Abstract: 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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Cite: Khvostov M.V. , Gladkova E.D. , Borisov S.A. , Zhukova N.A. , Marenina M.K. , Meshkova Y.V. , Luzina O.A. , Tolstikova T.G. , Salakhutdinov N.F.
Discovery of the first in class 9-N-berberine derivative as hypoglycemic agent with extra-strong action
Pharmaceutics. 2021. V.13. N12. 2138 :1-14. DOI: 10.3390/pharmaceutics13122138 WOS Scopus РИНЦ

Dates:

Submitted:	Jul 4, 2021
Accepted:	Dec 10, 2021
Published online:	Dec 12, 2021

Identifiers:

Web of science	WOS:000736566300001
Scopus	2-s2.0-85121426937
Elibrary	47544194
OpenAlex	W4200320717

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