Atriplex halimus is a medicinal plant traditionally used for various therapeutic purposes. This study evaluated the antioxidant, anti-inflammatory, cytotoxic, genotoxic, and anti-arthritic activities of the A. halimus aqueous extract (AHA). Anti-arthritic effects were investigated in Complete Freund’s Adjuvant (CFA)-induced arthritic rats treated with AHA (150 or 300 mg/kg) for 21 days. AHA significantly reduced paw swelling and arthritis severity and improved body weight, while a non-significant reduction in spleen enlargement was observed. Hematological and biochemical parameters were restored toward normal values, indicating anti-inflammatory, hepatoprotective, and nephroprotective effects. The extract also reduced oxidative stress by decreasing nitric oxide (NO) and malondialdehyde (MDA) levels and increasing glutathione (GSH) content and catalase (CAT) activity. Histopathological examination confirmed reduced inflammatory infiltration and protection against bone damage. Phytochemical analysis revealed polyphenols, flavonoids, and tannins, consistent with its antioxidant activity in DPPH, ABTS, CUPRAC, and o-phenanthroline assays. AHA also showed anti-inflammatory activity by inhibiting bovine serum albumin denaturation. The extract induced a moderate concentration-dependent reduction in HeLa cell viability without cytotoxicity toward HaCaT cells. Comet assay results demonstrated DNA damage in HeLa cells at higher concentrations, while AHA significantly suppressed zymosan-induced IL-1β gene expression. These findings indicate that AHA is a promising natural source of bioactive compounds with diverse biological activities.

Vasconcellea chilensis Planch. ex A. DC., an endemic Chilean wild relative of mountain papaya (V. pubescens) adapted to extreme coastal environments, is largely unexplored for fruit phytochemistry. The ethanol extract yielded six 27-O-caffeoyl lupane triterpenoids (1-6), including two novel C-28 methyl esters, vasconcellates A and B (5, 6), and one known lignan (7). This is the first report of caffeoyl lupanes in the Caricaceae family. Compounds 1-7 were evaluated for inhibition of the Wingless/Integrated (Wnt)/β-catenin signaling pathway in a colorectal cancer model. Compound 4 (27-O-E-caffeoylbetulinic acid) showed marked activity by disrupting Frizzled 4 (FZD4) and Dishevelled 1 (DVL1) interaction (EC₅₀ = 16.2 ± 1.1 μM), suppressing Wnt target gene transcription (IC₅₀ = 12.1 ± 0.7 μM), and reducing CaCo-2 cell proliferation by 40% at 30 μM after 48 h. Docking indicated binding to the FZD4 cholesterol pocket, suggesting allosteric modulation. These results identify V. chilensis fruit as a novel source of bioactive triterpenoids with potential for colorectal cancer prevention.

The journal retracts the article titled “Chamazulene-Rich Artemisia arborescens Essential Oils Affect the Cell Growth of Human Melanoma Cells” [...]

Epigallocatechin gallate (EGCG), the predominant catechin in green tea, comprises approximately 50% of its total polyphenol content and has garnered widespread recognition for its significant therapeutic potential. As the principal bioactive component of Camellia sinensis, EGCG is celebrated for its potent antioxidant, anti-inflammatory, cardioprotective, and antitumor properties. The bioavailability and metabolism of EGCG within the gut microbiota underscore its systemic effects, as it is absorbed in the intestine, metabolized into bioactive compounds, and transported to target organs. This compound has been shown to influence key physiological pathways, particularly those related to lipid metabolism and inflammation, offering protective effects against a variety of diseases. EGCG’s ability to modulate cell signaling pathways associated with oxidative stress, apoptosis, and immune regulation highlights its multifaceted role in health promotion. Emerging evidence underscores EGCG’s therapeutic potential in preventing and managing a range of chronic conditions, including cancer, cardiovascular diseases, neurodegenerative disorders, and metabolic syndromes. Given the growing prevalence of lifestyle-related diseases and the increasing interest in natural compounds, EGCG presents a promising avenue for novel therapeutic strategies. This review aims to summarize current knowledge on EGCG, emphasizing its critical role as a versatile natural bioactive agent with diverse clinical applications. Further exploration in both experimental and clinical settings is essential to fully unlock its therapeutic potential.

The first detailed phytochemical investigation of the aerial parts of the Turkish plant Centaurea patula DC. led to the isolation of 19 sesquiterpenoids belonging to the guaianolide (1-13), elemanolide (14-17), and germacrane (18-19) classes. These include the undescribed guaianolide cebellin Q (9), the glucosylated elemanolides 15-17, and the pair of germacrene diastereomers patulosins A (18) and B (19). The structures of the undescribed compounds were elucidated by detailed NMR-based spectroscopic analysis, while comparison of experimental 13C NMR data with those obtained by DFT-based quantum chemical calculations was used to define relative configurations. Based on the activity reported for the plant extract, all the isolated compounds were evaluated for their activity on Saccharomyces cerevisiae α-glucosidase.

This study showed that MYC2 transcriptionally regulates valuable metabolites in Taraxacum spp. through direct interaction with specific target gene promoters. The Russian dandelion (Taraxacum kok-saghyz) represents a promising alternative species, capable of producing several high-added-value compounds, including natural rubber. Nevertheless, further enhancements are required for its optimal utilization by the industry. Here, we explored the role of the bHLH transcription factor TksMYC2, homolog of AtMYC2, in the regulation of the biosynthesis of specialized metabolites and free fatty acids and in the control of natural rubber production. Metabolic analyses of Taraxacum kok-saghyz plants showed that the overexpression of TksMYC2 significantly affected the accumulation of metabolites in roots and leaves, such as sesquiterpene lactones, phenylpropanoids, and free fatty acids. Moreover, overexpressing plants presented a significant increase in natural rubber production in both Taraxacum kok-saghyz and its related species Taraxacum brevicorniculatum. The direct interaction of TksMYC2 with the regulatory regions of cis-prenyltransferase 2 (CPT2), small rubber particle proteins (SRPP1, SRPP3, and SRPP4), involved in the biosynthesis of natural rubber, and with the germacrene A oxidase (GAO), involved in the biosynthesis of sesquiterpenes, was demonstrated by chromatin immunoprecipitation coupled with quantitative PCR. Additionally, these genes were highly induced in the lines overexpressing TksMYC2. Our findings suggest that TksMYC2 and its downstream components may be valid targets for breeding programmes to increase the production of valuable metabolites, including natural rubber.

Basil (Ocimum basilicum L.) is widely cultivated for its economic value. Recently, diverse cultivation management practices have emerged to enhance the productivity and quality of plants and their bioactive compounds, including essential oils (EOs). In this study, bioformulations based on Azotobacter chroococcum 76A (76A), Trichoderma afroharzianum T22 (T22), 6-pentyl-alpha-pyrone (6PP, a lactone produced by Trichoderma), and a biopolymer (BP), were tested on sweet basil cv. Genovese grown in protected cultivation. The effects of the bioformulations on basil EO content, composition, and biological activities were evaluated. The content of EOs from biotreated plants in 6 out of the 9 bioformulations increased up to 0.68 % w/w in the treatment vs. 0.25 % w/w in the control. The bioformulation applications to the plants modified EOs composition, as was demonstrated by GC-MS analysis, particularly regarding eugenol and linalool percentages. All basil EOs inhibited the growth of different bacterial and fungal strains and reduced biofilm production in plate assays, but EOs from plants treated with T22 alone or in combination with 76A showed better performances, e.g. the EO from T22 + 76A treated plants inhibited up to 92.9 % biofilm production in Escherichia coli, demonstrating potential as alternative to synthetical chemical products for disease control applications in agriculture. The ability of EOs to prevent ROS formation and their wound-healing activity in vitro were also examined, with EOs from T22 + 76A treated plants demonstrating the major antioxidant activity. Our findings support the development of innovative formulations based on microbial consortia that can stimulate the production of aromatic and nutraceutical compounds in basil leaves.

Molecules containing indole cores are of interest due to their multiple biological applications and seem to be an alternative to face contemporary challenges in agriculture, especially the control of phytopathogens that affect fruit quality. In this research, starting from 5-bromoindole (A), eleven 3-acyl-5-bromoindole derivatives with linear (B-G) and aromatic (H-L) substitutions were obtained through microwave-assisted synthesis. The antifungal capacity of indole, 5-bromoindole (A) and their derivatives (B-L) were determined by in vitro assays on Monilinia fructicola and Botrytis cinerea, and a molecular docking was performed on mitochondrial complex II, succinate dehydrogenase (SDH). The results indicate that compounds A, B, G, and L were able to inhibit the growth of M. fructicola, while only A and J showed activity against B. cinerea. The acylation of A improved their ability to inhibit the germination of conidia on both pathogens. Compounds A, B and G are the most promising candidates for future research due to their inhibition on M. fructicola and/or B. cinerea and demonstrate favorable binding energies with SDH.

Sage (Salvia officinalis L.) is cultivated in many countries due to the medicinal and industrial importance of its essential oil (EO). The yield and quality of the crops to be included in the medicinal plant supply chain should be constant, but often this is not the case since they are both influenced by environmental variability and crop management. We therefore studied the influence of water availability and harvest time, during the balsamic period, on a sage crop cultivated at an experimental field site in the Molise Region (South-central Italy), evaluating the main agronomic and ecophysiological traits in terms of plant biomass production and photosynthetic performance. The yield and composition of the essential oils, extracted by hydrodistillation and analyzed by GC and CG/MS, were also evaluated. The well-watered crops harvested 42 days after beginning of flowering, exhibited higher dry biomass yield than rainfed plants as well as higher values of relative water content, photosynthesis and leaf CO2 conductance. Instead, at the same time (after 42 days) the EO content was higher in rainfed plants then in well-watered ones, in which it remained constant throughout all the harvesting period. All the EOs were rich in bioactive compounds such as α-thujone, β-thujone, camphor and borneol, but only in well-watered plants the content was constant throughout all the harvesting periods. In fact, the EO of rainfed plants analyzed over the harvest time was mainly rich at the beginning in camphor and borneol, whereas in the middle in α-thujone. Our study demonstrates that the crop performance is greatly influenced by the water availability during the balsamic period. The results of this study provide new knowledge to produce sage oil of adequate quality for the different uses.

A comprehensive phytochemical investigation of aerial parts obtained from Centaurea sicula L. led to the isolation of 14 terpenoids (1-14) and nine polyphenols (15-23). The sesquiterpenoid group (1-11) included three structural families, namely, elemanolides (1-6), eudesmanolides (7 and 8), and germacranolides (9-11) with four unreported secondary metabolites (5-8), whose structure has been determined by extensive spectroscopic analysis, including 1D/2D NMR, HR-MS, and chemical conversion. Moreover, an unprecedented alkaloid, named siculamide (24), was structurally characterized, and a possible biogenetic origin was postulated. Inspired by the traditional use of the plant and in the frame of ongoing research on compounds with potential activity on metabolic syndrome, all the isolated compounds were evaluated for their stimulation of glucose uptake, disclosing remarkable activity for dihydrocnicin (10) and the lignan salicifoliol (15).

Cardiovascular diseases (CVDs) remain a leading global cause of morbidity and mortality. These diseases have a multifaceted nature being influenced by a multitude of biochemical, genetic, environmental, and behavioral factors. Epigenetic modifications have a crucial role in the onset and progression of CVD. Epigenetics, which regulates gene activity without altering the DNA’s primary structure, can modulate cardiovascular homeostasis through DNA methylation, histone modification, and non-coding RNA regulation. The effects of environmental stimuli on CVD are mediated by epigenetic changes, which can be reversible and, hence, are susceptible to pharmacological interventions. This represents an opportunity to prevent diseases by targeting harmful epigenetic modifications. Factors such as high-fat diets or nutrient deficiencies can influence epigenetic enzymes, affecting fetal growth, metabolism, oxidative stress, inflammation, and atherosclerosis. Recent studies have shown that plant-derived bioactive compounds can modulate epigenetic regulators and inflammatory responses, contributing to the cardioprotective effects of diets. Understanding these nutriepigenetic effects and their reversibility is crucial for developing effective interventions to combat CVD. This review delves into the general mechanisms of epigenetics, its regulatory roles in CVD, and the potential of epigenetics as a CVD therapeutic strategy. It also examines the role of epigenetic natural compounds (ENCs) in CVD and their potential as intervention tools for prevention and therapy.

In the original publication [...].

Oomycetes such as Saprolegnia sp. are responsible for serious economic losses in aquaculture, the strategies for their control lead to concerns about their efficacy and environmental repercussions, so alternatives for their regulation are being sought. The aim of this study was to evaluate the in vitro susceptibility of 2 representative strains of Saprolegnia sp. toward 2,4-dihydroxy-5 '-prenyl-dihydrochalcone (A); dihydrochalcone isolated from the Chilean shrub Adesmia balsamica; and their derivatives oxyprenylated (B--G) with the purpose to develop naturally occurring products in order to cope with emerging resistance phenomena. The minimum inhibitory concentration (MIC) and minimum oomycetocidal concentration (MOC) values were then determined for the series of compounds tested, in comparison with the conventional fungicides bronopol (R) and fluconazole plus the natural compound safrole, by quantifying fungal growth. Significant growth inhibition was observed for prenylated derivatives B-G, evidencing dihydrochalcone E as the most active. This compound presented MIC and MOC values (0.24-0.26 mu M and 0.30-0.33 mu M, respectively) superior to those determined for commercial antifungal in both of the tested pathogenic strains.

The purple carrot cultivar ‘Purple Sun’ (Daucus carota L.) is characterized by a relevant content of phenolic compounds and anthocyanins, which may play an important role in reducing the risk of chronic diseases and in the treatment of metabolic syndrome. In the present study, the genetic diversity, phytochemical composition, and bioactivities of this outstanding variety were studied for the first time. Genetic analysis by molecular markers estimated the level of genetic purity of this carrot cultivar, whose purple-pigmented roots were used for obtaining the purple carrot ethanol extract (PCE). With the aim to identify specialized metabolites potentially responsible for the bioactivities, the analysis of the metabolite profile of PCE by LC-ESI/LTQ Orbitrap/MS/MS was carried out. LC-ESI/HRMS analysis allowed the assignment of twenty-eight compounds, putatively identified as isocitric acid (1), phenolic acid derivatives (2 and 6), hydroxycinnamic acid derivatives (9, 10, 12–14, 16, 17, 19, 22, and 23), anthocyanins (3–5, 7, 8, 11, and 18), flavanonols (15 and 21), flavonols (20 and 24), oxylipins (25, 26, and 28), and the sesquiterpene 11-acetyloxytorilolone (27); compound 26, corresponding to the primary metabolite trihydroxyoctanoic acid (TriHOME), was the most abundant compound in the LC-ESI/HRMS analysis of the PCE, and hydroxycinnamic acid derivatives followed by anthocyanins were the two most represented groups. The antioxidant activity of PCE, expressed in terms of reactive oxygen species (ROS) level and antioxidant enzymes activity, and its pro-metabolic effect were evaluated. Moreover, the antibacterial activity on Gram (−) and (+) bacterial strains was investigated. An increase in the activity of antioxidant enzymes (SOD, CAT, and GPx), reaching a maximum at 0.5 mg/mL of PCE with a plateau at higher PCE concentrations (1.25, 2.5, and 5.0 mg/mL), was observed. PCE induced an initial decrease in ROS levels at 0.1 and 0.25 mg/mL concentrations, reaching the ROS levels of control at 0.5 mg/mL of PCE with a plateau at higher PCE concentrations (1.25, 2.5, and 5.0 mg/mL). Moreover, significant antioxidant and pro-metabolic effects of PCE on myoblasts were shown by a reduction in ROS content and an increase in ATP production linked to the promotion of mitochondrial respiration. Finally, the bacteriostatic activity of PCE was shown on the different bacterial strains tested, while the bactericidal action of PCE was exclusively observed against the Gram (+) Staphylococcus aureus. The bioactivities of PCE were also investigated from cellular and molecular points of view in colon and hematological cancer cells. The results showed that PCE induces proliferative arrest and modulates the expression of important cell-cycle regulators. For all these health-promoting effects, also supported by initial computational predictions, ‘Purple Sun’ is a promising functional food and an optimal candidate for pharmaceutical and/or nutraceutical preparations.

Baccharis macraei Hook. & Arn (Asteraceae), commonly known as Vautro, is found in the coastal areas of central-southern Chile, including the industrial zone of Quintero-Puchuncaví, known for the contamination of its soils with heavy metals, which together with other factors generate abiotic stress in plant species, against which they present defensive mechanisms. For this reason, the objective was to evaluate the effect of abiotic stress generated by the proximity of B. macraei to the industrial complex by assessing the physiological and metabolic states reported by the extracts and compounds isolated from the species, as well as the photosynthetic capacity, metal content and production, and antioxidant activity and cytotoxicity against tumorigenic cell lines of the phytoconstituents. To this end, B. macraei was collected at two different distances from the industrial complex, observing that the closer the species is, the greater the concentration of copper in the soil, generating a decrease in the rate of electron transport in situ, but an increase in antioxidant activity with low cytotoxicity. This activity could be due to the presence of flavonoids such as Hispidulin, Cirsimaritina, and Isokaempferida, as well as monoterpenes, oxygenated and non-oxygenated sesquiterpenes identified in this study.

Natural products (NPs), broadly defined as chemicals produced by living organisms including microbes, marine organisms, animals, fungi and plants, are widely used as therapeutic agents for treating diseases and maintaining health and "wellness" [...].

The majority of blood malignancies is incurable and has unforeseeable remitting-relapsing paths in response to different treatments. Cynaropicrin, a natural sesquiterpene lactone from the edible parts of the artichoke plant, has gained increased attention as a chemotherapeutic agent. In this study, we investigated the effects of cynaropicrin against multiple myeloma (MM) cells in vitro and assessed its in vivo effectiveness in a xenograft tumor zebrafish model. We showed that cynaropicrin exerted potent cytotoxicity against a panel of nine MM cell lines and two leukemia cell lines with AMO1 being the most sensitive cell line (IC50 = 1.8 ± 0.3 µM). Cynaropicrin (0.8, 1.9, 3.6 µM) dose-dependently reduced c-Myc expression and transcriptional activity in AMO1 cells that was associated with significant downregulation of STAT3, AKT, and ERK1/2. Cell cycle analysis showed that cynaropicrin treatment arrested AMO1 cells in the G2M phase along with an increase in the sub-G0G1 phase after 24 h. With prolonged treatment times, cells accumulated more in the sub-G0G1 phase, implying cell death. Using confocal microscopy, we revealed that cynaropicrin disrupted the microtubule network in U2OS cells stably expressing α-tubulin-GFP. Furthermore, we revealed that cynaropicrin promoted DNA damage in AMO1 cells leading to PAR polymer production by PARP1 hyperactivation, resulting in AIF translocation from the mitochondria to the nucleus and subsequently to a novel form of cell death, parthanatos. Finally, we demonstrated that cynaropicrin (5, 10 µM) significantly reduced tumor growth in a T-cell acute lymphoblastic leukemia (T-ALL) xenograft zebrafish model. Taken together, these results demonstrate that cynaropicrin causes potent inhibition of hematopoietic tumor cells in vitro and in vivo.