In Vitro and In Silico of Cholinesterases Inhibition and In Vitro and In Vivo Anti-Melanoma Activity Investigations of Extracts Obtained from Selected <i>Berberis</i> Species

<i>Berberis</i> species have a long history of use in traditional Chinese medicine, Ayurvedic medicine, and Western herbal medicine. The aim of this study was the quantification of the main isoquinoline alkaloids in extracts obtained from various <i>Berberis</i> species by HP...

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Main Authors: Tomasz Tuzimski, Anna Petruczynik, Barbara Kaproń, Tomasz Plech, Anna Makuch-Kocka, Daria Janiszewska, Mateusz Sugajski, Bogusław Buszewski, Małgorzata Szultka-Młyńska
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Language:English
Published: MDPI AG 2024-02-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/29/5/1048
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author Tomasz Tuzimski
Anna Petruczynik
Barbara Kaproń
Tomasz Plech
Anna Makuch-Kocka
Daria Janiszewska
Mateusz Sugajski
Bogusław Buszewski
Małgorzata Szultka-Młyńska
author_facet Tomasz Tuzimski
Anna Petruczynik
Barbara Kaproń
Tomasz Plech
Anna Makuch-Kocka
Daria Janiszewska
Mateusz Sugajski
Bogusław Buszewski
Małgorzata Szultka-Młyńska
author_sort Tomasz Tuzimski
collection DOAJ
description <i>Berberis</i> species have a long history of use in traditional Chinese medicine, Ayurvedic medicine, and Western herbal medicine. The aim of this study was the quantification of the main isoquinoline alkaloids in extracts obtained from various <i>Berberis</i> species by HPLC, in vitro and in silico determination of anti-cholinesterase activity, and in vitro and in vivo investigations of the cytotoxic activity of the investigated plant extracts and alkaloid standards. In particular, <i>Berberis</i> species whose activity had not been previously investigated were selected for the study. In the most investigated <i>Berberis</i> extracts, a high content of berberine and palmatine was determined. Alkaloid standards and most of the investigated plant extracts exhibit significant anti-cholinesterase activity. Molecular docking results confirmed that both alkaloids are more favourable for forming complexes with acetylcholinesterase compared to butyrylcholinesterase. The kinetic results obtained by HPLC-DAD indicated that berberine noncompetitively inhibited acetylcholinesterase, while butyrylcholinesterase was inhibited in a mixed mode. In turn, palmatine exhibited a mixed inhibition of acetylcholinesterase. The cytotoxic activity of berberine and palmatine standards and plant extracts were investigated against the human melanoma cell line (A375). The highest cytotoxicity was determined for extract obtained from <i>Berberis pruinosa</i> cortex. The cytotoxic properties of the extract were also determined in the in vivo investigations using the <i>Danio rerio</i> larvae xenograft model. The obtained results confirmed a significant effect of the <i>Berberis pruinosa</i> cortex extract on the number of cancer cells in a living organism. Our results showed that extracts obtained from <i>Berberis</i> species, especially the <i>Berberis pruinosa</i> cortex extract, can be recommended for further in vivo experiments in order to confirm the possibility of their application in the treatment of neurodegenerative diseases and human melanoma.
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spelling doaj.art-cc010a843a834a4895db66daedf79b922024-03-12T16:50:53ZengMDPI AGMolecules1420-30492024-02-01295104810.3390/molecules29051048In Vitro and In Silico of Cholinesterases Inhibition and In Vitro and In Vivo Anti-Melanoma Activity Investigations of Extracts Obtained from Selected <i>Berberis</i> SpeciesTomasz Tuzimski0Anna Petruczynik1Barbara Kaproń2Tomasz Plech3Anna Makuch-Kocka4Daria Janiszewska5Mateusz Sugajski6Bogusław Buszewski7Małgorzata Szultka-Młyńska8Department of Physical Chemistry, Faculty of Pharmacy, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, PolandDepartment of Inorganic Chemistry, Faculty of Pharmacy, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, PolandDepartment of Clinical Genetics, Faculty of Medicine, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin, PolandDepartment of Clinical Genetics, Faculty of Medicine, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin, PolandDepartment of Clinical Genetics, Faculty of Medicine, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin, PolandDepartment of Environmental Chemistry and Bioanalytics, Faculty of Chemistry, Nicolaus Copernicus University, Gagarin 7, 87-100 Torun, PolandDepartment of Environmental Chemistry and Bioanalytics, Faculty of Chemistry, Nicolaus Copernicus University, Gagarin 7, 87-100 Torun, PolandDepartment of Environmental Chemistry and Bioanalytics, Faculty of Chemistry, Nicolaus Copernicus University, Gagarin 7, 87-100 Torun, PolandDepartment of Environmental Chemistry and Bioanalytics, Faculty of Chemistry, Nicolaus Copernicus University, Gagarin 7, 87-100 Torun, Poland<i>Berberis</i> species have a long history of use in traditional Chinese medicine, Ayurvedic medicine, and Western herbal medicine. The aim of this study was the quantification of the main isoquinoline alkaloids in extracts obtained from various <i>Berberis</i> species by HPLC, in vitro and in silico determination of anti-cholinesterase activity, and in vitro and in vivo investigations of the cytotoxic activity of the investigated plant extracts and alkaloid standards. In particular, <i>Berberis</i> species whose activity had not been previously investigated were selected for the study. In the most investigated <i>Berberis</i> extracts, a high content of berberine and palmatine was determined. Alkaloid standards and most of the investigated plant extracts exhibit significant anti-cholinesterase activity. Molecular docking results confirmed that both alkaloids are more favourable for forming complexes with acetylcholinesterase compared to butyrylcholinesterase. The kinetic results obtained by HPLC-DAD indicated that berberine noncompetitively inhibited acetylcholinesterase, while butyrylcholinesterase was inhibited in a mixed mode. In turn, palmatine exhibited a mixed inhibition of acetylcholinesterase. The cytotoxic activity of berberine and palmatine standards and plant extracts were investigated against the human melanoma cell line (A375). The highest cytotoxicity was determined for extract obtained from <i>Berberis pruinosa</i> cortex. The cytotoxic properties of the extract were also determined in the in vivo investigations using the <i>Danio rerio</i> larvae xenograft model. The obtained results confirmed a significant effect of the <i>Berberis pruinosa</i> cortex extract on the number of cancer cells in a living organism. Our results showed that extracts obtained from <i>Berberis</i> species, especially the <i>Berberis pruinosa</i> cortex extract, can be recommended for further in vivo experiments in order to confirm the possibility of their application in the treatment of neurodegenerative diseases and human melanoma.https://www.mdpi.com/1420-3049/29/5/1048inhibition of cholinesterase activitymolecular dockingcytotoxic activity<i>Danio rerio</i> larvae xenograft modelHPLC-DADLC-MS/MS
spellingShingle Tomasz Tuzimski
Anna Petruczynik
Barbara Kaproń
Tomasz Plech
Anna Makuch-Kocka
Daria Janiszewska
Mateusz Sugajski
Bogusław Buszewski
Małgorzata Szultka-Młyńska
In Vitro and In Silico of Cholinesterases Inhibition and In Vitro and In Vivo Anti-Melanoma Activity Investigations of Extracts Obtained from Selected <i>Berberis</i> Species
Molecules
inhibition of cholinesterase activity
molecular docking
cytotoxic activity
<i>Danio rerio</i> larvae xenograft model
HPLC-DAD
LC-MS/MS
title In Vitro and In Silico of Cholinesterases Inhibition and In Vitro and In Vivo Anti-Melanoma Activity Investigations of Extracts Obtained from Selected <i>Berberis</i> Species
title_full In Vitro and In Silico of Cholinesterases Inhibition and In Vitro and In Vivo Anti-Melanoma Activity Investigations of Extracts Obtained from Selected <i>Berberis</i> Species
title_fullStr In Vitro and In Silico of Cholinesterases Inhibition and In Vitro and In Vivo Anti-Melanoma Activity Investigations of Extracts Obtained from Selected <i>Berberis</i> Species
title_full_unstemmed In Vitro and In Silico of Cholinesterases Inhibition and In Vitro and In Vivo Anti-Melanoma Activity Investigations of Extracts Obtained from Selected <i>Berberis</i> Species
title_short In Vitro and In Silico of Cholinesterases Inhibition and In Vitro and In Vivo Anti-Melanoma Activity Investigations of Extracts Obtained from Selected <i>Berberis</i> Species
title_sort in vitro and in silico of cholinesterases inhibition and in vitro and in vivo anti melanoma activity investigations of extracts obtained from selected i berberis i species
topic inhibition of cholinesterase activity
molecular docking
cytotoxic activity
<i>Danio rerio</i> larvae xenograft model
HPLC-DAD
LC-MS/MS
url https://www.mdpi.com/1420-3049/29/5/1048
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