Search Results (65)

Leaves of Actinidia chinensis Planch. var. deliciosa (A.Chev.) A.Chev. (A. deliciosa) represent agro-industrial byproducts with potential for valorization. The present study evaluated the metabolomics profiling, cytotoxicity, genotoxicity, and antigenotoxicity of the methanolic extract of A. deliciosa leaves. The metabolomics profiling was determined using an untargeted metabolomic approach employing UPLC-HRMS. Cytotoxicity, genotoxicity, and antigenotoxicity were assessed in Chinese hamster ovary K1 (CHO-K1) cells using the in vitro cytokinesis-block micronucleus (CBMN) assay. The metabolic profile of A. deliciosa leaf extracts revealed the presence of three major classes of secondary/specialized metabolites: proanthocyanidins, flavonols, and triterpenoid saponins. Medium-polar metabolites were monomeric fla-van-3-ols, such as (+)-catechin and (−)-epicatechin, oligomeric procyanidins and prodelphinidins, and flavonols. Certain glycosylated flavonols and their derivatives, such as myricetin, quercetin, and kaempferol. Low-polarity metabolites were characterized by low-polarity triterpenoids such as maslinic, corosolic, oleanolic, and ursolic acids. At concentrations of 37.5, 75, and 150 µg/mL, the extract did not significantly increase micronuclei frequency compared to untreated control cells, indicating an absence of genotoxic potential. Moreover, co-treatment of CHO-K1 cells with the extract and mitomycin C (MMC) at 0.025 µg/mL resulted in a significant reduction in micronuclei formation induced by MMC at concentrations of 75 and 150 µg/mL, suggesting antigenotoxic activity likely associated with the phytochemical constituents presented in the extract. Full article

This study aimed to evaluate the potential of branches of black chokeberry, sea buckthorn, and black currant as raw materials for the development of pharmacologically active compounds, primarily oligomeric proanthocyanidins (OPCs), as they exhibit a broad spectrum of biological activities, including antioxidant, antimicrobial, anti-inflammatory, anticancer, etc. Branch biomass collected in spring and autumn of 2023–2025 was analyzed for its functional group profile and used for the isolation of OPCs with ethanol, an ethanol–water mixture (1:1, v/v), and an ethanol–acetone–water mixture (4:1:5, v/v/v). The highest yield of OPCs (up to 14% of DB) was achieved using the ethanol–acetone–water solvent mixture. Using LC-MS/MS, the OPC composition was analyzed and found to consist of dimers (m/z 577), trimers (m/z 865), and tetramers (m/z 1153). The maximum OPC content was observed in autumn samples. Mechanical pretreatment enhanced OPC accessibility by disrupting cell walls and increasing particle surface, facilitating release from the matrix and yielding up to 1.2-fold more OPCs than from untreated biomass. Quantification of 22 elements in the biomass by ICP-MS revealed low levels of toxic metals along with the presence of nutritionally relevant elements. Therefore, from a chemical safety perspective, biomass can be considered suitable for use as a source of OPCs. Full article

Background: Chronic inflammatory enteropathies (CIEs) in dogs are multifactorial disorders characterized by mucosal immune dysregulation, compromised epithelial barrier function, and increased exposure to microbial components such as lipopolysaccharide (LPS). The resulting oxidative stress and inflammation contribute to local and systemic pathology. Objective: This study aimed to evaluate the immunomodulatory and antioxidant effects of three naturally occurring flavonoids—quercetin, luteolin, and grape seed extract oligomeric proanthocyanidins (GSOPs)—in LPS-stimulated canine duodenal explants. Methods: Duodenal tissue samples were cultured in vitro and challenged with LPS derived from Escherichia coli and Salmonella enterica. Explants were co-incubated with flavonoid compounds, and endpoints included evaluation of histological architecture, inflammatory cytokine production, and reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation. Results: All three flavonoids attenuated LPS-induced mucosal inflammation and ROS production to varying degrees. In addition, GSOPs significantly reduced RNS levels under both basal and LPS-stimulated conditions. Quercetin and luteolin demonstrated pronounced downregulation of TNF-α, while both compounds also reduced IL-6 concentrations under non-stimulated conditions. These effects support the hypothesis that flavonoids can mitigate both inflammatory and oxidative responses under conditions relevant to CIE. Conclusion: Quercetin, luteolin, and GSOPs show promising in vitro efficacy in modulating key mechanisms implicated in canine CIE. Their multimodal actions highlight their potential as adjunctive nutraceuticals for the management of CIE in dogs. However, further in vivo validation is warranted. Full article

Background/Objectives: Tea, the world’s second most consumed beverage after water, contains diverse phytochemicals that have garnered growing interest for their potential ability to modulate inflammasome activation. This study examined the antioxidant and anti-inflammatory properties of oolong tea (OLT) extracts, with a specific focus on their regulatory effects on NLRP3 inflammasome assembly—a critical mediator in chronic inflammatory diseases. Methods: OLT extracts were prepared from the Jin-Xuan cultivar with quantification for bioactive components (total phenolics, flavonoids, condensed tannins, and proanthocyanidins). J774A.1 murine macrophages were primed with LPS and stimulated with ATP to induce inflammasome activation. Therapeutic potentials of OLT extracts were assessed by measuring cytokine secretion, expression of NLRP3 inflammasome-related proteins (NLRP3, ASC, Caspase-1, and IL-1β), inflammasome complex formation, and ROS generation via biochemical assays, immunoblotting, and fluorescence microscopy. Results: OLT extracts, particularly at 100 µg/mL, markedly suppressed both the priming and activation phases of NLRP3 inflammasome formation. OLT treatment reduced IL-1β secretion by more than 50%, attenuated ASC oligomerization and speck formation, inhibited caspase-1 cleavage, and lowered intracellular ROS levels by approximately 50%. Conclusions: These findings suggest that OLT extracts exert potent anti-NLRP3 inflammasome activity and offer immunomodulation potential in preventing inflammation-related diseases such as infections, cancer, and neurodegenerative disorders. Further in vivo investigations, followed by clinical applications and epidemiological studies, are warranted to validate these preventive effects in human populations. Full article

Background: Oligomeric proanthocyanidins (OPCs) are natural polyphenolic compounds with strong antitumor properties and have gained attention as potential agents to overcome drug resistance. Hepatocellular carcinoma (HCC) remains a major cause of cancer deaths worldwide, and although Lenvatinib is widely used, its effectiveness is limited by acquired resistance. This study explores the potential of OPCs to overcome Lenvatinib resistance in HCC. Methods: To evaluate the potential of OPCs to overcome Lenvatinib resistance in HCC, we established Lenvatinib-resistant Huh-7 and PLC-PRF-5 cell lines and conducted systematic cell culture experiments to assess their antitumor effects. Furthermore, genome-wide transcriptomic profiling, network pharmacology approaches, and pathway enrichment analysis were performed to identify resistance-associated signaling pathways that could serve as therapeutic targets. Results: The combination of OPCs and Lenvatinib demonstrated a significant synergistic anti-proliferative effect in resistant hepatocellular carcinoma cells, with the most synergistic dose combinations showing Bliss synergy scores exceeding 10. Transcriptomic profiling revealed that the adhesion molecule ITGA3 is a key factor in Lenvatinib resistance and contributes to the acquisition of anoikis resistance. The combination treatment suppressed ITGA3–EGFR–AKT signaling, restored anoikis sensitivity, significantly reduced spheroid formation (fold change = 0.10–0.12; p < 0.001), and markedly increased apoptosis (fold change = 2.7–5.0; p < 0.001). Conclusions: This study is the first to demonstrate that OPCs can overcome chemotherapy resistance by targeting the integrin pathway, providing scientific evidence for their potential use as an adjunctive therapy for chemotherapy-resistant HCC. Full article

Cancer cachexia is a multifactorial syndrome characterized by metabolic dysregulation, inflammation, and progressive loss of skeletal muscle mass. Frequently observed in colorectal cancer patients, it is associated with poor clinical outcomes and reduced treatment tolerance. Current therapies provide limited benefit, underscoring the need for integrative approaches. Grape seed polyphenols, particularly oligomeric proanthocyanidins, have demonstrated potential to modulate catabolic signaling, mitochondrial dysfunction, and inflammatory responses involved in cachexia pathophysiology. This review integrates preclinical and clinical evidence on the use of grape seed-derived products, highlighting their effects on NF-κB and AMPK pathways, redox homeostasis, and gut–muscle axis. Furthermore, the nutritional composition and bioactive properties of grape seed flour—rich in fiber and phenolic compounds—are discussed in the context of nutraceutical applications. A clinical trial currently underway in Brazil aims to evaluate the effects of grape seed flour supplementation in colorectal cancer patients with cachexia. Altogether, grape-derived compounds offer a safe, low-cost, and mechanistically grounded strategy for improving nutritional status and resilience in oncological care. Full article

Background/Objectives: Colorectal cancer (CRC) remains a major health challenge due to its high incidence and resistance to conventional therapies. Natural compounds have gained attention as potential adjuvant treatments. The study assesses whether combining Allium sativum and Vitis vinifera [rich in oligomeric proanthocyanidins condensed (OPCs)] extracts enhances cell viability reduction and migration inhibition. Methods: Human colorectal cancer cell lines (Caco-2 and HT-29) were treated with increasing concentrations of both extracts individually and in combination. Cell viability was assessed using MTT assays, while migration was evaluated through scratch wound assays. Synergistic effects were analyzed using Combenefit software. Results: Both extracts significantly reduced cell viability in a dose- and time-dependent manner. The combination of both extracts led to an enhanced reduction in cell viability, with a transient synergistic effect observed at 24 h in HT-29 cells. Regarding migration, OPCs showed a transient anti-migratory effect at 6 h in HT-29 cells, but no significant impact was observed in Caco-2 cells or at later time points. Conclusions: These findings suggest that Allium sativum and Vitis vinifera extracts have potential as complementary treatments for colorectal cancer, mainly through their effect on cell viability. This study opens a field of research on the possible therapeutic effects of natural extracts. Full article

Objectives: Modern lifestyles factors such as digital overload, aging, and poor sleep hygiene have led to increasing cases of sleep disturbances and inflammation-related disorders. These conditions are often associated with oxidative stress and immune dysregulation. Longan flower extract (LFE), traditionally used in East Asian medicine, has shown potential health benefits but remains scientifically underexplored. This study aims to investigate the chemical composition and bioactive effects of LFE on inflammation, oxidative stress, and melatonin biosynthesis in relevant cellular models. Methods: LFE was prepared using ethanol extraction and characterized for its total polyphenols, flavonoids, oligomeric proanthocyanidins (OPCs), and corilagin content via HPLC. Its anti-inflammatory, antioxidant, and neuroregulatory activities were assessed in LPS-stimulated RAW 264.7 macrophages and BV-2 microglial cells. Key assays included quantification of cytokines (TNF-α, IL-6), detection of nitric oxide (NO) and reactive oxygen species (ROS), and measurement of antioxidant enzyme activities (GPx, SOD). Gene expression of melatonin biosynthesis enzymes was evaluated using quantitative PCR. Results: LFE treatment significantly reduced LPS-induced TNF-α, IL-6, NO, and ROS production in both cell models. It enhanced GPx and SOD activity and increased intracellular glutathione levels. Moreover, LFE upregulated the expression of TPH1, DDC, AANAT, and ASMT, genes involved in melatonin biosynthesis, and promoted serotonin secretion. Conclusions: These findings suggest that LFE holds significant potential as a natural therapeutic supplement, particularly for alleviating sleep disturbances, reducing oxidative stress, and modulating inflammatory responses associated with modern lifestyle-related health conditions. Full article

Cadmium (Cd) is a toxic, non-essential metal that primarily enters animal bodies through the digestive and respiratory systems, leading to damage to multiple organs and tissues. Cd can accumulate in cartilage and induce damage to chondrocytes. Procyanidins (PAs), also known as concentrated tannic acid or oligomeric proanthocyanidins (OPCs), exhibit diverse biological and pharmacological activities. However, the mechanism of OPCs alleviates Cd-induced damage to chondrocytes in chickens remains to be further explored in vitro. Chondrocytes were isolated from both ends of the tibia of 17-day-old SPF chicken embryos, and then subsequently treated with various concentrations of Cd (0, 1, 2.5, 5, and 10 μmol/L) or OPCs (0, 5, 10, 20, and 40 μmol/L) to investigate the mechanism underlying extracellular matrix (ECM) degradation and damage. Cd reduced cell viability, glycosaminoglycan (GAG) secretion, and ECM degradation in chondrocytes by decreasing the expression of type II collagen alpha 1 (COL2A1) and aggrecan (ACAN) while increasing the release of cartilage oligomeric matrix protein (COMP), along with elevated levels of matrix-degrading enzymes, such as matrix metalloproteinases 1 (MMP1), MMP10, and MMP13, and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) and ADAMTS5. Cd induced phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) and the expression of matrix-degrading enzymes, impairing ECM synthesis, an effect that could be alleviated by ERK1/2 inhibitor U0126. Chondrocytes were treated with 5 μmol/L Cd and 10 μmol/L OPCs, and it was found that OPCs inhibited the activation of the ERK1/2 signaling pathway and the expression of matrix-degrading enzymes, while promoting ECM synthesis and alleviating Cd-induced ECM damage in chickens. This study provides a theoretical basis for clinical research on OPCs with respect to the prevention and treatment of Cd-induced chondrogenic diseases in poultry. Full article

Proanthocyanidins have received extensive attention due to their high functional value, but their sources are limited. Therefore, this experiment studied the preparation, biological activities, and characterization of proanthocyanidins from Chinese jujube (Ziziphus jujuba Mill. cv. Muzao) at different periods, aiming to explore a new source of proanthocyanidins and enhance their utilization value. Through ultrasonic-assisted enzymatic extraction, the optimal extraction conditions for PC from Muzao were determined, yielding a proanthocyanidin content of 2.01%. Purification using AB-8 macroporous resin increased the proanthocyanidin content by 11 times. The bioactivity results indicated that proanthocyanidins demonstrated significant in vitro antioxidant activity (scavenging rate ≥ 83.4%) and blood glucose-lowering activity (inhibition rate ≥ 84.7%). Both activities decreased with maturity, while the degree of polymerization also exhibited a positive effect. Mass spectrometry identified a total of 102 compounds, with cyanidin-based compounds being the most abundant, comprising 28 species. The comprehensive research results indicate that the oligomeric proanthocyanidins extracted, purified, and isolated from Muzao during the young fruit stage exhibit diverse biological activities and are abundant in content. They can be utilized for the extraction and purification of proanthocyanidins, offering a reference for the expansion of natural sources of proanthocyanidins and the development of functional foods. Full article

Background/Objectives: Benign prostatic hyperplasia (BPH) is one of the most common chronic diseases affecting the urinary tract that occurs mainly in men over 40 years of age. Among the natural therapies, proanthocyanidins (PACs), which can treat a wide range of immune-mediated inflammatory diseases (IMIDs), have been shown to play an important role in the treatment of pathologies concerning prostate health. In this regard, the present study aimed to evaluate the different bioactivities of a grape seed extract (GSE), rich in polymeric PACs, and its version processed under alkaline conditions (ATGSE), characterized by a higher content of oligomeric PACs, in an animal model of BPH induced by subcutaneous injection of testosterone (1 mg/mouse). Methods: These latter were divided into a control group (vehicle, olive oil), a BPH group (testosterone 1 mg/mouse), and four treatment groups treated with GSE (500 mg/kg) and ATGSE (125, 250, 500 mg/kg) by oral gavage. At the experimental endpoint (4 weeks), hematological and biochemical analyses of blood and tissues were performed. Results: Data showed that oral administration of ATGSE (250 mg/kg) was significantly more effective than GSE in reducing prostate (p ≤ 0.0001) and seminal vesicle (p ≤ 0.0001) weight. Moreover, ATGSE exhibited enhanced effectiveness in significantly reducing PSA levels (p ≤ 0.0001 vs. GSE) and the expression of key pro-inflammatory cyto-chemokines in prostate and seminal vesicles homogenates. Conclusions: These findings pave the way for the clinical application of ATGSE as a nutraceutical and/or functional food. Full article

Osteocyte senescence is associated with skeletal dysfunction, but how to prevent bone loss and find the effective therapeutic targets is a potential scientific concern. Cadmium (Cd) is a widespread environmental contaminant that causes substantial bone damage in both animals and humans. Oligomeric proanthocyanidins (OPC) are naturally polyphenolic substances found in various plants and demonstrate significant anti-senescence potential. Here, we investigated the protective effects of OPC against Cd-induced senescence of osteocytes and identify potential regulatory mechanisms. OPC alleviated Cd-induced senescence of osteocytes by attenuating cell cycle arrest, reducing ROS accumulation, and suppressing pro-inflammatory responses in vitro. Furthermore, OPC effectively prevented the Cd-induced breakdown of dendritic synapses in osteocytes in vitro. Correspondingly, OPC ameliorated Cd-induced damage of osteocytes through anti-senescence activity in vivo. Taken together, our results establish OPC as a promising therapeutic agent that ameliorates Cd-induced osteocyte senescence by mitigating oxidative stress and inflammatory responses. Full article

Antioxidant activity and flavonoid content are important characteristics of colored rice grains. Previously, we obtained a preliminary understanding of the metabolic markers of antioxidant activity, namely, phlorizin and trilobatin, in different colored rice varieties and purple rice grains at different growth stages, but the mechanisms associated with these markers have not yet been confirmed. In this study, purple rice was selected as the experimental material, and clover extract was applied during the grain-filling stage to explore the impact of clover extract on the total antioxidant capacity and flavonoid biosynthesis in purple rice grains. The results indicated that the total flavonoid content, total phenolic content, oligomeric proanthocyanidin content, and total antioxidant capacity of purple rice grains treated with an exogenous application of trilobatin (T30) were significantly greater than those of the control (CK). The flavonoids in the T30 and CK groups accounted for 29.81% of the total flavonoids. The phenylpropanoid biosynthesis and flavonoid biosynthesis metabolic pathways were constructed on the basis of the differentially abundant metabolites between the T30 and CK groups. Additionally, 1-O-sinapoyl-beta-D-glucose, coniferaldehyde, 6″-acetylapiin, and kaempferol-3-O-rutinoside were determined to be essential metabolites for trilobatin-mediated flavonoid biosynthesis in purple rice. The correlation network diagram between biochemical indexes and metabolites revealed that 1-O-sinapoyl-beta-D-glucose, coniferaldehyde, 6″-acetylapiin, and kaempferol-3-O-rutinoside were important metabolites. This study provides a scientific basis for improving the nutritional quality of rice grains and understanding the flavonoid biosynthesis pathway. Full article

Background: Proanthocyanidins (PACs) from black soybean seed coat have antioxidant and anti-tumorigenic properties. We investigated the anti-tumor properties and mechanisms of action of PACs on colorectal cancer (CRC). Methods: We fed the APC^min/+ mice, which are highly susceptible to spontaneous intestinal adenoma formation, diets supplemented with or without PACs for 7 weeks and assessed adverse effects, the number and size of intestinal polyps, and the expression of pro- and anti-proliferative proteins in the intestine. The mouse gut microbiome composition was analyzed, and the concentrations of gut short-chain fatty acids (SCFAs) were quantified. We also compared CRC incidence in Tamba in Japan, where black soybean is consumed frequently, with that in the rest of Japan. Results: The number and size of intestinal polyps notably decreased in the PAC-fed mice. Compared with control mice, the PAC-fed mice showed lower expression of proliferation markers proliferating cell nuclear antigen and β catenin and a higher expression of the anti-inflammatory protein oligomeric mucus gel-forming. PAC supplementation increased the prevalence and concentrations of beneficial gut microbes and SCFAs, respectively. Conclusions: Diet supplemented with black soybean-derived PACs could prevent CRC development in mice through gut microbiome remodeling. Regions consuming black soybeans have low CRC incidence. Notably, the incidence of CRC, breast cancer, and liver cancer was significantly lower in Tamba than in the rest of Hyogo Prefecture or Japan. Future studies should delineate the mechanisms underlying the CRC-protective effects of PACs. Nevertheless, our results demonstrate the potential of including PACs in dietary recommendations for cancer prevention. Full article

Few investigations have been conducted to evaluate pressurized liquid extraction (PLE) technology as a sustainable method for the recovery of phenolic compounds of grape seed by-products. In this study, PLE combined with an experimental design was evaluated for optimizing the sustainable extraction of phenolic compounds from grape seed by-products. The solvent ethanol content (X1, 0–100%), temperature (X2, 20–100 °C) and time (X3, 1–11 min) were studied as independent experimental factors. Yield, TPC, antioxidant activity and phenolic composition were analyzed as optimized dependent variables. Two optimal extraction conditions at different temperatures (20 °C and 100 °C) were found, but thermal degradations at 100 °C allowed for selecting the optimal condition as 75% ethanol, 11 min and 20 °C. The optimal extracts showed high phenolic content (TPC = 350.80 ± 3.97 mg GAE/g extract) and antioxidant activity (ABTS, 9.31 ± 0.33 mmol Trolox/g extract), mainly composed of polymeric and mono-oligomeric flavan-3-ols. The digestion process reduced the TPC and antioxidant activity due to the low bioaccessibility of the flavan-3-ols, mainly as catechin, epicatechin and polymeric proanthocyanidin losses during the digestion process. However, increases in the antioxidant activity of the basolateral side (DDPH, 0.061 ± 0.000 mmol Trolox/g extract) were determined after in vitro transepithelial transport, which is a consequence of bioavailable catechin and epicatechin and reduced amounts of dimer B₂, dimer B₁, epicatechin gallate and gallic acid. Consequently, PLE combined with hydroalcoholic solvents at a low temperature resulted in a valuable methodology to obtain sustainable extracts from grape seed by-products (contributing to the circular economy), containing bioavailable phenolic compounds, which are able to increase the antioxidant status. Full article