showed typical hallmarks of apoptotic cell death a significant anti-tumor activity on Capan-2 cells at a dose of 100 mg/kg and 200 mg/kg. S. laniceps has potential cytotoxic and apoptotic effects on human pancreatic carcinoma cells. Its mechanism of action might be associated with the apoptotic cell death through DNA fragmentation.