Lingonberry (Vaccinium vitis-idaea L.) Skin Extract Prevents Weight Gain and Hyperglycemia in High-Fat Diet-Induced Model of Obesity in Mice.

The percentage of obese people is increasing worldwide, causing versatile health problems. Obesity is connected to diseases such as diabetes and cardiovascular diseases, which are preceded by a state called metabolic syndrome. Diets rich in fruits and vegetables have been reported to decrease the risk of metabolic syndrome and type 2 diabetes. Berries with a high polyphenol content, including lingonberry (Vaccinium vitis-idaea L.), have also been of interest to possibly prevent obesity-induced metabolic disturbances. In the present study, we prepared an extract from the by-product of a lingonberry juice production process (press cake/pomace) and investigated its metabolic effects in the high-fat diet-induced model of obesity in mice. The lingonberry skin extract partly prevented weight and epididymal fat gain as well as a rise in fasting glucose level in high-fat diet-fed mice. The extract also attenuated high-fat diet-induced glucose intolerance as measured by an intraperitoneal glucose tolerance test (IPGTT). The extract had no effect on the levels of cholesterol, triglyceride or the adipokines adiponectin, leptin, or resistin. The results extend previous data on the beneficial metabolic effects of lingonberry. Further research is needed to explore the mechanisms behind these effects and to develop further health-promoting lingonberry applications.

Interactions between corn starch and lingonberry polyphenols and their effects on starch digestion and glucose transport.

This study investigated the interaction mechanism between corn starch (CS) and lingonberry polyphenols (LBP) during starch gelatinization, focusing on their effects on starch structure and physicochemical properties. Moreover, it explored the effect of this interaction on starch digestion and glucose transport. The results indicated that LBP interacted non-covalently with CS during starch gelatinization, disrupted the short-range ordered structure of starch, decreased gelatinization enthalpy of starch, and formed a dense network structure. Furthermore, the incorporation of LBP remarkably reduced the digestibility of CS. In particular, the addition of 10 % LBP decreased the terminal digestibility (C∞) from 77.87 % to 60.43 % and increased the amount of resistant starch (RS) by 21.63 %. LBP was found to inhibit α-amylase and α-glucosidase in a mixed manner. Additionally, LBP inhibited glucose transport in Caco-2 cells following starch digestion. When 10 % LBP was added, there was a 34.17 % decrease in glucose transport compared with starch digestion without LBP. This study helps establish the foundation for the development of LBP-containing starch or starch-based healthy foods and provides new insights into the mechanism by which LBP lowers blood glucose.

Fine-scale clonal structure of the lingonberry Vaccinium vitis-idaea under the nurse plant Pinus pumila vegetation in an alpine region, Mt. Norikura.

The nurse effect is a positive interaction in which a nurse plant improves the abiotic environment for another species (beneficiary plant) and facilitates its establishment. The evergreen shrub Vaccinium vitis-idaea (a beneficiary plant) grows mainly under the dwarf shrub Pinus pumila (a nurse plant) in the alpine regions of central Japan. However, whether V. vitis-idaea shrubs under various P. pumila shrubs spread through clonal growth and/or seeds remains unclear. We investigated the clonal structure of V. vitis-idaea under the nurse plant P. pumila in Japanese alpine regions. MIG-seq analysis was conducted to clarify the clonal diversity of V. vitis-idaea in isolated and patchy P. pumila plots on a ridge (PATs), and in a plot covered by dense P. pumila on a slope adjacent to the ridge (MAT) on Mt. Norikura, Japan. We detected 28 multilocus genotypes in 319 ramets of V. vitis-idaea across 11 PATs and MAT. Three genets expanded to more than 10 m in the MAT. Some genets were shared among neighboring PATs or among PATs and MAT. These findings suggest that the clonal growth of V. vitis-idaea plays an important role in the sustainability of populations. The clonal diversity of V. vitis-idaea was positively related with the spatial size of PATs and was higher in MAT than in PATs at a small scale. Therefore, the spatial spread of the nurse plant P. pumila might facilitate the nurse effect on the genetic diversity of beneficiary plants, leading to the sustainability of beneficiary populations.

Malolactic fermentation in lingonberry juice and its use as a preservative.

Lingonberry is a common wild berry that is often sold as jams and beverages. It naturally contains high amounts of the weak acid preservative benzoic acid making it an interesting ingredient for shelf-life extension. Despite this, their use as a raw ingredient is limited by the inherently intense sour taste. This study aimed to improve the taste of lingonberry juice by subjecting it to malolactic fermentation in order to reduce the sourness, and to investigate the benzoic acid in lingonberries as a natural preservative in juice blends by determining the microbial stability. After initial screening of lactic acid bacteria, a Lactiplantibacillus plantarum strain was used as the starter for subsequent investigations. Upon raising the pH, all malic acid was completely converted to lactic acid after seven days. The fermented juice was mixed with blackcurrant juice in different proportions. Challenge tests of the blends showed Listeria monocytogenes could not grow in any juice samples, while Candida albicans only grew in the pure blackcurrant juice. Aspergillus brasiliensis growth was delayed in all samples containing benzoic acid in a concentration-dependent manner. The sourness and astringency were substantially reduced in the juice with added L. plantarum compared to the unfermented juice.

Vascular plants and mosses as bioindicators of variability of the coastal pine forest (Empetro nigri-Pinetum).

Empetro nigri-Pinetum is a unique sea coast plant community developing along the Baltic Sea from Germany to Lithuania. Our detailed field research of bryophytes and vascular plants has highlighted the regional diversity of the Empetro nigri-Pinetum typicum plant community throughout its range in Central Europe. Our study indicated that vascular plants and mosses effectively discriminate against the described phytocoenoses, thus it was possible to distinguish three variants of the coastal forest: Calluna-Deschampsia (from Germany), Vaccinium vitis-idaea (from Poland) and Melampyrum-Deschampsia (from Lithuania). Redundancy analysis indicated that the division is related to the habitat conditions of the analyzed areas, with humidity having the greatest impact on this differentiation. Kohonen's artificial neural network (i.e. self-organising map, SOM) confirmed the heterogeneous nature of the studied phytocenoses, and combined with the IndVal index enabled identification of indicator species for respective studied patches: Deschampsia flexuosa for Calluna-Deschampsia group; Aulacomnium palustre, Calluna vulgaris, Carex nigra, Dicranum polysetum, Erica tetralix, Oxycoccus palustris, Sphagnum capillifolium, Vaccinium uliginosum and Vaccinium vitis-idaea for Vaccinium vitis-idaea group; and young specimens of Betula pendula, Lycopodium annotinum, Melampyrum pratense and Orthilia secunda for Melampyrum-Deschampsia group. Thereby, our study showed that individual groups of species can be very good bioindicators for each of the studied phytocoenoses.

Unveiling the evolutionary history of lingonberry (Vaccinium vitis-idaea L.) through genome sequencing and assembly of European and North American subspecies.

Lingonberry (Vaccinium vitis-idaea L.) produces tiny red berries that are tart and nutty in flavor. It grows widely in the circumpolar region, including Scandinavia, northern parts of Eurasia, Alaska, and Canada. Although cultivation is currently limited, the plant has a long history of cultural use among indigenous communities. Given its potential as a food source, genomic resources for lingonberry are significantly lacking. To advance genomic knowledge, the genomes for 2 subspecies of lingonberry (V. vitis-idaea ssp. minus and ssp. vitis-idaea var. 'Red Candy') were sequenced and de novo assembled into contig-level assemblies. The assemblies were scaffolded using the bilberry genome (Vaccinium myrtillus) to generate a chromosome-anchored reference genome consisting of 12 chromosomes each with a total length of 548.07 Mb [contig N50 = 1.17 Mb, BUSCO (C%) = 96.5%] for ssp. vitis-idaea and 518.70 Mb [contig N50 = 1.40 Mb, BUSCO (C%) = 96.9%] for ssp. minus. RNA-seq-based gene annotation identified 27,243 and 25,718 genes on the respective assembly, and transposable element detection methods found that 45.82 and 44.58% of the genome were repeats. Phylogenetic analysis confirmed that lingonberry was most closely related to bilberry and was more closely related to blueberries than cranberries. Estimates of past effective population size suggested a continuous decline over the past 1-3 MYA, possibly due to the impacts of repeated glacial cycles during the Pleistocene leading to frequent population fragmentation. The genomic resource created in this study can be used to identify industry-relevant genes (e.g. anthocyanin production), infer phylogeny, and call sequence-level variants (e.g. SNPs) in future research.

In Vitro Eradication of Planktonic, Saliva and Biofilm Bacteria Using Lingonberry Extract as a Photosensitizer for Visible Light Plus Water-Filtered Infrared-A Irradiation.

Antimicrobial photodynamic treatment (aPDT) with visible light plus water-filtered infrared-A irradiation (VIS-wIRA) and natural single- or multi-component photosensitizers (PSs) was shown to have potent antimicrobial activity. The aim of this study was to obtain information on the antimicrobial effects of aPDT-VIS-wIRA with lingonberry extract (LE) against bacteria that play a role in oral health. Planktonic bacterial cultures of the Gram-positive E. faecalis T9, S. mutans DSM20523, S. oralis ATCC 35037 and S. sobrinus PSM 203513, the Gram-negative N. oralis 14F2 FG-15-7B, F. nucleatum ATCC 25586, and V. parvula DSM, the anaerobic F. nucleatum ATCC 25586 and V. parvula DSM 2008, and the total mixed bacteria from pooled saliva and supra- and subgingival plaques of volunteers were all treated and compared. aPDT-VIS-wIRA with LE as PS significantly (p < 0.008) reduced the growth of all tested Gram-positive, Gram-negative, as well as aerobic and anaerobic bacterial strains, whereas without irradiation no reductions were seen (p < 0.0001). NaCl, with or without irradiation, was ineffective. After treatment with CHX 0.2%, the highest killing rate (100%) was observed, and no bacteria (0 log10 CFU) were cultivable. The method also significantly reduced all of the bacteria present in saliva and in the gingival biofilms. Three-dimensional visualization of viable and non-viable microorganisms revealed that LE penetrated deeper into the cell wall layers than CHX 0.2%. LE was an appropriate PS for eradicating microorganisms with VIS-wIRA, either in their planktonic form or in saliva and gingival plaque biofilms. These results encourage further investigation in order to determine which LE compounds contribute to the photosensitizing effect and to evaluate the size of the effect on maintaining oral health.

Exposing Salmonella Senftenberg and Escherichia coli Strains Isolated from Poultry Farms to Formaldehyde and Lingonberry Extract at Low Concentrations.

European Union (EU) countries strive to improve the quality and safety of food of animal origin. Food production depends on a good microbiological quality of fodder. However, feed can be a reservoir or vector of pathogenic microorganisms, including Salmonella or Escherichia coli bacteria. Salmonella spp. and E. coli are the two most important food-borne pathogens of public health concern. Contamination with these pathogens, mainly in the poultry sector, can lead to serious food-borne diseases. Both microorganisms can form biofilms on abiotic and biotic surfaces. The cells that form biofilms are less sensitive to disinfectants, which in turn makes it difficult to eliminate them from various surfaces. Because the usage of formaldehyde in animal feed is prohibited in European countries, the replacement of this antibacterial with natural plant products seems very promising. This study aimed to assess the inhibitory effectiveness of Vaccinium vitis-idaea extract against biofilm produced by model Salmonella enterica and E. coli strains. We found that formaldehyde could effectively kill both species of bacterial cells in biofilm, while the lingonberry extract showed some antibiofilm effect on S. enterica serovar Senftenberg. In conclusion, finding natural plant products that are effective against biofilms formed by Gram-negative bacteria is still challenging.

Ice holes microrefugia harbor genetically and functionally distinct populations of Vaccinium vitis-idaea (Ericaceae).

In the mountain terrain, ice holes are little depressions between rock boulders that are characterized by the exit of cold air able to cool down the rock surface even in summer. This cold air creates cold microrefugia in warmer surroundings that preserve plant species probably over thousands of years under extra-zonal climatic conditions. We hypothesized that ice hole populations of the model species Vaccinium vitis-idaea (Ericaceae) show genetic differentiation from nearby zonal subalpine populations, and high functional trait distinctiveness, in agreement with genetic patterns. We genotyped almost 30,000 single nucleotide polymorphisms using restriction site-associated DNA sequencing and measured eight functional traits indicative of individual performance and ecological strategies. Genetic results showed high differentiation among the six populations suggesting isolation. On siliceous bedrock, ice hole individuals exhibited higher levels of admixture than those from subalpine populations which could have experienced more bottlenecks during demographic fluctuations related to glacial cycles. Ice hole and subalpine calcareous populations clearly separated from siliceous populations, indicating a possible effect of bedrock in shaping genetic patterns. Trait analysis reflected the bedrock effect on populations' differentiation. The significant correlation between trait and genetic distances suggests the genetic contribution in shaping intraspecific functional differentiation. In conclusion, extra-zonal populations reveal a prominent genetic and phenotypic differentiation determined by history and ecological contingency. Therefore, microrefugia populations can contribute to the overall variability of the species and lead to intraspecific-driven responses to upcoming environmental changes.

Climate change will cause climatic niche contraction of Vaccinium myrtillus L. and V. vitis-idaea L. in Europe.

We estimated climate niche shifts and threat levels under various climate change scenarios for Vaccinium myrtillus L. and V. vitis-idaea L. We developed the MaxEnt species distribution models, and predicted future climatic optima for climate change scenarios for 2041-2060 and 2061-2080. The precipitation of the warmest quarter was the most important factor shaping the climatic niches of the studied species. We predicted the largest shifts in climate niches from the present to the 2040-2060 period, with the most pessimistic scenario predicting significant range losses for both species, mainly in Western Europe. Under the most optimistic SSP126 scenario, both species will lose 39 % of their climatic niche for both periods. In the worst-case scenario (SSP585) for 2061-2080, climatic niche contraction will cover 47 % and 39 % of the current climatic niche for V. myrtillus and V. vitis-idaea, respectively. The predicted changes in species distribution could have far-reaching consequences for temperate and boreal forests due to their crucial biocenotic role in forest ecosystems, high potential for carbon sequestration, and prevention of soil erosion. Furthermore, the changes would likely affect the economic potential regarding fruit production and culturally relevant uses of different parts of the plants, mainly fruits.

Nutritional and Physicochemical Properties of Wild Lingonberry (Vaccinium vitis-idaea L.)-Effects of Geographic Origin.

In recent years, much attention has been devoted to Vaccinium L. berries because of their substantial potential to be adapted for the development of innovative food and pharmaceutical applications. The accumulation of plant secondary metabolites is extremely dependent on climate and other environmental conditions. In order to increase the reliability of the findings, this study was conducted with samples collected in four regions in Northern Europe (Norway, Finland, Latvia, and Lithuania) and analyzed in a single laboratory using a standardized methodology. The study aims to provide a comprehensive understanding of the nutritional (biologically active compounds (phenolic (477-775 mg/100 g fw), anthocyanins (20-57 mg/100 g fw), pro-anthocyanidins (condensed tannins (141-269 mg/100 g fw)) and antioxidant activity in different systems (ABTS•+, FRAP). Physicochemical properties (acidity, soluble solids, color) of wild Vaccinium vitis-idaea L. were also evaluated. The results may contribute to the development of functional foods and nutraceuticals with potential health benefits in the future. To the best of our knowledge, this is the first comprehensive report on the evaluation of the biologically active compounds of wild lingonberries from different Northern European countries based on one laboratory's validated methods. The results indicated a geomorphological influence on the biochemical and physicochemical composition of wild Vaccinium vitis-idaea L. depending on their place of geographical origin.

Effect of ripening temperature on the chemical composition of lingonberries (Vaccinium vitis-idaea L.) of northern and southern origin.

Lingonberries (Vaccinium vitis-idaea L.) from two locations, northern (69°N, 18°E) and southern (59°N, 10°E) Norway, were grown under controlled conditions in a phytotron at two temperatures (9 and 15 °C) to study the effects of the ripening temperature and origin on the chemical composition of the berries. The concentrations of phenolic compounds, sugars, and organic acids as well as the profile of volatile organic compounds (VOCs) were determined using chromatographic and mass spectrometric methods. Five anthocyanins, eleven flavonols, eight cinnamic acid derivatives, three flavan-3-ols, three sugars, three organic acids, and 77 VOCs were identified, of which 40 VOCs had not previously been reported in lingonberries. Berries from both locations, were found to have higher contents of anthocyanins and cinnamic acid derivatives when ripened at lower temperature (9 °C), compared to the higher temperature (15 °C). Lingonberries of northern origin had a different VOC profile and higher contents of anthocyanins and organic acids than berries originating from the south. Lingonberries from the northern location also had higher proportions of cyanidin-3-O-glucoside and cyanidin-3-O-arabinoside than lingonberries from the southern location. The results show that the composition of lingonberries is influenced by both the environment and the origin of the plants, with phenolic compounds mainly influenced by the growth temperature and VOCs mainly influenced by plant origin.

Cranberry-lingonberry juice affects the gut and urinary microbiome in children - a randomized controlled trial.

The mechanism by which cranberry-lingonberry juice (CLJ) prevents urinary tract infections (UTI) in children remains unknown. We hypothesized that it alters the composition of the gut or urinary microbiome. Altogether, 113 children with UTIs were randomly allocated to drink either CLJ or a placebo juice for 6 months. We collected urinary samples at 3 months and fecal samples at 3, 6 and 12 months and used next-generation sequencing of the bacterial 16S gene. The children who consumed CLJ had a lower abundance of Proteobacteria (p = 0.03) and a higher abundance of Firmicutes phylum (p = 0.04) in their urinary microbiome at 3 months than did those in the placebo group. The abundance of Escherichia coli in the urinary microbiome was 6% in the CLJ group and 13% in the placebo group (p = 0.42). In the gut microbiome the abundance of Actinobacteria at 3 and 12 months was higher in the children receiving CLJ. The diversity of the urinary and gut microbiome did not differ between the groups. The children drinking CLJ had a different urinary and gut microbiome from those receiving a placebo juice. A healthy urinary microbiome may be important in preventing UTIs in children.

On the effect of flavonoids and dietary fibre in lingonberries on atherosclerotic plaques, lipid profiles and gut microbiota composition in Apoe-/- mice.

It has not been clarified whether the anti-atherosclerotic effect of lingonberry can be ascribed to its content of flavonoids or dietary fibre or both. The aim of this study was to evaluate the metabolic effects of whole lingonberries compared with isolated flavonoid and fibre fractions on atherosclerotic plaques, plasma lipid profiles, gut microbiota and microbiota-dependent metabolites in an Apoe-/- mouse model. Mice fed whole lingonberries showed the lowest amount of atherosclerotic plaques, while mice fed the fibre fraction had the highest formation of caecal butyric acid. Flavonoids, rather than dietary fibre, were suggested to be the components that favour proliferation of Akkermansia, as judged by the lowest abundance of this bacterium in mice fed the fibre fraction. All groups fed lingonberry diets had both, lower Firmicutes/Bacteroidetes ratios and creatinine concentrations, compared with the control. To conclude, different components in lingonberries are associated with different physiological effects in Apoe-/- mice.

Fermented lingonberry juice's effects on active MMP-8 (aMMP-8), bleeding on probing (BOP), and visible plaque index (VPI) in dental implants-A clinical pilot mouthwash study.

OBJECTIVES: We aimed to study the effects of fermented lingonberry juice (FLJ) as a mouthwash on the levels of active matrix metalloproteinase-8 (aMMP-8) in peri-implant sulcular fluid (PISF), bleeding on probing (BOP), and visible plaque index (VPI). We hypothesized that FLJ rinsing could reduce inflammation (aMMP-8 and BOP) and microbial load (VPI) in the oral cavity, especially around dental implants. MATERIALS AND METHODS: A clinical pilot study was performed using FLJ as a mouthwash. The inclusion criteria were at least one dental implant in the anterior or posterior areas with a screw-retained crown. Ten participants used 10 ml of mouthwash twice a day for 15 days, and 10 participants served as the control group. Point-of-care tests (POCTs) were used to measure aMMP-8 levels in the PISF, and BOP and VPI were recorded at the beginning of the trial and after 15 and 30 days. RESULTS: The FLJ mouthwash had a reductive effect on aMMP-8, VPI, and BOP in the mouthwash group; however, there was no significant difference compared to the control group. The difference in VPI and BOP levels between the groups diminished after the lingonberry regimen ended. The decrease in aMMP-8 levels appeared to continue even after discontinuation of the mouthwash regimen. CONCLUSION: The reduction in the amount of plaque, aMMP-8, and BOP by FLJ was promising and continuous considering the relatively short study period and sample size. FLJ is a natural and safe supplement for oral and dental implant home care. Further studies are required to verify these promising results.

Epigenomic insight of lingonberry and health-promoting traits during micropropagation.

Epigenetic variation plays a role in developmental gene regulation and responses to the environment. An efficient interaction of zeatin-induced cytosine methylation and secondary compounds has been displayed for the first time in tissue-culture shoots/plants of lingonberry (Vaccinium vitis-idaea L.) cultivar Erntedank in vitro (NC1, in a liquid medium; NC2, on a semi-solid medium), ex vitro (NC3, node culture-derived plants; LC1, leaf culture-derived plants) and its cutting-propagated (ED) plants. Through methylation-sensitive amplification polymorphism (MSAP) assay, we observed highest methylated sites in leaf regenerants (LC1) from all primer combinations (108 bands), along with the highest secondary metabolites. The four types of tissue culture-derived shoots/plants (NC1, NC2, NC3, LC1) showed higher methylation bands than cutting propagated donor plants (ED) that exhibited 79 bands of methylation, which is comparatively low. Our study showed more methylation in micropropagated shoots/plants than those derived from ED plants. On the contrary, we observed higher secondary metabolites in ED plants but comparatively less in micropropagated shoots (NC1, NC2) and plants (NC3, LC1).

Inhibitory effect of lingonberry extract on HepG2 cell proliferation, apoptosis, migration, and invasion.

Lingonberry (Vaccinium vitis-idaea L.) extract contains various active ingredients with strong inhibitory effects on cancer cell growth. HepG2 cells were treated with various concentrations of lingonberry extract, cell inhibition rate was measured by CCK-8 assay, and apoptosis rate by annexin-propidium iodide double-staining assay. The cell cycle was analyzed by flow cytometry, and cell migration and invasion by transwell assay. Real-time reverse transcription-PCR and western blotting were employed to analyze the expression of C-X-C motif chemokine ligand 3 (CXCL3). Ki-67, TUNEL, and transwell assays were used to verify the relationship between CXCL3 expression and cell proliferation, apoptosis, migration, and invasion. The composition of lingonberry extract was: 37.58% cyanidin-3-O-glucoside, 10.96% kaempferol 3-O-arabinoside, 4.52% epicatechin, 4.35% chlorogenic acid, 3.83% catechinic acid, 1.54% isoquercitrin, 1.05% 4-hydroxycinnamon acid, 1.03% cyanidin chloride, 0.85% 2,3-dihydroxybenzoic acid, 0.55% quercetin, 0.36% D-(-)-quininic acid, 0.96% caffeic acid, 0.16% ferulic acid, 0.12% oleanolic acid, and 0.03% ursolic acid. Lingonberry extract inhibited the proliferation of HepG2 cells in a dose-dependent manner. After 48 h exposure to 100 µg/mL extract the inhibition rate and IC50 were 80.89±6.05% and 22.62 µg/mL, respectively. Lingonberry extract promoted late apoptosis in HepG2 cells and arrested the cell cycle at G2/M and S phases. Lingonberry extract also promoted the apoptosis of HepG2 cancer cells, inhibiting their proliferation, migration, and invasion by regulating the expression of CXCL3. This study offers new insight into the antihepatoma activity of lingonberry extract and provides a basis for the development of pilot antitumor drugs.

Exploring Vaccinium vitis-idaea L. as a potential source of therapeutic agents: antimicrobial, antioxidant, and anti-inflammatory activities of extracts and fractions.

ETHNOPHARMACOLOGICAL RELEVANCE: Vaccinium vitis-idaea L. (lingonberry) leaves and fruits have traditionally been used in Asian and European countries as a natural solution for urinary tract infections, gastrointestinal distress, neurodegenerative diseases, and related inflammatory disorders, which are overall associated with free radical damage and presence of triggering pathogenic strains in the human body. Considering growing attention to natural products, there are not enough scientific data to confirm predominant specialized metabolites, responsible for the traditional therapeutic use of lingonberries. AIM OF THE STUDY: The present study aimed at an in-depth study of specialized metabolite profiling and biological activity evaluation of lingonberry crude extracts and isolated fractions. MATERIALS AND METHODS: Crude dry extracts and fractions from lingonberry leaves and fruits were analyzed by the UPLC-MS method. Potential inhibiting properties against different bacterial strains and hyaluronidase, ability to scavenge hydrogen peroxide, and effect on its production in a macrophage culture J774 were examined. RESULTS: Findings suggested the tentative presence of 59 compounds, mainly phenolics, displayed higher bioactivities of particular fractions than that of crude extracts and elucidated particular compounds as candidates in pharmaceuticals. Trimeric and dimeric proanthocyanidins from lingonberry leaves and fruits were shown to have the strongest antimicrobial, antioxidant, and anti-inflammatory potential. CONCLUSIONS: This study revealed specialized metabolites responsible for the traditional medicinal properties of lingonberries and pointed out demand for further purification and new research directions of proanthocyanidins in the frame of their multipharmacological perspectives.

Lingonberry Anthocyanins Inhibit Hepatic Stellate Cell Activation and Liver Fibrosis via TGFß/Smad/ERK Signaling Pathway.

Phytochemicals from lingonberry have rich pharmacological value and may play an essential role in treating liver diseases. We investigated the regulatory role of lingonberry anthocyanins (LA) on HSC activation in vitro and liver fibrogenesis in vivo. The viability of HSCs treated with LA was significantly reduced in a dose-dependent manner at the concentration of 25-100 µg/mL, in which the monomers of LA also reduced the proliferation of HSCs via IC50 assay. The inducer transforming growth factor ß1 (TGFß1) and the effector α-smooth muscle actin (α-SMA) of HSC activation were all decreased both in protein and RNA levels treated by LA. Moreover, LA alleviated CCl4-induced liver fibrosis in rats, reducing collagen aggregation and production and decreasing the hydroxyproline (HYP) and malondialdehyde (MDA) levels in the liver tissue. Moreover, LA reduced the indexes of serum liver fibrosis and reversed the index of serum liver function in CCl4-induced rats. Furthermore, the antioxidant enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT), in the liver tissue and serum were significantly increased upon treatment with LA. Importantly, LA promoted hepatic parenchymal cell proliferation and inhibited the expression of TGFß/Smad/extracellular regulated protein kinase (ERK) signaling pathway-related genes. This study demonstrates the anti-liver fibrosis activity of LA and investigates its mechanism, which may provide a novel strategy for treating liver fibrosis using lingonberry.