Solubility Studies of Oleanolic Acid and Betulinic Acid in Aqueous Solutions and Plant Extracts of Viscum album L.

Abstract

Mistletoe (Viscum album L.) contains the triterpene acids oleanolic acid (OA) and betulinic acid (BA), which were found to have anti-tumour properties. In this study, the solubilities of OA and BA were studied in water (up to 0.02 μg/mL in each case) and in alkaline solutions of 10 mM trisodium phosphate (pH 11.5; OA: 77.2 μg/mL; BA: 40.1 μg/mL). Furthermore, triterpene acids were quantified in aqueous mistletoe extracts (pH 7.3; drug to extract ratio 1 : 25). OA (1.1 μg/mL) and BA (0.9 μg/mL) were extracted with a yield of less than 5 %. Preparing plant extracts with basic pH values resulted in a triterpene acid content of 9.3 μg/mL OA and 5.2 μg/mL BA (pH 12.1), reaching neither the solubility limits nor a complete extraction of the plant material. The triterpene acid content of neutral plant extracts above the solubility limit could be due to interactions with biocolloids. Interaction studies were performed by gel permeation chromatography. Different mechanisms of the dissolution at pH 7.3 and pH 10.2 are discussed.

Abbreviations

BA:betulinic acid

CI:confidence interval (α = 0.05)

CV:coefficient of variation [%]

DER:drug-to-extract ratio

FID:flame ionisation detection

GC:gas chromatography

GPC:gel permeation chromatography

LOD:limit of detection

LOQ:limit of quantification

OA:oleanolic acid

Key words

Oleanolic acid - betulinic acid - solubility - synergy - Loranthaceae - Viscum album L. - aqueous mistletoe extracts

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