Study of Hypoglycemic Activity of Novel 9-N-alkyltetrahydroberberine Derivatives
Novel 9-N-alkyltetrahydroberberine derivatives were synthesized, among which, based on the results of OGTT, one compound containing the longest aliphatic substituent was selected for study in mice C57BL/6<sup>Ay</sup>, which demonstrate obesity, impaired glucose tolerance, and concomitan...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/22/14186 |
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| author | Mikhail V. Khvostov Elizaveta D. Gladkova Sergey A. Borisov Marina S. Fedotova Nataliya A. Zhukova Mariya K. Marenina Yuliya V. Meshkova Olga A. Luzina Tatiana G. Tolstikova Nariman F. Salakhutdinov |
| author_facet | Mikhail V. Khvostov Elizaveta D. Gladkova Sergey A. Borisov Marina S. Fedotova Nataliya A. Zhukova Mariya K. Marenina Yuliya V. Meshkova Olga A. Luzina Tatiana G. Tolstikova Nariman F. Salakhutdinov |
| author_sort | Mikhail V. Khvostov |
| collection | DOAJ |
| description | Novel 9-N-alkyltetrahydroberberine derivatives were synthesized, among which, based on the results of OGTT, one compound containing the longest aliphatic substituent was selected for study in mice C57BL/6<sup>Ay</sup>, which demonstrate obesity, impaired glucose tolerance, and concomitant liver non-alcoholic fatty disease. Administration of this substance at a dose of 15 mg/kg for four weeks improved the insulin sensitivity of mice, which resulted in a decrease in fasting glucose levels and improved the tolerance of mice to OGTT glucose loading. A decrease in the level of lactate in the blood and a decrease in the amount of glucokinase in the liver were also found. The introduction of compound 3c did not have a toxic effect on animals based on biochemical data, histological analysis, and measurements of general parameters such as body weight and feed intake. Thus, the 9-N-heptyltetrahydroberberine derivative showed prominent hypoglycemic effects, which makes it promising to obtain and study other derivatives with longer substituents. |
| first_indexed | 2024-03-09T18:17:00Z |
| format | Article |
| id | doaj.art-c19773552f9044a4926f1a121de33d8b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T18:17:00Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c19773552f9044a4926f1a121de33d8b2023-11-24T08:40:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123221418610.3390/ijms232214186Study of Hypoglycemic Activity of Novel 9-N-alkyltetrahydroberberine DerivativesMikhail V. Khvostov0Elizaveta D. Gladkova1Sergey A. Borisov2Marina S. Fedotova3Nataliya A. Zhukova4Mariya K. Marenina5Yuliya V. Meshkova6Olga A. Luzina7Tatiana G. Tolstikova8Nariman F. Salakhutdinov9N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9, Akademika Lavrentieva Ave., 630090 Novosibirsk, RussiaN. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9, Akademika Lavrentieva Ave., 630090 Novosibirsk, RussiaN. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9, Akademika Lavrentieva Ave., 630090 Novosibirsk, RussiaN. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9, Akademika Lavrentieva Ave., 630090 Novosibirsk, RussiaN. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9, Akademika Lavrentieva Ave., 630090 Novosibirsk, RussiaN. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9, Akademika Lavrentieva Ave., 630090 Novosibirsk, RussiaN. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9, Akademika Lavrentieva Ave., 630090 Novosibirsk, RussiaN. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9, Akademika Lavrentieva Ave., 630090 Novosibirsk, RussiaN. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9, Akademika Lavrentieva Ave., 630090 Novosibirsk, RussiaN. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9, Akademika Lavrentieva Ave., 630090 Novosibirsk, RussiaNovel 9-N-alkyltetrahydroberberine derivatives were synthesized, among which, based on the results of OGTT, one compound containing the longest aliphatic substituent was selected for study in mice C57BL/6<sup>Ay</sup>, which demonstrate obesity, impaired glucose tolerance, and concomitant liver non-alcoholic fatty disease. Administration of this substance at a dose of 15 mg/kg for four weeks improved the insulin sensitivity of mice, which resulted in a decrease in fasting glucose levels and improved the tolerance of mice to OGTT glucose loading. A decrease in the level of lactate in the blood and a decrease in the amount of glucokinase in the liver were also found. The introduction of compound 3c did not have a toxic effect on animals based on biochemical data, histological analysis, and measurements of general parameters such as body weight and feed intake. Thus, the 9-N-heptyltetrahydroberberine derivative showed prominent hypoglycemic effects, which makes it promising to obtain and study other derivatives with longer substituents.https://www.mdpi.com/1422-0067/23/22/14186berberine derivativesmetabolic syndromehypoglycemic activityOGTTagouti yellow mice |
| spellingShingle | Mikhail V. Khvostov Elizaveta D. Gladkova Sergey A. Borisov Marina S. Fedotova Nataliya A. Zhukova Mariya K. Marenina Yuliya V. Meshkova Olga A. Luzina Tatiana G. Tolstikova Nariman F. Salakhutdinov Study of Hypoglycemic Activity of Novel 9-N-alkyltetrahydroberberine Derivatives International Journal of Molecular Sciences berberine derivatives metabolic syndrome hypoglycemic activity OGTT agouti yellow mice |
| title | Study of Hypoglycemic Activity of Novel 9-N-alkyltetrahydroberberine Derivatives |
| title_full | Study of Hypoglycemic Activity of Novel 9-N-alkyltetrahydroberberine Derivatives |
| title_fullStr | Study of Hypoglycemic Activity of Novel 9-N-alkyltetrahydroberberine Derivatives |
| title_full_unstemmed | Study of Hypoglycemic Activity of Novel 9-N-alkyltetrahydroberberine Derivatives |
| title_short | Study of Hypoglycemic Activity of Novel 9-N-alkyltetrahydroberberine Derivatives |
| title_sort | study of hypoglycemic activity of novel 9 n alkyltetrahydroberberine derivatives |
| topic | berberine derivatives metabolic syndrome hypoglycemic activity OGTT agouti yellow mice |
| url | https://www.mdpi.com/1422-0067/23/22/14186 |
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