Jing Zhao, Jinhai Shen, Meiyu Gan, Cui-xiang Huang, Qihua You
The compatibility between ticagrelor and selected excipients (mannitol, calcium phosphate tribasic, sodium carboxymethyl starch, hydroxypropyl cellulose and magnesium stearate) was investigated by differential scanning calorimetry. The compatibility was further corroborated by Raman spectroscopy and isothermal stress testing experiments. These results revealed that ticagrelor has high compatibility with mannitol, calcium phosphate tribasic, sodium carboxymethyl starch, hydroxypropyl cellulose and magnesium stearate.
{"title":"Compatibility of ticagrelor with pharmaceutical excipients studied with thermal and spectroscopic techniques.","authors":"Jing Zhao, Jinhai Shen, Meiyu Gan, Cui-xiang Huang, Qihua You","doi":"10.1691/ph.2019.9070","DOIUrl":"https://doi.org/10.1691/ph.2019.9070","url":null,"abstract":"The compatibility between ticagrelor and selected excipients (mannitol, calcium phosphate tribasic, sodium carboxymethyl starch, hydroxypropyl cellulose and magnesium stearate) was investigated by differential scanning calorimetry. The compatibility was further corroborated by Raman spectroscopy and isothermal stress testing experiments. These results revealed that ticagrelor has high compatibility with mannitol, calcium phosphate tribasic, sodium carboxymethyl starch, hydroxypropyl cellulose and magnesium stearate.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"50 1","pages":"583-589"},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91128184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qiaobei Pan, Jing Zhang, Xiang Li, Xing Han, Qian Zou, Peng Zhang, Ying Luo, Yi Jin
In this study, micelles were designed to deliver an antitumor agent and a fluorescent marker to a tumor site. The micelles simultaneously encapsulated epirubicin (EPI) and polyethylene glycol (PEG)-modified graphene quantum dots (GQDs-PEG), and employed a PEG-polylactic acid block copolymer amphiphilic block polymer as a nanocarrier. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy were used to characterize the functional groups in the synthesized GQDs-PEG. A Malvern particle size meter and transmission electron microscopy were used to show that the particle size of the GQDs-PEG is approximately 2-9 nm, and that of the bifunctional EPI-loaded micelles (EPI-FIDCR) is 19.59±1.21 nm, with zeta potential at -22.87±0.85 mV. The EE% and DL% for EPI in EPI-FIDCR are 74.02±0.55 % and 3.78±0.28 %, respectively. The IC50 values of EPI-FIDCR and EPI solution (EPI-Free) for tumor cells were 7.03 μg/mL and 5.54 μg/mL, showing that EPI-FIDCR still maintained strong cytotoxicity. Fluorescence micrographs of HeLa cells incubated with GQDs-PEG and EPI-FIDCR for 6 h, respectively, show that only EPI-FIDCR could enter the cells. In vitro cellular uptake assays and an inhibition study indicated that EPI-FIDCR could deliver both EPI and GQDs-PEG into tumor cells, while maintaining an inhibitory effect similar to that of unencapsulated EPI. A pharmacokinetic study showed that EPI-FIDCR could persist in the circulation for a significant period of time. The AUC0→t calculated for the EPI-FIDCR formulation was 159.5-fold compared with that of EPI-Free, based on its improved stability and prolonged blood circulation time. The EPI-FIDCR enables both fluorescence imaging and controlled drug-release, exhibits prolonged systematic circulation time and has potential for the treatment of cancer.
{"title":"Preparation and pharmacokinetics of bifunctional epirubicin-loaded micelles.","authors":"Qiaobei Pan, Jing Zhang, Xiang Li, Xing Han, Qian Zou, Peng Zhang, Ying Luo, Yi Jin","doi":"10.1691/ph.2019/9059","DOIUrl":"https://doi.org/10.1691/ph.2019/9059","url":null,"abstract":"In this study, micelles were designed to deliver an antitumor agent and a fluorescent marker to a tumor site. The micelles simultaneously encapsulated epirubicin (EPI) and polyethylene glycol (PEG)-modified graphene quantum dots (GQDs-PEG), and employed a PEG-polylactic acid block copolymer amphiphilic block polymer as a nanocarrier. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy were used to characterize the functional groups in the synthesized GQDs-PEG. A Malvern particle size meter and transmission electron microscopy were used to show that the particle size of the GQDs-PEG is approximately 2-9 nm, and that of the bifunctional EPI-loaded micelles (EPI-FIDCR) is 19.59±1.21 nm, with zeta potential at -22.87±0.85 mV. The EE% and DL% for EPI in EPI-FIDCR are 74.02±0.55 % and 3.78±0.28 %, respectively. The IC50 values of EPI-FIDCR and EPI solution (EPI-Free) for tumor cells were 7.03 μg/mL and 5.54 μg/mL, showing that EPI-FIDCR still maintained strong cytotoxicity. Fluorescence micrographs of HeLa cells incubated with GQDs-PEG and EPI-FIDCR for 6 h, respectively, show that only EPI-FIDCR could enter the cells. In vitro cellular uptake assays and an inhibition study indicated that EPI-FIDCR could deliver both EPI and GQDs-PEG into tumor cells, while maintaining an inhibitory effect similar to that of unencapsulated EPI. A pharmacokinetic study showed that EPI-FIDCR could persist in the circulation for a significant period of time. The AUC0→t calculated for the EPI-FIDCR formulation was 159.5-fold compared with that of EPI-Free, based on its improved stability and prolonged blood circulation time. The EPI-FIDCR enables both fluorescence imaging and controlled drug-release, exhibits prolonged systematic circulation time and has potential for the treatment of cancer.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"14 1","pages":"577-582"},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88542094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jina Yang, P. Jadhav, M. Reaney, R. Sammynaiken, Jian Yang
Flaxseed orbitides (linusorbs) are a family of N to C linked bioactive cyclic octa-, nona-, and decapeptides present in flaxseed oil. They are highly hydrophobic and thermally stable. Our previous studies showed that [1-9-NαC]-linusorb B3 (LOB3) and [1-9-NαC]-linusorb B2 (LOB2) exhibited cytotoxic effects towards human breast cancer HER2-subtype Sk-Br-3 cells at a concentration of ~400 μM. However, this high concentration significantly limits their potential clinical applications. In the current study, we developed a novel polyethylene glycol-based formulation for linusorbs and showed that both LOB3 and LOB2, especially LOB3, exhibited strong cytotoxicity towards human breast cancer triple-negative-subtype MDA-MB-231 cells at low nanomolar concentrations.
亚麻籽轨道肽(linusorbs)是存在于亚麻籽油中的一个N - C连接的生物活性环八肽，壬基肽和十肽家族。它们具有高度疏水性和热稳定性。我们前期的研究表明，[1-9- n - α c]-linusorb B3 (LOB3)和[1-9- n - α c]-linusorb B2 (LOB2)在~400 μM浓度下对人乳腺癌her2亚型Sk-Br-3细胞具有细胞毒作用。然而，这种高浓度极大地限制了它们潜在的临床应用。在目前的研究中，我们开发了一种新的聚乙二醇基亚麻酸制剂，并表明在低纳摩尔浓度下，LOB3和LOB2，特别是LOB3，对人乳腺癌三阴性亚型MDA-MB-231细胞具有很强的细胞毒性。
{"title":"A novel formulation significantly increases the cytotoxicity of flaxseed orbitides (linusorbs) LOB3 and LOB2 towards human breast cancer MDA-MB-231 cells.","authors":"Jina Yang, P. Jadhav, M. Reaney, R. Sammynaiken, Jian Yang","doi":"10.1691/ph.2019.9055","DOIUrl":"https://doi.org/10.1691/ph.2019.9055","url":null,"abstract":"Flaxseed orbitides (linusorbs) are a family of N to C linked bioactive cyclic octa-, nona-, and decapeptides present in flaxseed oil. They are highly hydrophobic and thermally stable. Our previous studies showed that [1-9-NαC]-linusorb B3 (LOB3) and [1-9-NαC]-linusorb B2 (LOB2) exhibited cytotoxic effects towards human breast cancer HER2-subtype Sk-Br-3 cells at a concentration of ~400 μM. However, this high concentration significantly limits their potential clinical applications. In the current study, we developed a novel polyethylene glycol-based formulation for linusorbs and showed that both LOB3 and LOB2, especially LOB3, exhibited strong cytotoxicity towards human breast cancer triple-negative-subtype MDA-MB-231 cells at low nanomolar concentrations.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"47 1","pages":"520-522"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80042808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Insulin resistance is a typical precursor and primary feature of type 2 diabetes mellitus (T2DM). Sphingomyelin (SM) is a kind of sphingolipid located in animal brain, liver, kidney and muscle. Sphingomyelin synthase 2 (SMS2) is the key enzyme in the synthesis of sphingomyelin, inhibition of which shows protective effects on cardiovascular and glucose metabolism. We used Ly93, a selective sphingomyelin synthase 2 inhibitor, to investigate the effect of SMS2 inhibitor on insulin resistance in vitro and in vivo. Our previous studies have shown that Ly93 is able to dose-dependently inhibit the SMS activity and attenuate the atherosclerotic lesions in apoE knock out mice. In this present study, we found that high fat diet (HFD) induced insulin-resistant C57BL/6 mice treated with Ly93 were more sensitive to insulin than untreated mice, and presented lower blood insulin levels and improved insulin tolerance. Furthermore, insulin signal pathway related protein levels were detected by western blot, which indicated that SMS2 inhibitor significantly upregulated the phosphorylation of IRS-1, Akt and GSK-3β, thus enhanced the insulin signaling. In vitro, Ly93 enhanced the phosphorylation of Akt in HepG2 cells, which was reversed by exogenous sphingomyelin. These results suggest that SMS2 inhibitor could ameliorate insulin resistance via regulating the insulin signaling. Our findings support that SMS2 is a potential target for insulin resistance.
{"title":"A selective sphingomyelin synthase 2 inhibitor ameliorates diet induced insulin resistance via the IRS-1/Akt/GSK-3β signaling pathway.","authors":"Yutong Huang, Taomin Huang, X. Zhen, Yali Li, Mingguang Mo, Deyong Ye, Nengneng Cheng","doi":"10.1691/ph.2019.9310","DOIUrl":"https://doi.org/10.1691/ph.2019.9310","url":null,"abstract":"Insulin resistance is a typical precursor and primary feature of type 2 diabetes mellitus (T2DM). Sphingomyelin (SM) is a kind of sphingolipid located in animal brain, liver, kidney and muscle. Sphingomyelin synthase 2 (SMS2) is the key enzyme in the synthesis of sphingomyelin, inhibition of which shows protective effects on cardiovascular and glucose metabolism. We used Ly93, a selective sphingomyelin synthase 2 inhibitor, to investigate the effect of SMS2 inhibitor on insulin resistance in vitro and in vivo. Our previous studies have shown that Ly93 is able to dose-dependently inhibit the SMS activity and attenuate the atherosclerotic lesions in apoE knock out mice. In this present study, we found that high fat diet (HFD) induced insulin-resistant C57BL/6 mice treated with Ly93 were more sensitive to insulin than untreated mice, and presented lower blood insulin levels and improved insulin tolerance. Furthermore, insulin signal pathway related protein levels were detected by western blot, which indicated that SMS2 inhibitor significantly upregulated the phosphorylation of IRS-1, Akt and GSK-3β, thus enhanced the insulin signaling. In vitro, Ly93 enhanced the phosphorylation of Akt in HepG2 cells, which was reversed by exogenous sphingomyelin. These results suggest that SMS2 inhibitor could ameliorate insulin resistance via regulating the insulin signaling. Our findings support that SMS2 is a potential target for insulin resistance.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"34 1","pages":"553-558"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77672100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y. Urashima, K. Urashima, M. Ohnishi, K. Matsushita, K. Suzuki, K. Kurachi, M. Nishihara, T. Katsumata, M. Myotoku, K. Ikeda, Y. Hirotani
The gastrointestinal absorption of phenytoin (PHT), an antiepileptic drug, is often affected by its interaction with co-administered enteral nutrients through a nasogastric (NG) tube, resulting in decreased plasma PHT concentration. In this study, we measured the recovery rate (%) of PHT (Aleviatin® powder) passed through an NG tube when co-administered with distilled water or enteral nutrients (F2α®, Racol® NF, Ensure Liquid® and Renalen® LP). We also measured plasma PHT levels in rats, after oral co-administration of PHT with enteral nutrients. We demonstrate that PHT recovery rate was close to 100 % in all cases after passage through the NG tube. In the rat study, the AUC0→∞ of PHT concentration after oral administration significantly decreased when it was co-administered with F2α® and Racol® NF compared to distilled water. However, the AUC0→∞ of PHT was unchanged when co-administered with F2α® 2 h after initial PHT administration. We therefore conclude that the co-administration of PHT with F2α® and Racol® NF caused a reduction in the absorption of PHT from the gastrointestinal tract to the blood, without adsorption to the NG tube. The administration of enteral nutrients 2 h after PHT is one clear way to prevent a decrease in plasma PHT concentration.
{"title":"Interaction between phenytoin and enteral nutrients and its influence on gastrointestinal absorption.","authors":"Y. Urashima, K. Urashima, M. Ohnishi, K. Matsushita, K. Suzuki, K. Kurachi, M. Nishihara, T. Katsumata, M. Myotoku, K. Ikeda, Y. Hirotani","doi":"10.1691/ph.2019.9532","DOIUrl":"https://doi.org/10.1691/ph.2019.9532","url":null,"abstract":"The gastrointestinal absorption of phenytoin (PHT), an antiepileptic drug, is often affected by its interaction with co-administered enteral nutrients through a nasogastric (NG) tube, resulting in decreased plasma PHT concentration. In this study, we measured the recovery rate (%) of PHT (Aleviatin® powder) passed through an NG tube when co-administered with distilled water or enteral nutrients (F2α®, Racol® NF, Ensure Liquid® and Renalen® LP). We also measured plasma PHT levels in rats, after oral co-administration of PHT with enteral nutrients. We demonstrate that PHT recovery rate was close to 100 % in all cases after passage through the NG tube. In the rat study, the AUC0→∞ of PHT concentration after oral administration significantly decreased when it was co-administered with F2α® and Racol® NF compared to distilled water. However, the AUC0→∞ of PHT was unchanged when co-administered with F2α® 2 h after initial PHT administration. We therefore conclude that the co-administration of PHT with F2α® and Racol® NF caused a reduction in the absorption of PHT from the gastrointestinal tract to the blood, without adsorption to the NG tube. The administration of enteral nutrients 2 h after PHT is one clear way to prevent a decrease in plasma PHT concentration.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"65 1","pages":"559-562"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83744994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Clopidogrel-induced gastric injury is an important clinical problem. However, the exact mechanism was still unclarified. This study aimed to investigate the role of high mobility group box protein 1 (HMGB1) and the toll-like receptor 4 (TLR4) pathway in normal human gastric epithelial (GES-1) cells under clopidogrel exposure. Morphological alterations of the gastric epithelial cells were observed under a microscope. A laser scanning confocal microscope was used to determine the distribution of HMGB1 and TLR4 in clopidogrel-induced injury. MTT was used to compare the viability of GES-1 cell among the pretreated Cli-095 (TLR4 inhibitor) group, pretreated ethyl pyruvate (HMGB1 inhibitor) group, clopidogrel group, and control group. Moreover, expression of the HMGB1, TLR4, tight junction (TJ) proteins occludin and the phosphorylation of the mitogen-activated protein kinases (MAPK) p38 were examined by western blot. We found the expression of HMGB1 and TLR4 in the cytoplasm increased after clopidogrel administration. Besides, inhibited TLR4, which is a receptor of HMGB1, prevented the injury and occludin reducing caused by clopidogrel challenge. Furthermore, blocking HMGB1 or TLR4 activity by ethyl pyruvate (HMGB1 inhibitor) or cli-095(TLR4 inhibitor) can partially diminish the activation of p38MAPK. Gastric mucosal damages observed by clopidogrel challenge are associated with HMGB1, TLR4, through p38MAPK signal pathway.
{"title":"The activation of high mobility group Box1 and toll-like receptor 4 is involved in clopidogrel-induced gastric injury through p38 MAPK.","authors":"Zong-Dan Jiang, Zhibing Wang, Zhi Wang, Chao Li, Zhenyu Zhang, Weihao Sun","doi":"10.1691/ph.2019.9446","DOIUrl":"https://doi.org/10.1691/ph.2019.9446","url":null,"abstract":"Clopidogrel-induced gastric injury is an important clinical problem. However, the exact mechanism was still unclarified. This study aimed to investigate the role of high mobility group box protein 1 (HMGB1) and the toll-like receptor 4 (TLR4) pathway in normal human gastric epithelial (GES-1) cells under clopidogrel exposure. Morphological alterations of the gastric epithelial cells were observed under a microscope. A laser scanning confocal microscope was used to determine the distribution of HMGB1 and TLR4 in clopidogrel-induced injury. MTT was used to compare the viability of GES-1 cell among the pretreated Cli-095 (TLR4 inhibitor) group, pretreated ethyl pyruvate (HMGB1 inhibitor) group, clopidogrel group, and control group. Moreover, expression of the HMGB1, TLR4, tight junction (TJ) proteins occludin and the phosphorylation of the mitogen-activated protein kinases (MAPK) p38 were examined by western blot. We found the expression of HMGB1 and TLR4 in the cytoplasm increased after clopidogrel administration. Besides, inhibited TLR4, which is a receptor of HMGB1, prevented the injury and occludin reducing caused by clopidogrel challenge. Furthermore, blocking HMGB1 or TLR4 activity by ethyl pyruvate (HMGB1 inhibitor) or cli-095(TLR4 inhibitor) can partially diminish the activation of p38MAPK. Gastric mucosal damages observed by clopidogrel challenge are associated with HMGB1, TLR4, through p38MAPK signal pathway.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"9 1","pages":"547-552"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91210199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y. Noguchi, H. Nagasawa, T. Tachi, T. Tsuchiya, H. Teramachi
Among the mechanisms responsible for cognitive dysfunction in chronic kidney disease (CKD) are albuminuria and oxidative stress. However, there may be other causes not yet identified. In fact, the full relevance of CKD patient drug use and its relationship to dementia has hardly been barely investigated. We identified drugs affecting cognitive function in CKD patients by analyzing the spontaneous reporting system in Japan using Association rule mining (ARM) and Bayesian confidence propagation neural network (BCPNN). The signal detection criterion used were as follows: case ≥ 3, lift > 1, conviction > 1 (ARM) and IC025 >0 (BCPNN). Drugs with more than 20 cases were valaciclovir (lift: 11.21, conviction: 1.28, IC025: 3.12), amantadine (lift: 19.69, conviction: 1.68, IC025: 3.05), nalfurafine (lift: 8.35, conviction: 1.19, IC025: 2.18), pregabalin (lift: 6.05, conviction: 1.12, IC025: 1.78), and acyclovir (lift: 5.89, conviction: 1.12, IC025: 1.68). This study is the first report to use a large-scale medical database to identify drugs related to oral drugs-induced dementia in CKD.
{"title":"Signal detection of oral drug-induced dementia in chronic kidney disease patients using association rule mining and Bayesian confidence propagation neural network.","authors":"Y. Noguchi, H. Nagasawa, T. Tachi, T. Tsuchiya, H. Teramachi","doi":"10.1691/ph.2019.9426","DOIUrl":"https://doi.org/10.1691/ph.2019.9426","url":null,"abstract":"Among the mechanisms responsible for cognitive dysfunction in chronic kidney disease (CKD) are albuminuria and oxidative stress. However, there may be other causes not yet identified. In fact, the full relevance of CKD patient drug use and its relationship to dementia has hardly been barely investigated. We identified drugs affecting cognitive function in CKD patients by analyzing the spontaneous reporting system in Japan using Association rule mining (ARM) and Bayesian confidence propagation neural network (BCPNN). The signal detection criterion used were as follows: case ≥ 3, lift > 1, conviction > 1 (ARM) and IC025 >0 (BCPNN). Drugs with more than 20 cases were valaciclovir (lift: 11.21, conviction: 1.28, IC025: 3.12), amantadine (lift: 19.69, conviction: 1.68, IC025: 3.05), nalfurafine (lift: 8.35, conviction: 1.19, IC025: 2.18), pregabalin (lift: 6.05, conviction: 1.12, IC025: 1.78), and acyclovir (lift: 5.89, conviction: 1.12, IC025: 1.68). This study is the first report to use a large-scale medical database to identify drugs related to oral drugs-induced dementia in CKD.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"109 1","pages":"570-574"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79210329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
8-Methoxycoumarin (8-methoxy-chromen-2-one), isolated from R. graveolens L., is able to alleviate arthritis by inhibition of proinflammatory cytokines. However, its effects on melanogenesis have largely remained unreported. The present study examined the effects of 8-methoxycoumarin on melanogenesis in B16F10 murine cells, together with its effect on the mechanism of melanin synthesis. The cells were treated with different concentrations of 8-methoxycoumarin; α-MSH was used as the positive control. We found 8-methoxycoumarin to significantly increase the melanin content of the cells without exerting any cytotoxicity. In addition, it significantly upregulated the expression of tyrosinase and tyrosinase-related protein-1 and 2 via inducing the expression of microphthalmia-associated transcription factor. Furthermore, we demonstrated the involvement of mitogen-activated protein kinase (MAPK) pathway-mediated phosphorylation of p38 and c-Jun N-terminal kinase (JNK), and inhibition of phosphorylation of extracellular signal-regulated kinase (ERK) to be responsible for enhanced melanin production. Use of SB203580 (p38 inhibitor) and SP600125 (p-JNK inhibitor) corroborated these findings. Additionally, we investigated the effects of 8-methoxycoumarin on protein kinase B (AKT) phosphorylation and protein kinase A (PKA) signaling pathway (using H89, a PKA inhibitor). These results suggested that 8-methoxycoumarin increases melanogenesis via the MAPK signaling pathway. Based on these findings, we conclude that 8-methoxycoumarin could serve as a potential compound for treating hypopigmentation disorders. It could also serve as a promising chemical for hair depigmentation treatment in the cosmetic industry.
{"title":"8-Methoxycoumarin enhances melanogenesis via the MAPKase signaling pathway.","authors":"Y. Chung, Seung-Young Kim, C. Hyun","doi":"10.1691/ph.2019.9553","DOIUrl":"https://doi.org/10.1691/ph.2019.9553","url":null,"abstract":"8-Methoxycoumarin (8-methoxy-chromen-2-one), isolated from R. graveolens L., is able to alleviate arthritis by inhibition of proinflammatory cytokines. However, its effects on melanogenesis have largely remained unreported. The present study examined the effects of 8-methoxycoumarin on melanogenesis in B16F10 murine cells, together with its effect on the mechanism of melanin synthesis. The cells were treated with different concentrations of 8-methoxycoumarin; α-MSH was used as the positive control. We found 8-methoxycoumarin to significantly increase the melanin content of the cells without exerting any cytotoxicity. In addition, it significantly upregulated the expression of tyrosinase and tyrosinase-related protein-1 and 2 via inducing the expression of microphthalmia-associated transcription factor. Furthermore, we demonstrated the involvement of mitogen-activated protein kinase (MAPK) pathway-mediated phosphorylation of p38 and c-Jun N-terminal kinase (JNK), and inhibition of phosphorylation of extracellular signal-regulated kinase (ERK) to be responsible for enhanced melanin production. Use of SB203580 (p38 inhibitor) and SP600125 (p-JNK inhibitor) corroborated these findings. Additionally, we investigated the effects of 8-methoxycoumarin on protein kinase B (AKT) phosphorylation and protein kinase A (PKA) signaling pathway (using H89, a PKA inhibitor). These results suggested that 8-methoxycoumarin increases melanogenesis via the MAPK signaling pathway. Based on these findings, we conclude that 8-methoxycoumarin could serve as a potential compound for treating hypopigmentation disorders. It could also serve as a promising chemical for hair depigmentation treatment in the cosmetic industry.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"18 1","pages":"529-535"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81655536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Uchida, T. Nakamura, H. Watanabe, K. Kato, T. Miyamoto, K. Akashi, S. Masuda
Patients receiving cancer chemotherapy may experience a number of potentially severe adverse drug reactions. It is crucial for all members of the health care team to monitor the effect of medicines on the patient to ensure the safety and efficacy of the chemotherapy. The present study prepared medication instruction sheets (MISs) on hematological malignancy and conducted a questionnaire survey to verify their usefulness among physicians, dentists, and nurses. MISs were prepared for 103 chemotherapy and 44 pretreatment regimens for hematopoietic stem cell transplantation in the Department of Hematology at Kyushu University Hospital. Eight questions were prepared to investigate whether MISs could help physicians, dentists, and nurses manage cancer chemotherapy more safely, effectively, and efficiently, as well as in the sharing of information. A total of 35 medical staff working in inpatient wards, including 8 physicians, 3 dentists, and 24 nurses, participated in the questionnaire survey. All of the staff responded to the questionnaire survey, which showed that the MISs were favorably accepted by the participants. There was no negative opinion on the management of chemotherapy using the MISs. The MIS was a useful tool for sharing information on cancer chemotherapy between patients and medical staff and for enabling efficient management, thereby improving the safety and efficacy of treatment.
{"title":"Usefulness of medication instruction sheets for sharing information on cancer chemotherapy within the health care team.","authors":"M. Uchida, T. Nakamura, H. Watanabe, K. Kato, T. Miyamoto, K. Akashi, S. Masuda","doi":"10.1691/ph.2019.9467","DOIUrl":"https://doi.org/10.1691/ph.2019.9467","url":null,"abstract":"Patients receiving cancer chemotherapy may experience a number of potentially severe adverse drug reactions. It is crucial for all members of the health care team to monitor the effect of medicines on the patient to ensure the safety and efficacy of the chemotherapy. The present study prepared medication instruction sheets (MISs) on hematological malignancy and conducted a questionnaire survey to verify their usefulness among physicians, dentists, and nurses. MISs were prepared for 103 chemotherapy and 44 pretreatment regimens for hematopoietic stem cell transplantation in the Department of Hematology at Kyushu University Hospital. Eight questions were prepared to investigate whether MISs could help physicians, dentists, and nurses manage cancer chemotherapy more safely, effectively, and efficiently, as well as in the sharing of information. A total of 35 medical staff working in inpatient wards, including 8 physicians, 3 dentists, and 24 nurses, participated in the questionnaire survey. All of the staff responded to the questionnaire survey, which showed that the MISs were favorably accepted by the participants. There was no negative opinion on the management of chemotherapy using the MISs. The MIS was a useful tool for sharing information on cancer chemotherapy between patients and medical staff and for enabling efficient management, thereby improving the safety and efficacy of treatment.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"5 1","pages":"566-569"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82751742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Solid dispersions (SDs) have made great progress in the improvement of dissolution for poorly soluble drugs, however the low drug loading still limits their wide application. In the present paper, high carbamazepine (CBZ) loaded SDs with excellent dissolution and tabletability were prepared and characterized. The CBZ SDs were prepared with Eudragit EPO as carrier by hot-melt extrusion (HME) in the drug: carrier ratio of 4:1. Powder X-ray diffraction, differential scanning calorimetry, fourier transform infrared spectroscopy and powder dissolution was carried out to characterize the SDs. The results showed that the crystalline form the polymorph of CBZ in SDs was transformed into form I from form III after extruded at 140 °C. Wettability and microstructure of CBZ SDs were improved by the HME process, which promoted the dissolution significantly. More than 85 % drug dissolved within 5 min from CBZ SDs with even only 20 % Eudragit EPO as carrier. CBZ SDs tablets were prepared by direct tableting with a universal material testing machine at various compaction pressures. Compactibility and tabletability were enhanced significantly by the HME process. All of these results showed the CBZ SDs prepared by HME with 80 % CBZ and 20 % Eudragit EPO could improve the dissolution and tabletability significantly.
{"title":"Improvement of dissolution and tabletability of carbamazepine solid dispersions with high drug loading prepared by hot-melt extrusion.","authors":"Zilin Feng, Mengting Li, Wenxi Wang","doi":"10.1691/ph.2019.9008","DOIUrl":"https://doi.org/10.1691/ph.2019.9008","url":null,"abstract":"Solid dispersions (SDs) have made great progress in the improvement of dissolution for poorly soluble drugs, however the low drug loading still limits their wide application. In the present paper, high carbamazepine (CBZ) loaded SDs with excellent dissolution and tabletability were prepared and characterized. The CBZ SDs were prepared with Eudragit EPO as carrier by hot-melt extrusion (HME) in the drug: carrier ratio of 4:1. Powder X-ray diffraction, differential scanning calorimetry, fourier transform infrared spectroscopy and powder dissolution was carried out to characterize the SDs. The results showed that the crystalline form the polymorph of CBZ in SDs was transformed into form I from form III after extruded at 140 °C. Wettability and microstructure of CBZ SDs were improved by the HME process, which promoted the dissolution significantly. More than 85 % drug dissolved within 5 min from CBZ SDs with even only 20 % Eudragit EPO as carrier. CBZ SDs tablets were prepared by direct tableting with a universal material testing machine at various compaction pressures. Compactibility and tabletability were enhanced significantly by the HME process. All of these results showed the CBZ SDs prepared by HME with 80 % CBZ and 20 % Eudragit EPO could improve the dissolution and tabletability significantly.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"53 1","pages":"523-528"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84458001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：