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Archives of Pharmacal Research

Kwangsik Park, Juyoung Park, Handule Lee, Jonghye Choi, Wook-Joon Yu, Jinsoo Lee
Toxicity and target organ distribution of cerium oxide nanoparticles (CeNPs) were investigated via single intravenous injection and single oral administration, respectively. Rats were sacrificed at 24 h after treatment with doses of 30 and 300 mg/kg, and cerium concentrations were measured in liver, kidney, spleen, lung, blood, urine and feces. Results revealed cerium levels in blood and tissues were considerably low in oral treated groups and most cerium was detected in feces, meaning CeNPs would not be absorbed in the gastro-intestinal system...
September 3, 2018: Archives of Pharmacal Research
Yun-Shan Fang, Ming-Hui Yang, Le Cai, Jia-Peng Wang, Tian-Peng Yin, Jing Yu, Zhong-Tao Ding
Two new phenylpropanoids, retusiusines A (1) and B (2), and a pair of new phenylpropyl enantiomers, (±)-retusiusine C (3a and 3b), together with eight known compounds, dihydroconiferyl dihydro-p-coumarate (4), methyl 3-(4-hydroxyphenyl) propionate (5), 3-(4-hydroxyphenyl)-propanoic acid (6), dihydroferulic acid (7), methyl 3-(4-methoxyphenyl) propionate (8), 3-(3,4-dimethoxyphenyl)-2-propenal (9), trans-p-coumaric acid (10) and dihydroconiferyl alcohol (11), were isolated from the tubers of Bulbophyllum retusiusculum...
August 27, 2018: Archives of Pharmacal Research
Juhee Lim, Yeojin Bang, Hyun Jin Choi
Parkinson's disease (PD) is a common progressive neurodegenerative disorder characterized by motor dysfunction, including bradykinesia, tremor, rigidity, and postural instability. Recent clinical findings recognize PD as a complex disease with diverse neuropsychiatric complications. Depression is the most frequent non-motor psychiatric symptom experienced in PD, and it is associated with poor quality of life. While the pathophysiology of PD-associated depression is not directly related to neurodegenerative processes in the substantia nigra, underlying mechanisms remain unclear and there are few symptomatic treatments...
August 22, 2018: Archives of Pharmacal Research
Yoonjin Nam, Young Sil Min, Uy Dong Sohn
Irritable bowel syndrome (IBS), a common gastrointestinal (GI) disorder, is associated with various factors, including lifestyle, infection, stress, intestinal flora, and related diseases. The pharmacotherapeutic stimulation of receptors and downstream signaling pathways is effective in reducing IBS symptoms; however, it is still associated with adverse effects. Various receptors related to GI motility and visceral hypersensitivity should be considered to enhance the benefit/risk ratio of IBS treatments. This review discusses recent pharmacological advances in IBS management...
August 21, 2018: Archives of Pharmacal Research
Xue Zhu, Ke Wang, Fanfan Zhou, Ling Zhu
Abnormal accumulation of the free-form all-trans-retinal (atRAL), a major intermediate of human visual cycle, is considered to be a key cause of retinal pigment epithelial (RPE) dysfunction in the pathogenesis of retinal degenerative diseases such as age-related macular degeneration (AMD). Paeoniflorin (PF), a monoterpene glucoside isolated from Paeonia lactiflora Pall., has been used in clinical treatment of retinal degenerative diseases in China for several years; however, the underlying mechanism remains unclear...
August 16, 2018: Archives of Pharmacal Research
Mina Kim, Young Sil Min, Uy Dong Sohn
Indomethacin is a non-steroidal anti-inflammatory drug with clearly known side effects on the gastrointestinal tract. The purpose of the present study was to investigate whether eupatilin inhibit cell injury induced by indomethacin in cultured feline esophageal epithelial cells (EECs). EECs were used to investigate the ability of eupatilin to induce the expression of heat shock proteins (HSP27 and HSP70) and analyze its cytoprotective effect against indomethacin-induced damage. The treatment of EECs with indomethacin for 8 h decreased cell viability...
August 14, 2018: Archives of Pharmacal Research
Hae Chan Ha, Ji Min Jang, Dan Zhou, Han Gyeol Kim, Moon Jung Back, In Chul Shin, So Yoon Yun, Yongwei Piao, Jong Min Choi, Jong Hoon Won, Dae Kyong Kim
Drug repositioning is a strategy that explores new pharmaceutical applications of previously launched or failed drugs, and is advantageous since it saves capital and time. In this study, we examined the inhibition of TLR2 signaling by drug candidates. HEK-Blue™-hTLR2 cells were pretreated with drugs and stimulated using the TLR2 ligand, Pam3CSK4. Among the drugs that inhibited TLR2 signaling, we selected TRIAC, which is yet to be patented. Pretreatment with TRIAC decreased the TLR2 level and the phosphorylation of Akt and MAPKs in HEK-Blue™-hTLR2 cells...
August 11, 2018: Archives of Pharmacal Research
Zhi-Ning Huang, Han Liang, Hong Qiao, Bao-Rui Wang, Ning Qu, Hua Li, Run-Run Zhou, Li-Juan Wang, Shan-Hua Li, Fu-Nan Li
Guided by bioisosterism and pharmacokinetic parameters, we designed and synthesized a series of novel benzamide derivatives. Preliminary in vitro studies indicated that compounds 10b and 10j show significant inhibitory bioactivity in HepG2 cells (IC50 values of 0.12 and 0.13 μM, respectively). Compounds 10b and 10j induced the expression of HIF-1α protein and downstream target gene p21, and upregulated the expression of cleaved caspase-3 to promote tumor cells apoptosis.
July 11, 2018: Archives of Pharmacal Research
Huan-Ge Zhao, Song-Lin Zhou, Ying-Ying Lin, Hua Wang, Hao-Fu Dai, Feng-Ying Huang
Toxicarioside N (Tox N), a natural product extract from Antiaris toxicaria, has been reported to induce apoptosis in human gastric cancer cells. However, the mechanism and actual role of autophagy in Tox N-induced apoptosis of human gastric cancer cells remains poorly understood. In the current study, we demonstrated that Tox N could induce autophagy by inhibiting the Akt/mTOR signaling pathway in SGC-7901 cells. Moreover, we found that the inhibition of autophagy by 3-methyladenine, an autophagy inhibitor, enhanced Tox N-induced apoptotic cell death...
July 10, 2018: Archives of Pharmacal Research
Huynh Nguyen Khanh Tran, Thao Quyen Cao, Jeong Ah Kim, Ui Joung Youn, Sanghee Kim, Mi Hee Woo, Byung Sun Min
Five new compounds, 9,3'-dimethoxyhierochin A (1), 6-oxo-trans-neocnidilide (2), (±)-(3E)-trans-6-hydroxy-7-methoxydihydroligustilide (3), (±)-cnidiumin (4), and 6-(1-oxopentyl)-salicylic acid methyl ester (5), together with twenty known compounds (6-25), were isolated from the rhizome of Cnidium officinale. The chemical structures of new compounds were established by NMR spectroscopic techniques, mass spectrometry, Mosher's method, and CD spectrum. Their anti-inflammatory activities were evaluated against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophage RAW 264...
June 30, 2018: Archives of Pharmacal Research
Ji-Young Byeon, Young-Hoon Kim, Choong-Min Lee, Se-Hyung Kim, Won-Ki Chae, Eui-Hyun Jung, Chang-Ik Choi, Choon-Gon Jang, Seok-Yong Lee, Jung-Woo Bae, Yun Jeong Lee
Cytochrome P450 (CYP) 2D6 is present in less than about 2% of all CYP enzymes in the liver, but it is involved in the metabolism of about 25% of currently used drugs. CYP2D6 is the most polymorphic among the CYP enzymes. We determined alleles and genotypes of CYP2D6 in 3417 Koreans, compared the frequencies of CYP2D6 alleles with other populations, and observed the differences in pharmacokinetics of metoprolol, a prototype CYP2D6 substrate, depending on CYP2D6 genotype. A total of 3417 unrelated healthy subjects were recruited for the genotyping of CYP2D6 gene...
September 2018: Archives of Pharmacal Research
Ji-Yeong Byeon, Young-Hoon Kim, Se-Hyung Kim, Choong-Min Lee, Eui-Hyun Jung, Won-Ki Chae, Choon-Gon Jang, Seok-Yong Lee, Yun Jeong Lee
Zolpidem is predominantly metabolized by CYP3A4, and to a lesser extent by CYP2C9, CYP1A2, CYP2D6 and CYP2C19. The aim of this study was to identify the effects of CYP2C9*3 allele on the pharmacokinetics of zolpidem. Healthy male subjects were divided into two genotype groups, CYP2C9*1/*1 and CYP2C9*1/*3. They received a single oral dose of 5 mg zolpidem, and the plasma concentrations of zolpidem were determined up to 12 h after drug administration. In addition, since zolpidem is metabolized at a high rate by CYP3A4, the effect of CYP2C9*3 allele on the pharmacokinetics of zolpidem was also observed in the condition where CYP3A4 was sufficiently inhibited by the steady-state concentration of clarithromycin, a potent CYP3A4 inhibitor...
September 2018: Archives of Pharmacal Research
Seung Hwa Kim, Kyung Hwa Cho, Yu Na Kim, Bo Young Jeong, Chang Gyo Park, Gang Min Hur, Hoi Young Lee
Unfortunately, there are some errors in Fig. 1b and Fig. 3a of the article.
September 2018: Archives of Pharmacal Research
Wook-Ha Park, Young-Chul Kang, Ying Piao, Daniel Hyungseok Pak, Youngmi Kim Pak
We regret that there is an error in the labeling of Fig. 4 of the published original article. The concentration of MPP+ should be corrected to 1.0 mM instead of 0.5 mM. The corrected figure should be.
September 2018: Archives of Pharmacal Research
Hyojeong Choi, Aree Moon
Unfortunately, there is an error in the original version of the article. The original published article contains an incomplete 'Acknowledgements' section. Please find the full 'Acknowledgements' section below.
September 2018: Archives of Pharmacal Research
Kyuri Lee, Bora Jang, You-Ri Lee, Eun-Young Suh, Ji-Seon Yoo, Mi-Jin Lee, Joo-Young Lee, Hyukjin Lee
siRNA therapeutics allows precise regulation of disease specific gene expression to treat various diseases. Although gene silencing approaches using siRNA therapeutics shows some promising results in the treatment of gene-related diseases, the practical applications has been limited by problems such as inefficient in vivo delivery to target cells and nonspecific immune responses after systemic or local administration. To overcome these issues, various in vivo delivery platforms have been introduced. Here we provide an overview for three different platform technologies for the in vivo delivery of therapeutic siRNAs (siRNA-GalNAc conjugate, SAMiRNA technology, and LNP-based delivery method) and their applications in the treatment of various diseases...
September 2018: Archives of Pharmacal Research
Masahiro Sato, Masato Ohtsuka, Shingo Nakamura, Takayuki Sakurai, Satoshi Watanabe, Channabasavaiah B Gurumurthy
The discovery of sequence specific nucleases such as ZFNs, TALENs, and CRISPR/Cas9 has revolutionized genome editing. The CRISPR/Cas9 system has particularly emerged as a highly simple and efficient approach towards generating genome-edited animal models of most of the experimental species. The limitation of these novel genome editing tools is that, till date, they depend on traditional pronuclear injection (PI)-based transgenic technologies developed over the last three decades. PI requires expensive micromanipulator systems and the equipment operators must possess a high level of skill...
September 2018: Archives of Pharmacal Research
Ramu Gopalappa, Myungjae Song, Arun Pandian Chandrasekaran, Soumyadip Das, Saba Haq, Hyun Chul Koh, Suresh Ramakrishna
Targeted genome editing by clustered regularly interspaced short palindromic repeats (CRISPR-Cas9) raised concerns over off-target effects. The use of double-nicking strategy using paired Cas9 nickase has been developed to minimize off-target effects. However, it was reported that the efficiency of paired nickases were comparable or lower than that of either corresponding nuclease alone. Recently, we conducted a systematic comparison of the efficiencies of several paired Cas9 with their corresponding Cas9 nucleases and showed that paired D10A Cas9 nickases are sometimes more efficient than individual nucleases for gene disruption...
September 2018: Archives of Pharmacal Research
Jong Geol Lee, Young Hoon Sung, In-Jeoung Baek
The key to successful drug discovery and development is to find the most suitable animal model of human diseases for the preclinical studies. The recent emergence of engineered endonucleases is allowing for efficient and precise genome editing, which can be used to develop potentially useful animal models for human diseases. In particular, zinc finger nucleases, transcription activator-like effector nucleases, and the clustered regularly interspaced short palindromic repeat systems are revolutionizing the generation of diverse genetically-engineered experimental animals including mice, rats, rabbits, dogs, pigs, and even non-human primates that are commonly used for preclinical studies of the drug discovery...
September 2018: Archives of Pharmacal Research
Jiyeon Kweon, Yongsub Kim
The CRISPR-Cas9 system is a powerful tool for genome engineering, and its programmability and simplicity have enabled various types of gene manipulation such as gene disruption and transcriptional and epigenetic perturbation. Particularly, CRISPR-based pooled libraries facilitate high-throughput screening for functional regulatory elements in the human genome. In this review, we describe recent advances in CRISPR-Cas9 technology and its use in high-throughput genetic screening. We also discuss its potential for drug target discovery and current challenges of this technique in biomedical research...
September 2018: Archives of Pharmacal Research
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