The Journal of Croatian Pharmaceutical Society

Acta Pharmaceutica

Acta Pharmaceutica ONL

<abstract><title style='display:none'>Abstract</title>Substances available in nature with potential therapeutic effects are the subject of research that raises tremendous hopes for new challenges in medicine. Fungi are the most common organisms in the ecosystem and the most interesting in this respect. This review discusses two species of edible fungi, used for centuries in Eastern natural medicine, with the best-documented effect – <italic>Hericium erinaceus</italic> (He) and <italic>Trametes versicolor</italic> (Tv). The results of <italic>in vivo</italic> and <italic>in vitro</italic> studies conducted on mice and human cell lines demonstrate immunomodulatory, potentially, anticancer, anti-inflammatory and neuroregenerative effects of substances isolated from these fungi. The substances contained in the extracts of He and Tv seem to have immunomodulatory effects that may support chemotherapy. The use of these extracts is justified stronger than the other supportive treat ments based on supplements.</abstract>

Abstract

Department of Internal Medicine and Oncological Chemotherapy

Keywords

<article-title>The use of <italic>Hericium erinaceus</italic> and <italic>Trametes versicolor</italic> extracts in supportive treatment in oncology</article-title>

The use of  and  extracts in supportive treatment in oncology

<abstract><title style='display:none'>Abstract</title>Effects of paraben toxicity, <italic>i.e.</italic>, endocrine-disruption properties, are in the focus of researchers for decades, but still – they are a hot subject of debate. Parabens are aliphatic esters of <italic>p</italic>-hydroxybenzoic acid, which are widely used as antimicrobial agents for the preservation of cosmetics, pharmaceuticals and foods. Mostly used parabens are methyl-, ethyl-, propyl- and butylparaben. Although the toxicity of parabens is reported in animals and in <italic>in vitro</italic> studies, it cannot be taken for granted when discussing hazards for human health due to an unrealistic exposure -safety profile. Many studies have demonstrated that parabens are non-teratogenic, non-mutagenic, non-carcinogenic and the real evidence for their toxicity in humans has not been established. For now, methyl-, ethyl- and propylparaben are considered safe for use in cosmetics and pharmaceuticals within the recommended range of doses. Regarding alternatives for parabens, a variety of approaches have been proposed, but every substitute would need to be tested rigorously for toxicity and safety.</abstract>

University of Zagreb Faculty of Pharmacy and Biochemistry

<article-title>The controversies of parabens – an overview nowadays</article-title>

The controversies of parabens – an overview nowadays

{"article-title":"The controversies of parabens \u2013 an overview nowadays"}

<abstract><title style='display:none'>Abstract</title>Interleukin-2 (IL-2) is involved in the activation and differentiation of T-helper cells. Uncontrolled activated T cells play a key role in the pathophysiology by stimulating inflammation and autoimmune diseases like arthritis, psoriasis and Crohn’s disease. T cells activation can be suppressed either by preventing IL-2 production or blocking the IL-2 interaction with its receptor. Hence, IL-2 is now emerging as a target for novel therapeutic approaches in several autoimmune disorders. This study was carried out to set up an effective virtual screening (VS) pipeline for IL-2. Four docking/scoring approaches (FRED, MOE, GOLD and Surflex-Dock) were compared in the re-docking process to test their performance in producing correct binding modes of IL-2 inhibitors. Surflex-Dock and FRED were the best in predicting the native pose in its top-ranking position. Shapegauss and CGO scoring functions identified the known inhibitors of IL-2 in top 1, 5 and 10 % of library and differentiated binders from non-binders efficiently with average <italic>AUC</italic> of &gt; 0.9 and &gt; 0.7, resp. The applied docking protocol served as a basis for the VS of a large database that will lead to the identification of more active compounds against IL-2.</abstract>

Dr. Panjwani Center for Molecular Medicine and Drug Research International Center for Chemical and Biological Sciences

<article-title><italic>In silico</italic> data mining of large-scale databases for the virtual screening of human interleukin-2 inhibitors</article-title>

 data mining of large-scale databases for the virtual screening of human interleukin-2 inhibitors

<abstract><title style='display:none'>Abstract</title>The objective of the present study was to develop a robust, simple, economical and sensitive HPLC-UV method using the “quality-by-design” approach for the estimation of irinotecan (IRI) in marketed formulations. RP-HPLC method was developed by applying Box-Behnken design with Hyper-Clone (Phenomenex®) C18 column (250 × 4.6 mm id, particle size 5 µm, ODS 130 Å) as a stationary phase. Acetonitrile and 20 mmol L−1 potassium phosphate buffer (pH 2.5) containing 0.1 % triethylamine in a ratio of 45:55 % (<italic>V/V</italic>) was used as a mobile phase. The sample was injected in a volume of 20 µL into the HPLC system. UV detector at 254 nm was used to estimate and quantify IRI. Isocratic elution was opted while the flow rate was maintained at 0.75 mL min−1. The retention time of IRI was found to be 4.09 min. The responses were found to be linear for concentration range of 0.5 to 18.0 µg mL−1 and the coefficient of determination value was found to be 0.9993. Percent relative standard deviation for intra- and inter-day precisions was found in the range of 0.1 to 0.4 %. <italic>LOD</italic> and <italic>LOQ</italic> values were found to be 4.87 and 14.75 ng mL−1, resp. Robustness studies confirmed that the developed method is robust with RSD of a maximum 0.1 %. The method is simple, precise, sensitive, robust and economical making it applicable to the estimation of IRI in an injectable formulation.</abstract>

Department of Pharmaceutics Manipal College of Pharmaceutical Sciences

<article-title>An analytical “quality by design” approach in RP-HPLC method development and validation for reliable and rapid estimation of irinotecan in an injectable formulation</article-title>

An analytical “quality by design” approach in RP-HPLC method development and validation for reliable and rapid estimation of irinotecan in an injectable formulation

<abstract><title style='display:none'>Abstract</title>This study explores the use of a statistical model to build a design space for freeze-drying two formulations with ibuprofen. A 2 × 3 factorial experimental design was used to evaluate independent variables (filling volume and annealing time) and responses as residual moisture content, specific surface area and reconstitution time. A statistical model and response surface plots were generated to define the interactions among the selected variables. The models constructed for both formulations suggest that 1 mL of filled volume and no annealing should be used to achieve optimal residual moisture content, specific surface area and reconstitution time. The proposed models were validated with additional experiments, in which the responses observed were mainly in close agreement with the predicted ones. Additionally, the established models demonstrate the reliability of the evaluation procedure in predicting the selected responses.</abstract>

<article-title>Investigation of design space for freeze-drying injectable ibuprofen using response surface methodology</article-title>

Investigation of design space for freeze-drying injectable ibuprofen using response surface methodology

<abstract><title style='display:none'>Abstract</title>Eplerenone is a drug that protects the cardiovascular system. 11α-Hydroxycanrenone is a key intermediate in eplerenone synthesis. We found that although the cytochrome P450 (CYP) enzyme system in <italic>Aspergillus ochraceus</italic> strain MF018 could catalyse the conversion of canrenone to 11α-hydroxycanrenone, its biocatalytic efficiency is low. To improve the efficiency of 11α-hydroxycanrenone production, the CYP monooxygenase-coding gene of MF018 was predicted and cloned based on whole-genome sequencing results. A recombinant <italic>A. ochraceus</italic> strain MF010 with the high expression of CYP monooxygenase was then obtained through homologous recombination. The biocatalytic rate of this recombinant strain reached 93 % at 60 h without the addition of organic solvents or surfactants and was 17–18 % higher than that of the MF018 strain. Moreover, the biocatalytic time of the MF010 strain was reduced by more than 30 h compared with that of the MF018 strain. These results show that the recombinant <italic>A. ochraceus</italic> strain MF010 can overcome the limitation of substrate biocatalytic efficiency and thus holds a high poten tial for application in the industrial production of eplerenone.</abstract>

Department of Bioengineering Shanghai Institute of Technology

<article-title>Improved 11α-hydroxycanrenone production by modification of cytochrome P450 monooxygenase gene in <italic>Aspergillus ochraceus</italic></article-title>

Improved 11α-hydroxycanrenone production by modification of cytochrome P450 monooxygenase gene in 

<abstract><title style='display:none'>Abstract</title>The glyoxalase system, particularly glyoxalase-I (GLO-I), has been approved as a potential target for cancer treatment. In this study, a set of structurally diverse polyphenolic natural compounds were investigated as potential GLO-I inhibitors. Ellagic acid was found, computationally and experimentally, to be the most potent GLO-I inhibitor among the tested compounds which showed an <italic>IC</italic>50 of 0.71 mmol L−1. Its binding to the GLO-I active site seemed to be mainly driven by ionic interaction <italic>via</italic> its ionized hydroxyl groups with the central Zn ion and Lys156, along with other numerous hydrogen bonding and hydrophobic interactions. Due to its unique and rigid skeleton, it can be utilized to search for other novel and potent GLO-I inhibitors <italic>via</italic> computational approaches such as pharmacophore modeling and similarity search methods. Moreover, an inspection of the docked poses of the tested compounds showed that chlorogenic acid and dihydrocaffeic acid could be considered as lead compounds worthy of further optimization.</abstract>

Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy

Jordan University of Science and Technology

Department of Pharmaceutical Technology, Faculty of Pharmacy

<article-title>Ellagic acid: A potent glyoxalase-I inhibitor with a unique scaffold</article-title>

Ellagic acid: A potent glyoxalase-I inhibitor with a unique scaffold

{"article-title":"Ellagic acid: A potent glyoxalase-I inhibitor with a unique scaffold"}

<abstract><title style='display:none'>Abstract</title>This study investigates antioxidant capacity and protective effects of phenolic compounds oleuropein (OLP) and hydroxytyrosol (HT), present in olive oil and olive leaves, against H2O2-induced DNA damage in human peripheral lymphocytes. Antioxidant potency was determined using the measurement of radical-scavenging activity (ABTS∙+ assay), ferric reducing power (FRAP assay) and cupric reducing antioxidant capacity (CUPRAC assay). Both substances were found to be potent antioxidant agents due to their free radical-scavenging activities. Antigenotoxic effects of oleuropein and hydroxytyrosol against H2O2-induced damage in human lymphocytes were evaluated <italic>in vitro</italic> by alkaline comet assay. At tested concentrations (1, 5, 10 µmol L−1), oleuropein and hydroxytyrosol did not induce a significant increase of primary DNA damage in comparison with the negative control. Pretreatment of human lymphocytes with each of the substances for 120 min produced a dose-dependent reduction of primary DNA damage in the tested cell type. Hydroxytyrosol showed a better protective effect against H2O2-induced DNA breaks than oleuropein which could be associated with their free radical-scavenging efficacy.</abstract>

Institute for Medical Research and Occupational Health

Faculty of Pharmacy and Biochemistry Department of Pharmaceutical Analysis

Faculty of Pharmacy and Biochemistry Department of Microbiology

<article-title>Protective effects of olive oil phenolics oleuropein and hydroxytyrosol against hydrogen peroxide-induced DNA damage in human peripheral lymphocytes</article-title>

Protective effects of olive oil phenolics oleuropein and hydroxytyrosol against hydrogen peroxide-induced DNA damage in human peripheral lymphocytes

<abstract><title style='display:none'>Abstract</title>The influence of different chromatographic conditions and the process of spot visualization on determining the limit of detection as well as quantification (<italic>LOD</italic> and <italic>LOQ</italic>) of meloxicam by TLC-densitometric technique was estimated. Of all chromatographic conditions tested, the lowest limiting values, thus the best sensitivity, in the NP-TLC system was achieved on silica gel 60F254 and neutral aluminum oxide plates developed with the mobile phase consisting of ethyl acetate/toluene/<italic>n</italic>-butylamine (2:2:1, <italic>V</italic>/<italic>V</italic>/<italic>V</italic>). In the case of the RP-TLC method, a mixture of methanol/water (8:2, <italic>V</italic>/<italic>V</italic>) enabled densitometric detection of meloxicam at the lowest concentration level on RP-8F254 and RP-18F254 plates. Additionally, the smallest <italic>LOD</italic> value of meloxicam ensured crystalline violet and gentian violet as visualization agents on silica gel 60F254 and neutral aluminum oxide 150F254 plates, resp. Comparison of the densitometrically obtained spectra of meloxicam drug and its standard after the use of appropriate visualization agents could be a good and cheap alternative tool for the identification of meloxicam as an active pharmaceutical ingredient.</abstract>

Department of Analytical Chemistry Faculty of Pharmaceutical Sciences in Sosnowiec

Medical University of Silesia in Katowice

<article-title>A cost-effective and sensitive TLC-densitometric identification of meloxicam</article-title>

A cost-effective and sensitive TLC-densitometric identification of meloxicam

{"article-title":"A cost-effective and sensitive TLC-densitometric identification of meloxicam"}

<abstract><title style='display:none'>Abstract</title><italic>Manilkara kauki</italic> L. Dubard is a tropical plant in the genus <italic>Manilkara</italic> of family Sapotaceae. This study investigated the total phenolic and flavonoid contents, and antioxidant and antityrosinase activities in different parts of <italic>M. kauki</italic> (fruits, leaves, seeds, stem barks and woods) and in fractions of stem barks. The total phenolic and flavonoid contents of the methanol and aqueous crude extracts of different parts of <italic>M. kauki</italic> ranged from 10.87 to 176.56 mg GAE (gallic acid equivalents) per gram of crude extract and 14.33 to 821.67 mg QE (quercetin equivalents) per gram of crude extract, resp. Leaves and stem barks exhibited higher total phenolic and flavonoid contents and antioxidant and anti-tyrosinase activities than fruits, seeds and woods. Stem barks were sequentially extracted with <italic>n</italic>-hexane, ethyl acetate, methanol and water and then the fractionated extracts were subjected to antioxidant and antityrosinase activities testing. The ethyl acetate and methanol extracts of stem barks exhibited higher total phenolic and flavonoid contents and antioxidant and antityrosinase activities than the <italic>n</italic>-hexane and aqueous extracts. Moreover, ethyl acetate extract of <italic>M. kauki</italic> stem exhibited the highest antityrosinase activity. It may be a potential source of tyrosinase inhibitors for pharmaceutical and cosmetic applications.</abstract>

Institute of Biotechnology and Genetic Engineering

Molecular Crop Research Unit, Faculty of Science

<article-title><italic>In vitro</italic> antioxidant and antityrosinase activities of <italic>Manilkara kauki</italic></article-title>

 antioxidant and antityrosinase activities of 

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Acta Pharmaceutica ist in den folgenden Services indiziert: <ul> <li> Baidu Scholar </li> <li> CABI (over 50 subsections) </li> <li> Case </li> <li> Chemical Abstracts Service (CAS) - CAplus </li> <li> Chemical Abstracts Service (CAS) - SciFinder </li> <li> CNKI Scholar (China National Knowledge Infrastructure) </li> <li> CNPIEC - cnpLINKer </li> <li> Derwent Drug File </li> <li> Dimensions </li> <li> DOAJ (Directory of Open Access Journals) </li> <li> EBSCO </li> <li> Embase </li> <li> ExLibris </li> <li> Genamics JournalSeek </li> <li> Google Scholar </li> <li> IBIDS (National Institutes of Health) </li> <li> Japan Science and Technology Agency (JST) </li> <li> J-Gate </li> <li> Journal Citation Reports/Science Edition </li> <li> JournalGuide </li> <li> JournalTOCs </li> <li> KESLI-NDSL (Korean National Discovery for Science Leaders) </li> <li> Medline </li> <li> Meta </li> <li> MyScienceWork </li> <li> Naver Academic </li> <li> Naviga (Softweco) </li> <li> ProQuest </li> <li> Publons </li> <li> PubMed </li> <li> PubsHub </li> <li> QOAM (Quality Open Access Market) </li> <li> ReadCube </li> <li> Reaxys </li> <li> Referativnyi Zhurnal (VINITI) </li> <li> SCImago (SJR) </li> <li> SCOPUS </li> <li> Semantic Scholar </li> <li> Sherpa/RoMEO </li> <li> TDNet </li> <li> Ulrich's Periodicals Directory/ulrichsweb </li> <li> WanFang Data </li> <li> Web of Science - Biological Abstracts </li> <li> Web of Science - BIOSIS Previews </li> <li> Web of Science - Science Citation Index Expanded </li> <li> WorldCat (OCLC) </li> <li> X-MOL </li> </ul>

Editor-in-Chief Svjetlana Luterotti, Zagreb, Croatia Croatian Pharmaceutical Society, Zagreb, Croatia Managing Editor Maja Jakševac Mikša, Croatian Pharmaceutical Society, Zagreb, Croatia Editorial Board Karmela Barišiæ (Faculty of Pharmacy and Biochemistry, Zagreb, Croatia) Jelena Filipoviæ-Grèiæ (Faculty of Pharmacy and Biochemistry, Zagreb, Croatia) Mojca Kerec Kos (Faculty of Pharmacy, Ljubljana, Slovenia) Jasmina Lovriæ (Faculty of Pharmacy and Biochemistry, Zagreb, Croatia) Svjetlana Luterotti (Croatian Pharmaceutical Society, Zagreb, Croatia) Željan Maleš (Faculty of Pharmacy and Biochemistry, Zagreb, Croatia) Izidor Sosiè (Faculty of Pharmacy, Ljubljana, Slovenia) Željka Vaniæ (Faculty of Pharmacy and Biochemistry, Zagreb, Croatia) Donatella Verbanac (Faculty of Pharmacy and Biochemistry, Zagreb, Croatia) Branka Zorc (Faculty of Pharmacy and Biochemistry, Zagreb, Croatia) Alenka Zvonar Pobirk ((Faculty of Pharmacy, Ljubljana, Slovenia) Technical Editor Professor Branka Zorc, PhD University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia Contacts Professor Svjetlana Luterotti, PhD Editor-in-Chief Croatian Pharmaceutical Society, Masarykova 2, HR-10000 Zagreb, Croatia e-mail: <A href="mailto:svjetlana.luterotti@gmail.com">svjetlana.luterotti@gmail.com</A>; <A href="mailto:svjetlana.luterotti@pharma.hr">svjetlana.luterotti@pharma.hr</A> Professor Branka Zorc, PhD Technical Editor Faculty of Pharmacy and Biochemistry University of Zagreb, HR-10000 Zagreb, Ante Kovačića 1 e-mail: <A href="mailto:bzorc.AP@farmaceut.org">bzorc.AP@farmaceut.org</A> Maja Jakševac-Mikša, PhD Managing Editor Croatian Pharmaceutical Society, HR-10000 Zagreb, Masarykova 2 phone: +385 1 48 72 849 fax: +385 1 48 72 853 e-mail: <A href="mailto:maja.jaksevac-miksa@zg.t-com.hr">maja.jaksevac-miksa@zg.t-com.hr</A>; <A href="mailto:hfd-fg-ap@zg.t-com.hr">hfd-fg-ap@zg.t-com.hr</A>; <A href="mailto:info@farmaceut.org">info@farmaceut.org</A> Section Editors Professor Karmela Barišić, PhD University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia Professor Mojca Kerec Kos, PhD University of Ljubljana Faculty of Pharmacy, Ljubljana, Slovenia Professor Željka Vanić, PhD University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia Professor Donatella Verbanac, PhD University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia Publisher De Gruyter Poland Bogumiła Zuga 32A Str. 01-811 Warsaw, Poland T: +48 22 701 50 15

Please submit your manuscripts to Acta Pharmaceutica via email to: <A href="mailto:svjetlana.luterotti@gmail.com">svjetlana.luterotti@gmail.com</A> or <A href="mailto:svjetlana.luterotti@pharma.hr">svjetlana.luterotti@pharma.hr</A> PUBLICATION CHARGES Because of the high cost of preparing and publishing articles in Acta Pharmaceutica payment of publication fee is mandatory for all articles accepted for publication. Current charge is 900 € per manuscript (excl. VAT). For more information please visit <A href="https://sciendo-parsed-data-feed.s3.eu-central-1.amazonaws.com/ACPH/Instrucions_for_Authors.pdf">Instructions for Authors</A>. Open Access Statement The journal is an Open Access journal that allows a free unlimited access to all its contents without any restrictions upon publication to all users. <A href="https://sciendo-parsed-data-feed.s3.eu-central-1.amazonaws.com/ACPH/Open_Access_License.doc">Open Access License</A>

Acta Pharmaceutica (AP) is an international, scientific, multidisciplinary journal, devoted to the pharmaceutical and allied sciences, which contains articles predominantly on core biomedical and health subjects. The aim of AP is to increase the impact of pharmaceutical research in academia, industry and laboratories. With a strong emphasis on quality and originality, AP publishes reports from the discovery of a drug up to clinical practice, in the form of preliminary and short communications, original research papers and reviews. Book reviews are published also. AP is a quarterly, single-blind peer-reviewed journal in biomedicine with fully open access and “early bird” platform. All articles are submitted to scrutinized evaluation and fair judgement. AP above all puts scientific honesty and integrity. To reach the highest standards in publication ethics all the parties (authors, editors, reviewers) are required to behave responsibly and ethically. This implies submittance by authors on an exclusive basis, of only their own and new data; novelty and originality are prioritized. Also, secure handling of confidential data by reviewers and editors is a must. AP is indexed in numerous world top international bibliographic bases, like Clarivate Analytics´s Web of Science® Core Collection (SCI-Expanded, JCR/Science Edition, etc.), EMBASE/Excerpta Medica, MEDLINE/PubMed, Scopus/SCImago, and others. According to SCImago JR it is a Q2 journal (pharmaceutical sciences) with a steadily increasing Clarivate JIF value reaching 2.230 in 2020 Topics covered are: <UL> <LI>drug design </LI> <LI>molecular modelling/docking studies </LI> <LI>pharmaceutical chemistry/medicinal chemistry </LI> <LI>drug metabolism </LI> <LI>analytics of drugs </LI> <LI>pharmaceutical technology/formulation studies/nanosystems/cosmetology </LI> <LI>pharmaceutical biotechnology </LI> <LI>pharmaceutics/biopharmacy (including pharmacokinetics) and pharmacodynamics </LI> <LI>drug delivery/disposition and stability </LI> <LI>pharmacognosy and　phytopharmacy </LI> <LI>pharmacology (clinical and animal) </LI> <LI>toxicology </LI> <LI>clinical pharmacy </LI> <LI>pharmacovigilance </LI> <LI>pharmaceutical and clinical biochemistry </LI> <LI>pharmaceutical biology with genetics/pharmacogenomics/cell biology </LI> <LI>pharmacoepidemiology/pharmacoeconomics/social pharmacy </LI> <LI>physical pharmacy </LI> <LI>radiopharmaceuticals </LI> <LI>medicine (including diagnostics and therapy) </LI> <LI>peptide and protein chemistry/protein design </LI></UL> Why subscribe and read <UL> <LI>To get informed on the latest research in pharmaceutical and related sciences. </LI></UL> Why submit <UL> <LI>fair and constructive peer review by the experts in the field, </LI> <LI>editorial help and language revision services, </LI> <LI>articles abstracted by online indexing services, </LI> <LI>listed in WoS MJL by Clarivate. </LI></UL> Archiving Sciendo archives the contents of this journal in <A href="https://www.portico.org/">Portico</A> - digital long-term preservation service of scholarly books, journals and collections. Plagiarism Policy The editorial board is participating in a growing community of <A href="https://www.crossref.org/services/similarity-check/">Similarity Check System's</A> users in order to ensure that the content published is original and trustworthy. Similarity Check is a medium that allows for comprehensive manuscripts screening, aimed to eliminate plagiarism and provide a high standard and quality peer-review process.

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Volume 71 (2021): Issue 1 (March 2021)

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