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

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

Journal

Pharmaceutics
ISSN: 1999-4923

Output data

Year: 2023, Volume: 15, Number: 1, Pages: 44 Pages count : 1 DOI: 10.3390/pharmaceutics15010044

Tags

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

Authors

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

Affiliations

1	N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of Siberian Branch of Russian Academy of Sciences
2	Novosibirsk State University

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 Scopus OpenAlex

Submitted:	Dec 5, 2022
Accepted:	Dec 21, 2022
Published print:	Dec 22, 2022

Web of science:	WOS:000927219300001
Scopus:	2-s2.0-85146618299
OpenAlex:	W4312173380

DB	Citing
OpenAlex	1
Web of science	2