Search Results (88)

The visual colorimetric sensing of total volatile basic nitrogen (TVB-N) allows for convenient dynamic monitoring of animal-derived food freshness to ensure food safety. The agarose hydrogel loaded with the natural dye juglone (Jug@AG) prepared in this study exhibits visible multicolor changes from yellow to grayish-yellow and then to brownish with increasing TVB-N gas concentration, achieving sensitive detection of TVB-N gas at concentrations as low as 0.05 mg/dm³ within 8 min. The minimum observable amounts of TVB-N in spiked pork and fish samples are 8.43 mg/100 g and 8.27 mg/100 g, respectively, indicating that the Jug@AG hydrogel possesses sensitive colorimetric sensing capability in practical applications. The Jug@AG hydrogel also shows significant changes in color difference value (∆C) under both room temperature (25 °C) and cold storage (4 °C) conditions, with the changing trends of ∆C showing consistency with the measured TVB-N and total viable counts (TVC) during the transition of pork and fish samples from freshness to early spoilage and then to spoilage. The results indicate that the Jug@AG hydrogel can be used as a colorimetric sensor to achieve real-time dynamic freshness monitoring of animal-derived food. Full article

Prostate cancer (PCa) therapy faces challenges due to tumor heterogeneity, plasticity, and progression. Metabolic reprogramming, a dynamic process, has emerged as a key focus in PCa treatment. However, conventional therapies targeting cancer-specific metabolic pathways or employing chemosensitizers are often limited by compensatory mechanisms and metabolic complexity. This review highlights the roles of transcription factors, including AR, p53, c-Myc, HIF-1, Nrf2, and PPARγ, in regulating PCa metabolism by influencing signaling pathways, enzymes, and gene expression. Multi-target compounds, particularly natural products, show potential for disrupting multiple metabolic enzymes, opening up new research possibilities. Notable examples include β-elemene, juglone, tannic acid, and withaferin A, which target critical metabolic processes through enzyme inhibition, transcription factor modulation, epigenetic changes, and protein interaction disruption. Naturally derived metabolites can elicit transversal responses in diverse metabolic pathways, particularly in p53 and MYC transcription factors. Additionally, compounds such as pentacyclic terpenoids (ursolic acid with ursane skeleton), sulforaphane, and isothiocyanate-related moieties may induce metabolic and epigenetic changes through S-adenosyl methionine (SAM) and acetyl-CoA modulation, potentially affecting new areas of research through metabolic processes. We propose a cooperative crosstalk between metabolic reprogramming and transcription factors/epigenetic modulation in PCa. This approach holds potential for expanding PCa therapeutics and opening new avenues for research. Full article

Background: Colorectal cancer is the third most common cancer worldwide, accounting for about 10% of all cancer cases. There is an urgent need to improve treatment outcomes and survival rates for colorectal cancer. Juglone is an anthraquinone with anti-inflammatory, antiviral, and anti-cancer properties that have shown promise in inhibiting tumor cell growth. Objectives: This study aims to explore the mechanism behind Juglone’s anti-cancer effects on colorectal cancer. Methods: Network pharmacology, molecular docking and molecular dynamics simulation were used to explore the specific targets of Juglone in the treatment of colorectal cancer. For in vitro validation, we used the CCK–8 (Cell Counting Kit–8) method, flow cytometry, ROS (Reactive Oxygen Species) detection, and Western blot analysis to assess the survival ability of colorectal cancer cells and validate the expression of proteins most closely associated with the pathways. Results: Network pharmacology identified TP53 as a key target of Juglone, involved in anti-tumor pathways. Molecular docking and molecular dynamics simulations showed that the p53 has strong affinity and stability with Juglone. Results from cytotoxicity experiments, flow cytometry, ROS detection, and Western blotting indicated that the anti-colorectal cancer effect of Juglone depends on concentration and is mediated by promoting intracellular ROS generation and upregulating the expression level of p53 protein, thereby inhibiting the progression of colorectal cancer. Conclusions: Juglone can achieve anti-colorectal cancer effects by increasing ROS levels and regulating the p53 protein. Full article

Colorectal cancer is a major global health challenge, with current treatments limited by toxicity and resistance. Thiazole derivatives, known for their bioactivity, are emerging as promising alternatives. Juglone (5-hydroxy-1,4-naphthoquinone) is a naturally occurring compound with known anticancer properties, and its incorporation into thiopyrano[2,3-d]thiazole scaffolds may enhance their therapeutic potential. This study examined the cytotoxicity of thiopyrano[2,3-d]thiazoles and their effects on apoptosis in colorectal cancer cells. Les-6547 and Les-6557 increased the population of ROS-positive HT-29 cancer cells approximately 10-fold compared with control cells (36.3% and 38.5% vs. 3.8%, respectively), potentially contributing to various downstream effects. Elevated ROS levels were associated with cell cycle arrest, inhibition of DNA biosynthesis, and reduced cell proliferation. A significant shift in the cell cycle distribution was observed, with an increase in S-phase (from 17.3% in the control to 34.7% to 51.3% for Les-6547 and Les-6557, respectively) and G2/M phase (from 24.3% to 39.9% and 28.8%). Additionally, Les-6547 and Les-6557 inhibited DNA biosynthesis in HT-29 cells, with IC₅₀ values of 2.21 µM and 2.91 µM, respectively. Additionally, ROS generation may initiate the intrinsic apoptotic pathway. Les-6547 and Les-6557 activated both intrinsic and extrinsic apoptotic pathways, demonstrated by notable increases in the activity of caspase 3/7, 8, 9, and 10. This study provides a robust basis for investigating the detailed molecular mechanisms of action and therapeutic potential of Les-6547 and Les-6557. Full article

Globalization has greatly expanded the opportunities for plant species to enter new areas through a wide range of pathways. Elucidating the pathways of spread of alien species and the characteristics of organisms that make them invasive is one of the most pressing problems in ecological sciences. Once established, alien species may have serious implications for communities and vice versa. Allelopathy has been proposed as one of the possible invasion mechanisms of exotic plants. Impatiens parviflora and Impatiens glandulifera are among the widely spread invasive plant species in the Baltic region. The aim of the study was to evaluate the allelopathic effect of invasive Lithuanian Impatiens spp. and their neighboring plants (11 pristine species) using parameters of germination and seedling growth of biotest species Lepidium sativum, and to expand this study by determining the content of phenolic compounds and the radical scavenging activity in the leaf extracts of Lithuanian Impatiens spp. populations (20 of each Impatiens species). Leaf extracts of all species examined had an inhibitory effect on Lepidium sativum germination and morphology of the seedlings. In our study, at all leaf extract concentrations, significantly higher allelopathic potential on radicle growth was characteristic of I. glandulifera compared to native species Alnus glutinosa, Calystegia sepium, and Urtica dioica. At all leaf extract concentrations, I. parviflora showed significantly higher allelopathic potential on radicle growth compared to native species Urtica dioica. Impatiens glandulifera had a higher juglone index than Impatiens parviflora. I. glandulifera also had the highest juglone index compared to all neighboring species studied. The differences between the populations in the content of phenolic compounds, DPPH and ABTS radical scavenging activity were 2.3, 2.2 and 2.7 times for I. glandulifera and 2.6, 5.2 and 2.7 times for I. parviflora. The mean values of total phenolic content, DPPH and ABTS radical scavenging activity of I. glandulifera populations were 2.1, 2.7 and 3.3 times higher than those of I. parviflora populations, respectively. In general, our results about allelopathic potential and phenolics content, as well as free radical scavenging ability, confirm the supreme competitive ability of I. glandulifera compared to both I. parviflora and to the native co-occurring species. Full article

Background and Objectives: PIN1 is overexpressed in several human cancers, including prostate cancer, breast cancer, and oral squamous carcinomas. Juglone (J), derived from walnut, was reported to selectively inhibit PIN1 by modifying its sulfhydryl groups. In this study, the potential effects of juglone, also known as PIN1 inhibitor, on oral cancer and carcinogenesis were investigated at the molecular level. Materials and Methods: 4-Nitroquinoline N-oxide (4-NQO) was used to create an oral cancer model in animals. Wistar rats were divided into five groups: Control, NQO, Juglone, NQO+J, and NQO+J*. The control group received the basal diet and tap water throughout the experiment. The NQO group received 4-NQO for 8 weeks in drinking water only. The Juglone group was administered intraperitoneally in a juglone solution for 10 weeks (1 mg/kg/day). The NQO+J group received 4-NQO in drinking water for 8 weeks, starting 1 week after the cessation of 4-NQO treatment. They were then administered intraperitoneally in a juglone solution for 10 weeks. (1 mg/kg/day). NQO+J* group: received 4 NQO for 8 weeks in drinking water and administered intraperitoneally in a juglone solution for 10 weeks (1 mg/kg/day). They were sacrificed at the end of the 22-week experimental period. The tongue tissues of the rats were isolated after the experiment, morphological changes were investigated by histological examinations, and the molecular apoptotic process was investigated by rt-qPCR and western blot. Results: Histological results indicate that tumors are formed in the tongue tissue with 4-NQO, and juglone treatment largely corrects the epithelial changes that developed with 4-NQO. It has been determined that apoptotic factors p53, Bax, and caspases are induced by the effect of juglone, while antiapoptotic factors such as Bcl-2 are suppressed. However, it was observed that the positive effects were more pronounced in rats given juglone together with 4-NQO. Conclusions: The use of PIN1 inhibitors such as juglone in place of existing therapeutic approaches might be a promising and novel approach to the preservation and treatment of oral cancer and carcinogenesis. However, further research is required to investigate the practical application of such inhibitors. Full article

The aim of our study was the detailed polyphenol profiling of Juglans nigra and the characterization of the membrane permeability and antiproliferative properties of its main phenolics. A total of 161 compounds were tentatively identified in J. nigra bark, leaf, and pericarp extracts by ultrahigh-performance liquid chromatography–high-resolution tandem mass spectrometry (UHPLC-HR-MS/MS). Eight compounds including myricetin-3-O-rhamnoside (86), quercetin-3-O-rhamnoside (106), quercetin-3-O-xyloside (74), juglone (141), 1,2,3,4-tetrahydro-7,8-dihydroxy-4-oxonaphthalen-1-yl-6-O-galloyl-glucoside (92), ellagic acid (143), gallic acid (14), and ethyl gallate (58) were isolated from J. nigra pericarp. The in vitro antiproliferative activity of the isolated compounds was investigated against three human cancer cell lines, confirming that juglone (141) inhibits cell proliferation in all of them, and has similar activity as the clinical standards. The permeability of the isolated compounds across biological membranes was evaluated by the parallel artificial membrane permeability assay (PAMPA). Both juglone (141) and ethyl-gallate (58) showed positive results in the blood–brain-barrier-specific PAMPA-BBB study. Juglone (141) also possesses logPe values which indicates that it may be able to cross both the GI and BBB membranes via passive diffusion. Full article

1,4-naphthoquinones (NQs) catalytically oxidize H₂S to per- and polysufides and sulfoxides, reduce oxygen to superoxide and hydrogen peroxide, and can form NQ-SH adducts through Michael addition. Here, we measured oxygen consumption and used sulfur-specific fluorophores, liquid chromatography tandem mass spectrometry (LC-MS/MS), and UV-Vis spectrometry to examine H₂S oxidation by NQs with various substituent groups. In general, the order of H₂S oxidization was DCNQ ~ juglone > 1,4-NQ > plumbagin >DMNQ ~ 2-MNQ > menadione, although this order varied somewhat depending on the experimental conditions. DMNQ does not form adducts with GSH or cysteine (Cys), yet it readily oxidizes H₂S to polysulfides and sulfoxides. This suggests that H₂S oxidation occurs at the carbonyl moiety and not at the quinoid 2 or 3 carbons, although the latter cannot be ruled out. We found little evidence from oxygen consumption studies or LC-MS/MS that NQs directly oxidize H₂S_2–4, and we propose that apparent reactions of NQs with inorganic polysulfides are due to H₂S impurities in the polysulfides or an equilibrium between H₂S and H₂S_n. Collectively, NQ oxidation of H₂S forms a variety of products that include hydropersulfides, hydropolysulfides, sulfenylpolysulfides, sulfite, and thiosulfate, and some of these reactions may proceed until an insoluble S₈ colloid is formed. Full article

The current study investigated the impact of cold stress on the morphological, physiological, and phytochemical properties of Juglans regia L. (J. regia) using in vitro microclone cultures. The study revealed significant stress-induced changes in the production of secondary antioxidant metabolites. According to gas chromatography–mass spectrometry (GC–MS) analyses, the stress conditions profoundly altered the metabolism of J. regia microclones. Although the overall spectrum of metabolites was reduced, the production of key secondary antioxidant metabolites significantly increased. Notably, there was a sevenfold (7×) increase in juglone concentration. These findings are crucial for advancing walnut metabolomics and enhancing our understanding of plant responses to abiotic stress factors. Additionally, study results aid in identifying the role of individual metabolites in these processes, which is essential for developing strategies to improve plant resilience and tolerance to adverse conditions. Full article

Concern for the future of the next generation leads to the search for alternative solutions for the proper management of materials considered as useless waste. This study fits into this research trend. Its aim is to demonstrate the potential of walnut husks as a source of compounds with antioxidant properties that can be used in non-food industries. Pressurized liquid extraction, i.e., one of the modern green extraction techniques used on an industrial scale, as well as conventional extraction in Soxhlet and maceration were applied to prepare the extracts. In order to assess in depth their antioxidant activity in relation to the content of characteristic components, various activity assessment methods were used in this research. The results proved that the husk components have such antioxidant properties that they can be of interest to the cosmetics and pharmaceutical industries regarding the management of this waste. The results confirmed the usefulness of assisted extraction in increasing the ecological and economic values of the proposed waste disposal. Moreover, they showed that juglonehas very weak antioxidant properties, and the antioxidant effect of the mixture containing husk extract and juglone solution is mainly additive. Full article

The pharmacological activity and medicinal significance of Amauroderma rugosum (AR) have rarely been documented. We examined the antioxidant and neuroprotective effects of AR on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in an SH-SY5Y human neuroblastoma cell model of Parkinson’s disease (PD) and explored the active ingredients responsible for these effects. The results showed that the AR aqueous extract could scavenge reactive oxygen species and reduce SH-SY5Y cell death induced by 6-OHDA. In addition, the AR aqueous extract increased the survival of Caenorhabditis elegans upon juglone-induced toxicity. Among the constituents of AR, only polysaccharides and gallic acid exhibited antioxidant and neuroprotective effects. The AR aqueous extract reduced apoptosis and increased the expression of phospho-Akt, phospho-mTOR, phospho-MEK, phospho-ERK, and superoxide dismutase-1 in 6-OHDA-treated SH-SY5Y cells. The polysaccharide-rich AR extract was slightly more potent than the aqueous AR extract; however, it did not affect the expression of phospho-Akt or phospho-mTOR. In conclusion, the AR aqueous extract possessed antioxidant and neuroprotective properties against 6-OHDA-induced toxicity in SH-SY5Y cells. The mechanism of action involves the upregulation of the Akt/mTOR and MEK/ERK-dependent pathways. These findings indicate the potential utility of AR and its active ingredients in preventing or treating neurodegenerative disorders associated with oxidative stress such as PD. Full article

Juglone, a quinonic compound present in walnut extracts, was proposed as a restoring agent for hair keratin treated with permanent or discoloration processes. The proposed mechanism of restoration by juglone involves the formation of a Michael adduct between the quinone and the thiol moieties of cysteine residues. To this purpose, the first part of the present paper involved the spectroscopic study of the product of the reaction between juglone and N-acetyl-L-cysteine as a model compound. IR spectroscopy and Scanning Electron Microscopy (SEM) monitored the chemical and morphological variations induced by applying juglone to hair keratin. In order to simulate the most common hair treatments (i.e., permanent and discoloration), juglone was applied to hair that had been previously treated with a reducing agent, i.e., methyl thioglycolate (MT) or with bleaching agents (based on hydrogen peroxide and persulfates) followed by sodium hydrogen sulfite. IR spectroscopy allowed us to monitor the formation of Michael adducts between juglone and cysteine residues: the Michael adducts’ content was related to the cysteine content of the samples. In fact, MT and sodium hydrogen sulfite favored the reduction of the disulfide bonds and increased the content of free cysteine residues, which can react with juglone. SEM analyses confirmed the trend observed by IR spectroscopy since hair samples treated with juglone adopted a more regular hair surface and more imbricated scales, thus supporting the possible use of juglone as a restoring agent for damaged hair keratins. Full article

Pancreatic cancer remains a formidable challenge due to limited treatment options and its aggressive nature. In recent years, the naturally occurring anticancer compound juglone has emerged as a potential therapeutic candidate, showing promising results in inhibiting tumor growth and inducing cancer cell apoptosis. However, concerns over its toxicity have hampered juglone’s clinical application. To address this issue, we have explored the use of polymeric micelles as a delivery system for juglone in pancreatic cancer treatment. These micelles, formulated using Poloxamer 407 and D-α-Tocopherol polyethylene glycol 1000 succinate, offer an innovative solution to enhance juglone’s therapeutic potential while minimizing toxicity. In-vitro studies have demonstrated that micelle-formulated juglone (JM) effectively decreases proliferation and migration and increases apoptosis in pancreatic cancer cell lines. Importantly, in-vivo, JM exhibited no toxicity, allowing for increased dosing frequency compared to free drug administration. In mice, JM significantly reduced tumor growth in subcutaneous xenograft and orthotopic pancreatic cancer models. Beyond its direct antitumor effects, JM treatment also influenced the tumor microenvironment. In immunocompetent mice, JM increased immune cell infiltration and decreased stromal deposition and activation markers, suggesting an immunomodulatory role. To understand JM’s mechanism of action, we conducted RNA sequencing and subsequent differential expression analysis on tumors that were treated with JM. The administration of JM treatment reduced the expression levels of the oncogenic protein MYC, thereby emphasizing its potential as a focused, therapeutic intervention. In conclusion, the polymeric micelles-mediated delivery of juglone holds excellent promise in pancreatic cancer therapy. This approach offers improved drug delivery, reduced toxicity, and enhanced therapeutic efficacy. Full article

Parkinson’s disease (PD) is a degenerative disease that affects approximately 6.1 million people and is primarily caused by the loss of dopaminergic neurons. Naphthoquinones have several biological activities explored in the literature, including neuroprotective effects. Therefore, this review shows an overview of naphthoquinones with neuroprotective effects, such as shikonin, plumbagin and vitamin K, that prevented oxidative stress, in addition to multiple mechanisms. Synthetic naphthoquinones with inhibitory activity on the P2X7 receptor were also found, leading to a neuroprotective effect on Neuro-2a cells. It was found that naphthazarin can act as inhibitors of the MAO-B enzyme. Vitamin K and synthetic naphthoquinones hybrids with tryptophan or dopamine showed inhibition of the aggregation of α-synuclein. Synthetic derivatives of juglone and naphthazarin were able to protect Neuro-2a cells against neurodegenerative effects of neurotoxins. In addition, routes for producing synthetic derivatives were also discussed. With the data presented, 1,4-naphthoquinones can be considered as a promising class in the treatment of PD and this review aims to assist the scientific community in the application of these compounds. The derivatives presented can also support further research that explores their structures as synthetic platforms, in addition to helping to understand the interaction of naphthoquinones with biological targets related to PD. Full article

Cirsium japonicum DC. var. australe Kitam. has been used as an herbal remedy and often involves using the whole plant or roots. However, the bioactivities of different parts of the plant have been far less explored. This study aimed to evaluate the antioxidative ability of methanol extracts from the flowers, leaves, stems, and roots of the Cirsium plant and their possible active components against juglone-induced oxidative stress in the nematode Caenorhabditis elegans. The results showed that the highest dry weight (12.3 g per plant) was observed in leaves, which was followed by stems (8.0 g). The methanol extract yields from the flowers, leaves, and roots were all similar (13.0–13.8%), while the yield from stems was the lowest (8.6%). The analysis of the silymarin contents in the extracts indicated that the flowers, leaves, stems, and roots contained silychristin and taxifolin; however, silydianin was only found in the leaves, stems, and roots. The flower, leaf, and stem extracts, at a concentration of 10 mg/L, significantly reduced juglone-induced oxidative stress in C. elegans, which was potentially due to the presence of silychristin and taxifolin. Overall, C. japonicum DC. var. australe Kitam. contains a significant amount of silymarin and exhibits in vivo antioxidative activity, suggesting that the prospects for the plant in terms of health supplements or as a source of silymarin are promising. Full article