Products of lingonberries are widely used in the human diet; they are also promising beauty and health therapeutic candidates in the cosmetic and pharmaceutical industries. It is important to examine the sugar profile of these berries, due to potential deleterious health effects resulting from high sugar consumption. The aim of this study was to determine the composition of sugars in wild clones and cultivars or lower taxa of lingonberries by HPLC-ELSD method of analysis. Acceptable system suitability, linearity, limits of detection and quantification, precision, and accuracy of this analytical method were achieved. The same sugars with moderate amounts of fructose, glucose, and low amounts of sucrose were found in wild and cultivated lingonberries. Cultivar 'Erntekrone' and wild lingonberries collected from full sun, dry pine tree forests with lower altitude and latitude of the location, distinguished themselves with exclusive high contents of sugars. The changes in the sugar levels during the growing season were apparent in lingonberries and the highest amounts accumulated at the end of the vegetation. According to our findings, lingonberries seem to be an appropriate source of dietary sugars.

Lingonberry leaves are the subject of numerous studies because of antioxidant properties, positive influence on the health and potential use in the prevention and treatment of chronic diseases. In this work, the radical scavenging, reducing, chelating activities, and phenolic composition of ten lingonberry leaves cultivars, one subspecies, and one variety were investigated. Furthermore, the antioxidant activity of individual phenolic compounds, that can be found in lingonberry leaves, were analyzed, and structure-activity relationship was determined. Wide diversity for phenolic profile and antioxidant properties of lingonberry leaves has been observed in the present material. Cultivars 'Kostromskaja rozovaja', 'Rubin', and Vaccinium vitis-idaea var. leucocarpum surpassed all others tested cultivars and lower taxa by contents of phenolic compounds and antioxidant activity. Leaves of lingonberry cultivars and lower taxa are rich in arbutin, flavonol glycosides, proanthocyanidins, and the latter were considered to be the major contributor to antioxidant properties of lingonberry leaves.

Lingonberry leaves and fruits are associated with a range of potential bioactivities related to their phenolic content and composition, but the identification of major biological activity markers remains limited. The present study aimed at the isolation of lingonberry phenolic fractions and biological activity evaluation of them. Crude dry extracts of lingonberry leaves and fruits were fractionated by chromatography using Sephadex LH-20 and analyzed by validated HPLC-PDA method. For each fraction, the anticancer activity against human clear cell renal cell carcinoma (CaKi-1), human colon adenocarcinoma (HT-29), and human malignant melanoma (IGR39) cell lines was determined using MTT assay, and the radical scavenging, reducing, and chelating activities were investigated using ABTS, FRAP, and FIC assays, respectively. Further, 28 phenolics were identified and quantified in the crude extract of lingonberry leaves and 37 in the extract of fruits. These compounds, during fractionation steps, were selectively eluted into active fractions, enriched with different groups of phenolics-monophenols, anthocyanins, phenolic acids, catechins, flavonols, or proanthocyanidins. Fractions of lingonberry leaves and fruits, obtained by the last fractionation step, proved to be the most active against tested cancer cell lines and possessed the greatest antioxidant activity. In this perspective, the predominant compounds of these fractions-polymeric and mainly A-type dimeric proanthocyanidins-also quercetin can be considered to be anticancer and antioxidant activity markers of lingonberries.

Vaccinium vitis-idaea L. (lingonberry) fruits are promising sources of bioactive components with high potential in biomedical applications. Selection in plant breeding, determination of perspective wild clones with optimal growing conditions, and appropriate harvesting time leading to standardized extracts are key factors for achieving phytochemical quality to meet consumer's needs. In the present study, lingonberry fruits collected along different phenological stages and from different geographical locations were analyzed for the composition of 56 constituents using validated chromatographic techniques. Early stages of lingonberries vegetation were determined as the best stages for obtaining high levels of most phenolics and triterpenoids, while the end of berry vegetation could be chosen as the optimal harvesting time in terms of anthocyanins. Furthermore, intensified continuous biosynthesis of triterpenoids and phenolic acids precursors after vegetation season in the winter sample was observed. Chemodiversity of lingonberries was affected by geographical factors as well as climatic and edaphic conditions, indicating different favorable growing conditions for the accumulation of particular compounds. Present findings could serve for breeders to obtain the highest yields of desirable lingonberry constituents, relevant in food and pharmaceutical industries.

Lingonberry leaves have been proposed as a potential raw material for nutraceutical products and functional food due to the richness of phenolic and triterpenic compounds. However, contents of these bioactive compounds tend to vary greatly with physiological, climatic, and edaphic conditions, resulting in lingonberry leaves' nutritional-pharmaceutical quality changes. In this context, we examined the effects of seasonal and geographical factors on phenolic and triterpenoid contents in lingonberry leaves. Quantitative and qualitative differences between samples were determined using validated HPLC-PDA methods. A total of 43 bioactive compounds were found at a detectable level throughout the year in young and old lingonberry leaves, with the highest contents of most compounds observed in samples collected in autumn-first half of spring. This suggests the potential to exploit the continuous biosynthesis for a longer harvesting season. Considerable variations in phytochemical profiles of lingonberry leaves, obtained from 28 locations in Lithuania, were found. Correlation analyses revealed significant negative correlations between contents of particular constituents and sunshine duration, temperature, and precipitation, and positive correlation with air humidity, longitudes, and altitudes of collecting locations and macronutrients in soil. These results suggest that harsh weather is favorable for most identified compounds and it may be possible to achieve appropriate accumulation of secondary metabolites by adjusting edaphic conditions. Taken together, the accumulation of phenolics and triterpenoids in lingonberry leaves highly depends on phenological and geographical factors and the influence of both variables differ for the particular compounds due to different metabolic processes in response to stresses.

The compositions and health-beneficial properties of lingonberry leaves (Vaccinium vitis-idaea L.) are well established; however, their proanthocyanidins are still heavily underutilized. Optimizing their delivery systems is key to enabling their wider applications. The present study investigates the phytochemical and 'wound-healing' properties of proanthocyanidin-rich fraction(s) (PRF) from lingonberry leaves as well as the development of optimal dermal film as a proanthocyanidin delivery system. The obtained PRF was subjected to HPLC-PDA and DMAC analyses to confirm the qualitative and quantitative profiles of different polymerization-degree proanthocyanidins. A 'wound healing' in vitro assay was performed to assess the ability of PRF to modulate the wound environment for better healing. Low concentrations of lingonberry proanthocyanidins were found to accelerate 'wound' closures, while high levels inhibited human fibroblast migration. Fifteen dermal films containing PRF were prepared and evaluated based on their polymer (MC, HEC, PEG 400) compositions, and physical, mechanical, and biopharmaceutical properties using an experimental design. The composition containing 0.30 g of MC, 0.05 g of HEC, and 3.0 g of PEG 400 was selected as a promising formulation for PRF delivery and a potentially effective functional wound dressing material, supporting the need for further investigations.

Fruit and leaf cuticular waxes are valuable source materials for the isolation of triterpenoids that can be applied as natural antioxidants and anticancer agents. The present study aimed at the semi-preparative fractionation of triterpenoids from cuticular wax extracts of Vaccinium vitis-idaea L. (lingonberry) leaves and fruits and the evaluation of their cytotoxic potential. Qualitative and quantitative characterization of obtained extracts and triterpenoid fractions was performed using HPLC-PDA method, followed by complementary analysis by GC-MS. For each fraction, cytotoxic activities towards the human colon adenocarcinoma cell line (HT-29), malignant melanoma cell line (IGR39), clear renal carcinoma cell line (CaKi-1), and normal endothelial cells (EC) were determined using MTT assay. Furthermore, the effect of the most promising samples on cancer spheroid growth and viability was examined. This study allowed us to confirm that particular triterpenoid mixtures from lingonberry waxes may possess stronger cytotoxic activities than crude unpurified extracts. Fractions containing triterpenoid acids plus fernenol, complexes of oleanolic:ursolic acids, and erythrodiol:uvaol were found to be the most potent therapeutic candidates in the management of cancer diseases. The specificity of cuticular wax extracts of lingonberry leaves and fruits, leading to different purity and anticancer potential of obtained counterpart fractions, was also enclosed. These findings contribute to the profitable utilization of lingonberry cuticular waxes and provide considerable insights into the anticancer effects of particular triterpenoids and pharmacological interactions.