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 microg/mL in each case) and in alkaline solutions of 10 mM trisodium phosphate (pH 11.5; OA: 77.2 microg/mL; BA: 40.1 microg/mL). Furthermore, triterpene acids were quantified in aqueous mistletoe extracts (pH 7.3; drug to extract ratio 1:25). OA (1.1 microg/mL) and BA (0.9 microg/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 microg/mL OA and 5.2 microg/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.

Highly lipophilic 3-epi-betulinic acid derivatives as potent and selective TGR5 agonists with improved cellular efficacy

“…In fact, two isoxazolecarboxamide TGR5 agonists have demonstrated that systemic exposure is not neces- www.nature.com/aps Wang XY et al Acta Pharmacologica Sinica npg sary to achieve the desired effect of stimulating GLP-1 secretion in vivo [24] . Previous studies have shown that triterpenoids often have poor solubility and poor absorption in the gastrointestinal tract, leading to low plasma exposure [28,29] . This may reduce the activation of TGR5 in gallbladder and other tissues caused by high plasma exposure, thereby reducing the side effects.…”

Effect of a controlled-release drug delivery system made of oleanolic acid formulated into multivesicular liposomes on hepatocellular carcinoma in vitro and in vivo

“…The conventional clinical formulations of OA are tablets and capsules, which possess significant first-pass effect of hepar and undergoes low dissolution in gastrointestinal tract because of the poor water solubility. [12][13][14] Therefore, it is essential to develop a novel dosage form for OA to improve the treatment efficiency for HCC.…”

Tumour cell derived effects on monocyte/macrophage polarization and function and modulatory potential of Viscum album lipophilic extract in vitro

“…Besides the hydrophilic active substances, the plant itself contains several pentacyclic triterpenes, among them oleanolic acid, betulinic acid, ursolic acid and lupeol [22,23]. Due to their insolubility in water these compounds are not represented in significant amounts in aqueous mistletoe extracts [24]. However, previous studies have shown apoptosis inducing and antiangiogenic activity of these lipophilic mistletoe compounds in vitro and in vivo [20,22,[25][26][27][28].…”