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.
Highlights
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The results indicated that two of them, namely compounds 2a,b, exhibited model of b-cell-membrane chromatography and a model of alloxan-induced diabetes in antihyperglycemic activity
Spectra were recorded in deuterated dimethyl sulfoxide d6); residual
Summary
Berberine has been used in the traditional Chinese medicine to treat various diseases [1,2,3], one of its strongest features is reported to be its anti-diabetic activity. Berberine inhibits α-glucosidase reducing the intestinal absorption of monosaccharides. Berberine regulates the peroxisome proliferator-activated receptors and the expression of positive transcription elongation factor b in diabetic adipocytes [4]. Some other possible berberine mechanisms of action against obesity are modulation of the gut microbiota by increasing the amount of intestinal peptides (such as GLP-1, GLP-2 and peptide YY), decreasing the number of inhibitory gastric polypeptides by inhibiting the LXR alpha expression, cholesterol absorption and hepatic gluconeogenesis [10,11], suppression of adipocyte differentiation and proliferation by reducing galectin-3 levels [12], blocking adipogenesis by inhibiting CREB activity [13]. Its anti-diabetic properties are likely to be of multitarget nature
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