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

• Published in: Molecules (Basel, Switzerland) Vol. 29; no. 5; p. 1048
• Main Authors: Tuzimski, Tomasz, Petruczynik, Anna, Kaproń, Barbara, Plech, Tomasz, Makuch-Kocka, Anna, Janiszewska, Daria, Sugajski, Mateusz, Buszewski, Bogusław, Szultka-Młyńska, Małgorzata
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.02.2024; MDPI
• Subjects: Acetylcholinesterase; Alkaloids - pharmacology; Antineoplastic Agents; Berberine - pharmacology; Berberis; Butyrylcholinesterase; Cancer; Cholinesterase Inhibitors - pharmacology; Chromatography; cytotoxic activity; Cytotoxicity; Danio rerio larvae xenograft model; Disease; Drugs; Fruits; Herbal medicine; HPLC-DAD; Humans; inhibition of cholinesterase activity; LC-MS/MS; Medical research; Melanoma; molecular docking; Molecular Docking Simulation; Plant Extracts - pharmacology; Zebrafish; LC-MS/MS; molecular docking; Berberis species; HPLC-DAD; Danio rerio larvae xenograft model; cytotoxic activity; inhibition of cholinesterase activity
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules29051048

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 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, species whose activity had not been previously investigated were selected for the study. In the most investigated 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 cortex. The cytotoxic properties of the extract were also determined in the in vivo investigations using the larvae xenograft model. The obtained results confirmed a significant effect of the cortex extract on the number of cancer cells in a living organism. Our results showed that extracts obtained from species, especially the 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.