G. Hrčková, T. Mačák Kubašková, D. Mudroňová, A. Bardelčíková
Abstract Aims Silymarin (SIL), a mixture of phenolic compounds, has a pleiotropic mode of action on various cell types, including immune cells. In this study, we investigated the concentration-dependent effect of SIL on proliferation of concanavalin A (CoA)-stimulated mouse spleen T lymphocytes, their viability, and secretion of IFN-g and IL-4 cytokines ex vivo in relation to gene expressions of transcription factors nuclear factor kappa B and Foxp3. In addition, metabolic activity of T cells was determined as changes in the mitochondrial membrane potential and apoptosis. Material/Methods Isolated splenocytes were stimulated with lectin CoA and treated with SIL atthe concentrations of 5, 10, 20, and 40 μg/ml for 70 h and unstimulated cells served as the control. Cultures of splenocytes were evaluated for proliferation index following BrdU incorporation and viability of cells after trypan blue staining. Gene expressions of transcription factors and cytokines were assessed using real-time PCR, whereas ELISA test was applied to measure cytokine secretion. Mitochondrial membrane potential and apoptosis were determined by flow cytometry. Results We demonstrated that CoA-activated mouse spleen T lymphocytes show different susceptibilities to low (£10 μg/ml) and higher (20 and 40 μg/ml) SIL concentrations. Low concentrations resulted in increased proliferation, cytokine secretion, and mitochondrial membrane potential and reduced transition of cells to apoptosis. High concentration of SIL had the opposite effect without exerting significant cytotoxicity and upregulated genes for cytokines and transcription factors on mRNA level. It is possible that individual subpopulations of T cells induced by CoA were differentially affected by the various SIL concentrations and the dose of 40 μg/ml had the profound suppressive effect. This correlated with the highest expression of Foxp3 factor, indicating that this dose stimulated preferential differentiation to Tregs lymphocytes. Conclusions Treatment with suitable doses of SIL can provide potential benefits in the modulation of host immune functions in various diseases.
{"title":"Concentration-dependent effect of silymarin on concanavalin A-stimulated mouse spleen cells in vitro","authors":"G. Hrčková, T. Mačák Kubašková, D. Mudroňová, A. Bardelčíková","doi":"10.2478/afpuc-2020-0003","DOIUrl":"https://doi.org/10.2478/afpuc-2020-0003","url":null,"abstract":"Abstract Aims Silymarin (SIL), a mixture of phenolic compounds, has a pleiotropic mode of action on various cell types, including immune cells. In this study, we investigated the concentration-dependent effect of SIL on proliferation of concanavalin A (CoA)-stimulated mouse spleen T lymphocytes, their viability, and secretion of IFN-g and IL-4 cytokines ex vivo in relation to gene expressions of transcription factors nuclear factor kappa B and Foxp3. In addition, metabolic activity of T cells was determined as changes in the mitochondrial membrane potential and apoptosis. Material/Methods Isolated splenocytes were stimulated with lectin CoA and treated with SIL atthe concentrations of 5, 10, 20, and 40 μg/ml for 70 h and unstimulated cells served as the control. Cultures of splenocytes were evaluated for proliferation index following BrdU incorporation and viability of cells after trypan blue staining. Gene expressions of transcription factors and cytokines were assessed using real-time PCR, whereas ELISA test was applied to measure cytokine secretion. Mitochondrial membrane potential and apoptosis were determined by flow cytometry. Results We demonstrated that CoA-activated mouse spleen T lymphocytes show different susceptibilities to low (£10 μg/ml) and higher (20 and 40 μg/ml) SIL concentrations. Low concentrations resulted in increased proliferation, cytokine secretion, and mitochondrial membrane potential and reduced transition of cells to apoptosis. High concentration of SIL had the opposite effect without exerting significant cytotoxicity and upregulated genes for cytokines and transcription factors on mRNA level. It is possible that individual subpopulations of T cells induced by CoA were differentially affected by the various SIL concentrations and the dose of 40 μg/ml had the profound suppressive effect. This correlated with the highest expression of Foxp3 factor, indicating that this dose stimulated preferential differentiation to Tregs lymphocytes. Conclusions Treatment with suitable doses of SIL can provide potential benefits in the modulation of host immune functions in various diseases.","PeriodicalId":12070,"journal":{"name":"European Pharmaceutical Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46749247","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}
Abstract Aim Literary sources on qualitative composition, quantitative content of biologically active substances, and standardization methods of pumpkin seeds have been studied. It has been established that, along with Δ7-sterols, whose action is associated with treatment of the prostate gland, pumpkin seeds contain amino acids, cucurbitin in particular, which are responsible for their antihelminthic effect. The aim is to study the qualitative and quantitative content of amino acids in domestic samples of pumpkin seeds in order to clarify the possibility of pumpkin seed standardization for this class of biologically active substances. Methods The investigation of the possibility of amino acids’ identification in the herbal drug by the thin-layer chromatography (TLC) method was carried out on silica gel 60 F254 plates, Merck and Silica gel 60, Merck, on aluminum and glass supports in a mixture of the following solvents: butanol–acetone–acetic acid–water (35:35:10:20). The conclusions have been made based on the presence of characteristic zones of amino acids in the chromatograms after the treatment with ninhydrin solution. Quantitative determination of amino acids in the herbal drug was carried out by absorption spectrometry using HP spectrophotometer HP-8453 UV-VIS, Hewlett Packard (USA). Results The chromatographic profile of the amino acid fraction of domestic samples of pumpkin seeds was studied using a TLC technique. In the chromatograms of test solutions from all samples, the zones were detected at the level of histidine, aspartic acid, glutamic acid, glycine, and leucine zones, as well as a zone with color (olive) that differs from the other zones of amino acids and which is possibly a zone of cucurbitin. On the basis of the results of qualitative research, the quantitative content of the sum of amino acids according to a UV method developed has been determined, which including purification from the fatty oil, further extraction with an aqueous alcohol solution, selection of aliquots for the reaction with ninhydrin solution, and subsequent determination of the absorbance of the test solution and the solution of glutamic acid at a wavelength of 400 nm. It has been established that the content of the sum of amino acids expressed as glutamic acid in domestic samples is about 2%. Conclusions The research of the possibility of pumpkin seed standardization by the content of amino acids was carried out. The chromatographic profile of the amino acid fraction of domestic samples of pumpkin seeds was studied using a TLC method developed. The quantitative content of the amino acids sum by the absorption spectrophotometry method was investigated. The techniques developed will be recommended for inclusion in the draft of national monograph “Pumpkin seeds.”
{"title":"Study of qualitative and quantitative content of amino acids in pumpkin seeds for further standardization of the herbal drug","authors":"E. Kotova, S. Kotov, T. Gontova, A. Kotov","doi":"10.2478/afpuc-2020-0001","DOIUrl":"https://doi.org/10.2478/afpuc-2020-0001","url":null,"abstract":"Abstract Aim Literary sources on qualitative composition, quantitative content of biologically active substances, and standardization methods of pumpkin seeds have been studied. It has been established that, along with Δ7-sterols, whose action is associated with treatment of the prostate gland, pumpkin seeds contain amino acids, cucurbitin in particular, which are responsible for their antihelminthic effect. The aim is to study the qualitative and quantitative content of amino acids in domestic samples of pumpkin seeds in order to clarify the possibility of pumpkin seed standardization for this class of biologically active substances. Methods The investigation of the possibility of amino acids’ identification in the herbal drug by the thin-layer chromatography (TLC) method was carried out on silica gel 60 F254 plates, Merck and Silica gel 60, Merck, on aluminum and glass supports in a mixture of the following solvents: butanol–acetone–acetic acid–water (35:35:10:20). The conclusions have been made based on the presence of characteristic zones of amino acids in the chromatograms after the treatment with ninhydrin solution. Quantitative determination of amino acids in the herbal drug was carried out by absorption spectrometry using HP spectrophotometer HP-8453 UV-VIS, Hewlett Packard (USA). Results The chromatographic profile of the amino acid fraction of domestic samples of pumpkin seeds was studied using a TLC technique. In the chromatograms of test solutions from all samples, the zones were detected at the level of histidine, aspartic acid, glutamic acid, glycine, and leucine zones, as well as a zone with color (olive) that differs from the other zones of amino acids and which is possibly a zone of cucurbitin. On the basis of the results of qualitative research, the quantitative content of the sum of amino acids according to a UV method developed has been determined, which including purification from the fatty oil, further extraction with an aqueous alcohol solution, selection of aliquots for the reaction with ninhydrin solution, and subsequent determination of the absorbance of the test solution and the solution of glutamic acid at a wavelength of 400 nm. It has been established that the content of the sum of amino acids expressed as glutamic acid in domestic samples is about 2%. Conclusions The research of the possibility of pumpkin seed standardization by the content of amino acids was carried out. The chromatographic profile of the amino acid fraction of domestic samples of pumpkin seeds was studied using a TLC method developed. The quantitative content of the amino acids sum by the absorption spectrophotometry method was investigated. The techniques developed will be recommended for inclusion in the draft of national monograph “Pumpkin seeds.”","PeriodicalId":12070,"journal":{"name":"European Pharmaceutical Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43148905","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. Krivosova, M. Kertys, M. Grendár, I. Ondrejka, I. Hrtanek, I. Tonhajzerova, N. Sekaninova, J. Mokrý
Abstract Depression is a common mental disorder affecting more than 264 million people in the world and 5.1% of the Slovak population. Although various antidepressant approaches have been used; still, about 40% of patients do not respond to a first-choice drug administration and one third of patients do not achieve total remission. Therapeutic drug monitoring (TDM) is a method used for quantification and interpreting the drug concentrations in plasma in order to optimize the pharmacotherapy. The aim of this study was to measure the plasma concentrations of venlafaxine, the fourth most prescribed antidepressant in Slovakia, as well as its active metabolite and interpret them with the relevant patients’ characteristics. The study was of retrospective nature and 28 adult patients in total were included. The concentrations of venlafaxine and its active metabolite O-desmethylvenlafaxine (ODV) in plasma were quantified using the validated UHPLC-MS/MS method. The effects of potential influencing factors were evaluated by a multivariate linear regression model. Only 39% of patients reached the venlafaxine active moiety concentrations within the recommended therapeutic range. Plasma concentrations were dependent on age, gender, and duration of the therapy. Venlafaxine metabolism expressed as a metaboliteto-parent concentrations ratio was influenced by a combination of age, gender, and body mass index (BMI). We did not observe any significant difference in plasma concentrations between the patients with a single and recurrent diagnosis of depression. Combining variables made an additive effect on plasma concentrations, for example, active moiety plasma concentrations were higher in older women. In contrast, drug metabolism was higher in older men and men with lower BMI. TDM of venlafaxine is recommended in clinical practice, especially in the elderly when beginning the pharmacotherapy.
{"title":"Therapeutic Drug Monitoring of Venlafaxine and Impact of Age, Gender, BMI, and Diagnosis","authors":"M. Krivosova, M. Kertys, M. Grendár, I. Ondrejka, I. Hrtanek, I. Tonhajzerova, N. Sekaninova, J. Mokrý","doi":"10.2478/afpuc-2020-0005","DOIUrl":"https://doi.org/10.2478/afpuc-2020-0005","url":null,"abstract":"Abstract Depression is a common mental disorder affecting more than 264 million people in the world and 5.1% of the Slovak population. Although various antidepressant approaches have been used; still, about 40% of patients do not respond to a first-choice drug administration and one third of patients do not achieve total remission. Therapeutic drug monitoring (TDM) is a method used for quantification and interpreting the drug concentrations in plasma in order to optimize the pharmacotherapy. The aim of this study was to measure the plasma concentrations of venlafaxine, the fourth most prescribed antidepressant in Slovakia, as well as its active metabolite and interpret them with the relevant patients’ characteristics. The study was of retrospective nature and 28 adult patients in total were included. The concentrations of venlafaxine and its active metabolite O-desmethylvenlafaxine (ODV) in plasma were quantified using the validated UHPLC-MS/MS method. The effects of potential influencing factors were evaluated by a multivariate linear regression model. Only 39% of patients reached the venlafaxine active moiety concentrations within the recommended therapeutic range. Plasma concentrations were dependent on age, gender, and duration of the therapy. Venlafaxine metabolism expressed as a metaboliteto-parent concentrations ratio was influenced by a combination of age, gender, and body mass index (BMI). We did not observe any significant difference in plasma concentrations between the patients with a single and recurrent diagnosis of depression. Combining variables made an additive effect on plasma concentrations, for example, active moiety plasma concentrations were higher in older women. In contrast, drug metabolism was higher in older men and men with lower BMI. TDM of venlafaxine is recommended in clinical practice, especially in the elderly when beginning the pharmacotherapy.","PeriodicalId":12070,"journal":{"name":"European Pharmaceutical Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48405751","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}
V. Minarchenko, I. Tymchenko, L. Glushchenko, V. Pidchenko
Abstract This study presents the results of our comparative evaluation of diagnostic morphological characteristics of raw material from 11 species of genus Thymus L. of medicinal and raw material importance occurring in Ukraine. The following taxa were evaluated: T. serpyllum L., T. odoratissimus Mill. (T. glabrescens Willd.), T. borysthenicus Klokov & Des.-Shost., T. pallasianus Heinr. Braun, T. moldavicus Klokov & Des.-Shost., T. calcareus Klokov & Des.-Shost., T. alpestris Tausch ex A. Kern., T. × dimorphus Klokov & Des.-Shost., T. pannonicus All. s.l. (including T. marschallianus Willd.), T. pulegioides L. and T. roegneri K. Koch (T. alternans Klokov). Among wild species of thyme, only raw material of Thymus serpyllum is officially allowed for use with the purpose for production of pharmaceuticals and medicines. A comparison of the main characteristics is particularly important in view of the fact that raw material is represented by parts of plants (stems, leaves and flowers), which makes any whole comparison of species hardly possible. This study has revealed that stem pubescence, calyx structure, configuration/arrangement and type of leaf venation can provide valuable information for diagnostics of raw material of Thymus species. The results exhibited that according to characters of stem pubescence, calyx structure, shape and size of leaves the most similar are raw material samples of T. serpyllum and T. moldavicus. However, these species are rather well separated geographically, so the possibility of mixing of their raw material is negligible. Other species have significant morphological differences in certain characteristics by which they can be diagnosed in the raw material.
{"title":"Comparative morphological studies of raw parts of the most common species of Thymus in Ukraine","authors":"V. Minarchenko, I. Tymchenko, L. Glushchenko, V. Pidchenko","doi":"10.2478/afpuc-2020-0004","DOIUrl":"https://doi.org/10.2478/afpuc-2020-0004","url":null,"abstract":"Abstract This study presents the results of our comparative evaluation of diagnostic morphological characteristics of raw material from 11 species of genus Thymus L. of medicinal and raw material importance occurring in Ukraine. The following taxa were evaluated: T. serpyllum L., T. odoratissimus Mill. (T. glabrescens Willd.), T. borysthenicus Klokov & Des.-Shost., T. pallasianus Heinr. Braun, T. moldavicus Klokov & Des.-Shost., T. calcareus Klokov & Des.-Shost., T. alpestris Tausch ex A. Kern., T. × dimorphus Klokov & Des.-Shost., T. pannonicus All. s.l. (including T. marschallianus Willd.), T. pulegioides L. and T. roegneri K. Koch (T. alternans Klokov). Among wild species of thyme, only raw material of Thymus serpyllum is officially allowed for use with the purpose for production of pharmaceuticals and medicines. A comparison of the main characteristics is particularly important in view of the fact that raw material is represented by parts of plants (stems, leaves and flowers), which makes any whole comparison of species hardly possible. This study has revealed that stem pubescence, calyx structure, configuration/arrangement and type of leaf venation can provide valuable information for diagnostics of raw material of Thymus species. The results exhibited that according to characters of stem pubescence, calyx structure, shape and size of leaves the most similar are raw material samples of T. serpyllum and T. moldavicus. However, these species are rather well separated geographically, so the possibility of mixing of their raw material is negligible. Other species have significant morphological differences in certain characteristics by which they can be diagnosed in the raw material.","PeriodicalId":12070,"journal":{"name":"European Pharmaceutical Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44942530","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}
Abstract Resveratrol and caffeic acid belong to plant polyphenols and are known for their antioxidant effects. The aim of our research was to study their impact on Maillard reaction. This one occurs when the reducing saccharides react with amino groups of biomolecules including proteins, alter their protein conformation and transform to the variety of advanced glycation end products (AGEs). AGEs exhibit browning and generate fluorescence. There exist expectations that this oxidative protein glycosylation could be prevented by antioxidants. In this study, we incubated bovine serum albumin (BSA) with glucose for 7 days at 37°C and measured characteristic fluorescence and UV absorbance of the formed AGEs. Surprisingly, resveratrol and caffeic acid enhanced transformation of BSA to glycation products, which was confirmed either when cupric Cu(II) or ferric Fe(III) ions in nanomolar concentration were added to the system as pro-oxidant agent.
{"title":"In Vitro Pro-Glycative Effects of Resveratrol and Caffeic Acid","authors":"E. Kurin, P. Mučaji, M. Nagy","doi":"10.2478/afpuc-2019-0004","DOIUrl":"https://doi.org/10.2478/afpuc-2019-0004","url":null,"abstract":"Abstract Resveratrol and caffeic acid belong to plant polyphenols and are known for their antioxidant effects. The aim of our research was to study their impact on Maillard reaction. This one occurs when the reducing saccharides react with amino groups of biomolecules including proteins, alter their protein conformation and transform to the variety of advanced glycation end products (AGEs). AGEs exhibit browning and generate fluorescence. There exist expectations that this oxidative protein glycosylation could be prevented by antioxidants. In this study, we incubated bovine serum albumin (BSA) with glucose for 7 days at 37°C and measured characteristic fluorescence and UV absorbance of the formed AGEs. Surprisingly, resveratrol and caffeic acid enhanced transformation of BSA to glycation products, which was confirmed either when cupric Cu(II) or ferric Fe(III) ions in nanomolar concentration were added to the system as pro-oxidant agent.","PeriodicalId":12070,"journal":{"name":"European Pharmaceutical Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45202657","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}
Abstract Valproic acid, beside its anticonvulsant action, is widely used as a mood stabilizer in the therapy of bipolar disorder. The potential antidepressant action of valproic acid has not been sufficiently characterized so far. The aim of the present study was to evaluate the antidepressant effect of valproic acid in an aldosterone model of depression. Subchronic treatment with valproic acid resulted in a reduction of the time spent in immobility in the forced swim test. In conclusion, the present study provides evidence on antidepressant effects of valproic acid using a classical behavioral approach for testing the efficacy of antidepressant drug in animal models.
{"title":"Antidepressant effects of valproic acid in an animal model of depression","authors":"K. Buzgoova, L. Balagova, N. Hlavacova, D. Jezova","doi":"10.2478/afpuc-2019-0006","DOIUrl":"https://doi.org/10.2478/afpuc-2019-0006","url":null,"abstract":"Abstract Valproic acid, beside its anticonvulsant action, is widely used as a mood stabilizer in the therapy of bipolar disorder. The potential antidepressant action of valproic acid has not been sufficiently characterized so far. The aim of the present study was to evaluate the antidepressant effect of valproic acid in an aldosterone model of depression. Subchronic treatment with valproic acid resulted in a reduction of the time spent in immobility in the forced swim test. In conclusion, the present study provides evidence on antidepressant effects of valproic acid using a classical behavioral approach for testing the efficacy of antidepressant drug in animal models.","PeriodicalId":12070,"journal":{"name":"European Pharmaceutical Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47260608","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. Sunaryo, S. Siska, E. Hanani, RS. Anindita, N. Yanti, Lisa
Abstract Trees and shrubs of the genus Cordia are widely distributed in the warmer regions, including Indonesia. The aim of this study was to evaluate the analgesic and anti-inflammatory properties of the ethanolic extract of plant leaves in Wistar albino rats. The analgesic activity was evaluated using the hot plate method and acetic acid-induced writhing, and the anti-inflammatory activity was determined using carrageenan-induced paw oedema. The results showed that the Cordia sebestena ethanol extract (100, 200 and 400 mg/kg) exhibited significant analgesic effects in a dose-dependent manner in the two pain models tested. The extract also exhibited significant anti-inflammatory effects in the carrageenan-induced inflammation test. The data obtained support the traditional folklore therapeutic claim about its analgesic and anti-inflammatory properties. Nonetheless, further scientific investigation is required to establish its analgesic and anti-inflammatory properties in other experimental models and clinical settings.
{"title":"Evaluation of analgesic and anti-inflammatory activities of ethanolic extract of Cordia sebestena L.","authors":"H. Sunaryo, S. Siska, E. Hanani, RS. Anindita, N. Yanti, Lisa","doi":"10.2478/afpuc-2019-0018","DOIUrl":"https://doi.org/10.2478/afpuc-2019-0018","url":null,"abstract":"Abstract Trees and shrubs of the genus Cordia are widely distributed in the warmer regions, including Indonesia. The aim of this study was to evaluate the analgesic and anti-inflammatory properties of the ethanolic extract of plant leaves in Wistar albino rats. The analgesic activity was evaluated using the hot plate method and acetic acid-induced writhing, and the anti-inflammatory activity was determined using carrageenan-induced paw oedema. The results showed that the Cordia sebestena ethanol extract (100, 200 and 400 mg/kg) exhibited significant analgesic effects in a dose-dependent manner in the two pain models tested. The extract also exhibited significant anti-inflammatory effects in the carrageenan-induced inflammation test. The data obtained support the traditional folklore therapeutic claim about its analgesic and anti-inflammatory properties. Nonetheless, further scientific investigation is required to establish its analgesic and anti-inflammatory properties in other experimental models and clinical settings.","PeriodicalId":12070,"journal":{"name":"European Pharmaceutical Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48989763","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. Miatmoko, H. Salim, S. M. Zahro’, F. Annuryanti, R. Sari, E. Hendradi
Abstract Primaquine (PQ) has long been recognized as the only effective drug in the treatment of hepatic stage malaria. However, severe toxicity limits its therapeutical application. Combining PQ with chloroquine (CQ) has been reported as enhancing the former’s efficacy, while simultaneously reducing its toxicity. In this study, the optimal conditions for encapsulating PQ-CQ in liposome, including incubation time, temperature and drug to lipid ratio, were identified. Furthermore, the effect of the loading combination of these two drugs on liposomal characteristics and the drug released from liposome was evaluated. Liposome is composed of HSPC, cholesterol and DSPE-mPEG2000 at a molar ratio of 55:40:5 and the drugs were loaded by means of the transmembrane pH gradient method. The particle size, ζ-potential and drug encapsulation efficiency were subsequently evaluated. The results showed that all liposome was produced with a similar particle size and ζ -potential. PQ and CQ could be optimally loaded into liposome by incubating the mixtures at 60°C for 20 minutes at a respective drug to lipid ratio of 1:3 for PQ and CQ. However, compared to single drug loading, dual-loading of PQ+CQ into liposome resulted in lower drug encapsulation and slower drug release. In conclusion, PQ and CQ can be jointly loaded into liposome with differing profiles of encapsulation and drug release.
{"title":"Dual Loading Of Primaquine And Chloroquine Into Liposome","authors":"A. Miatmoko, H. Salim, S. M. Zahro’, F. Annuryanti, R. Sari, E. Hendradi","doi":"10.2478/afpuc-2019-0009","DOIUrl":"https://doi.org/10.2478/afpuc-2019-0009","url":null,"abstract":"Abstract Primaquine (PQ) has long been recognized as the only effective drug in the treatment of hepatic stage malaria. However, severe toxicity limits its therapeutical application. Combining PQ with chloroquine (CQ) has been reported as enhancing the former’s efficacy, while simultaneously reducing its toxicity. In this study, the optimal conditions for encapsulating PQ-CQ in liposome, including incubation time, temperature and drug to lipid ratio, were identified. Furthermore, the effect of the loading combination of these two drugs on liposomal characteristics and the drug released from liposome was evaluated. Liposome is composed of HSPC, cholesterol and DSPE-mPEG2000 at a molar ratio of 55:40:5 and the drugs were loaded by means of the transmembrane pH gradient method. The particle size, ζ-potential and drug encapsulation efficiency were subsequently evaluated. The results showed that all liposome was produced with a similar particle size and ζ -potential. PQ and CQ could be optimally loaded into liposome by incubating the mixtures at 60°C for 20 minutes at a respective drug to lipid ratio of 1:3 for PQ and CQ. However, compared to single drug loading, dual-loading of PQ+CQ into liposome resulted in lower drug encapsulation and slower drug release. In conclusion, PQ and CQ can be jointly loaded into liposome with differing profiles of encapsulation and drug release.","PeriodicalId":12070,"journal":{"name":"European Pharmaceutical Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45404144","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}
N. Tsiferova, O. Khamidova, A. Amonov, M. Rakhimova, S. Rustamova, R. S. Kurbannazaova, P. Merzlyak, N. Abdulladjanova, R. Sabirov
Abstract The volume-sensitive outwardly rectifying anion channel (VSOR) is a key component of volume regulation system critical for cell survival in non-isosmotic conditions. The aim of the present study was to test the effects of four tannin extracts with defined compositions on cell volume regulation and VSOR. Preparation I (98% of hydrolysable tannins isolated from leaves of sumac Rhus typhina L.) and Preparation II (100% of hydrolysable tannins isolated from leaves of broadleaf plantain Plantago major L) completely and irreversibly abolished swelling-activated VSOR currents in HCT116 cells. Both preparations profoundly suppressed the volume regulation in thymocytes with half-maximal effects of 40.9 μg/ml and 12.3 μg/ml, respectively. The inhibition was more efficient at lower concentrations but reverted at higher doses due to possible non-specific membrane-permeabilizing activity. Preparations III and IV (54,7% and 54.3% of hydrolysable tannins isolated, respectively, from roots and aboveground parts of Fergana spurge Euphorbia ferganensis B.Fedtch) inhibited VSOR activity in a partially reversible manner and suppressed the volume regulation with substantially higher half-maximal doses of 270 and 278 μg/ml, respectively, with no secondary reversion at higher doses. Hydrolysable tannins represent a novel class of VSOR channel inhibitors with the capacity to suppress the cell volume regulation machinery.
体积敏感的向外整流阴离子通道(VSOR)是非等渗条件下细胞存活的关键体积调节系统的关键组成部分。本研究的目的是测试四种特定成分的单宁提取物对细胞体积调节和VSOR的影响。制剂I(从苏木叶中分离98%的可水解单宁)和制剂II(从阔叶大车前草叶中分离100%的可水解单宁)完全不可逆地消除HCT116细胞肿胀激活的VSOR电流。两种制剂均能较好地抑制胸腺细胞的体积调节，半最大作用分别为40.9 μg/ml和12.3 μg/ml。在较低的浓度下抑制更有效，但在较高的剂量下由于可能的非特异性膜渗透活性而恢复。制剂III和IV(分别从Fergana spurge Euphorbia ferganensis B.Fedtch的根和地上部分分离得到54.7%和54.3%的水解单宁)以部分可逆的方式抑制了VSOR活性，并抑制了体积调节，其半最大剂量分别为270和278 μg/ml，在高剂量下无二次逆转作用。水解单宁是一类新型的VSOR通道抑制剂，具有抑制细胞体积调节机制的能力。
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Š. Husár, M. Sýkorová, K. Rumlová, K. Chomaničová, B. Vladovičová
Abstract The goal of the present study is to prepare a stable, multiple-unit, extended-release dosage form containing oxycodone pellets coated with aqueous ethylcellulose (EC) dispersion, Surelease E-7-19050. The application of 18% w/w of EC leads to the similar drug release with the hydrophobic, non-swelling, matrix reference product containing 20 mg of oxycodone. Increasing the compression force to 9 kN and including more than 50% w/w of oxycodone pellets into the formulation resulted in faster drug release, indicating the damaging to the EC film coating. The physical appearance of the final formulation, assay of oxycodone, moisture content, and dissolution data over the stability period showed that the multiple-unit pellet system (MUPS) is efficient for the production of highly stable product.
{"title":"Formulation and evaluation of new oxycodone extended release multiple unit pellet system","authors":"Š. Husár, M. Sýkorová, K. Rumlová, K. Chomaničová, B. Vladovičová","doi":"10.2478/afpuc-2019-0019","DOIUrl":"https://doi.org/10.2478/afpuc-2019-0019","url":null,"abstract":"Abstract The goal of the present study is to prepare a stable, multiple-unit, extended-release dosage form containing oxycodone pellets coated with aqueous ethylcellulose (EC) dispersion, Surelease E-7-19050. The application of 18% w/w of EC leads to the similar drug release with the hydrophobic, non-swelling, matrix reference product containing 20 mg of oxycodone. Increasing the compression force to 9 kN and including more than 50% w/w of oxycodone pellets into the formulation resulted in faster drug release, indicating the damaging to the EC film coating. The physical appearance of the final formulation, assay of oxycodone, moisture content, and dissolution data over the stability period showed that the multiple-unit pellet system (MUPS) is efficient for the production of highly stable product.","PeriodicalId":12070,"journal":{"name":"European Pharmaceutical Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48919384","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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