9-N-n-alkyl Berberine Derivatives: Hypoglycemic Activity Evaluation

9-N-n-alkyl Berberine Derivatives: Hypoglycemic Activity Evaluation Научная публикация

Журнал

Pharmaceutics
ISSN: 1999-4923

Вых. Данные

Год: 2023, Том: 15, Номер: 1, Страницы: 44 Страниц : 1 DOI: 10.3390/pharmaceutics15010044

Ключевые слова

berberine derivatives; metabolic syndrome; hypoglycemic activity; OGTT; agouti yellow mice; hepatic steatosis

Авторы

Khvostov Mikhail V. ¹ , Gladkova Elizaveta D. ¹ , Borisov Sergey A. ¹ , Fedotova Marina S. ^1,2 , Zhukova Nataliya A. ¹ , Marenina Mariya K. ¹ , Meshkova Yulia V. ¹ , Valutsa Nicolae ² , Luzina Olga A. ¹ , Tolstikova Tatiana G. ¹ , Salakhutdinov Nariman F. ¹

Организации

1	Новосибирский институт органической химии им. Н.Н. Ворожцова СО РАН
2	Новосибирский национальный исследовательский государственный университет

Several novel 9-N-n-alkyl derivatives of berberine (C5, C7, C10, C12) were synthesized. They were analyzed in vitro and in vivo for their hypoglycemic activity. In vitro studies showed that the derivatives with shorter alkyl substitutes at concentrations ranging from 2.5 to 10 μM were able to stimulate glucose consumption by HepG2 cells more prominently than the derivatives with longer substitutes (C10 and C12). All compounds demonstrated a better effect compared to berberine. Their impact on cells’ viability also depended on the alkyl substitutes length, but in this case, C10 and C12 derivatives demonstrated the best results. A similar correlation was also found in the OGTT, where the C5 derivative demonstrated a pronounced hypoglycemic effect at a dose of 15 mg/kg and C12 was less effective. This compound was further investigated in C57BL/6Ay mice for four weeks and was administered at a dose of 15 mg/kg. Pronounced effect of C12 on carbohydrate metabolism in mice was discovered: there was a decrease in fasting glucose levels and an increase in glucose tolerance in OGTT on the 14th and 28th days of the experiment. However, at the end of the experiment, signs of hepatosis exacerbation and an increase in the content of hepatic aminotransferases in blood were found.

Khvostov M.V. , Gladkova E.D. , Borisov S.A. , Fedotova M.S. , Zhukova N.A. , Marenina M.K. , Meshkova Y.V. , Valutsa N. , Luzina O.A. , Tolstikova T.G. , Salakhutdinov N.F.
9-N-n-alkyl Berberine Derivatives: Hypoglycemic Activity Evaluation
Pharmaceutics. 2023. V.15. N1. P.44. DOI: 10.3390/pharmaceutics15010044 WOS

Поступила в редакцию:	5 дек. 2022 г.
Принята к публикации:	21 дек. 2022 г.
Опубликована в печати:	22 дек. 2022 г.

Web of science	WOS:000927219300001
OpenAlex	W4312173380