Search Results (3,933)

The multidirectional bioactivity of betulin (BN), its widespread occurrence in plants, relatively low toxicity, and acceptable safety profile make it an attractive scaffold for scientific research and potential therapeutic applications. Due to the presence of reactive functional groups (C-3-OH and C-28-OH), BN is an interesting source of new semisynthetic bioactive compounds obtained via structural modifications of the parent backbone. In our study, we designed new BN–amino acid (BNAA) molecular hybrids, aiming to exploit synergistically the properties of both components. We prepared and evaluated a total of 18 new compounds for antitumor activity against the two human cancer cell lines (HCT 116 and MCF-7) and one non-cancerous cell line (NHDF) using a standard Cell Counting Kit-8 (CCK-8) assay. The potential signaling pathways of the obtained BN derivatives were identified based on the measurement of p21 and Bax mRNA expression levels using the RT-qPCR method. We successfully synthesized a series of new BN hybrids by conjugation of the C-3 and C-28 hydroxyl groups via a succinyl (-CO-CH₂-CH₂-CO-, Suc) linker with selected amino acid methyl esters. The structures of all obtained BNAA molecular hybrids were confirmed by spectroscopic analysis (¹H and ¹³C NMR) and high-resolution mass spectrometry (HR-MS). Analysis of the biological activity of the obtained BN derivatives indicated that both the attached amino acids and the substituents at C3 carbon alter BN activity. The obtained BN–amino acid hybrids represent a useful platform for further optimization, especially derivatives (3a, 3e, 3f, and 7d), which showed the most relevant biological profiles in this study. Full article

Background/Objectives: Liuwei Dihuang (LWDH) is a classical plant-derived herbal formula widely used for cognitive decline. This study aimed to evaluate its efficacy and safety in cognitive disorders and to explore its potential pharmacological mechanisms using network pharmacology. Methods: We searched 11 databases through November 2024 for randomized controlled trials comparing LWDH plus conventional therapy with conventional therapy alone in cognitive disorders. Meta-analysis was performed for clinical outcomes, and herb–compound–target and disease-target datasets were integrated to identify core molecular modules. Results: Twelve randomized controlled trials involving 1137 participants were included. Adjunctive LWDH was associated with improvements in Mini-Mental State Examination scores (MD = 2.34, 95% CI 0.88–3.79), activities of daily living, and quality of life. However, substantial heterogeneity and methodological limitations, including unclear randomization and blinding, were observed across studies, indicating a potential risk of bias. Fewer adverse events were reported in the LWDH plus conventional treatment group, although reporting quality was limited. The overall risk of bias was judged as “some concerns”. Network pharmacology analysis identified a broad set of overlapping genes between LWDH-associated targets and cognitive disorder-related genes, which were further refined through filtering procedures. Subsequent analyses suggested associations with pathways related to neurodegeneration, apoptosis, and central nervous system function; however, these findings are exploratory and based on in silico predictions. Conclusions: LWDH may be associated with potential adjunctive benefits in cognitive disorders. However, given the methodological limitations and clinical heterogeneity of the included studies, the findings should be interpreted with caution. The proposed pharmacological mechanisms are exploratory and require further validation. Well-designed randomized controlled trials are needed to establish more robust evidence. Full article

Compounds of plant origin have increasingly emerged as anticancer agents through direct cytotoxicity and sensitizing mechanisms. Melanoma remains the most aggressive form of skin cancer that exhibits a steadily increasing number of new cases globally each year, thus urgently requiring more effective therapeutic strategies. Therefore, phytochemicals can be considered promising candidates, particularly when used in combination with immune checkpoint inhibitors. Their ability to optimize therapeutic efficacy and strengthen antitumor immune responses is mediated through various mechanisms that include the stimulation of T cell activity, the regulation of the TME, the activation of intrinsic immune responses and cytokine signaling, and the regulation of immune checkpoints such as PD-1/PD-L1, CTLA-4, and LAG-3. Additionally, these compounds can alter key signaling pathways that control immune regulation. Nevertheless, the extrapolation of preclinical studies to clinical applications remains limited by insufficient clinical evidence, the lack of standardized therapeutic protocols, and poor pharmacokinetic behavior. Consequently, further studies are required in order to clarify their actual efficacy and to better define their role in modern oncology. This article aims to review the mechanisms that underlie the anticancer sensitizing activity of major classes of plant-derived compounds such as polyphenols, flavonoids, terpenoids, alkaloids, and isothiocyanates. The available preclinical and clinical evidence were reported together with their potential synergistic effects when combined with immune checkpoint inhibitors. An important aspect related to the anticancer effects of these compounds lies in their ability to simultaneously target multiple signaling pathways. Furthermore, advanced formulations such as nanoparticulated delivery systems are discussed as strategies to optimize their clinical application and therapeutic outcomes. Full article

Rising temperatures, driven by global climate change, are profoundly altering high-latitude ecosystems, influencing vegetation phenology and productivity. However, understanding the long-term, nuanced responses of these ecosystems remains a critical challenge. Soil warming experiments have served as useful tools for understanding these shifts. However, many of these studies have relied on a single measure, predominantly the Normalized Difference Vegetation (NDVI), measured at a single level of warming. This approach often fails to separate structural greening from underlying physiological responses. To address these gaps, this study provided a comprehensive snapshot assessment of growing season vegetation dynamics in a subarctic grassland ecosystem in Iceland that had been exposed to continuous geothermal soil warming for over 60 years. Using high-resolution multispectral drone imagery, twelve different vegetation indices (VIs) were derived to assess not only greenness but also physiological stress and photosynthetic efficiency across a range of mean annual soil temperatures (MATs). Using linear regression and redundancy analysis (RDA), the responses of these indices to warming and their relationships with other environmental drivers, such as standing biomass and plant nutrient concentrations (nitrogen and phosphorus), were analyzed. The results revealed significant positive linear relationships between most of the indices and MATs across the 5 to 11 °C range. This indicated that higher MATs led to increased biomass and structural growth, without revealing any significant thresholds or tipping points in vegetation response within the observed warming range. However, the Photochemical Reflectance (PRI) showed a significant negative relationship with warming, suggesting a decoupling between structural greening and photosynthetic light-use efficiency. Furthermore, RDA results indicated that, while most of the VIs were primarily driven by biomass, the decline in PRI was likely a compounding effect of physical canopy self-shading and plant phosphorus constraints. Ultimately, this study demonstrated that, while these subarctic grasslands exhibited local evidence of “Arctic greening” under further warming, multispectral drone remote sensing could detect underlying physiological adjustments and nutrient constraints that traditional greenness indices might overlook, providing a more nuanced understanding of ecosystem response. Full article

Spatholobus suberectus is a medicinal and edible plant widely recognized for its pharmacological potential. Although its stems have been extensively studied and utilized, its leaves are often discarded as agricultural waste, leading to significant resource underutilization. To promote the sustainable valorization of these leaves, this study aimed to provide a predictive evaluation of their bioactive constituents and pharmacological potential. Leaves of S. suberectus were collected at six growth stages (January, March, May, July, September and November). A total of 6750 metabolites were identified, primarily comprising amino acids and derivatives (26.74%), organic acids (15.33%), and bioactive secondary metabolites, including flavonoids and phenolic acids (27.98%). Metabolic profiling revealed clear seasonal patterns, allowing the classification of the six harvest months into three distinct stages: January and March (G1), May and September (G2), and July and November (G3). Among these, the G1 stage was notably enriched in defensive secondary metabolites, particularly flavonoids and phenolic acids. To predict the bioactivity of these metabolites and elucidate potential mechanisms of action, network pharmacology and molecular docking analyses were employed. Network pharmacology and molecular docking were employed to predict anti-inflammatory mechanisms. From the metabolome, 83 potential bioactive compounds were screened, interacting with 306 targets. Network analysis identified 60 core anti-inflammatory targets (e.g., TNF, AKT1, PTGS2, STAT3) that were significantly enriched in MAPK and PI3K-Akt pathways. Molecular docking revealed strong binding affinities, with pelargonidin showing the highest affinity for PTGS2 (−11.72 kcal/mol). Candidate metabolites peaked in January, and extracts from this period exhibited notable COX-2 inhibitory activity (IC50 = 16.41 μg/mL). This research provides essential chemical characterization and preliminary bioactivity evidence to support the valorization of S. suberectus leaves and identifies January as the optimal harvest time to maximize their bioactive potential. Full article

Background/Objectives: Although plant-derived dietary fiber and protein are favorable factors for improving host metabolic disorders, it remains unclear whether these two macronutrients exhibit synergistic health benefits. Methods: To address this gap, utilizing oat dietary fiber (GLU) and soybean protein (SBP) as representative bioactive models, we investigated the effects of 5% GLU, 20% SBP, and their combined supplementation on high-fat diet (HFD)-induced metabolic dysregulation in C57BL/6J mice. Results: Our results demonstrated that the combined GLU + SBP intervention provided comprehensive protection against HFD-induced obesity, significantly attenuating body weight gain (12.29 ± 2.02 g vs. 21.90 ± 2.86 g, p < 0.05) and adiposity (3.34 ± 1.19% vs. 10.77 ± 1.16%, p < 0.05) compared with HFD mice, without altering caloric intake. Crucially, the compound formulation exhibited synergistic superiority over individual components, as evidenced by greater reductions in serum aspartate aminotransferase (AST) activity (113.13 ± 28.50 U/L vs. 158.00 ± 30.25 U/L, p < 0.05) and improved glucose tolerance, with lower OGTT AUC values (999.09 ± 95.83 vs. 1434.66 ± 80.56 mmol/L·min, p < 0.05). Mechanistically, 16S rRNA sequencing revealed a distinct remodeling of the gut microbial community, highlighted by a substantial enrichment of Akkermansia. Functional prediction analysis specifically linked this microbial shift to the modulation of Akkermansia-associated metabolic pathways, which subsequently facilitated the activation of host metabolic networks to combat lipid deposition and systemic metabolic stress. Conclusions: Collectively, the GLU + SBP combination offers synergistic metabolic benefits driven by a distinct gut microbiota signature, supporting a feasible “soluble fiber + plant protein” strategy for developing functional foods targeting metabolic health. Full article

Fish-derived products are extensively acknowledged for their substantial role in fostering balanced diets and supporting a healthy way of life. This research is aimed at formulating, analyzing and evaluating a fish-based food product. The methodology adopted in this study adheres to contemporary food safety standards, prioritizing the utilization of minimal technological processes and natural ingredients, a focus that is gaining prominence within contemporary industrial practices. Thus, the proposal for a formulation obtained by integrating powders and extracts from plant byproducts (Citrus) represents a concrete application direction with real potential for commercialization. The product has been enriched with biocomponents derived from orange peel, namely orange extract (OE) and orange peel powder (PPO). The research focused on product development and the in situ evaluation of the effects of OE and PPO. The physicochemical composition, bioactive compound content, and antioxidant activity were evaluated, along with the microbiological status under post-opening refrigeration conditions, in order to simulate actual consumer use. In addition, the product’s color parameters and sensory attributes were analyzed. The results highlight significant potential for the development of a clean-label fish-based product, characterized by a simplified and easily implementable formulation, aligned with current production and consumption requirements. Compared to the control sample, both OE and PPO significantly influenced the analyzed parameters. Differences in physicochemical composition were observed in the experimental samples. In addition, PPO increased the antioxidant activity of the samples and the profile of bioactive compounds. Microbiological analysis, performed on day 0 and after 3 and 7 days of storage at 4 °C showed opening, confirmed the absence of Escherichia coli and Staphylococcus aureus in all samples and had an influence on the growth of fungi. The acceptability of fish-based products is often limited by odor perception, which is one of the main factors leading to consumer rejection. Sensory evaluation demonstrated that citrus-enriched samples were distinguished by the perception of particular sensory attributes. This formulation presents a practical solution to address this constraint, thereby enhancing the product’s sensory acceptability. The integration of OE and PPO yielded a more harmonized sensory profile, as evidenced by elevated hedonic scores and an intermediate placement in both principal component analysis (PCA) and external preference mapping. This research furnishes a thorough characterization of a fish-based food product, underscoring its potential as a viable option for balanced dietary regimens. Simultaneously, the findings support the product’s adherence to sustainability principles through the utilization of bioactive compounds sourced from plant byproducts, thus satisfying contemporary requirements for foods that possess an optimal nutritional profile and a diminished environmental footprint. Full article

Botanical extracts represent a rich and sustainable source of polyphenolic compounds with significant potential in anticancer research. Among these, hesperidin, naringenin, hydroxytyrosol, oleuropein, and quercetin have attracted considerable attention due to their abundance in widely consumed plants such as citrus fruits, olive derivatives, and various fruits and vegetables. However, their clinical translation is hindered by intrinsic limitations including poor solubility, low stability, and limited bioavailability. In this context, nanotechnology-based drug delivery systems have emerged as a promising strategy to enhance the therapeutic performance of these bioactive compounds. This review provides an overview of polyphenol-rich botanical matrices and focuses on recent advances in their nanoformulation. Various nanocarriers, including polymeric nanoparticles, liposomes, solid lipid nanoparticles, and nanoemulsions, are discussed in terms of their ability to improve physicochemical properties, protect against degradation, and enhance delivery efficiency. Special attention is given to the challenges associated with the encapsulation of complex botanical extracts and the need to preserve their compositional integrity and synergistic effects. Overall, nanoformulation represents a powerful approach to overcome current limitations and unlock the full potential of plant-derived polyphenols in anticancer applications. Full article

The increasing global demand for animal-derived food products, combined with growing environmental and public health concerns, has intensified the search for sustainable strategies in livestock production. Among emerging nutritional approaches, phytogenic feed additives (PFAs) have gained attention as natural alternatives to conventional synthetic growth promoters. PFAs, derived from herbs, spices, essential oils, and plant extracts, contain diverse bioactive compounds such as phenolics, flavonoids, alkaloids, terpenoids, and saponins. These compounds exhibit antimicrobial, antioxidant, anti-inflammatory, and immunomodulatory activities that can support animal health, productivity, and product quality. Current research indicates that PFAs positively influence digestive physiology by modulating gut microbiota, improving intestinal integrity, and stimulating digestive enzyme secretion. These mechanisms enhance nutrient utilization, feed efficiency, and growth performance. In addition, the antioxidant and immunomodulatory properties of plant-derived compounds strengthen the ability of animals to cope with physiological stress and disease, potentially reducing reliance on synthetic antimicrobials and supporting antibiotic-free production systems. PFAs may also improve reproductive performance and physiological stability, particularly in small livestock species and indigenous breeds. Beyond productivity benefits, phytogenic additives contribute to environmental sustainability by improving feed conversion efficiency and reducing nutrient excretion. The present literature review confirms that although variability in plant composition and the need for standardization remain challenges, PFAs represent a valuable component of integrated nutritional strategies aimed at achieving resilient, environmentally responsible, and economically sustainable livestock production systems. Full article

Background/Objectives: Achillea millefolium is a well-known medicinal plant recognized in several pharmacopeias, while the Balkan endemic species Achillea clypeolata lacks a pharmacopeial monograph and remains insufficiently studied despite its traditional use. This study aimed to comparatively evaluate the phytochemical composition and biological potential of both species. Methods: Chemical composition was studied using UHPLC-MS/MS, HPLC, and FT-IR; anti-inflammatory potential was analyzed by erythrocyte membrane stabilization assay (heat- and hypotonicity-induced hemolysis); and enzyme-inhibitory activity was tested against collagenase, elastase, hyaluronidase, and tyrosinase. In addition, antioxidant activity was evaluated using DPPH, ABTS, and DCFDA assays; antimicrobial activity was determined using the broth microdilution method; and cytotoxic potential was investigated by the MTT assay. Results: The major constituents in water–ethanolic extracts were quinic acid derivatives, flavonoids, phenolic acids, and coumarins, with chlorogenic acid, 3,5-dicaffeoylquinic acid, cosmosiin, cynaroside, rutin, and hyperoside as dominant in both species. Extracts exhibited marked anti-inflammatory activity, where A. millefolium provided greater protection under heat-induced hemolysis, and both extracts showed comparable efficacy under osmotic stress. Concentration-dependent inhibition of collagenase, elastase, hyaluronidase, and tyrosinase (concentration from 62.5 to 1000 µg/mL), along with significant antioxidant activity in ABTS and DPPH assays, was observed. In MRC-5 cells, the extracts reduced AAPH-induced ROS levels up to 50 µg/mL, while higher concentrations showed diminished effects. Moderate cytotoxicity was observed, with A. clypeolata displaying stronger effects at 50–100 µg/mL. Both Achillea species exhibited broad-spectrum antimicrobial activity, with pronounced effects against Gram-positive bacteria. Conclusions: The results support the traditional use of Achillea species and highlight A. clypeolata as a promising, yet underexplored, source of bioactive compounds for dermatological and pharmaceutical applications. Full article

Plant-derived bioactive compounds represent a major foundation of modern anticancer therapy and remain a prolific source of molecules with clinically relevant activity. This review provides an integrated classification of plant-derived anticancer compounds based on their clinical development status and predominant molecular mechanisms of action. Established chemotherapeutic agents, including taxanes, vinca alkaloids, and camptothecin derivatives, are distinguished from investigational phytochemicals such as polyphenols, flavonoids, terpenoids, and alkaloids that are under preclinical or clinical evaluation. These compounds target key hallmarks of cancer through modulation of microtubule dynamics, inhibition of topoisomerases, regulation of oncogenic signaling and epigenetic processes, and suppression of angiogenesis, invasion, and metastasis. Particular emphasis is placed on multitarget phytochemicals that interfere with PI3K/Akt, NF-κB, JAK/STAT, and MAPK pathways, induce apoptosis, and promote epigenetic reprogramming. In addition, major translational challenges, especially limited bioavailability, are discussed alongside advances in nano-enabled delivery systems designed to enhance therapeutic efficacy and reduce systemic toxicity. Collectively, this framework highlights the continuing relevance of plant-derived compounds in oncology and supports their rational integration into precision cancer therapy. Full article

Simazine (SIM), a triazine herbicide and potential environmental risk factor, has been associated with neurotoxicity; however, the underlying mechanisms remain poorly characterized. Salidroside (SAL), a natural antioxidant with mitochondrial protective properties, has been reported to alleviate SIM-induced neuronal injury. Using an integrated strategy combining network toxicology and network pharmacology with experimental validation, this study systematically investigated the neurotoxic mechanisms of SIM and the neuroprotective effects of SAL. Bioinformatics analyses revealed that SIM- and SAL-related targets were significantly enriched in apoptosis- and autophagy-associated pathways. In vitro experiments demonstrated that SIM induced mitochondrial structural damage, metabolic dysfunction, and dopaminergic neuron-like SH-SY5Y cells apoptosis by inhibiting PINK1/Parkin-mediated mitophagy. Conversely, SAL effectively protected SH-SY5Y cells against SIM-induced neurotoxicity by restoring PINK1/Parkin signaling, thereby enhancing mitophagy and suppressing apoptosis. The present study elucidates the central mechanism of SIM-induced PD-like neurotoxicity in vitro and, for the first time, confirms the potential protective effect of SAL. These findings provide a novel theoretical basis for investigating nerve injury induced by SIM exposure and underscore the potential of plant-derived compounds in preventing nerve injuries related to environmental toxicants. Full article

Medicinal plants have long served as a primary source of bioactive compounds with essential therapeutic applications. Recent advances in functional genomics and plant biotechnology now enable precise manipulation of metabolic pathways to enhance the production of specialized metabolites with medicinal value. However, an integrative understanding of how genomic discovery can be linked with pathway engineering, scalable production systems, and healthcare applications remains insufficiently developed. This knowledge gap limits the effective translation of molecular insights into the sustainable production of medicinally important compounds. The novelty of this review lies in its integrated framework linking functional genomic discovery with pathway engineering, synthetic biology, artificial intelligence-assisted prediction, and scalable production systems for medicinal plant-derived therapeutics. This review aims to provide a comprehensive overview of cutting-edge approaches in medicinal plant research, emphasizing high-throughput RNA sequencing, CRISPR/Cas9 gene editing, synthetic biology, and metabolic engineering for optimizing the production of key bioactive compounds, including artemisinin, cannabinoids, ginsenosides, and taxol. It further examines how these tools collectively support metabolite discovery, pathway elucidation, yield improvement, and biotechnological production in major medicinal plant systems. We explore the application of genomic and biotechnological approaches in plants such as Artemisia annua, Cannabis sativa, Panax ginseng, and Taxus baccata to enhance metabolite yields and promote sustainable production. The review highlights case studies that demonstrate how genetic modification, metabolic engineering, and synthetic pathway design have been successfully employed to increase the synthesis of key medicinal compounds. Moreover, we discuss the integration of artificial intelligence and machine learning to predict gene–metabolite relationships, support personalized phytochemical therapies, and facilitate sustainable, large-scale production. Finally, the review addresses the implications of these innovations for the pharmaceutical industry, healthcare, and agriculture, while also highlighting sustainable and scalable directions for future medicinal plant biotechnology. Full article

Hydrodistillation of aromatic plants for essential oil production generates substantial amounts of solid and liquid residues that are commonly discarded despite their potential value as sources of bioactive compounds. In this study, the essential oil and post-distillation residues of Rhododendron tomentosum Harmaja were evaluated within a waste-to-value framework to recover phenolic compounds with antioxidant and antimicrobial properties. Dry extracts obtained from liquid (DEA) and solid (DEE) residues were characterized in terms of total phenolic and flavonoid contents, antioxidant capacity (DPPH assays), and antimicrobial activity against selected microorganisms. Quantitative HPLC–PDA analysis revealed multiple phenolic compounds. Extracts derived from solid residues exhibited significantly higher phenolic and flavonoid contents and stronger antioxidant activity than those obtained from liquid residues, indicating that solid by-products constitute a richer phenolic matrix. Antimicrobial assays revealed pronounced activity for extracts prepared from plant material harvested in October, particularly those based on propylene glycol and glycerin, which were effective against both Gram-positive bacteria and selected Gram-negative clinical isolates. The essential oil showed broad-spectrum antimicrobial activity, including inhibition of Aspergillus niger. Stability studies demonstrated that the phenolic composition and bioactivity of the dry extracts were largely preserved after one year of storage. These findings demonstrate that R. tomentosum hydrodistillation residues represent a promising source of natural antioxidants and antimicrobial agents, supporting their potential utilization as value-added ingredients in food and cosmetic applications and contributing to circular economy strategies. Full article

A quantitative NMR assay was utilized to identify methylglyoxal-scavenging natural products from Rhodophytes, Chondrus crispus and Gracilaria vermiculophylla. This revealed the activity of guanylurea-containing amino acid derivatives, gongrine and gigartinine. The molecules share structural features with the frontline blood glucose-lowering drug and plant natural product derivative, metformin, and scavenge methylglyoxal via the same mechanism, resulting in an imidazole-containing Advanced Glycation Endproduct or AGE. The protective effect of the molecules reported here was evaluated in a cell-based model for reactive aldehyde stress using methylglyoxal exposure to reduce cell viability. Gongrine, gigartinine, and metformin all preserve cell viability in HepG2 following methylglyoxal exposure. This is the first report of methylglyoxal scavenging and cell viability protection of these macroalgae-derived guanylurea-containing natural products, which can be found in high abundance in commonly consumed and industrially produced macroalgae species. The compounds presented here, along with their algal sources, offer a unique opportunity to produce guanylureas with therapeutic potential through sustainable production methods from easily cultivated algal sources. Full article