| Autor: |
Khvostov MV; N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 Akademika Lavrentieva Ave., 630090 Novosibirsk, Russia., Gladkova ED; N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 Akademika Lavrentieva Ave., 630090 Novosibirsk, Russia., Borisov SA; N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 Akademika Lavrentieva Ave., 630090 Novosibirsk, Russia., Zhukova NA; N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 Akademika Lavrentieva Ave., 630090 Novosibirsk, Russia., Marenina MK; N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 Akademika Lavrentieva Ave., 630090 Novosibirsk, Russia., Meshkova YV; N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 Akademika Lavrentieva Ave., 630090 Novosibirsk, Russia., Luzina OA; N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 Akademika Lavrentieva Ave., 630090 Novosibirsk, Russia., Tolstikova TG; N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 Akademika Lavrentieva Ave., 630090 Novosibirsk, Russia., Salakhutdinov NF; N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 Akademika Lavrentieva Ave., 630090 Novosibirsk, Russia. |
| Abstrakt: |
Berberine is well known for its ability to reduce the blood glucose level, but its high effective dose and poor bioavailability limits its use. In this work we synthesized a new derivative of berberine, 9-(hexylamino)-2,3-methylenedioxy-10-methoxyprotoberberine chloride ( SHE-196 ), and analyzed the profile of its hypoglycemic effects. Biological tests have shown that the substance has a very pronounced hypoglycemic activity due to increased insulin sensitivity after single and multiple dosing. In obese type 2 diabetes mellitus (T2DM) mice, it was characterized by improved glucose tolerance, decreased fasting insulin levels and sensitivity, decreased total body weight and interscapular fat mass, and increased interscapular brown fat activity. All these effects were also confirmed histologically, where a decrease in fatty degeneration of the liver, an improvement in the condition of the islets of Langerhans and a decrease in the size of fat droplets in brown adipose tissue were found. Our results indicate that 9-(hexylamino)-2,3-methylenedioxy-10-methoxyprotoberberine chloride could be the first in a new series of therapeutic agents for the treatment of diabetes mellitus. |
