Search Results (180)

Infectious diseases have been treated using plants and their compounds for thousands of years. This knowledge has enabled modern techniques to identify specific antiviral remedies and to understand their molecular mechanism of action. Numerous active phytochemicals, such as alkaloids, terpenoids, polyphenols (phenolic acids, flavonoids, stilbenes, and lignans), coumarins, thiophenes, saponins, furyl compounds, small proteins, and peptides, are promising options for treating and preventing viral infections. It has been shown that plant-derived products can prevent or inhibit viral entry into and replication by host cells. Biotechnological advances have made it possible to engineer plants with an increased capacity for the production and accumulation of natural antiviral compounds. Plants can also be engineered to produce various types of antivirals (cytokines, antibodies, vaccines, and lectins). This study summarizes the current understanding of the antiviral activity of specific plant-derived metabolites, emphasizing their mechanisms of action and exploring the enormous potential of plants as biological factories. Full article

There is a growing interest in using agri-food by-products and a demand for natural substances that might help maintain healthy honey bee colonies. We investigated a by-product of the wine industry, a grape pomace (GP) of the autochthonous Prokupac grape cultivar from Serbia. A hydroethanolic extract (50% (w/v) ethanol) of GP (Prokupac GP extract) obtained by the pressurized liquid extraction (PLE) method was subjected to qualitative profiling of phenolic composition by liquid chromatography with OrbiTrap Exploris 120 mass spectrometer. Then, the extracts’ antioxidant and redox-modulatory activities were evaluated through Electron Paramagnetic Resonance (EPR) spectroscopy. Finally, the extract’s potential to modulate cellular redox status was evaluated using cultured AmE-711 honey bee cells. The results show that the Prokupac GP extract contains a wide array of flavonoids, anthocyanins, stilbenes, and their various conjugated derivatives and that anthocyanins, particularly malvidin-based compounds, dominate. EPR measurements showed strong scavenging activity against superoxide anion (O₂^•−) and hydroxyl radicals (^•OH), with inhibition efficiencies of 84.37% and 81.81%, respectively, while activity against the DPPH radical was lower (17.75%). In the cell-based assay, the Prokupac GP extract consistently provided strong antioxidant protection and modulated the cellular response to oxidative stress by over 14%. In conclusion, while the Prokupac GP extract demonstrated antioxidant properties and the ability to modulate cellular responses to oxidative stress, in vivo studies on honey bees are required to confirm its efficacy and safety for potential use in beekeeping practice. Full article

Despite their broad pharmacological potential, the clinical application of stilbenes derived from Cajanus cajan (L.) Millsp. leaves (CCMLs) is limited by their poor aqueous solubility, resulting in low oral bioavailability. In this study, an inclusion complex of stilbenes extracted from CCMLs and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) was successfully developed to improve their solubility and oral bioavailability. The preparation conditions were optimized using the response surface methodology, with an optimum mass ratio of CCML extract (CCMLE) to HP-β-CD of 1.0:8.2 (g/g) and an optimal temperature of 33 °C for 2 h. The maximum inclusion efficiency of stilbenes was 82%, and the physicochemical properties of the inclusion complex were characterized. Both in vitro dissolution studies and in vivo pharmacokinetic evaluation demonstrated that HP-β-CD encapsulation significantly improved the solubility and dissolution rate of stilbenes compared to those of unformulated CCMLE. Notably, the relative bioavailability of cajaninstilbene acid (CSA), longistyle C (LLC) and 4-O-methylpinosylvic acid (MPA) increased to 198%, 177% and 131%, respectively. This work provides a simple and effective strategy to enhance the solubility and bioavailability of naturally derived stilbenes, offering promising potential for the development of other insoluble natural components for both functional food and pharmaceuticals. Full article

The Onocleaceae family, a small group within the Pteridophytes, comprises four genera, but has been phytochemically studied mainly for Pentarhizidium orientale, Pentarhizidium intermedium, and Matteuccia struthiopteris. To date, a total of 91 compounds have been isolated from these three species, including 15 flavonoids, 48 flavonoid glycosides, 6 stilbenes, 4 isocoumarins, 2 phthalides, 3 chromones, 2 lignan glycosides, 8 isoprenoid derivatives, and 3 phenolic compounds. Notably, most flavonoids and flavonoid glycosides possess C-methyl groups at the C-6 and/or C-8 positions, with several conjugated to (S)-3-hydroxy-3-methylglutaryl (HMG) moieties. Although not all isolates have been evaluated for their pharmacological activities, several compounds have demonstrated bioactivities such as antiviral, anti-inflammatory, α-glucosidase inhibitory, aldose reductase inhibitory, and antioxidant effects. Full article

Plant species of the genus Cannabis L. are predominantly recognized for their cannabinoids, which have garnered significant attention due to their bioactive properties. However, Cannabis also produces a diverse array of bioactive compounds with promising pharmacological potential that remain underexplored. This review focuses primarily on phytochemicals derived from Cannabis sativa L. subspecies, including both its drug-type and fiber-type varieties, which are the most widely cultivated and studied within the genus. Among these, nitrogen-containing compounds such as spermidine alkaloids exhibit neuroprotective and anti-aging properties, while hydroxycinnamic acids and hydroxycinnamic acid amides, including N-trans-caffeoyltyramine and N-trans-feruloyltyramine, have demonstrated notable antioxidant and anti-inflammatory activities. Additionally, Cannabis species are a valuable source of unique stilbenes, such as canniprene, and flavonoids, including cannflavin A and B, which demonstrated potent anti-inflammatory and antiproliferative effects. Despite this rich phytochemical diversity, research on these compounds remains limited, largely due to historical legal restrictions. This literature review consolidates and updates current knowledge on these lesser-studied phytochemicals of Cannabis, detailing their biosynthetic pathways, metabolic precursors, and emerging therapeutic applications. By expanding the research focus beyond cannabinoids, this work aims to enhance our understanding of Cannabis’s full pharmacological potential and promote further investigation into its diverse chemical constituents. Full article

This review covers preclinical studies of stilbene derivative compounds (both natural and synthetic) with potential preventive and therapeutic effects against Alzheimer’s disease (AD). AD is a worldwide neurodegenerative disease characterized by the destruction of nerve cells in the brain and the loss of cognitive function due to aging. Stilbenes are a unique class of natural phenolic compounds distinguished by a C6-C2-C6 (1,2-diphenylethylene) structure and two aromatic rings connected by an ethylene bridge. Stilbenes’ distinct features make them an intriguing subject for pharmacological research and development. Several preclinical studies have suggested that stilbenes may have neuroprotective effects by reducing Aβ generation and oligomerization, enhancing Aβ clearance, and regulating tau neuropathology through the prevention of aberrant tau phosphorylation and aggregation, as well as scavenging reactive oxygen species. Synthetic stilbene derivatives also target multiple pathways involved in neuroprotection and have demonstrated promising biological activity in vitro. However, some properties of stilbenes, such as sensitivity to physiological conditions, low solubility, poor permeability, instability, and low bioavailability, limit their usefulness in clinical applications. To address this issue, current investigations have developed new drug delivery systems based on stilbene derivative molecules. This review aims to shed light on the development of next-generation treatment strategies by examining in detail the role of stilbenes in Alzheimer’s pathophysiology and their therapeutic potential. Full article

Vegetative propagation of European grapevine (Vitis vinifera L.) requires grafting onto American rootstocks due to susceptibility to phylloxera. However, the grafting yield is compromised by the presence of grapevine trunk diseases (GTDs) such as Esca. This study investigates the phenolic response and enzyme activity in grapevine callus from grafts obtained by scions with different GTD status (healthy, asymptomatic, and symptomatic) treated with different disinfection methods (Beltanol, Beltanol in combination with thermotherapy, Serenade^® ASO, Remedier, BioAction ES, and sodium bicarbonate). Twenty-three phenolic compounds were identified in the graft callus, with flavanols, stilbenes, and condensed tannins predominating. Scion disinfection with BioAction ES led to a significant increase in total phenolic content in the callus, especially in symptomatic scions, for on average 510.3 µg/g fresh weight (FW) higher total phenolic content, compared to grafts where scions were treated with Beltanol. Phenolics such as epicatechin gallate, procyanidin derivatives, and resveratrol hexoside were significantly increased, indicating a strong elicitor effect of BioAction ES. Enzymatic activity analysis showed that the disinfection methods affected the activity of key enzymes involved in the phenylpropanoid metabolic pathway. In particular, BioAction ES significantly increased phenylalanine ammonia lyase (PAL) activity in callus from grafts with healthy scions by 3.4-fold and flavanone 3β-hydroxylase (FHT) activity in callus from grafts with infected scions by 4.9-fold (asymptomatic) and 6.9-fold (symptomatic) compared to callus from grafts with Beltanol-treated scions. The results highlight the potential of environmentally friendly disinfection methods, particularly BioAction ES, in influencing phenolic content and enzymatic activity in graft callus, potentially affecting the success of grapevine grafting. Full article

Plant-based stilbenes are low-molecular-weight polyphenolic compounds that exhibit anti-oxidant, anti-microbial, anti-fungal, anti-inflammatory, anti-diabetic, cardioprotective, neuroprotective, and anti-cancer activities. They are phytoalexins produced in diverse plant species in response to stress, such as fungal and bacterial infections or excessive UV irradiation. Plant-derived dietary products containing stilbenes are common components of the human diet. Stilbenes appear to be promising chemopreventive and chemotherapeutic agents. Accumulating evidence indicates that stilbenes are able to trigger both apoptotic and autophagic molecular pathways in many human cancer cell lines. Of note, the molecular crosstalk between autophagy and apoptosis under cellular stress conditions determines the cell fate. The autophagy and apoptosis relationship is complex and depends on the cellular context, e.g., cell type and cellular stress level. Apoptosis is a type of regulated cell death, whereas autophagy may act as a pro-survival or pro-death mechanism depending on the context. The interplay between autophagy and apoptosis may have an important impact on chemotherapy efficiency. This review focuses on the in vitro effects of stilbenes in different human cancer cell lines concerning the interplay between autophagy and apoptosis. Full article

This study investigated the neuroprotective activity of oligomeric stilbenes (OSs) derived from Alpha grape stems in various in vitro models of Parkinson’s disease (PD). Using neurotoxin-induced cellular models, including 1-methyl-4-phenylpyridine (MPP+), paraquat (PQ), 6-hydroxydopamine (6-OHDA), and rotenone, we screened the cytoprotective effects of ampelopsin A (1), ε-viniferin (2), vitisin D (3), vitisin A (4), α-viniferin (5), trans-vitisin B (6), cis-vitisin B (7), and melanoxylin A (8). The results demonstrate that certain stilbenes significantly enhanced cell viability and reduced reactive oxygen species (ROS) levels in neurotoxin-treated Neuro-2a cells. Notably, vitisin A and trans-vitisin B exhibited promising neuroprotective properties by decreasing mitochondrial ROS and cardiolipin peroxidation. This study highlights the potential of these compounds in mitigating oxidative stress and inflammation associated with PD. Additionally, we provided new insights into the antioxidant mechanisms of these stilbenes, including their direct ROS-scavenging abilities. Our findings contribute to the understanding of oligomeric stilbenes as potential therapeutic agents for the prevention and treatment of neurodegenerative diseases, particularly those associated with oxidative damage. Further research is warranted to explore its clinical applications and underlying mechanisms of action. Full article

Background: Wine production generates significant amounts of grape marc, which can serve as a potential source of bioactive compounds, including polyphenols. Objectives: In this study, we aimed to investigate the polyphenol content of skin and seeds separated from grape marc, and test their extracts against two significant bacteria, Listeria monocytogenes (LM) and Staphylococcus aureus (SA). Methods: A comprehensive analysis of the phenolic composition in the skin, seeds, and juice/wine derived from Cabernet Sauvignon grape berries was conducted over an 18-day fermentation period. High-performance liquid chromatography was performed to identify and quantify the main flavan-3-ols, flavonols, anthocyanins, and stilbenes. In addition, the total phenolic content (TPC) was determined by the Folin–Ciocalteu method. Results: The TPC of both seeds and skins significantly decreased over time. In parallel, the TPC in the wine gradually increased, indicating a release of phenolic compounds into the wine. We found that the TPC in seeds was consistently higher than in the skin at all examined time points. The main flavonoids in seeds were flavan-3-ols (catechin and epicatechin), while anthocyanins (delphinidin-, cyanidin-, petunidin-, peonidin-, and malvidin-3-O-glucoside) were the predominant ones in skins. Crude seed and skin extracts enriched in phenolics were prepared, of which only the crude seed extract was proven effective against LM and SA. Following the time-kill assay, our findings revealed that the minimal bactericidal concentration of the crude seed extract against LM was 5.02 mg/mL after 12 h incubation, demonstrating the eradication of the living bacterial cell number by ~6 log. A 24 h exposure time was required for complete inactivation of SA, but a lower concentration was sufficient (2.54 mg/mL). Conclusions: Grape waste remains a valuable source of polyphenols, with grape seeds, in particular, exhibiting significant antimicrobial activity against certain foodborne pathogens. Full article

Resveratrol, a naturally occurring phenolic stilbene molecule, has been intensively researched for its anti-inflammatory, anticancer, antioxidant, antibacterial, and neuroprotective properties. However, due to its limited absorption and probable hepatotoxicity, it is difficult to employ directly as a medication, limiting its therapeutic applicability. Over the last five years, numerous structural changes in resveratrol have been widely studied, resulting in considerable improvements in pharmacological activity and drug availability. This work reviews the biological activities and structure–activity relationships (SARs) of resveratrol derivatives, with the goal of providing useful insights for the discovery of new resveratrol derivatives. Full article

Scientific research on stilbenes is conducted for their chemopreventive and therapeutic properties. In experimental studies, natural and synthetic trans-stilbenes exhibit antioxidant, anti-inflammatory, cardioprotective, and anticancer effects. The antitumor activity of some natural and synthetic stilbenes is associated with their interaction with cytochrome P450 family 1, which leads to the inhibition of procarcinogen activation. In the present study, three-dimensional quantitative structure–activity relationship analysis (3D-QSAR) was performed on a series of forty-one trans-stilbene derivatives to identify the most significant features of the molecules responsible for their CYP1B1 inhibitory activity. The developed 3D-QSAR model presented a cross-validated correlation coefficient Q² of 0.554. The model’s predictive ability was confirmed by external validation (r² = 0.808). The information provided by 3D-QSAR analysis is expected to be valuable for the rational design of novel CYP1B1 inhibitors. Full article

Background/Objectives: Inflammatory bowel disease (IBD) is a persistent inflammatory condition affecting the gastrointestinal tract, distinguished by the impairment of the intestinal epithelial barrier, dysregulation of the gut microbiota, and abnormal immune responses. Cajanus cajan (L.) Millsp., traditionally used in Chinese herbal medicine for gastrointestinal issues such as bleeding and dysentery, has garnered attention for its potential therapeutic benefits. However, its effects on IBD remain largely unexplored. Methods: In this study, the major compounds from Cajanus cajan leaf extract (CCLE) were initially characterized by LCMS-IT-TOF. The IBD model was developed in C57BL/6 mice by administering continuous 4% (w/v) dextran sodium sulfate (DSS) aqueous solution over a period of seven days. The body weight, colon length, disease activity index (DAI), and histopathological examination using hematoxylin and eosin (H&E) staining were performed in the IBD model. The levels of the main inflammatory factors, specifically TNF-α, IL-1β, IL-6, and myeloperoxidase (MPO), were quantified by employing enzyme-linked immunosorbent assay (ELISA) kits. Additionally, the levels of tight junction proteins (ZO-1, Occludin) and oxidative stress enzymes (iNOS, SOD1, CAT) were investigated by qPCR. Subsequently, flow cytometry was employed to analyze the populations of various immune cells within the spleen, thereby assessing the impact of the CCLE on the systemic immune homeostasis of IBD mice. Finally, 16S rDNA sequencing was conducted to examine the composition and relative abundance of gut microbiota across different experimental groups. In addition, molecular docking analysis was performed to assess the interaction between the principal components of CCLE and the aryl hydrocarbon receptor (AHR). Results: We identified seven bioactive compounds in CCLE: catechin, cajachalcone, 2-hydroxy-4-methoxy-6-(2-phenylcinyl)-benzoic acid, longistylin A, longistylin C, pinostrobin, amorfrutin A, and cajaninstilbene acid. Our results demonstrated that oral administration of CCLE significantly alleviates gastrointestinal symptoms in DSS-induced IBD mice by modulating the balance of gut-derived pro- and anti-inflammatory cytokines. This modulation is associated with a functional correction in M1/M2 macrophage polarization and the Th17/Treg cell balance in splenic immune cells, as well as shifts in the populations of harmful bacteria (Erysipelatoclostridium and Staphylococcus) and beneficial bacteria (Odoribacter, unidentified Oscillospiraceae, Lachnoclostridium, and Oscillibacter) in the gut. Furthermore, cajaninstilbene acid, longistylin A, and longistylin C were identified as potential AhR agonists. Conclusions: The present results suggested that CCLE, comprising stilbenes like cajaninstilbene acid, longistylin A, and longistylin C, protects the epithelial barrier’s structure and function against DSS-induced acute IBD by restoring gut microbiota balance and systemic immune response as AhR agonists. Overall, CCLE represents a promising natural product-based therapeutic strategy for treating IBD by restoring gut microbiota balance and modulating systemic immune responses. Full article

Stilbenes, like resveratrol, are natural small molecules with several applications in the treatment of chronic illnesses, diabetes, and neurological and cardiovascular conditions. Considering the molecular structure of stilbenes and the biological activities of resveratrol, we investigated the synthesis and biological activity of a novel styryl quinolinium (SQ) derivative. The SQ was synthesized using the alkylation of lepidine and methyl 4-methylbenzenesulfonate and further Knoevenagel condensation with 2-hydroxy naphthaldehyde. Its structure was determined using NMR, IR, Raman, UV-Vis, and MS. The current trend of research has shifted toward the synthesis of novel SQ as resveratrol’s analog. Therefore, its anti-inflammatory and antioxidant activities were evaluated. The compound exerted very good anti-inflammatory effects in preventing albumin denaturation, which were confirmed by ex vivo immunohistochemical studies. Density functional theory (DFT) analyses were conducted on the SQ structure to gain detailed insights into its active sites, energy gap, quantum properties, and electronic behavior. The biological evaluation of the compound was completed, assessing its antioxidant potential using DPPH radical scavenging assay. In addition, molecular docking simulations were utilized to assess the SQ compound’s potential inhibitory effect on human serum albumin (HSA). Full article

In spite of significant advancements in diagnosis and treatment, cancer remains one of the major threats to human health due to its ability to cause disease with high morbidity and mortality. A multifactorial and multitargeted approach is required towards intervention of the multitude of signaling pathways associated with carcinogenesis inclusive of angiogenesis and metastasis. In this context, plants provide an immense source of phytotherapeutics that show great promise as anticancer drugs. There is increasing epidemiological data indicating that diets rich in vegetables and fruits could decrease the risks of certain cancers. Several studies have proved that natural plant polyphenols, such as flavonoids, lignans, phenolic acids, alkaloids, phenylpropanoids, isoprenoids, terpenes, and stilbenes, could be used in anticancer prophylaxis and therapeutics by recruitment of mechanisms inclusive of antioxidant and anti-inflammatory activities and modulation of several molecular events associated with carcinogenesis. The current review discusses the anticancer activities of principal phytochemicals with focus on signaling circuits towards targeted cancer prophylaxis and therapy. Also addressed are plant-derived anti-cancer vaccines, nanoparticles, monoclonal antibodies, and immunotherapies. This review article brings to light the importance of plants and plant-based platforms as invaluable, low-cost sources of anti-cancer molecules of particular applicability in resource-poor developing countries. Full article