Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Chemical Composition and Insulin-Resistance Activity of Arginine-Loaded American Cranberry (Vaccinium macrocarpon Aiton) Leaves Extracts

Version 1 : Received: 3 October 2023 / Approved: 3 October 2023 / Online: 3 October 2023 (10:57:18 CEST)

A peer-reviewed article of this Preprint also exists.

Koshovyi, O.; Vlasova, I.; Laur, H.; Kravchenko, G.; Krasilnikova, O.; Granica, S.; Piwowarski, J.P.; Heinämäki, J.; Raal, A. Chemical Composition and Insulin-Resistance Activity of Arginine-Loaded American Cranberry (Vaccinium macrocarpon Aiton, Ericaceae) Leaf Extracts. Pharmaceutics 2023, 15, 2528. Koshovyi, O.; Vlasova, I.; Laur, H.; Kravchenko, G.; Krasilnikova, O.; Granica, S.; Piwowarski, J.P.; Heinämäki, J.; Raal, A. Chemical Composition and Insulin-Resistance Activity of Arginine-Loaded American Cranberry (Vaccinium macrocarpon Aiton, Ericaceae) Leaf Extracts. Pharmaceutics 2023, 15, 2528.

Abstract

One of the key pathogenetic links of type 2 diabetes mellitus (T2DM) is the formation of insulin resistance (IR). Besides a wide selection of synthetic antidiabetic drugs, various plant-origin extracts are also available to support the treatment of T2DM. This study aimed to investigate and gain knowledge of the chemical composition and potential IR correction effect of American cranberry (Vaccinium macrocarpon Aiton) leaf extracts and formulate novel 3D-printed oral dosage forms for such extracts. The bioactivity and IR of L-arginine-loaded cranberry leaf extracts were studied in vivo in rats. The cranberry leaf extracts consisted of quinic, 3-caffeoylquinic (chlorogenic), p-coumaroylquinic acids, quercetin 3-O-galactoside, quercetin-3-O-glucoside, quercetin-3-xyloside, quercetin-3-O-arabino-pyranoside, quercetin-3-O-arabinofuranoside, quercetin 3-O-rhamnoside and quercetin-O-p-coumaroyl-hexoside-2 identified by HPLC. In-vivo studies with rats showed that the oral administration of the cranberry leaf extracts had a positive effect on insulin sensitivity coefficients under ITT test, and affected HOMA-IR levels and liver lipid content with experimental IR. A novel 3D-printed immediate-release dosage form was developed for the oral administration of cranberry leaf extracts using polyethylene oxide (PEO) as a carrier gel in a semi-solid extrusion (SSE) 3D printing. In conclusion, American cranberry leaf extracts loaded with L-arginine could find uses in preventing health issues associated with IR.

Keywords

American cranberry; Vaccinium macrocarpon; leaf extract; chemical composition; L-arginine; insulin resistance effect; 3D printing

Subject

Medicine and Pharmacology, Pharmacy

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