Jingrui Liu, Xiaojiao Li, Hong Zhang, Guiling Chen, Hong Chen, Yue Hu, J. Niu, Yanhua Ding
Background: Donafenib is a novel compound similar to sorafenib that functions as a multikinase inhibitor. This phase 1b trial aimed to assess the safety, pharmacokinetics and efficacy of donafenib in treating Chinese patients with advanced hepatocellular carcinoma. Methods: From July 2014 to April 2015, 27 eligible advanced hepatocellular carcinoma patients were enrolled in the trial. They were randomly divided into 200 mg and 300 mg bid groups and received these oral doses of donafenib until the appearance of intolerance or disease progression. Results: Overall, donafenib was safe and well tolerated in the two groups, and most adverse events were grade 1 or 2. Elevated transaminase (n=19, 70.4 %), hypocalcemia (n=19, 70.4 %), and skin toxicity (n=17, 63.0 %) were the most frequently encountered adverse events. Donafenib exhibited high variability in pharmacokinetic parameters. Areas under the plasma concentration-time curve from 0-12 h increased disproportionally to the dose escalation. The treatment resulted in partial response in two patients and a stable disease status in 17 patients, and the median time to progression was 120 days for both groups. Conclusion: The results from this phase 1b trial indicate a favorable safety profile and notable anticancer efficacy of donafenib for treating advanced hepatocellular carcinoma. Comparable or better safety and efficacy were observed for a lower dosage of donafenib compared with sorafenib in the literature.
{"title":"Safety, pharmacokinetics and efficacy of donafenib in treating advanced hepatocellular carcinoma: report from a phase 1b trial.","authors":"Jingrui Liu, Xiaojiao Li, Hong Zhang, Guiling Chen, Hong Chen, Yue Hu, J. Niu, Yanhua Ding","doi":"10.1691/ph.2019.9626","DOIUrl":"https://doi.org/10.1691/ph.2019.9626","url":null,"abstract":"Background: Donafenib is a novel compound similar to sorafenib that functions as a multikinase inhibitor. This phase 1b trial aimed to assess the safety, pharmacokinetics and efficacy of donafenib in treating Chinese patients with advanced hepatocellular carcinoma. Methods: From July 2014 to April 2015, 27 eligible advanced hepatocellular carcinoma patients were enrolled in the trial. They were randomly divided into 200 mg and 300 mg bid groups and received these oral doses of donafenib until the appearance of intolerance or disease progression. Results: Overall, donafenib was safe and well tolerated in the two groups, and most adverse events were grade 1 or 2. Elevated transaminase (n=19, 70.4 %), hypocalcemia (n=19, 70.4 %), and skin toxicity (n=17, 63.0 %) were the most frequently encountered adverse events. Donafenib exhibited high variability in pharmacokinetic parameters. Areas under the plasma concentration-time curve from 0-12 h increased disproportionally to the dose escalation. The treatment resulted in partial response in two patients and a stable disease status in 17 patients, and the median time to progression was 120 days for both groups. Conclusion: The results from this phase 1b trial indicate a favorable safety profile and notable anticancer efficacy of donafenib for treating advanced hepatocellular carcinoma. Comparable or better safety and efficacy were observed for a lower dosage of donafenib compared with sorafenib in the literature.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"12 1","pages":"688-693"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86245010","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}
The influence of icaritin on the proliferation, migration, and invasion of human nasopharyngeal carcinoma cell CNE2 and the influencing mechanisms were discussed. Results indicated that icaritin can realize dosage-dependent inhibition of CNE2 cell proliferation, migration, and invasion and inhibit the expression levels of VEGF, KDR, bFGF, MMP2, and MMP9. It can also inhibit STAT3 phosphorylation without affecting STAT3 expression. Icaritin exerts multiple bonding effects on the SH2 structural domain of STAT3. Therefore, icaritin can become a candidate drug for resisting nasopharyngeal carcinoma, and its mechanism is related to the blocking of STAT3 signaling pathway activation.
{"title":"Inhibitory effect of icaritin on proliferation, migration, and invasion of human nasopharyngeal carcinoma cell CNE2 by regulating STAT3 activation.","authors":"Xiangdong Li, Chunlei Li, Peiyu Zhou, Shaohua Chen","doi":"10.1691/ph.2019.9632","DOIUrl":"https://doi.org/10.1691/ph.2019.9632","url":null,"abstract":"The influence of icaritin on the proliferation, migration, and invasion of human nasopharyngeal carcinoma cell CNE2 and the influencing mechanisms were discussed. Results indicated that icaritin can realize dosage-dependent inhibition of CNE2 cell proliferation, migration, and invasion and inhibit the expression levels of VEGF, KDR, bFGF, MMP2, and MMP9. It can also inhibit STAT3 phosphorylation without affecting STAT3 expression. Icaritin exerts multiple bonding effects on the SH2 structural domain of STAT3. Therefore, icaritin can become a candidate drug for resisting nasopharyngeal carcinoma, and its mechanism is related to the blocking of STAT3 signaling pathway activation.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"42 1","pages":"685-687"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86689231","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}
S. Marais, J. D. du Preez, L. D. du Plessis, J. du Plessis, M. Gerber
A novel HPLC method with UV detection was developed and validated in skin penetration (in vitro) studies to identify and quantify lovastatin, mevastatin, rosuvastatin and simvastatin. A Venusil XBP C18 (2), 150 x 4.6 mm, 5 μm column (Agela Technologies, Newark, DE) was used with gradient elution (start at 45 % acetonitrile and increase linearly to 90 % after 1 min; hold at 90 % until 6 min and then re-equilibrate at start conditions) and the mobile phase consisted of (A) Milli-Q ® water and 0.1% orthophosphoric acid, and (B) HPLC grade acetonitrile. The flow rate was set at 1 ml/min, 240 nm UV detection and an injection volume of 10 μl. Linearity was obtained over a range of 0.50-200.00 μg/ml and correlation coefficients ranging from 0.998-1.000 were obtained. Average recovery ranged from 95.9-100.6 %. The LOD and LOQ values obtained from the slope of a calibration curve and the standard deviation of the response ranged from 0.0138-0.0860 μg/ml and 0.0419-0.2615 μg/ml, respectively, where lovastatin and simvastatin could be detected at a concentration similar to the other statins, but could only be quantified at a higher concentration than the remaining statins. The specificity of the method was proved as accurate and quantification of statins was found, even within the incorporation of other compounds.
{"title":"Determination of lovastatin, mevastatin, rosuvastatin and simvastatin with HPLC by means of gradient elution.","authors":"S. Marais, J. D. du Preez, L. D. du Plessis, J. du Plessis, M. Gerber","doi":"10.1691/ph.2019.8192","DOIUrl":"https://doi.org/10.1691/ph.2019.8192","url":null,"abstract":"A novel HPLC method with UV detection was developed and validated in skin penetration (in vitro) studies to identify and quantify lovastatin, mevastatin, rosuvastatin and simvastatin. A Venusil XBP C18 (2), 150 x 4.6 mm, 5 μm column (Agela Technologies, Newark, DE) was used with gradient elution (start at 45 % acetonitrile and increase linearly to 90 % after 1 min; hold at 90 % until 6 min and then re-equilibrate at start conditions) and the mobile phase consisted of (A) Milli-Q ® water and 0.1% orthophosphoric acid, and (B) HPLC grade acetonitrile. The flow rate was set at 1 ml/min, 240 nm UV detection and an injection volume of 10 μl. Linearity was obtained over a range of 0.50-200.00 μg/ml and correlation coefficients ranging from 0.998-1.000 were obtained. Average recovery ranged from 95.9-100.6 %. The LOD and LOQ values obtained from the slope of a calibration curve and the standard deviation of the response ranged from 0.0138-0.0860 μg/ml and 0.0419-0.2615 μg/ml, respectively, where lovastatin and simvastatin could be detected at a concentration similar to the other statins, but could only be quantified at a higher concentration than the remaining statins. The specificity of the method was proved as accurate and quantification of statins was found, even within the incorporation of other compounds.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"32 1","pages":"658-660"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82037782","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}
In this study, we aimed to explore whether ginkgolide A (GA) would exhibit cardio-protective effects in mice with pressure overload through enhancing antioxidation and nitric oxide (NO) bioavailability. 21 male mice were randomly assigned into three groups as follows: sham group (10 ml/kg/day PBS, n=7), transverse aortic constriction (TAC) group (TAC and 10 ml/kg/day PBS, n=7) and GA group (TAC and 20 mg/kg/day GA, n=7). All groups received an intraperitoneal injection for four weeks. Heart and body mass were measured. Cardiac function was assessed by echocardiography. The collagen deposition, area of cardiomyocytes, number of capillaries and cell apoptosis were evaluated using Masson's staining, WGA staining, CD31 staining and TUNEL assay, respectively. Cadiac oxidative and antioxidative indexes were measured by colorimetry. Nitrotyrosine (NT) and transforming growth factor-β (TGF-β) were determined by ELISA. Phospho-endothelial NO synthases (eNOS) (Ser1177), phospho-eNOS (Thr 495), eNOS, neuronal NOS (nNOS), inducible NOS (iNOS) and GAPDH were analyzed by western blot. GA treatment greatly improved cardiac dysfunction, suppressed cardiac hypertrophy and increased capillary number at 4 weeks after TAC (P<0.05). Fibrotic area, cardiomyocyte area, and cell apoptosis of GA group were declined notably as compared to those of TAC group (P<0.05). GA administration substantially attenuated cardiac oxidative stress, and reduced NT and TGF-β levels (P<0.05). Besides, GA medication can enhance eNOS signaling, resulting in increased cardiac NO production (P<0.05). GA had a cardioprotective effect in mice with pressure overload, which was closely related with reducing oxidative stress and enhancing NO bioavailability in hearts.
{"title":"Ginkgolide A protects adverse cardiac remodeling through enhancing antioxidation and nitric oxide utilization in mice with pressure overload.","authors":"W. You, Zhi-ming Wu, F. Ye, Xiang-Qi Wu","doi":"10.1691/ph.2019.9615","DOIUrl":"https://doi.org/10.1691/ph.2019.9615","url":null,"abstract":"In this study, we aimed to explore whether ginkgolide A (GA) would exhibit cardio-protective effects in mice with pressure overload through enhancing antioxidation and nitric oxide (NO) bioavailability. 21 male mice were randomly assigned into three groups as follows: sham group (10 ml/kg/day PBS, n=7), transverse aortic constriction (TAC) group (TAC and 10 ml/kg/day PBS, n=7) and GA group (TAC and 20 mg/kg/day GA, n=7). All groups received an intraperitoneal injection for four weeks. Heart and body mass were measured. Cardiac function was assessed by echocardiography. The collagen deposition, area of cardiomyocytes, number of capillaries and cell apoptosis were evaluated using Masson's staining, WGA staining, CD31 staining and TUNEL assay, respectively. Cadiac oxidative and antioxidative indexes were measured by colorimetry. Nitrotyrosine (NT) and transforming growth factor-β (TGF-β) were determined by ELISA. Phospho-endothelial NO synthases (eNOS) (Ser1177), phospho-eNOS (Thr 495), eNOS, neuronal NOS (nNOS), inducible NOS (iNOS) and GAPDH were analyzed by western blot. GA treatment greatly improved cardiac dysfunction, suppressed cardiac hypertrophy and increased capillary number at 4 weeks after TAC (P<0.05). Fibrotic area, cardiomyocyte area, and cell apoptosis of GA group were declined notably as compared to those of TAC group (P<0.05). GA administration substantially attenuated cardiac oxidative stress, and reduced NT and TGF-β levels (P<0.05). Besides, GA medication can enhance eNOS signaling, resulting in increased cardiac NO production (P<0.05). GA had a cardioprotective effect in mice with pressure overload, which was closely related with reducing oxidative stress and enhancing NO bioavailability in hearts.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"19 1","pages":"698-702"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88686552","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. Tanaka, R. Matsubara, K. Furukawa, S. Satonaka, S. Kasaoka
The objective of this study was to evaluate the influence of viscosity-enhancing agents on oral absorption of metoprolol (MPL) and bisoprolol (BPL). Although the viscosity values were similar for MPL and BPL in hydroxypropyl methylcellulose (HPMC, 1.2 % (w/w)) and polyvinyl alcohol (PVA, 8.8 % (w/w)) solutions, the order of diffusion rate constants of the drugs in media were phosphate buffer solution (reference) > HPMC solution > PVA solution. In in vivo rat intestinal absorption experiments showed that the Cmax and AUC values of the drugs were lowest when they were administered into the rat jejunum in a PVA solution. In vitro binding studies showed that this may have been due to adsorption of the drugs to PVA molecules, resulting in decreased free fractions of the drugs. Our results indicated that intestinal absorption of the drugs in PVA solution was influenced both by decreased diffusion of the drugs and by interaction with PVA. Since various viscosity-enhancing agents are widely used as pharmaceutical and food additives, these findings may be of significance for understanding therapeutic efficacy and safety of oral drug products.
{"title":"The influence of viscosity-enhancing agents on oral absorption of drugs.","authors":"Y. Tanaka, R. Matsubara, K. Furukawa, S. Satonaka, S. Kasaoka","doi":"10.1691/ph.2019.9097","DOIUrl":"https://doi.org/10.1691/ph.2019.9097","url":null,"abstract":"The objective of this study was to evaluate the influence of viscosity-enhancing agents on oral absorption of metoprolol (MPL) and bisoprolol (BPL). Although the viscosity values were similar for MPL and BPL in hydroxypropyl methylcellulose (HPMC, 1.2 % (w/w)) and polyvinyl alcohol (PVA, 8.8 % (w/w)) solutions, the order of diffusion rate constants of the drugs in media were phosphate buffer solution (reference) > HPMC solution > PVA solution. In in vivo rat intestinal absorption experiments showed that the Cmax and AUC values of the drugs were lowest when they were administered into the rat jejunum in a PVA solution. In vitro binding studies showed that this may have been due to adsorption of the drugs to PVA molecules, resulting in decreased free fractions of the drugs. Our results indicated that intestinal absorption of the drugs in PVA solution was influenced both by decreased diffusion of the drugs and by interaction with PVA. Since various viscosity-enhancing agents are widely used as pharmaceutical and food additives, these findings may be of significance for understanding therapeutic efficacy and safety of oral drug products.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"99 1","pages":"661-664"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77233055","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}
A. Makowska, L. Wolff, F. Sączewski, P. Bednarski, A. Kornicka
Two series of 2-imino-coumarin based hybrids: 3-(benzoxazol-2-yl)-2H-chromen-2-imines 3-9 (series A-I) and 3-(benzothiazol-2-yl)-2H-chromen-2-imines 10-16 (series A-II), as well as their coumarin analogues: 3-(benzoxazol-2-yl)-2H-chromen-2-ones 17-21 (series B-I) and 3-(benzothiazol-2-yl)-2H-chromen-2-ones 22-28 (series B-II) were prepared as potential antitumor agents. The in vitro cytotoxic potency of the synthesized compounds was evaluated against five human cancer cell lines: DAN-G, A-427, LCLC-103H, RT-4 and SISO, and relationships between structure and anticancer activity are discussed. Among the compounds tested, 3-(benzo[d] oxazol-2-yl)-N,N-diethyl-2-imino-2H-chromen-7-amine (6, series A-I) and 3-(benzo[d]thiazol-2-yl)-6-fluoro-2H-chromen-2-one (26, series B-II) exhibited the most potent cytotoxic activity with IC50 values ranging from <0.01 μM to 1.1 μM. In particular, compound 6 demonstrated remarkable cytotoxicity against the A-427 ovarian cancer, the lung cancer LCLC-103H, urinary bladder cancer RT-4 and cervical cancer SISO cell lines with IC50 <0.01-0.30μM, inducing apoptosis in two representative cell lines.
{"title":"Synthesis and cytotoxic evaluation of benzoxazole/benzothiazole-2-imino-coumarin hybrids and their coumarin analogues as potential anticancer agents.","authors":"A. Makowska, L. Wolff, F. Sączewski, P. Bednarski, A. Kornicka","doi":"10.1691/ph.2019.9664","DOIUrl":"https://doi.org/10.1691/ph.2019.9664","url":null,"abstract":"Two series of 2-imino-coumarin based hybrids: 3-(benzoxazol-2-yl)-2H-chromen-2-imines 3-9 (series A-I) and 3-(benzothiazol-2-yl)-2H-chromen-2-imines 10-16 (series A-II), as well as their coumarin analogues: 3-(benzoxazol-2-yl)-2H-chromen-2-ones 17-21 (series B-I) and 3-(benzothiazol-2-yl)-2H-chromen-2-ones 22-28 (series B-II) were prepared as potential antitumor agents. The in vitro cytotoxic potency of the synthesized compounds was evaluated against five human cancer cell lines: DAN-G, A-427, LCLC-103H, RT-4 and SISO, and relationships between structure and anticancer activity are discussed. Among the compounds tested, 3-(benzo[d] oxazol-2-yl)-N,N-diethyl-2-imino-2H-chromen-7-amine (6, series A-I) and 3-(benzo[d]thiazol-2-yl)-6-fluoro-2H-chromen-2-one (26, series B-II) exhibited the most potent cytotoxic activity with IC50 values ranging from <0.01 μM to 1.1 μM. In particular, compound 6 demonstrated remarkable cytotoxicity against the A-427 ovarian cancer, the lung cancer LCLC-103H, urinary bladder cancer RT-4 and cervical cancer SISO cell lines with IC50 <0.01-0.30μM, inducing apoptosis in two representative cell lines.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"1 1","pages":"648-657"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91231629","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}
H. Cai, Liyan Gong, Jie Liu, Qinfei Zhou, Zengguang Zheng
The present paper describes the molecular mechanism of diosgenin on tumor microenvironment angiogenesis and the regulation of GRP78 in angiogenesis signaling pathway. CCK8 method was used to evaluate the effect of different concentrations of diosgenin on HUVEC activity in hypoxic microenvironment. Apoptosis was detected by Annexin V/PI staining. Tube Formation experiment was conducted to evaluate angiogenesis. Western Blot assay was applied to detect the expressions and phosphorylation levels of the angiogenesis-related pathways HIF-1α, GRP78, VEGF/VEGFR, PI3K/AKT, ERK, and FAK in rheumatoid HUVEC. Silencing GRP78 by siRNA interference technology was employed to investigate the mechanism of GRP78 involved in the regulation of angiogenesis. The results indicated that diosgenin can significantly inhibit the cell viability of hypoxic HUVEC and the significance is dependent on drug concentration. As the concentration increases, HUVEC activity decreases. Cell apoptosis is induced in a dose-dependent manner and angiogenesis can be significantly inhibited. The hypoxic microenvironment can significantly increase the expressions of HIF-lα, GRP78, VEGF/VEGFR, PI3K/AKT, ERK, FAK proteins in angiogenesis-related pathways, and can also enhance the phosphorylation of AKT, ERK1/2 and FAK proteins, which can be decreased by drug intervention. After silencing GRP78, the angiogenesis-related pathway proteins HIF-lα and VEGF/VEGFR are significantly reduced, thus inhibiting the activation of AKT, ERK1/2, and FAK. The anti-tumor angiogenesis mechanism of diosgenin inhibiting the expression of HIF-lα, GRP78, VEGF/VEGFR, PI3K/AKT, ERK1/2 and FAK signaling pathways may be through multiple pathways and targets, and GRP78 is involved in the regulation of angiogenesis signaling pathway.
{"title":"Diosgenin inhibits tumor angiogenesis through regulating GRP78-mediated HIF-1α and VEGF/VEGFR signaling pathways.","authors":"H. Cai, Liyan Gong, Jie Liu, Qinfei Zhou, Zengguang Zheng","doi":"10.1691/ph.2019/9526","DOIUrl":"https://doi.org/10.1691/ph.2019/9526","url":null,"abstract":"The present paper describes the molecular mechanism of diosgenin on tumor microenvironment angiogenesis and the regulation of GRP78 in angiogenesis signaling pathway. CCK8 method was used to evaluate the effect of different concentrations of diosgenin on HUVEC activity in hypoxic microenvironment. Apoptosis was detected by Annexin V/PI staining. Tube Formation experiment was conducted to evaluate angiogenesis. Western Blot assay was applied to detect the expressions and phosphorylation levels of the angiogenesis-related pathways HIF-1α, GRP78, VEGF/VEGFR, PI3K/AKT, ERK, and FAK in rheumatoid HUVEC. Silencing GRP78 by siRNA interference technology was employed to investigate the mechanism of GRP78 involved in the regulation of angiogenesis. The results indicated that diosgenin can significantly inhibit the cell viability of hypoxic HUVEC and the significance is dependent on drug concentration. As the concentration increases, HUVEC activity decreases. Cell apoptosis is induced in a dose-dependent manner and angiogenesis can be significantly inhibited. The hypoxic microenvironment can significantly increase the expressions of HIF-lα, GRP78, VEGF/VEGFR, PI3K/AKT, ERK, FAK proteins in angiogenesis-related pathways, and can also enhance the phosphorylation of AKT, ERK1/2 and FAK proteins, which can be decreased by drug intervention. After silencing GRP78, the angiogenesis-related pathway proteins HIF-lα and VEGF/VEGFR are significantly reduced, thus inhibiting the activation of AKT, ERK1/2, and FAK. The anti-tumor angiogenesis mechanism of diosgenin inhibiting the expression of HIF-lα, GRP78, VEGF/VEGFR, PI3K/AKT, ERK1/2 and FAK signaling pathways may be through multiple pathways and targets, and GRP78 is involved in the regulation of angiogenesis signaling pathway.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"28 1","pages":"680-684"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88789605","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}
A. C. S. Ré, M. P. Ferreira, O. Freitas, C. P. Aires
The aim of this study was to evaluate a semi-solid system containing metronidazole (MDZ) in presence of challenging conditions for drug release, as well its antimicrobial effect against Porphyromonas gingivalis biofilm. Biofilms grown in culture medium were exposed to a formulation containing MDZ or its vehicle. After 24, 48, and 72 h, biofilm viability were analyzed while MDZ was quantified in culture medium and buffer solution (control). MDZ formulation reduced bacterial viability when compared to control groups. The vehicle formulation also affected bacterial viability in relation to control at all periods. Culture medium impaired MDZ release compared to buffer solution at 24 h. The semi-solid system reported herein is able to release MDZ and maintain its levels at concentrations that control viability of P. gingivalis in 1- to 3-day-old biofilms.
{"title":"Antimicrobial effect of a local release system containing metronidazole against a Porphyromonas gingivalis biofilm.","authors":"A. C. S. Ré, M. P. Ferreira, O. Freitas, C. P. Aires","doi":"10.1691/ph.2019.8241","DOIUrl":"https://doi.org/10.1691/ph.2019.8241","url":null,"abstract":"The aim of this study was to evaluate a semi-solid system containing metronidazole (MDZ) in presence of challenging conditions for drug release, as well its antimicrobial effect against Porphyromonas gingivalis biofilm. Biofilms grown in culture medium were exposed to a formulation containing MDZ or its vehicle. After 24, 48, and 72 h, biofilm viability were analyzed while MDZ was quantified in culture medium and buffer solution (control). MDZ formulation reduced bacterial viability when compared to control groups. The vehicle formulation also affected bacterial viability in relation to control at all periods. Culture medium impaired MDZ release compared to buffer solution at 24 h. The semi-solid system reported herein is able to release MDZ and maintain its levels at concentrations that control viability of P. gingivalis in 1- to 3-day-old biofilms.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"13 1","pages":"665-666"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73724058","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}
Nephroprotective drug development for optimizing treatment of chronic kidney disease (CKD) is an important task of pharmaceutical science. Our study evaluated nephroprotective properties of the two glucosamine derivatives N-acetylglucosamine and glucosamine hydrochloride in a 3-week-long parenteral and oral daily administration at doses of 50 mg/kg in rats with doxorubicin nephropathy. Nephroprotective activity (NA) was evaluated by determining the functional state of the kidneys, the level of azotemia and the activity of free-radical processes in the renal tissue. The results show a significant increase in renal excretory function, normalization of nitrogen metabolism and a decline of free-radical processes under the influence of both studied amino sugars in rats with doxorubicin nephropathy. I. m. route of administration yielded the highest efficacy for both amino sugars with the highest level of NA (83.3%) shown by N-acetylglucosamine. Thus N-acetylglucosamine in i. m. injections has the highest NA among the glucosamine derivatives, and is a promising agent for CKD treatment.
{"title":"N-Acetylglucosamine is the most effective glucosamine derivative for the treatment of membranous nephropathy in rats.","authors":"S. Shebeko, I. Zupanets, O. S. Popov","doi":"10.1691/ph.2019.9733","DOIUrl":"https://doi.org/10.1691/ph.2019.9733","url":null,"abstract":"Nephroprotective drug development for optimizing treatment of chronic kidney disease (CKD) is an important task of pharmaceutical science. Our study evaluated nephroprotective properties of the two glucosamine derivatives N-acetylglucosamine and glucosamine hydrochloride in a 3-week-long parenteral and oral daily administration at doses of 50 mg/kg in rats with doxorubicin nephropathy. Nephroprotective activity (NA) was evaluated by determining the functional state of the kidneys, the level of azotemia and the activity of free-radical processes in the renal tissue. The results show a significant increase in renal excretory function, normalization of nitrogen metabolism and a decline of free-radical processes under the influence of both studied amino sugars in rats with doxorubicin nephropathy. I. m. route of administration yielded the highest efficacy for both amino sugars with the highest level of NA (83.3%) shown by N-acetylglucosamine. Thus N-acetylglucosamine in i. m. injections has the highest NA among the glucosamine derivatives, and is a promising agent for CKD treatment.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"29 1","pages":"667-670"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89765957","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}
Zhengping Wu, Chung-Yi Chen, C. Kao, Yi-Hai Jiang, Chi-Ming Liu
Docosahexaenoic acid (DHA) is rich in fish oil with many pharmacological impacts such as anti-inflammation and anti-cancer activities. In the present study, we aimed to investigate the inhibitory effects of DHA on the invasion and inflammation in prostate cancer cells. The cytotoxicity of DHA with or without lipopolysaccharides (LPS) treatment was evaluated by MTT assay. The invasion and wound healing assays were used to determine the roles of DHA in cell migration and invasion after LPS treatment. The expression levels of IL-6 and IL-8 were detected using ELISA assay. The protein expression was investigated by Western blotting. DHA exhibited significant cytotoxicity at the concentration of 100 μM in PC3 cells. Exposure to DHA (6, 12 and 25 μM) dose-dependently inhibited invasion and wound closure potential in PC3 cells after LPS treatment. DHA dose-dependently downregulated LPS-induced expression levels of IL-6 and IL-8. In addition, the LPS-induced protein levels of p-AKT and COX-2 were suppressed by DHA treatment. Our results indicate that low doses of DHA effectively inhibit metastasis by decreasing IL-6, IL-8, p-AKT and COX-2 expression levels after LPS treatment.
{"title":"Docosahexaenoic acid inhibits lipopolysaccharide-induced metastatic activities by decreasing inflammation on prostate cancer cell.","authors":"Zhengping Wu, Chung-Yi Chen, C. Kao, Yi-Hai Jiang, Chi-Ming Liu","doi":"10.1691/ph.2019.9686","DOIUrl":"https://doi.org/10.1691/ph.2019.9686","url":null,"abstract":"Docosahexaenoic acid (DHA) is rich in fish oil with many pharmacological impacts such as anti-inflammation and anti-cancer activities. In the present study, we aimed to investigate the inhibitory effects of DHA on the invasion and inflammation in prostate cancer cells. The cytotoxicity of DHA with or without lipopolysaccharides (LPS) treatment was evaluated by MTT assay. The invasion and wound healing assays were used to determine the roles of DHA in cell migration and invasion after LPS treatment. The expression levels of IL-6 and IL-8 were detected using ELISA assay. The protein expression was investigated by Western blotting. DHA exhibited significant cytotoxicity at the concentration of 100 μM in PC3 cells. Exposure to DHA (6, 12 and 25 μM) dose-dependently inhibited invasion and wound closure potential in PC3 cells after LPS treatment. DHA dose-dependently downregulated LPS-induced expression levels of IL-6 and IL-8. In addition, the LPS-induced protein levels of p-AKT and COX-2 were suppressed by DHA treatment. Our results indicate that low doses of DHA effectively inhibit metastasis by decreasing IL-6, IL-8, p-AKT and COX-2 expression levels after LPS treatment.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"16 1","pages":"675-679"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72965577","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}
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