TY - JOUR

T1 - Study of Hypoglycemic Activity of Novel 9-N-alkyltetrahydroberberine Derivatives

AU - Khvostov, Mikhail V.

AU - Gladkova, Elizaveta D.

AU - Borisov, Sergey A.

AU - Fedotova, Marina S.

AU - Zhukova, Nataliya A.

AU - Marenina, Mariya K.

AU - Meshkova, Yuliya V.

AU - Luzina, Olga A.

AU - Tolstikova, Tatiana G.

AU - Salakhutdinov, Nariman F.

N1 - Funding Information: This research was financially supported by the Russian Science Foundation, project No. 20-13-00029. Publisher Copyright: © 2022 by the authors.

PY - 2022/11

Y1 - 2022/11

N2 - 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/6Ay, 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.

AB - 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/6Ay, 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.

KW - agouti yellow mice

KW - berberine derivatives

KW - hypoglycemic activity

KW - metabolic syndrome

KW - OGTT

KW - Glucose Tolerance Test

KW - Animals

KW - Mice, Inbred C57BL

KW - Mice

KW - Glucose

KW - Hypoglycemic Agents/pharmacology

KW - Insulin

UR - http://www.scopus.com/inward/record.url?scp=85142808872&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/a000de04-6f44-39af-be23-ebbb6e2c9f8d/

U2 - 10.3390/ijms232214186

DO - 10.3390/ijms232214186

M3 - Article

C2 - 36430664

AN - SCOPUS:85142808872

VL - 23

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 22

M1 - 14186

ER -