Search Results (95)

This study integrated non-targeted metabolomics and transcriptomics to investigate dynamic changes in Antheraea pernyi pupae across five developmental stages. Metabolomic analysis identified 1246 metabolites, primarily organic acids, lipids, heterocyclic compounds, and oxygen-containing organics. Principal component analysis revealed stage-specific metabolic profiles: amino acid derivatives (pyruvate, proline, lysine) declined, while pyrimidines (cytidine, uridine, β-alanine) and monosaccharides (glucose, mannose) increased. 18β-glycyrrhetinic and ursolic acids accumulated significantly in the middle and late stages. Transcriptomic analysis identified 7230 differentially expressed genes (DEGs), with 366, 1705, and 5159 significantly differentially expressed genes in the T1, T3, and T5 comparison groups, respectively. KEGG enrichment highlighted ABC transporters, amino acid/pyrimidine metabolism, and tyrosine pathways as developmentally critical, with aminoacyl-tRNA biosynthesis upregulated in later phases. Integrated multi-omics analysis revealed coordinated shifts in metabolites and genes across developmental phases, reflecting dynamic nutrient remodeling during pupal maturation. This study systematically delineates the molecular transitions driving pupal development in Antheraea pernyi pupae, uncovering conserved pathway interactions and mechanistic insights into nutrient metabolism. These findings provide a scientific foundation for leveraging pupal resources in functional food innovation and bioactive compound discovery for pharmaceutical applications. 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

Erica spiculifolia Salisb. (formerly Bruckenthalia spiculifolia Benth.) (Balkan heath) is renowned for its traditional usage as a diuretic, anti-inflammatory and antioxidant agent. For the first time, acylquinic acids, flavonoids and numerous proanthocyanidin oligomers were annotated/dereplicated by liquid chromatography–high-resolution mass spectrometry in methanol–aqueous extracts from E. spiculifolia aerial parts harvested at the early and full flowering stage. Chlorogenic acid and proanthocyanidin tetra- and trimer A, B-type together with quercitrin and (+) catechin were the predominant compounds in the semi-quantitative analysis. Neutral triterpenoids, triterpenoid acids and phytosterols were determined in apolar extracts by gas chromatography–mass spectrometry. Triterpenoid acids accounted for 80% of the total triterpenoid content, dominated by ursolic and oleanolic acid, reaching up to 32.2 and 6.1 mg/g dw, respectively. Ursa/olean-2,12-dien-28-oic acids and 3-keto-derivatives together with α-amyrin acetate as a chemotaxonomic marker, α-amyrenone, α- and β-amyrin were evaluated. Total phenolic and flavonoid contents were 83.85 ± 0.89 mg gallic acid equivalents/g and 78.91 ± 0.41 mg rutin equivalents/g, respectively. The extract actively scavenged DPPH and ABTS radicals (540.01 and 639.11 mg Trolox equivalents (TE)/g), possessed high potential to reduce copper and iron ions (660.32 and 869.22 mg TE/g, respectively), and demonstrated high metal chelating capacity (15.57 Ethylenediaminetetraacetic acid equivalents/g). It exhibited prominent anti-lipase (18.32 mg orlistat equivalents/g) and anti-tyrosinase (71.90 mg kojic acid equivalents/g) activity. The extract inhibited α-glucoside (1.35 mmol acarbose equivalents/g) and acetylcholinesterase (2.56 mg galanthamin equivalents/g), and had moderate effects on α-amylase, elastase, collagenase and hyaluronidase. Balkan heath could be recommended for raw material production with antioxidant and enzyme inhibitory properties. Full article

Melanoma is one of the most aggressive forms of skin cancer, characterized by high metastatic potential and resistance to conventional therapies. Natural compounds, particularly terpenoids, have gained attention for their chemopreventive potential and anticancer properties. These plant-derived compounds exhibit diverse biological activities, e.g., cell viability and proliferation inhibition, apoptosis induction, cell cycle regulation, and immune system modulation. The review evaluates the current state of the art on the chemopreventive and anticancer activity of lupane- (betulinic acid), oleanane- (oleanolic acid, β-amyrin, escin, hederagenin, glycyrrhetinic acid), and ursane-type (ursolic acid, asiatic acid, madecassic acid, α-amyrin) triterpenoids in melanoma, highlighting their mechanisms of action, therapeutic potential, and challenges in clinical application. Full article

Major depressive disorder (MDD) is a widespread psychiatric condition with substantial socioeconomic impacts, yet single-target pharmacotherapies often yield responses. To address its multifactorial nature, this study employed a multiscale network analysis of herbs, their active components, and MDD-associated protein targets. Using a biased random walk with restart, we calculated interactions between disease-related and herb-derived targets, identifying herbs highly correlated with MDD. Enrichment analysis further revealed key signaling pathways, including oxidative stress, neuroinflammation, and hormone metabolism, underlying these herbs’ therapeutic effects. We identified Ephedrae herba, Glehniae radix, Euryales semen, and Campsitis flos as promising candidates, each containing multiple bioactive compounds (such as ephedrine, psoralen, xanthine, and ursolic acid) that modulate critical processes like oxidation–reduction, inflammatory cytokine regulation, and transcriptional control. Network visualization showed how these herbs collectively target both shared and distinct pathways, supporting a synergistic, multi-target therapeutic strategy. This approach underscores the significance of network-based methodologies in addressing complex disorders such as MDD, where focusing on a single target may overlook synergistic interactions. By integrating diverse molecular data, this study provides a systematic framework for identifying novel interventions. Future experimental validation will be crucial to confirm these predictions and facilitate the translation of findings into effective MDD therapies. Full article

Agricultural residues, including Pleurotus ostreatus spent mushroom substrate (SMS) and roots of (hydroponic) leafy vegetables (RLV), were tested in various proportions as substrates in new P. ostreatus cultivations, where wheat straw was the control. The impact of SMS and RLV was first evaluated by the mycelial growth rate (Kr, mm/day). Afterwards, mushroom cultivation was conducted in bags, where production characteristics like earliness (the time from substrate inoculation to first harvest) and biological efficiency (BE %, the ratio of fresh mushroom weight to dry substrate weight × 100) were examined. The study also evaluated mushroom quality, nutritional composition and bioactive content. The highest intra-cellular polysaccharide (IPS) value (50.93%, w/w) was observed in the substrate containing SMS 90%, while combining SMS with RLV resulted in higher IPS values compared to mixtures that also included wheat bran (WB) and soybean flour (SF). Furthermore, the use of RLV reduced the fat content compared to the control substrate, except in the case of the SMS 50%–RLV 40% substrate, where the highest fat content was observed in the produced mushrooms (4.68% w/w). Additionally, the protein content increased with the use of RLV. The highest triterpene content was found in the SMS 90%–RLV 10% (11.52 ursolic acid mg/g d.w.). However, the control substrate exhibited the fastest Kr (6.5 mm/d), as well as the highest BE (87.8%) and total phenolic compound value (30.31 mg GAE/g d.w.). Significant antioxidant activity was observed in all extracts, while the total flavonoid content was low. Glucose was the dominant monosaccharide (over 51.5%, w/w), and linoleic acid (18:2; over 57.05%, w/w) was the primary fatty acid across all mushrooms. This study also enhances our knowledge by which SMS and RLV influence the NFE2L2/HMOX-1 molecular pathway, thereby affecting specific antioxidant-related genes. These effects were observed through the impact of P. ostreatus protein and carbohydrate extracts on LPS-challenged THP-1-derived macrophages. A positive impact on the gene expression of HMOX1, CAT and NFE2L2 during incubation with the aforementioned samples was observed. These findings support the sustainable use of agricultural by-products in mushroom cultivation, offering an environmentally friendly approach while producing valuable products like mushrooms. Full article

Alzheimer’s disease (AD) poses a significant public health issue. Despite the fact that today there are several methods of maintenance therapy, one of the most widely used methods is designed to correct the deficiency of acetylcholine. In the search for new potential inhibitors of cholinesterase enzymes, eight new derivatives of 3-oxo- or 2,3-indolo-triterpenic acid conjugated with amino-quinuclidine bicyclic cores were designed and synthesized. Then, the obtained compounds were screened in Ellman’s assays for their ability to inhibit acetylcholinesterase enzyme, and for each of the active compounds, the type of inhibition was determined. The obtained results demonstrate the dependence of the activity on the triterpenoid structure and the type of substituents. The best activity for ursolic acid derivatives was observed for the 3-oxoamide 8, with an IC₅₀ value of 0.43 µM, acting as a mixed-type inhibitor. In turn, for the oleanane type, the amide with an indole unit in the A ring 11 exhibited the best activity with an IC₅₀ value of 0.47 µM (while the ursane-type analog was weakly active) and led to an uncompetitive type of inhibition. Thus, 3-amidoquinuclidine-triterpenoids conjugates could be considered novel inhibitors of acetylcholinesterase with a different mechanism of action. Full article

Oregano (Origanum vulgare L.) is one of the most commercially popular aromatic spices which has long been used in folk medicine as a medicinal plant due to the presence of a wide group of bioactive secondary metabolites. The experimental data available to date indicate that plants of individual species within the Lamiaceae family implement different strategies for the absorption and distribution of selenium (Se) and differ in their metabolic response to Se treatment. In this regard, the present study investigated the effect of Se application (in the form of sodium selenate) at various concentrations (2.0, 5.0, 10.0, 20.0, and 40.0 μM) on the growth and accumulation of Se in oregano plant shoots and roots, as well as on nutritional components and secondary metabolites in shoots. The addition of Se to the nutrient solution at concentrations of 2–20 μM did not adversely affect the growth and accumulation of biomass in the oregano plants, which were characterized by a significant ability to transfer Se from roots to shoots (the translocation factor was >2). The Se treatment enhanced the nutritional proprieties of the oregano and, particularly, it stimulated the accumulation of carbohydrates and proteins (by 30 and 17%) and minerals (calcium and manganese). The total contents of phenolic compounds, flavonoids, hydroxycinnamic acids, luteolin-7-glucoside and its derivatives, catechin, 3,4-dihydroxybenzoic acid, rosmarinic acid and oleanolic and ursolic acids, as well as the percentage of essential oil, showed a dose-dependent increase in the oregano under the Se treatment. Changes in the relative content of the four main components of oregano essential oil (sabinene, germacrene D, β-caryophyllene, and (Z)-β-ocimene) under the Se treatment were not significant. The relative proportions of β-caryophyllene oxide and terpinen-4-ol increased with Se concentration augmentation in the nutrient solution. The obtained results indicate the prospect of using Se at 5–20 μM concentrations in nutrient solution in hydroponically grown oregano to produce Se-biofortified plants with higher levels of health beneficial compounds and antioxidant activity without yield reduction. Full article

Obesity, characterized by abnormal or excessive fat accumulation, has become a chronic degenerative health condition that poses significant threats to overall well-being. Pharmacological intervention stands at the forefront of strategies to combat this issue. Recent studies, notably by Umut Ozcan’s team, have uncovered the remarkable potential of Celastrol, a small-molecule compound derived from the traditional Chinese herb thunder god vine (Tripterygium wilfordii) as an anti-obesity agent. In this research, computational chemical analysis was employed, incorporating the “TriDimensional Hierarchical Fingerprint Clustering with Tanimoto Representative Selection (3DHFC-TRS)” algorithm to systematically explore 139 active small molecules from thunder god vine. These compounds were classified into six categories, with a particular focus on Category 1 molecules for their exceptional binding affinity to obesity-related targets, offering new avenues for therapeutic development. Using advanced molecular docking techniques and Cytoscape prediction models, six representative Celastrol-like molecules were identified, namely 3-Epikatonic Acid, Hederagenin, Triptonide, Triptotriterpenic Acid B, Triptotriterpenic Acid C, and Ursolic Acid. These compounds demonstrated superior binding affinity and specificity toward two key obesity targets, PPARG and PTGS2, suggesting their potential to regulate fat metabolism and mitigate inflammatory responses. To further substantiate these findings, molecular dynamics simulations and MM-PBSA free-energy calculations were applied to analyze the dynamic interactions between these small molecules and the enzymatic active sites of their targets. The results provide robust theoretical evidence that support the feasibility of these molecules as promising candidates for anti-obesity therapies. This study underscores the power of the 3DHFC-TRS algorithm in uncovering bioactive compounds from natural sources, such as thunder god vine, and highlights the therapeutic promise of PPARG and PTGS2 as novel obesity-related targets. Furthermore, it emphasizes the essential role of computational science in expediting drug discovery, paving the way for personalized and precision-based treatments for obesity and heralding a future of more effective healthcare solutions. Full article

The cider-making industry in Asturias generates between 9000 and 12,000 tons of apple pomace per year. This by-product, the remains of the apple pressing, and made up of peel, flesh, seeds and stems, is a valuable material, containing substantial amounts of antioxidant compounds associated with healthy properties. Polyphenols such as dihydrochalcones and quercetin glycosides, and triterpenic acids, among which ursolic acid is a major compound, are the main antioxidant families described in apple pomace. The simultaneous recovery of those families has been accomplished by low frequency ultrasound-assisted extraction. Working extraction conditions were optimised by response surface methodology (RSM): time, 5.1 min; extractant composition, 68% ethanol in water; solid/liquid ratio, 1/75 and ultrasonic wave amplitude, 90%. This procedure was further applied to analyse those components in the whole apple pomace (WAP), apple peel (AP) and apple flesh (AF). On average, dry WAP contained almost 1300 µg/g of flavonols, 1200 µg/g of dihydrochalcones and 4200 µg/g of ursolic acid. These figures increased in the apple peel to, respectively 2500, 1400 and 8500 µg/g dry matter. Two linear multivariate regression models allowed the antioxidant activity of apple by-products to be predicted on the basis of their bioactive composition. The results derived from this study confirm the potential of industrial cider apple pomace as a source of high-value bioactive compounds, and the feasibility of the ultrasound-assisted extraction technique to recover those components in a simple and efficient way. Full article

Ursolic acid (UA) and its derivatives have garnered significant attention due to their extensive pharmacological activity. UA is a pentacyclic triterpenoid found in a variety of plants, such as apples, rosemary, thyme, etc., and it possesses a range of pharmacological properties. Researchers have synthesized various derivatives of UA through structural modifications to enhance its potential pharmacological properties. Various in vitro and in vivo studies have indicated that UA and its derivatives possess diverse biological activities, such as anticancer, antifungal, antidiabetic, antioxidant, antibacterial, anti-inflammatory and antiviral properties. This review article provides a review of the biological activities of UA and its derivatives to show their valuable therapeutic properties useful in the treatment of different diseases, mainly focusing on the relevant structure-activity relationships (SARs), the underlying molecular targets/pathways, and modes of action. Full article

Cancer is a global health problem, with the incidence rate estimated to reach 40% of the population by 2030. Although there are currently several therapeutic methods, none of them guarantee complete healing. Plant-derived natural products show high therapeutic potential in the management of various types of cancer, with some of them already being used in current practice. Among different classes of phytocompounds, pentacyclic triterpenoids have been in the spotlight of research on this topic. Ursolic acid (UA) and its structural isomer, oleanolic acid (OA), represent compounds intensively studied and tested in vitro and in vivo for their anticancer and chemopreventive properties. Since natural compounds can rarely be used in practice as such due to their characteristic physico-chemical properties, to tackle this problem, their derivatization has been attempted, obtaining compounds with improved solubility, absorption, stability, effectiveness, and reduced toxicity. This review presents various UA and OA derivatives that have been synthesized and evaluated in recent studies for their anticancer potential. It can be observed that the most frequent structural transformations were carried out at the C-3, C-28, or both positions simultaneously. It has been demonstrated that conjugation with heterocycles or cinnamic acid, derivatization as hydrazide, or transforming OH groups into esters or amides increases anticancer efficacy. Full article

The leaves of Ilex paraguariensis (known as Yerba mate), used as a popular beverage, are a very well-recognized plant material with various biological activities, including analeptic (because of caffeine), anti-obesity (phenolics, saponins), antimicrobial, and antiviral (phenolics, saponins). Here, the chemical compositions of the leaves of two European Ilex species (× meserveae and aquifolium) with three varieties each were investigated. The terpenoid, saponin, and polyphenolic fractions were submitted for LC-MS or GC-MS analysis against a standard Mate leaf. In addition, the aroma profiles of all the species were analysed using HS-SPME-Arrow prior to GC-MS analysis. All fractions were subjected to antiviral and cytotoxic assays. We found 86 compounds in all accessions, with limonene, linalool, and p-cymene being predominant. There were minor similarities between the volatile compositions of the European and South American species. We found ursolic and oleanolic acid to be the main compounds in the terpenoid fraction. Mono-caffeoylquinic acids and di-caffeoylquinic acids were the main constituents of the polar fractions. About 180 compounds from the saponin group were tentatively identified, of which 9 and 3 were selected as distinctive markers for I. meserveae and I. aquifolium, respectively. Based on chemical screening, I. aquifolium Silver Queen was chosen as the source of terpenoid and saponin fractions and polyphenol extracts. The most substantial inhibition of cancer cell growth was observed with saponin in the case of the MCF7 (human breast cancer) cell line, while for LoVo and L929 cell lines (human colorectal cancer and reference mouse fibroblasts), it was slightly weaker. These results should be analysed further as a promising chemoprevention of colorectal and gastrointestinal cancers. Saponin and polyphenolic extracts exhibited similar activities against HSV-1 and HAdV-5, with 4-log reduction in virus titres. This study focuses our attention on a field of potential antiviral formulations derived from European holly. Full article

Recently, there has been great interest in plant-derived compounds known as phytochemicals. The pentacyclic oleanane-, ursane-, and lupane-type triterpenes are phytochemicals that exert significant activity against diseases like cancer. Lung cancer is the leading cause of cancer-related death worldwide. Although chemotherapy is the treatment of choice for lung cancer, its effectiveness is hampered by the dose-limiting toxic effects and chemoresistance. Herein, we investigated six pentacyclic triterpenes, oleanolic acid, ursolic acid, asiatic acid, betulinic acid, betulin, and lupeol, on NSCLC A549 cells. These triterpenes have several structural variations that can influence the activation/inactivation of key cellular pathways. From our results, we determined that most of these triterpenes induced apoptosis, S-phase and G2/M-phase cycle arrest, the downregulation of ribonucleotide reductase (RR), reactive oxygen species, and caspase 3 activation. For chemoresistance markers, we found that most triterpenes downregulated the expression of MAPK/PI3K, STAT3, and PDL1. In contrast, UrA and AsA also induced DNA damage and autophagy. Then, we theoretically determined other possible molecular targets of these triterpenes using the online database ChEMBL. The results showed that even slight structural changes in these triterpenes can influence the cellular response. This study opens up promising perspectives for further research on the pharmaceutical role of phytochemical triterpenoids. Full article

Melanoma is one of the most dangerous forms of skin cancer, characterized by early metastasis and rapid development. In search for effective treatment options, much attention is given to triterpenoids of plant origin, which are considered promising drug candidates due to their well described anticancer properties and relatively low toxicity. This paper comprehensively summarizes the antimelanoma potential of natural triterpenoids, that are also used as scaffolds for the development of more effective derivatives. These include betulin, betulinic acid, ursolic acid, maslinic acid, oleanolic acid, celastrol and lupeol. Some lesser-known triterpenoids that deserve attention in this context are 22β-hydroxytingenone, cucurbitacins, geoditin A and ganoderic acids. Recently described mechanisms of action are presented, together with the results of preclinical in vitro and in vivo studies, as well as the use of drug delivery systems and pharmaceutical technologies to improve the bioavailability of triterpenoids. This paper also reviews the most promising structural modifications, based on structure–activity observations. In conclusion, triterpenoids of plant origin and some of their semi-synthetic derivatives exert significant cytotoxic, antiproliferative and chemopreventive effects that can be beneficial for melanoma treatment. Recent data indicate that their poor solubility in water, and thus low bioavailability, can be overcome by complexing with cyclodextrins, or the use of nanoparticles and ethosomes, thus making these compounds promising antimelanoma drug candidates for further development. Full article