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Detalles de la revista
Formato
Revista
eISSN
1846-9558
Publicado por primera vez
28 Feb 2007
Periodo de publicación
4 veces al año
Idiomas
Inglés

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Volumen 71 (2021): Edición 4 (December 2021)

Detalles de la revista
Formato
Revista
eISSN
1846-9558
Publicado por primera vez
28 Feb 2007
Periodo de publicación
4 veces al año
Idiomas
Inglés

Buscar

12 Artículos
Acceso abierto

Quality-by-design in pharmaceutical development: From current perspectives to practical applications

Publicado en línea: 03 Apr 2021
Páginas: 497 - 526

Resumen

Abstract

Current pharmaceutical research directions tend to follow a systematic approach in the field of applied research and development. The concept of quality-by-design (QbD) has been the focus of the current progress of pharmaceutical sciences. It is based on, but not limited, to risk assessment, design of experiments and other computational methods and process analytical technology. These tools offer a well-organized methodology, both to identify and analyse the hazards that should be handled as critical, and are therefore applicable in the control strategy. Once implemented, the QbD approach will augment the comprehension of experts concerning the developed analytical technique or manufacturing process. The main activities are oriented towards the identification of the quality target product profiles, along with the critical quality attributes, the risk management of these and their analysis through in silico aided methods. This review aims to offer an overview of the current standpoints and general applications of QbD methods in pharmaceutical development.

Palabras clave

  • quality-by-design
  • pharmaceutical development
  • risk assessment
  • software-aided development
Acceso abierto

Recent advancements to enhance the therapeutic efficacy of antiepileptic drugs

Publicado en línea: 03 Apr 2021
Páginas: 527 - 544

Resumen

Abstract

Epilepsy is a multifactorial neurological disorder characterized by recurrent or unprovoked seizures. Over the past two decades, many new antiepileptic drugs (AEDs) were developed and are in use for the treatment of epilepsy. However, drug resistance, drug-drug interaction and adverse events are common problems associated with AEDs. Antiepileptic drugs must be used only if the ratio of efficacy, safety, and tolerability of treatment are favorable and outweigh the disadvantages including treatment costs. The application of novel drug delivery techniques could enhance the efficacy and reduce the toxicity of AEDs. These novel techniques aim to deliver an optimal concentration of the drug more specifically to the seizure focus or foci in the CNS without numerous side-effects. The purpose of this article is to review the recent advancements in antiepileptic treatment and summarize the novel modalities in the route of administration and drug delivery, including gene therapy, for effective treatment of epilepsy.

Palabras clave

  • antiepileptic drugs
  • drug delivery
  • epilepsy
  • gene therapy
  • liposomes
  • nanoparticles
Acceso abierto

New derivatives of sulfonylhydrazone as potential antitumor agents: Design, synthesis and cheminformatics evaluation

Publicado en línea: 03 Apr 2021
Páginas: 545 - 565

Resumen

Abstract

Phosphoinositide 3-kinase α (PI3Kα) is a propitious target for designing anticancer drugs. A series of new N’-(diphenylmethylene)benzenesulfonohydrazide was synthesized and characterized using FT-IR, NMR (1H and 13C), HRMS, and elemental analysis. Target compounds exhibited an antiproliferative effect against the human colon carcinoma (HCT-116) cell line. Our cheminformatics analysis indicated that the para-tailored derivatives [p-NO2 (3) and p-CF3 (7)] have better ionization potentials based on calculated Moran autocorrelations and ionization potentials. Subsequent in vitro cell proliferation assays validated our cheminformatics results by providing experimental evidence that both derivatives 3 and 7 exhibited improved antiproliferative activities against HCT-116. Hence, our results emphasized the importance of electron-withdrawing groups and hydrogen bond-acceptors in the rational design of small-molecule chemical ligands targeting PI3Kα. These results agreed with the induced-fit docking against PI3Kα, highlighting the role of p-substituted aromatic rings in guiding the ligand-PI3Kα complex formation, by targeting a hydrophobic pocket in the ligand-binding site and forming π-stacking interactions with a nearby tryptophan residue.

Palabras clave

  • sulfonylhydrazones
  • antitumor
  • HCT-116
  • PI3Kα-inhibitors
  • cheminformatics
  • docking
Acceso abierto

Identification and pharmacokinetics of saponins in Rhizoma Anemarrhenae after oral administration to rats by HPLC-Q-TOF/MS and HPLC-MS/MS

Publicado en línea: 03 Apr 2021
Páginas: 567 - 585

Resumen

Abstract

Rhizoma Anemarrhenae is a well-known herbal medicine with saponins as its commonly regarded major bioactive components. It is essential to classify the properties of saponins which are associated with their toxicity and efficacy. In this study, 25 compounds were identified by HPLC-Q-TOF/MS in the extract of Rhizoma Anemarrhenae and 8 saponins were detected in rat plasma by HPLC-MS/MS after oral administration of this extract. These were neomangiferin, mangiferin, timosaponin E1, timosaponin E, timosaponin B-II, timosaponin B-III, timosaponin A-III and timosaponin A-I. A sensitive and accurate HPLC-MS/MS method was developed and successfully applied to a pharmacokinetic study of the abovementioned eight saponins after oral administration of the Rhizoma Anemarrhenae extract to rats. The method validation, including specificity, linearity, precision, accuracy, recovery, matrix effect and robustness, met the requirements of the intended use. The pharmacokinetic parameter, Tmax value, ranged from 2 to 8 h for these eight saponins whereas their elimination half-life (t1/2) ranged from 4.06 to 9.77 h, indicating slow excretion. The plasma concentrations of these eight saponins were all very low, indicating a relatively low oral bioavailability. All these results provide support for further clinical studies.

Palabras clave

  • saponin
  • identification
  • pharmacokinetics
  • HPLC-Q-TOF/MS
  • HPLC-MS/MS
Acceso abierto

Upregulation of p53 by tannic acid treatment suppresses the proliferation of human colorectal carcinoma

Publicado en línea: 03 Apr 2021
Páginas: 587 - 602

Resumen

Abstract

The present study’s objective is to clarify the molecular mechanisms of tannic acid effects on the viability of human colorectal carcinoma (CRC). Tannic acid is stable for up to 48 h and is localized in both cytoplasm and nucleus. It dose-dependently inhibited the viability of CRC cell lines; SW-620 and HT-29 with IC50 values of 7.2 ± 0.8 and 37.6 ± 1.4 µmol L–1. Besides, metastatic, invasive, and colony formation properties of CRC cells were significantly inhibited following the tannic acid treatment (p < 0.001). Tannic acid has been found to modulate enzyme, protein, and gene expressions of NQO1 in different levels and the upregulation of protein/gene expressions of p53 (p < 0.001), which leads the cells to trigger apoptosis. In conclusion, the present in vitro study may supply a significant background for in vivo studies in which the molecular mechanisms of antioxidant and chemopreventive activities of tannic acid will completely clarify.

Palabras clave

  • tannic acid
  • colorectal carcinoma
  • wound healing
  • cell viability
  • NQO1
  • p53
Acceso abierto

Antioxidant and antihyperglycemic activities of Scorzonera cinerea radical leaves in streptozocin-induced diabetic rats

Publicado en línea: 03 Apr 2021
Páginas: 603 - 617

Resumen

Abstract

Scorzonera species are used for treating various diseases. They are consumed raw, especially in the spring, and have nutritious and dietetic values. This study evaluated the antidiabetic and antioxidant effects of ethanolic extracts of Scorzonera cinerea (Sc) radical leaves in diabetes mellitus. Five random groups of Wistar rats (n = 8) were created – control, diabetic, acarbose, Sc-Dried, and Sc-Frozen. Phenolic profiles of extracts were determined by HPLC. Free radical scavenging capacity was measured using DPPH and ABTS tests. The inhibitory effects of Sc extracts on α-glucosidase and α-amylase activities were also evaluated. Moreover, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities, glutathione (GSH) concentration, malondialdehyde (MDA), total antioxidant status (TAS) and total oxidant status (TOS) were analyzed in the liver tissues. While dried Scorzonera extract was more effective in α-amylase inhibitory activity, frozen Scorzonera extract was more effective in α-glucosidase inhibitory activity. Sc-Dried and Sc-Frozen extracts lowered blood glucose and HbA1c levels, they also increased insulin. Although liver MDA and TOS were significantly increased in the diabetic group, their values were significantly lower in the Sc-Dried- and Sc-Frozen-treated groups. GSH, TAS, and anti-oxidant enzyme activities decreased in the diabetic group, but Sc-Dried and Sc-Frozen supplements significantly enhanced liver antioxidant values. In conclusion, S. cinerea treatment exerts potential hypoglycemic and antioxidant effects in diabetes. Thus, it can be considered as a candidate dietary supplement for health benefits in diabetes.

Palabras clave

  • radical leaves
  • ethanolic extract
  • antidiabetic
  • antioxidant
  • α-glucosidase
Acceso abierto

Determination of penicillamine, tiopronin and glutathione in pharmaceutical formulations by kinetic spectrophotometry

Publicado en línea: 03 Apr 2021
Páginas: 619 - 630

Resumen

Abstract

A novel and simple method for the determination of penicillamine (PEN), tiopronin (mercaptopropionyl glycine, MPG) and glutathione (GSH) in pharmaceutical formulations by kinetic spectrophotometry has been developed and validated. It is based on the redox reaction where the thiol compound (RSH) reduces CuII-neocuproine complex to CuI-neocuproine complex. The non-steady state signal of the formed CuI- neocuproine complex is measured at 458 nm. The initial rate and fixed time (at 1 min) methods were validated. The calibration graph was linear in the concentration range from 8.0 × 10‒7 to 8.0 × 10‒5 mol L−1 for the initial rate method and from 6.0 × 10‒7 to 6.0 × 10−5 mol L−1 for the fixed time method, with the detection limits of 2.4 × 10−7 and 1.4 × 10‒7 mol L−1, resp. Levels of PEN, MPG and GSH in pharmaceutical formulations were successfully assayed by both methods. The advantages of the presented methods include sensitivity, short analysis time, ease of application and low cost.

Palabras clave

  • penicillamine
  • tiopronin
  • glutathione
  • kinetic spectrophotometry
  • pharmaceutical formulations
Acceso abierto

Piperazine sulfonamides as DPP-IV inhibitors: Synthesis, induced-fit docking and in vitro biological evaluation

Publicado en línea: 03 Apr 2021
Páginas: 631 - 643

Resumen

Abstract

Diabetes mellitus is a chronic illness that needs persistent medical attention and continuous patient self-management to avoid acute complications. Dipeptidyl peptidase-IV (DPP-IV) inhibitors minimize glucagon and blood glucose levels by increasing the incretin levels, glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic poly-peptide (GIP), leading to insulin secretion from pancreatic beta cells. In the present study, nine 1,4-bis(phenylsulfonyl) piperazine derivatives 1a-i were synthesized and identified using 1H NMR, 13C NMR, MS and IR spectroscopies. These compounds were tested in vitro and showed inhibitory activity ranging from 11.2 to 22.6 % at 100 µmol L–1 concentration. Piperazine sulfonamide derivatives were found to be promising DPP-IV inhibitors, where the presence of electron-withdrawing groups such as Cl (1a-c) improved the activity of the compounds more than electron-donating groups such as CH3 (1d-f) at the same position. Additionally, meta-substitution is disfavored (1b, 1e, 1g). Induced-fit docking studies suggested that the targeted compounds 1a-i occupy the binding domain of DPP-IV and form H-bonding with the backbones of R125, E205, E206, F357, K554, W629, Y631, Y662 and R669.

Palabras clave

  • piperazine sulfonamide
  • dipeptidyl peptidase-IV inhibitor
  • diabetes mellitus
  • induced-fit docking
Acceso abierto

Anticancer effects of 7,8-dihydromethysticin in human leukemia cells are mediated via cell-cycle dysregulation, inhibition of cell migration and invasion and targeting JAK/STAT pathway

Publicado en línea: 03 Apr 2021
Páginas: 645 - 655

Resumen

Abstract

The main focus of this research work was to study the anti-cancer properties of 7,8-dihydromethysticin against HL-60 leukemia cells. Investigations were also performed to check its impact on the phases of the cell cycle, cell migration and invasion, JAK/STAT signalling pathway and intracellular mitochondrial membrane potential (MMP) and reactive oxygen species (ROS). Cell proliferation was assessed through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and effects on colony formation were examined via clonogenic assay. Flow cytometry and Western blott analysis were performed to investigate the distribution of cell cycle phases. Flow cytometric analysis was performed for the examination of MMP and ROS production. The effect on JAK/STAT signalling pathway was examined through Western blot analysis. Results depicted that 7,8-dihydromethysticin induced concentration- as well as time-dependent inhibition of cell proliferation in leukemia HL-60 cells. Clonogenic assay indicated potential suppression in leukemia HL-60 cell colonies. The 7,8-dihydromethysticin molecule also caused cell cycle arrest at G2/M-phase along with concentration-dependent inhibition of cyclin B1, D1 and E. ROS and MMP measurements indicated significant ROS enhancement and MMP suppression with increasing 7,8-dihydromethysticin concentrations. Additionally, 7,8-dihydromethysticin led to remarkable dose-reliant inhibition of cell invasion as well as cell migration. Therefore, 7,8-dihydromethysticin should be considered a valuable candidate for leukemia research and chemoprevention.

Palabras clave

  • leukemia
  • 7
  • 8-dihydromethysticin
  • flow cytometry
  • cell cycle
  • signalling pathway
Acceso abierto

Propolis – quality analysis and use in topical formulations

Publicado en línea: 03 Apr 2021
Páginas: 657 - 667

Resumen

Abstract

The aim of this study was to produce propolis extracts, assess their quality and effect on skin cells and determine the penetration of active ingredients from designed semi-solid topical formulations. The use of higher-concentration ethanol and a larger amount of raw material allows extracting a larger quantity of active ingredients from raw propolis. Ultrasound extraction is an effective method for the production of aqueous extracts of propolis. The results show that depending on concentration, propolis extracts reduce the viability of keratinocytes. The phenolic compounds under observation penetrated the epidermis and dermis from designed formulations. The base of semi-solid formulation influences the efficacy of propolis preparations. The overall quantity of phenolic compounds that penetrated the skin was around 2 % from the ointment and 1.5 % from the cream.

Palabras clave

  • phenolic compounds
  • propolis extracts
  • skin penetration
  • cell viability
Acceso abierto

Pinocembrin flavanone inhibits cell viability in PC-3 human prostate cancer by inducing cellular apoptosis, ROS production and cell cycle arrest

Publicado en línea: 03 Apr 2021
Páginas: 669 - 678

Resumen

Abstract

The main purpose of the present study was to evaluate the antitumor effects of pinocembrin in human prostate cancer cells (PC-3) along with investigating its effects on cell apoptosis, endogenous ROS production and cell cycle. MTT assay and clonogenic assays were used to study the effects on cell viability and cancer colony formation, respectively. Fluorescence microscopy along with Western blotting was used to study apoptotic effects induced by pinocembrin. Flow cytometry was used to study effects on ROS production and cell cycle phase distribution. Results indicated that pinocembrin promoted inhibition cell proliferation along with reducing cancer colony formation of PC-3 cells in a dose-dependent manner. Pinocembrin induced regulatory effects over expressions of caspase-3, caspase-9, Bax and Bcl-2, thereby promoting apoptotic cell death in PC-3 cells. It also led to the dose-dependent G0/G1 cell cycle arrest. In conclusion, pinocembrin exhibits strong anticancer effects in human prostate cancer cells mediated via apoptosis, endogenous ROS production and G0/G1 cell cycle arrest.

Palabras clave

  • prostate cancer
  • flavones
  • pinocembrin
  • apoptosis
  • cell cycle arrest
Acceso abierto

Pharmacokinetics study of a supersaturatable self-microemulsifying drug delivery system for ellagic acid by UHPLC-Q-TOF-MS

Publicado en línea: 03 Apr 2021
Páginas: 679 - 687

Resumen

Abstract

To evaluate the bioavailability of ellagic acid loaded super-saturatable self-microemulsifying drug delivery system (S-SMEDDS), its pharmacokinetic properties were studied in rats with an ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. The plasma samples were treated by solid-phase extraction method, and gallic acid was used as the internal standard when determining the concentration of ellagic acid. Results showed that the established analytical method was sensitive and accurate, which is applicable to the pharmacokinetic study of ellagic acid. The drug was found to be absorbed rapidly in vivo, and the plasma concentration-time curve showed double peaks, indicating that ellagic acid were reabsorbed by entero-hepatic circulation after oral administration. Compared with ellagic acid suspension, the apparent clearance of ellagic acid-loaded S-SMEDDS and SMEDDS reduced significantly, and the AUC0~t of them were 4.7 and 5.8-fold increase, respectively. Therefore, the bioavailability of ellagic acid-loaded S-SMEDDS was higher than that of the suspension and SMEDDS.

Palabras clave

  • ellagic acid
  • supersaturatable self-microemulsion
  • pharmacokinetics
  • UHPLC-Q-TOF-MS
12 Artículos
Acceso abierto

Quality-by-design in pharmaceutical development: From current perspectives to practical applications

Publicado en línea: 03 Apr 2021
Páginas: 497 - 526

Resumen

Abstract

Current pharmaceutical research directions tend to follow a systematic approach in the field of applied research and development. The concept of quality-by-design (QbD) has been the focus of the current progress of pharmaceutical sciences. It is based on, but not limited, to risk assessment, design of experiments and other computational methods and process analytical technology. These tools offer a well-organized methodology, both to identify and analyse the hazards that should be handled as critical, and are therefore applicable in the control strategy. Once implemented, the QbD approach will augment the comprehension of experts concerning the developed analytical technique or manufacturing process. The main activities are oriented towards the identification of the quality target product profiles, along with the critical quality attributes, the risk management of these and their analysis through in silico aided methods. This review aims to offer an overview of the current standpoints and general applications of QbD methods in pharmaceutical development.

Palabras clave

  • quality-by-design
  • pharmaceutical development
  • risk assessment
  • software-aided development
Acceso abierto

Recent advancements to enhance the therapeutic efficacy of antiepileptic drugs

Publicado en línea: 03 Apr 2021
Páginas: 527 - 544

Resumen

Abstract

Epilepsy is a multifactorial neurological disorder characterized by recurrent or unprovoked seizures. Over the past two decades, many new antiepileptic drugs (AEDs) were developed and are in use for the treatment of epilepsy. However, drug resistance, drug-drug interaction and adverse events are common problems associated with AEDs. Antiepileptic drugs must be used only if the ratio of efficacy, safety, and tolerability of treatment are favorable and outweigh the disadvantages including treatment costs. The application of novel drug delivery techniques could enhance the efficacy and reduce the toxicity of AEDs. These novel techniques aim to deliver an optimal concentration of the drug more specifically to the seizure focus or foci in the CNS without numerous side-effects. The purpose of this article is to review the recent advancements in antiepileptic treatment and summarize the novel modalities in the route of administration and drug delivery, including gene therapy, for effective treatment of epilepsy.

Palabras clave

  • antiepileptic drugs
  • drug delivery
  • epilepsy
  • gene therapy
  • liposomes
  • nanoparticles
Acceso abierto

New derivatives of sulfonylhydrazone as potential antitumor agents: Design, synthesis and cheminformatics evaluation

Publicado en línea: 03 Apr 2021
Páginas: 545 - 565

Resumen

Abstract

Phosphoinositide 3-kinase α (PI3Kα) is a propitious target for designing anticancer drugs. A series of new N’-(diphenylmethylene)benzenesulfonohydrazide was synthesized and characterized using FT-IR, NMR (1H and 13C), HRMS, and elemental analysis. Target compounds exhibited an antiproliferative effect against the human colon carcinoma (HCT-116) cell line. Our cheminformatics analysis indicated that the para-tailored derivatives [p-NO2 (3) and p-CF3 (7)] have better ionization potentials based on calculated Moran autocorrelations and ionization potentials. Subsequent in vitro cell proliferation assays validated our cheminformatics results by providing experimental evidence that both derivatives 3 and 7 exhibited improved antiproliferative activities against HCT-116. Hence, our results emphasized the importance of electron-withdrawing groups and hydrogen bond-acceptors in the rational design of small-molecule chemical ligands targeting PI3Kα. These results agreed with the induced-fit docking against PI3Kα, highlighting the role of p-substituted aromatic rings in guiding the ligand-PI3Kα complex formation, by targeting a hydrophobic pocket in the ligand-binding site and forming π-stacking interactions with a nearby tryptophan residue.

Palabras clave

  • sulfonylhydrazones
  • antitumor
  • HCT-116
  • PI3Kα-inhibitors
  • cheminformatics
  • docking
Acceso abierto

Identification and pharmacokinetics of saponins in Rhizoma Anemarrhenae after oral administration to rats by HPLC-Q-TOF/MS and HPLC-MS/MS

Publicado en línea: 03 Apr 2021
Páginas: 567 - 585

Resumen

Abstract

Rhizoma Anemarrhenae is a well-known herbal medicine with saponins as its commonly regarded major bioactive components. It is essential to classify the properties of saponins which are associated with their toxicity and efficacy. In this study, 25 compounds were identified by HPLC-Q-TOF/MS in the extract of Rhizoma Anemarrhenae and 8 saponins were detected in rat plasma by HPLC-MS/MS after oral administration of this extract. These were neomangiferin, mangiferin, timosaponin E1, timosaponin E, timosaponin B-II, timosaponin B-III, timosaponin A-III and timosaponin A-I. A sensitive and accurate HPLC-MS/MS method was developed and successfully applied to a pharmacokinetic study of the abovementioned eight saponins after oral administration of the Rhizoma Anemarrhenae extract to rats. The method validation, including specificity, linearity, precision, accuracy, recovery, matrix effect and robustness, met the requirements of the intended use. The pharmacokinetic parameter, Tmax value, ranged from 2 to 8 h for these eight saponins whereas their elimination half-life (t1/2) ranged from 4.06 to 9.77 h, indicating slow excretion. The plasma concentrations of these eight saponins were all very low, indicating a relatively low oral bioavailability. All these results provide support for further clinical studies.

Palabras clave

  • saponin
  • identification
  • pharmacokinetics
  • HPLC-Q-TOF/MS
  • HPLC-MS/MS
Acceso abierto

Upregulation of p53 by tannic acid treatment suppresses the proliferation of human colorectal carcinoma

Publicado en línea: 03 Apr 2021
Páginas: 587 - 602

Resumen

Abstract

The present study’s objective is to clarify the molecular mechanisms of tannic acid effects on the viability of human colorectal carcinoma (CRC). Tannic acid is stable for up to 48 h and is localized in both cytoplasm and nucleus. It dose-dependently inhibited the viability of CRC cell lines; SW-620 and HT-29 with IC50 values of 7.2 ± 0.8 and 37.6 ± 1.4 µmol L–1. Besides, metastatic, invasive, and colony formation properties of CRC cells were significantly inhibited following the tannic acid treatment (p < 0.001). Tannic acid has been found to modulate enzyme, protein, and gene expressions of NQO1 in different levels and the upregulation of protein/gene expressions of p53 (p < 0.001), which leads the cells to trigger apoptosis. In conclusion, the present in vitro study may supply a significant background for in vivo studies in which the molecular mechanisms of antioxidant and chemopreventive activities of tannic acid will completely clarify.

Palabras clave

  • tannic acid
  • colorectal carcinoma
  • wound healing
  • cell viability
  • NQO1
  • p53
Acceso abierto

Antioxidant and antihyperglycemic activities of Scorzonera cinerea radical leaves in streptozocin-induced diabetic rats

Publicado en línea: 03 Apr 2021
Páginas: 603 - 617

Resumen

Abstract

Scorzonera species are used for treating various diseases. They are consumed raw, especially in the spring, and have nutritious and dietetic values. This study evaluated the antidiabetic and antioxidant effects of ethanolic extracts of Scorzonera cinerea (Sc) radical leaves in diabetes mellitus. Five random groups of Wistar rats (n = 8) were created – control, diabetic, acarbose, Sc-Dried, and Sc-Frozen. Phenolic profiles of extracts were determined by HPLC. Free radical scavenging capacity was measured using DPPH and ABTS tests. The inhibitory effects of Sc extracts on α-glucosidase and α-amylase activities were also evaluated. Moreover, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities, glutathione (GSH) concentration, malondialdehyde (MDA), total antioxidant status (TAS) and total oxidant status (TOS) were analyzed in the liver tissues. While dried Scorzonera extract was more effective in α-amylase inhibitory activity, frozen Scorzonera extract was more effective in α-glucosidase inhibitory activity. Sc-Dried and Sc-Frozen extracts lowered blood glucose and HbA1c levels, they also increased insulin. Although liver MDA and TOS were significantly increased in the diabetic group, their values were significantly lower in the Sc-Dried- and Sc-Frozen-treated groups. GSH, TAS, and anti-oxidant enzyme activities decreased in the diabetic group, but Sc-Dried and Sc-Frozen supplements significantly enhanced liver antioxidant values. In conclusion, S. cinerea treatment exerts potential hypoglycemic and antioxidant effects in diabetes. Thus, it can be considered as a candidate dietary supplement for health benefits in diabetes.

Palabras clave

  • radical leaves
  • ethanolic extract
  • antidiabetic
  • antioxidant
  • α-glucosidase
Acceso abierto

Determination of penicillamine, tiopronin and glutathione in pharmaceutical formulations by kinetic spectrophotometry

Publicado en línea: 03 Apr 2021
Páginas: 619 - 630

Resumen

Abstract

A novel and simple method for the determination of penicillamine (PEN), tiopronin (mercaptopropionyl glycine, MPG) and glutathione (GSH) in pharmaceutical formulations by kinetic spectrophotometry has been developed and validated. It is based on the redox reaction where the thiol compound (RSH) reduces CuII-neocuproine complex to CuI-neocuproine complex. The non-steady state signal of the formed CuI- neocuproine complex is measured at 458 nm. The initial rate and fixed time (at 1 min) methods were validated. The calibration graph was linear in the concentration range from 8.0 × 10‒7 to 8.0 × 10‒5 mol L−1 for the initial rate method and from 6.0 × 10‒7 to 6.0 × 10−5 mol L−1 for the fixed time method, with the detection limits of 2.4 × 10−7 and 1.4 × 10‒7 mol L−1, resp. Levels of PEN, MPG and GSH in pharmaceutical formulations were successfully assayed by both methods. The advantages of the presented methods include sensitivity, short analysis time, ease of application and low cost.

Palabras clave

  • penicillamine
  • tiopronin
  • glutathione
  • kinetic spectrophotometry
  • pharmaceutical formulations
Acceso abierto

Piperazine sulfonamides as DPP-IV inhibitors: Synthesis, induced-fit docking and in vitro biological evaluation

Publicado en línea: 03 Apr 2021
Páginas: 631 - 643

Resumen

Abstract

Diabetes mellitus is a chronic illness that needs persistent medical attention and continuous patient self-management to avoid acute complications. Dipeptidyl peptidase-IV (DPP-IV) inhibitors minimize glucagon and blood glucose levels by increasing the incretin levels, glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic poly-peptide (GIP), leading to insulin secretion from pancreatic beta cells. In the present study, nine 1,4-bis(phenylsulfonyl) piperazine derivatives 1a-i were synthesized and identified using 1H NMR, 13C NMR, MS and IR spectroscopies. These compounds were tested in vitro and showed inhibitory activity ranging from 11.2 to 22.6 % at 100 µmol L–1 concentration. Piperazine sulfonamide derivatives were found to be promising DPP-IV inhibitors, where the presence of electron-withdrawing groups such as Cl (1a-c) improved the activity of the compounds more than electron-donating groups such as CH3 (1d-f) at the same position. Additionally, meta-substitution is disfavored (1b, 1e, 1g). Induced-fit docking studies suggested that the targeted compounds 1a-i occupy the binding domain of DPP-IV and form H-bonding with the backbones of R125, E205, E206, F357, K554, W629, Y631, Y662 and R669.

Palabras clave

  • piperazine sulfonamide
  • dipeptidyl peptidase-IV inhibitor
  • diabetes mellitus
  • induced-fit docking
Acceso abierto

Anticancer effects of 7,8-dihydromethysticin in human leukemia cells are mediated via cell-cycle dysregulation, inhibition of cell migration and invasion and targeting JAK/STAT pathway

Publicado en línea: 03 Apr 2021
Páginas: 645 - 655

Resumen

Abstract

The main focus of this research work was to study the anti-cancer properties of 7,8-dihydromethysticin against HL-60 leukemia cells. Investigations were also performed to check its impact on the phases of the cell cycle, cell migration and invasion, JAK/STAT signalling pathway and intracellular mitochondrial membrane potential (MMP) and reactive oxygen species (ROS). Cell proliferation was assessed through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and effects on colony formation were examined via clonogenic assay. Flow cytometry and Western blott analysis were performed to investigate the distribution of cell cycle phases. Flow cytometric analysis was performed for the examination of MMP and ROS production. The effect on JAK/STAT signalling pathway was examined through Western blot analysis. Results depicted that 7,8-dihydromethysticin induced concentration- as well as time-dependent inhibition of cell proliferation in leukemia HL-60 cells. Clonogenic assay indicated potential suppression in leukemia HL-60 cell colonies. The 7,8-dihydromethysticin molecule also caused cell cycle arrest at G2/M-phase along with concentration-dependent inhibition of cyclin B1, D1 and E. ROS and MMP measurements indicated significant ROS enhancement and MMP suppression with increasing 7,8-dihydromethysticin concentrations. Additionally, 7,8-dihydromethysticin led to remarkable dose-reliant inhibition of cell invasion as well as cell migration. Therefore, 7,8-dihydromethysticin should be considered a valuable candidate for leukemia research and chemoprevention.

Palabras clave

  • leukemia
  • 7
  • 8-dihydromethysticin
  • flow cytometry
  • cell cycle
  • signalling pathway
Acceso abierto

Propolis – quality analysis and use in topical formulations

Publicado en línea: 03 Apr 2021
Páginas: 657 - 667

Resumen

Abstract

The aim of this study was to produce propolis extracts, assess their quality and effect on skin cells and determine the penetration of active ingredients from designed semi-solid topical formulations. The use of higher-concentration ethanol and a larger amount of raw material allows extracting a larger quantity of active ingredients from raw propolis. Ultrasound extraction is an effective method for the production of aqueous extracts of propolis. The results show that depending on concentration, propolis extracts reduce the viability of keratinocytes. The phenolic compounds under observation penetrated the epidermis and dermis from designed formulations. The base of semi-solid formulation influences the efficacy of propolis preparations. The overall quantity of phenolic compounds that penetrated the skin was around 2 % from the ointment and 1.5 % from the cream.

Palabras clave

  • phenolic compounds
  • propolis extracts
  • skin penetration
  • cell viability
Acceso abierto

Pinocembrin flavanone inhibits cell viability in PC-3 human prostate cancer by inducing cellular apoptosis, ROS production and cell cycle arrest

Publicado en línea: 03 Apr 2021
Páginas: 669 - 678

Resumen

Abstract

The main purpose of the present study was to evaluate the antitumor effects of pinocembrin in human prostate cancer cells (PC-3) along with investigating its effects on cell apoptosis, endogenous ROS production and cell cycle. MTT assay and clonogenic assays were used to study the effects on cell viability and cancer colony formation, respectively. Fluorescence microscopy along with Western blotting was used to study apoptotic effects induced by pinocembrin. Flow cytometry was used to study effects on ROS production and cell cycle phase distribution. Results indicated that pinocembrin promoted inhibition cell proliferation along with reducing cancer colony formation of PC-3 cells in a dose-dependent manner. Pinocembrin induced regulatory effects over expressions of caspase-3, caspase-9, Bax and Bcl-2, thereby promoting apoptotic cell death in PC-3 cells. It also led to the dose-dependent G0/G1 cell cycle arrest. In conclusion, pinocembrin exhibits strong anticancer effects in human prostate cancer cells mediated via apoptosis, endogenous ROS production and G0/G1 cell cycle arrest.

Palabras clave

  • prostate cancer
  • flavones
  • pinocembrin
  • apoptosis
  • cell cycle arrest
Acceso abierto

Pharmacokinetics study of a supersaturatable self-microemulsifying drug delivery system for ellagic acid by UHPLC-Q-TOF-MS

Publicado en línea: 03 Apr 2021
Páginas: 679 - 687

Resumen

Abstract

To evaluate the bioavailability of ellagic acid loaded super-saturatable self-microemulsifying drug delivery system (S-SMEDDS), its pharmacokinetic properties were studied in rats with an ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. The plasma samples were treated by solid-phase extraction method, and gallic acid was used as the internal standard when determining the concentration of ellagic acid. Results showed that the established analytical method was sensitive and accurate, which is applicable to the pharmacokinetic study of ellagic acid. The drug was found to be absorbed rapidly in vivo, and the plasma concentration-time curve showed double peaks, indicating that ellagic acid were reabsorbed by entero-hepatic circulation after oral administration. Compared with ellagic acid suspension, the apparent clearance of ellagic acid-loaded S-SMEDDS and SMEDDS reduced significantly, and the AUC0~t of them were 4.7 and 5.8-fold increase, respectively. Therefore, the bioavailability of ellagic acid-loaded S-SMEDDS was higher than that of the suspension and SMEDDS.

Palabras clave

  • ellagic acid
  • supersaturatable self-microemulsion
  • pharmacokinetics
  • UHPLC-Q-TOF-MS

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