Research output: Contribution to journal › Article › peer-review
Study of Hypoglycemic Activity of Novel 9-N-alkyltetrahydroberberine Derivatives. / Khvostov, Mikhail V.; Gladkova, Elizaveta D.; Borisov, Sergey A. et al.
In: International Journal of Molecular Sciences, Vol. 23, No. 22, 14186, 11.2022.Research output: Contribution to journal › Article › peer-review
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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 -
ID: 40099959