Search Results (2,804)

Chronic stress is increasingly recognized as a major contributor to systemic disease. Prolonged or repeated activation of the hypothalamic–pituitary–adrenal (HPA) axis and sympathoadrenal systems may contribute to glucocorticoid receptor resistance and chronic low-grade inflammation, although stress-related responses vary depending on stressor characteristics, population, age, sex, health status, and study design. Elevated levels of pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), oxidative stress, and NF-κB activation contribute to immune dysfunction, neuroinflammation, metabolic disturbances, reproductive and endocrine imbalance, as well as structural and functional alterations in stress-sensitive brain regions. Prolonged exposure to stress may contribute to the development of neuropsychiatric, cardiovascular, metabolic, neurodegenerative, and malignant diseases, highlighting the need for effective strategies to mitigate the detrimental consequences of chronic stress. Given the limitations and adverse effects associated with conventional pharmacological approaches, increasing attention has been directed toward natural bioactive compounds. Terpenes represent a diverse class of phytochemicals with reported anti-inflammatory, antioxidant, and neuromodulatory properties. Terpenes such as limonene and β-caryophyllene, as well as terpenoids such as linalool, may modulate NF-κB, MAPK, and Nrf2 signaling pathways and interact with the endocannabinoid system, thereby attenuating neuroinflammation, oxidative stress, and stress-induced immune dysregulation. This review summarizes current evidence regarding the mechanisms linking chronic stress, HPA axis dysfunction, and systemic disease, with particular emphasis on endocrine, immune, and nervous system alterations. In addition, it critically evaluates the mechanistic and translational potential of terpenes as possible indirect neuroimmune and redox modulators of stress-related pathophysiology. Full article

Jing Guan Fang (JGF) is a traditional multi-herb formula used for hyperinflammatory conditions associated with severe viral infections; however, its protein-level effects in macrophage-mediated inflammation remain incompletely characterised. In this study, we combined ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS)-based phytochemical profiling, functional anti-inflammatory assays, and discovery-level proteomic and secretome analyses to investigate the anti-inflammatory effects of JGF in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Phytochemical profiling revealed predominantly flavonoid- and phenolic-related annotated features, together with selected terpenoid- and alkaloid-related annotations. Functionally, JGF treatment was associated with reduced nitric oxide production and differential effects on pro-inflammatory cytokine release, with a clearer concentration-dependent reduction in interleukin-6 (IL-6) and a more variable tumour necrosis factor-α (TNF-α) response, without reducing cell viability. Label-free quantitative proteomics suggested that JGF treatment was associated with modulation of LPS-induced protein changes, including reduced abundance of inflammation-associated proteins such as myristoylated alanine-rich C-kinase substrate (MARCKS) and inducible nitric oxide synthase (NOS2), together with partial restoration of selected regulatory proteins such as AIMP1 and AIMP2. Secretome analysis further suggested that JGF reduced extracellular inflammatory and tissue-remodelling-related mediators, including SERPINE1/PAI-1. Exploratory pathway analysis indicated that JGF treatment was associated with changes in inflammation-related and oxidative stress-related signalling networks. Collectively, these findings provide discovery-level molecular insights into the anti-inflammatory effects of JGF in LPS-stimulated macrophages and support further targeted validation of its pharmacological activity as a candidate multi-component anti-inflammatory formula. Full article

Space-induced mutation is a novel approach in tea plant breeding, but its effect on processing-induced aroma formation remains unclear. This study analyzed the dynamic changes in VOCs during the processing of space-induced mutants of Dahongpao tea. The results showed that processing significantly reshaped the VOC profile, with the fermentation stage exerting the greatest impact and terpenoids serving as the major contributors. Seven characteristic VOCs (α-phellandrene, β-phellandrene, d-sylvestrene, iso-geraniol, seudenone, hexyl benzene, and nerol) were identified and a transformation network linking floral, green, woody, almond, and fruity attributes was constructed. Molecular docking revealed that VOCs exhibiting green, woody and almond characteristics could form strong binding interactions with more than 100 olfactory receptors, whereas those with floral and fruity characteristics bound to fewer receptors. This finding indicates that during the processing, the first three odor characteristics may be perceived more prominently. Overall, this study provided a theoretical basis for the aroma evaluation of space-induced mutant tea. Full article

Cannabis sativa and Curcuma longa have traditionally been used for the management of skin disorders; however, scientific evidence supporting their combined topical use in eczema and psoriasis remains limited. To characterize the phytochemical composition, evaluate the biological activities, investigate potential molecular mechanisms, and assess the preliminary clinical performance of a topical herbal cream containing C. sativa and C. longa extracts. Ethanolic extracts were analyzed using UHPLC and GC-MS. Antioxidant, antibacterial, cytotoxicity, and nitric oxide inhibition assays were performed. Molecular docking studies were conducted against inflammation-related protein targets. A pilot clinical study evaluated the effects of the herbal cream in patients with eczema and psoriasis over four weeks using EASI, PASI, and DLQI scores. The herbal formulation contained cannabinoids, terpenoids, and curcuminoids with measurable antioxidant activity. The extract exhibited low cytotoxicity and moderate inhibition of nitric oxide production in LPS-stimulated macrophages (0.0001–0.1 mg/mL). Docking analyses suggested favorable interactions between selected phytochemicals and inflammation-associated targets. Preliminary clinical observations indicated improvements in EASI (from 4.11 ± 3.14 to 1.28 ± 1.46), PASI (from 39 to 16.2), and DLQI (from 6.25 ± 5.25 to 1.00 ± 0.82) scores among study completers. The herbal cream demonstrated antioxidant and anti-inflammatory properties and showed preliminary clinical potential in inflammatory skin disorders. Larger controlled clinical studies are required to confirm efficacy and establish therapeutic value. Full article

Ginsenoside accumulation is tissue- and germplasm-specific, yet its transcriptional regulation remains unclear. We combined HPLC, PacBio full-length transcriptome, and Illumina RNA-seq to compare 4-year cultivated ginseng with 26-year wild-simulated ginseng. After clustering and error correction, we obtained 265,373 (CG) and 210,343 (WSG) non-redundant full-length transcript isoforms. Total saponins ranked leaves > roots > stems. In leaves, PPT type (Re and Rg1) predominated and was significantly higher in CG than WSG; in roots, PPD type dominated, and all monomer saponins in WSG were significantly higher. Transcriptome analysis revealed widespread alternative splicing (mainly retained introns), with key genes like CYP716A47 showing differential expression and splicing. WGCNA identified a yellow module positively correlated with PPD-type ginsenosides, enriched in terpenoid and CYP/UGT pathways and containing CYP716A47 and multiple UGT candidates. qRT-PCR validated 12 selected genes (6 known, 6 novel). Our findings reveal multilevel transcriptional and post-transcriptional regulation associated with the distinct production backgrounds of cultivated and wild-simulated ginseng and provide candidate targets for future functional studies and metabolic engineering. Full article

Senotherapeutic agents targeting senescent cell (SnC) accumulation represent a promising frontier in aging research. These agents encompass senolytics that selectively eliminate accumulated SnCs and senomorphics that suppress the pathological persistence of the senescence-associated secretory phenotype (SASP). Concerns regarding off-target effects of synthetic senolytics have intensified interest in plant-derived alternatives that offer multitargeted mechanisms and favorable safety profiles. This scoping review was conducted following Joanna Briggs Institute guidelines and PRISMA-ScR, mapped preclinical evidence on plant-derived senotherapeutics published between 2015 and 2025 across PubMed, Scopus, Web of Science, Wiley Library and Google Scholar. Of 1355 identified articles, 111 studies met inclusion criteria. Most characterized compound classes included flavonoids, non-flavonoid polyphenols and stilbenes, terpenoids and alkaloids, and combination and complex plant extracts. Mechanistically, BCL-2/BCL-XL apoptosis, PI3K/AKT/mTOR and p53/p21/p16^INK4a modulation emerged as senolytic mechanisms, while NF-κB-mediated SASP suppression predominated among senomorphic agents. Ginkgetin-mediated cyclic GMP-AMP-synthase–stimulator of interferon genes (cGAS-STING) inhibition was identified as a mechanistically novel target within natural senotherapy. Metabolomics demonstrated dual utility in guiding compound discovery from complex plant matrices (e.g., phenolamides from Allium hookeri) and mechanistic validation by characterizing senescence-associated metabolic remodeling, including retinoic acid metabolism restoration, lipotoxic metabolites attenuation, tricarboxylic acid (TCA) cycle, and choline-betaine-TCA cascade regulation. However, challenges in pharmacokinetic optimization, methodological heterogeneity in senescence induction and biomarker panels persist. Plant-derived senotherapy characterized through metabolomics-guided pipelines provides a compelling foundation for their progression toward clinical validation and functional food applications as accessible interventions for healthy aging and age-related disease management. Full article

Lung cancer remains a leading cause of cancer-related mortality worldwide, underscoring the need for safer and more effective therapeutic strategies. In this study, zinc oxide nanoparticles (ZnO NPs) were synthesized via a green, biogenic approach using Lantana camara L. flower aqueous extract and evaluated for their anticancer potential against human non-small cell lung cancer (NSCLC) NCI-H460 cells. The biosynthesized ZnO NPs were characterized using UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), Transmission electron microscopy (TEM), energy-dispersive X-ray analysis (EDX), X-ray diffraction (XRD) and particle size analysis, confirming the formation of nanocrystalline ZnO. LC-MS profiling of the Lantana camara flower extract revealed the presence of several bioactive phytochemicals, including phenolic compounds, terpenoids, fatty acids, and alkaloids, which may contribute to the reduction and stabilization of ZnO NPs during green synthesis. Cytotoxicity assessment of ZnO NPs using MTT and trypan blue exclusion assays revealed a dose-dependent reduction in cell viability, with an IC₅₀ value of 50 µg/mL. Mechanistic investigations demonstrated that ZnO NP exposure induced significant oxidative stress, evidenced by increased nitric oxide, lipid peroxidation, and reactive oxygen species levels, along with depletion of intracellular glutathione. Apoptotic cell death was further confirmed by nuclear DNA fragmentation, mitochondrial membrane depolarization, and G0/G1 phase cell cycle arrest. Quantitative real-time PCR analysis revealed upregulation of the pro-apoptotic genes Bax and p53, accompanied by downregulation of the anti-apoptotic gene Bcl-2, indicating activation of a mitochondrial-dependent intrinsic apoptotic pathway. Collectively, these findings suggest that Lantana camara L. flower-mediated ZnO nanoparticles induced apoptotic responses associated with oxidative stress in NSCLC cells, highlighting their ability as an eco-friendly nanoplatform for further anticancer investigations. Full article

Prunus salicina × P. armeniaca, an interspecific hybrid of Chinese plum and apricot, shows substantial variation in peel and flesh color and quality traits. Ten cultivars were characterized by integrating physicochemical measurements, spectrophotometric assays of phytochemical content and antioxidant capacity, and widely targeted ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) metabolite profiling. Tissue type was the main source of chemical variation. Peel contained higher total phenolic (TPC), flavonoid (TFC), and anthocyanin (TAC) contents and greater 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging capacity, 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical-scavenging capacity, and ferric reducing antioxidant power (FRAP), whereas flesh showed higher relative abundances of sugars, sugar alcohols, organic acids, amino acid derivatives, lipids, nucleotides, and terpenoids. Among 248 annotated metabolites, flavonoids were predominant, and color-related differentially accumulated metabolites were mainly enriched in phenylpropanoid and flavonoid pathways, particularly in purple–yellow comparisons. Integrating tissue-specific correlations, random forest models, and color-gradient patterns prioritized cyanidin-3-O-glucoside, dihydromyricetin, genistin, and orientin as cross-tissue color-associated metabolites. Cyanidin-3-O-glucoside showed the strongest association with coloration and anthocyanin content, whereas 4′-O-glucosylvitexin was strongly connected with phenolic, flavonoid, anthocyanin, and antioxidant traits. Comprehensive nutritional quality index rankings further distinguished cultivar-specific peel and flesh quality profiles. These results provide a tissue-resolved metabolic basis for evaluating and utilizing plum–apricot hybrid germplasm. Full article

Cancer prevention through dietary intervention utilizing bioactive natural compounds has garnered significant attention due to the therapeutic limitations of conventional cancer treatments. These plant-derived active compounds, including polyphenols, terpenoids, organosulfur compounds, bioactive peptides, and alkaloids, possess potent anticancer properties. This systemic review addresses a critical gap in the scientific literature by elucidating the precise multitargeted oncogenic regulatory mechanisms of these molecules. A comprehensive methodology was employed, involving a systematic literature search across major electronic databases (including PubMed, Web of Science, Embase, and SCOPUS) to identify relevant original peer-reviewed studies. The evidence gathered demonstrates that these active compounds deliver significant health benefits and protect cells by modulating crucial molecular targets involved in cell cycle regulation, apoptosis, oncogenic signaling, epigenetic control, angiogenesis, oxidative stress, and inflammation. Specifically, they operate via multi-targeted cascades, such as inhibiting the PI3K/Akt, NF-κB, and STAT3 pathways. To provide a clear structural overview, these active compounds are categorized comprehensively based on their botanical and structural origins, including spices, fruits, and rhizomes. However, despite their promising bioactivities, these compounds have not yet been fully translated into clinical therapy due to challenges such as low bioavailability, rapid metabolism, limited systematic exposure, and a lack of convincing evidence from large-scale clinical trials. Although most current evidence remains rooted in in vitro and experimental animal models, clinical validation through high-quality trials is still required. Ultimately, this review underscores the potential of these active compounds and highlights how advances in formulation and nano delivery strategies offer promising solutions for effective cancer prevention. Full article

Breast cancer (BC) is the most frequently diagnosed malignancy and generally the leading cause of cancer-related mortality among women worldwide. Molecular targeted therapies, including endocrine treatment for hormone-responsive tumors, anti-HER2 agents for HER2-positive tumors and PARP inhibitors (PARPis) for homologous recombination-deficient (HRD) tumors, have significantly improved patient outcomes, but several clinical challenges are still open. The development of acquired resistance strongly limits the long-term efficacy of current treatment strategies, underscoring the necessity to identify novel therapeutic approaches for breast cancer therapy. In this review, we summarize and discuss recently investigated natural compounds with anti-breast cancer activity, ranging from polyphenols, terpenoids, alkaloids, sulfur-containing compounds and the emerging plant-derived extracellular vesicles. We focus on their ability to induce DNA damage or oxidative stress, modulating the DNA damage response (DDR) and interfering with key oncogenic signaling pathways. We also discuss the potential of these compounds to enhance the efficacy of conventional therapies, thereby offering a promising role in overcoming clinical resistance. Despite clinical relevance remains under development and further studies are required; many of the natural compounds examined here appear to effectively target DDR signaling and oncogenic pathways, supporting their potential use in breast cancer therapy. Full article

Active molecules derived from traditional Chinese medicine (TCM) represent a valuable source of lead compounds for modern drug discovery, demonstrating considerable potential in the prevention and treatment of chronic diseases, cancer therapy, and immune modulation. Nevertheless, their clinical translation is often impeded by intrinsic limitations such as poor aqueous solubility, low bioavailability, inadequate chemical stability, and significant gastrointestinal irritation. Cyclodextrins (CDs) and their derivatives, characterized by a hydrophobic internal cavity, are capable of forming inclusion complexes with TCM and their derived active constituents, thereby improving their physicochemical and pharmacokinetic profiles. Over the past five years, substantial progress has been made in this domain. CD-based inclusion strategies have been shown to markedly enhance the solubility and dissolution rate of poorly water-soluble TCM compounds, including flavonoids, alkaloids, and terpenoids. Moreover, this approach contributes to improved drug stability, effective taste masking, and the achievement of modified release profiles, such as sustained or targeted delivery, ultimately leading to enhanced therapeutic efficacy and reduced adverse effects. The development of novel CD derivatives and smart delivery systems has further broadened their application potential. This review summarizes recent advances in the CD-based encapsulation of TCM active molecules, highlighting key formulation strategies that address persistent challenges in the modernization of TCM. It also provides a foundation for future research and development in natural product-based therapeutics. Full article

To investigate sex-specific differences in gonad quality and flavor characteristics of the sea urchin Heliocidaris crassispina, female and male gonads were compared using proximate composition, colorimetry, E-tongue, E-nose, LC-MS, and HS-SPME-GC-MS. No significant sex differences were observed in wet weight, test diameter, gonadosomatic index, moisture, or crude fat, whereas female gonads showed higher crude protein content, lightness, and yellowness. E-tongue and E-nose analyses revealed distinct sex-dependent taste and odor fingerprints. Metabolomics identified 366 differential non-volatile metabolites and 53 differential volatile metabolites, mainly involving lipids, organic acids and derivatives, dipeptides, nucleotide-related compounds, hydrocarbons, terpenoids, aldehydes, ketones, and esters. Female gonads were enriched in phospholipids, lysophospholipids, dipeptides, and nucleotide precursors, whereas male gonads contained higher levels of acylcarnitines, hydroxy fatty acids, 3-carene, and hydrocarbons. These findings provide metabolomic evidence for sex-dependent flavor differences and support quality evaluation of sea urchin products. Full article

Sanghuangporus baumii, a medicinal macrofungus, remains unexplored in its response to aluminum stress, despite the widespread environmental relevance of this metal. This study investigated the dose-dependent effects of Al³⁺ on mycelial growth and metabolic regulation. Exposure to 1 mM Al³⁺ moderately stimulated growth (1.11-fold of control) and induced mild oxidative stress, which activated an effective antioxidant response—including increased SOD, CAT, and POD activities and elevated reduced glutathione content—thereby maintaining redox balance and increasing soluble sugar content. In contrast, 10 mM Al³⁺ led to pronounced intracellular Al³⁺ accumulation, severe growth inhibition, and marked oxidative damage, accompanied by impairment of the antioxidant system, yet a marked increase in total triterpenoid content (1.72-fold). Transcriptomic analysis identified 642 and 3019 differentially expressed genes (DEGs) in the 1 and 10 mM Al³⁺ treatments, respectively. KEGG enrichment analysis revealed concentration-dependent alterations in pathways related to peroxisome function, glutathione metabolism, starch and sucrose metabolism, and terpenoid backbone biosynthesis. Collectively, these findings suggest that Al³⁺ modulates S. baumii growth and metabolism in a dose-dependent manner, with redox remodeling as a potential mechanism, offering novel insights into fungal metal adaptation and the targeted modulation of medicinal metabolite production. Full article

Myocardial fibrosis (MF) is a hallmark of pathological cardiac remodeling, driven by extracellular matrix (ECM) accumulation, fibroblast activation, and oxidative stress. Diverse natural products—notably alkaloids, flavonoids, terpenoids, and saponins—exhibit emerging antifibrotic potential. A comprehensive literature synthesis through July 2026 across PubMed, Web of Science, and Scopus categorized these agents by phytochemical class and disease models, delineating direct antifibrotic efficacy from indirect cardioprotection. Mechanistically, these compounds target TGF-β signaling, endothelial-to-mesenchymal transition (EndMT), autophagy/mitophagy, and ECM turnover. Robust preclinical evidence correlates with integrated histopathological assessment, specifically collagen and α-SMA quantification. However, translation remains impeded by model limitations, inadequate phytochemical standardization, and a critical paucity of clinical trials. Currently, no natural product holds clinical approval for MF. Future directives necessitate rigorous botanical authentication, pharmacokinetic/pharmacodynamic profiling, and adoption of human-relevant models, such as induced pluripotent stem cell-derived cardiomyocytes, to bridge the bench-to-bedside gap. Full article

Wheat stripe rust (yellow rust), a devastating disease caused by the phytopathogen Puccinia striiformis f. sp. tritici (Pst), poses a major threat to global wheat (Triticum aestivum L.) production. Under ongoing climate warming, the highly virulent Pst race CYR34 has become predominant in China and exhibits increased tolerance to elevated temperatures. Although temperature is known to influence Pst urediniospore germination, the molecular mechanisms underlying temperature sensitivity during this process remain poorly understood. In this study, we combined histological examinations with transcriptome sequencing across multiple temperature regimes to identify temperature-responsive genes and characterize the predicted protein association networks in Pst. Urediniospore germination of three Pst races was tested; stronger heat tolerance was observed in CYR34-8 with 67.40–77.40% germination at 9–16 °C. RNA-Seq analysis identified 89 differentially expressed genes (DEGs) associated with temperature sensitivity, and their expression patterns were validated by qRT-PCR. The DEGs were significantly enriched in ubiquinone and other terpenoid-quinone biosynthesis, glycan degradation, and longevity-regulating pathways. Among these DEGs, genes annotated as encoding an ABC transporter, malate dehydrogenase, Hsp70, and a class 3 lipase were identified as putative hub genes in the predicted protein association network and may be associated with the coordination of temperature responses and metabolic processes. Full article