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Integrated phytochemical and bioactivity profiling of Xanthium strumarium fruits from Korea and China: Implications for origin-specific quality specification.

BACKGROUND: Geographic origin influences the phytochemical composition and biological activities of medicinal plant resources. Xanthium strumarium L. (XS) fruit is widely used in East Asian traditional medicine. However, current pharmacopeial standards primarily recognize Chinese-derived material, despite the availability and traditional use of XS in Korea. To address this gap and support origin-informed quality specification, we compared fruits from Korea (XS-K) and China (XS-C) using chloroplast genome sequencing, targeted phytochemical profiling (high-performance liquid chromatography (HPLC) for selected phenolics and gas chromatography-flame ionization detection (GC-FID) for fatty acids and phytosterols, and multivariate chemometric analysis. RESULTS: Chloroplast genome analysis revealed high overall similarity but localized divergence around the rpoC2 locus and a greater mutation burden in XS-C, supporting origin-associated genomic differentiation. Phytochemical profiling revealed distinct origin-dependent metabolic signatures. XS-K showed higher levels of phytosterols, chlorogenic acid, 4,5-dicaffeoylquinic acid (4,5-DCQ), and xanthatin was detected only in XS-K, whereas XS-C exhibited greater abundance of total fatty acids, particularly oleic acid. Unsupervised clustering and log2 fold-change ranking confirmed clear compositional separation, and variable importance in projection (VIP) analysis identified chlorogenic acid, β-sitosterol, oleic acid, 4,5-DCQ, and xanthatin as major discriminators between origins. Bioactivity assays demonstrated that XS-K exerted stronger antioxidant effects in ABTS, DPPH and FRAP assays, stronger skin-related enzyme inhibition, and greater antibacterial activity against Staphylococcus aureus, consistent with its enriched phenolic and sterol profile. CONCLUSION: Together, chloroplast sequence variation, targeted metabolite quantification, and screening bioassays consistently distinguished XS-K from XS-C. These findings support the use of candidate markers for the origin-based authentication and quality control of XS fruit-derived ingredients. © 2026 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Fruit

Mechanistic Perspectives From Genomics and Pangenomics of Medicinal and Aromatic Plants: Linking Genome Architecture to Phytochemical Diversity.

Medicinal and aromatic plants (MAPs) produce a remarkable diversity of specialized metabolites with significant pharmaceutical, nutraceutical, and industrial value. Although advances in long-read sequencing, chromosome-scale genome assembly, and pangenomics have greatly expanded genomic resources, the mechanistic links between genome architecture and phytochemical diversity remain incompletely understood. The present review synthesizes current evidence describing how structural genomic variation may contribute to phytochemical diversity, while acknowledging that many proposed genome-to-metabolite relationships require further experimental validation. Examples illustrate how genome architecture is associated with specialized-metabolite biosynthesis through multiple regulatory processes. However, the strength of supporting evidence varies considerably among MAP species. Moreover, relatively few genome-to-metabolite relationships have been confirmed through direct functional validation. We further discuss how pangenomics, multiomics integration, genome editing, synthetic biology, and artificial intelligence support the discovery, validation, and engineering of specialized metabolic pathways. Casual conclusions are evaluated according to the strength of available evidence, highlighting where causal relationships have been experimentally established and where conclusions remain primarily association-based. Overall, this review provides an integrated conceptual and evidence-based perspective summarizing proposed relationships between genome architecture and phytochemical diversity and outlines future priorities for functional genomics, precision breeding, metabolic engineering, and sustainable utilization of MAPs.

artificial intelligence

Phytochemical Characterization and Effects of Randia monantha Benth. Leaf and Fruit Extracts on the Viability of Human Cancer Cell Lines.

Randia monantha, commonly known as crucetillo, is a medicinal plant traditionally used in Mexico to treat conditions such as diabetes, venomous animal bites, and cancer; however, its effects on cancer cell viability remain underexplored. In this study, hexane, ethyl acetate, and methanolic extracts from the leaves and fruits of Randia monantha were phytochemically characterized and evaluated for their effects on cell viability in HeLa cervical cancer and DU-145 prostate cancer cell lines using the MTT assay. Phytochemical analyses revealed differences in metabolite composition across solvents of varying polarity and plant tissues. Methanolic leaf extracts contained higher levels of terpenoids and polyphenols and produced the greatest reduction in HeLa cell viability, with an estimated IC50 of 4.87 µg/mL after 48 h of treatment. In contrast, DU-145 cells exhibited a different response pattern depending on the extract evaluated. Correlation analysis suggested that flavonoids were associated with reduced HeLa cell viability. Overall, leaf extracts produced greater reductions in cancer cell viability than fruit extracts, highlighting leaves as a promising but comparatively underexplored source of bioactive compounds in Randia monantha.

Humans

Metabolic Dysfunction-Associated Carcinogenesis: Molecular Mechanisms and the Preventive Roles of Phytochemicals Part I: Pathophysiological Mechanisms Linking Metabolic Dysfunction to Cancer.

The global cancer burden is projected to escalate to 27 million new cases annually by 2040, a trajectory that parallels the rising prevalence of obesity, metabolic dysfunction, and related metabolic disorders. While genetic and environmental factors are well-recognized, the systemic metabolic environment is increasingly identified as a critical determinant of tumorigenesis. This review (Part I) systematically delineates the molecular and cellular framework through which metabolic dysfunction orchestrates a tumor-permissive landscape. We evaluate six primary pathophysiological axes: (1) chronic low-grade inflammation that fuels a protumorigenic milieu, (2) oxidative stress and redox imbalance leading to genomic instability, (3) insulin resistance and insulin-like growth factor axis activation which stimulate mitogenic pathways, (4) aberrant lipid metabolism and lipotoxicity-driven cell transformation, (5) gut microbiota dysbiosis and its modulation of the tumor microenvironment, and (6) metabolism-associated epigenetic remodeling that sustains oncogenic gene expression. Unlike previous literature that has focused on isolated pathways, this synthesis emphasizes the synergistic crosstalk among these mechanisms, illustrating how they collectively reinforce cancer initiation and progression. Furthermore, this mechanistic framework provides a biological rationale for targeting metabolism-associated carcinogenesis through dietary phytochemicals and bioactive compounds, which will be comprehensively discussed in Part II. By providing an integrated overview of the metabolic dysfunction-cancer axis, this work establishes a mechanistic foundation for the preventive potential of phytochemicals. These insights are crucial for developing multitarget dietary strategies against metabolism-associated malignancies.

carcinogenesis

Proteomic regulation of anti-proliferative and anti-migratory activity by potent phytochemicals from Pistacia integerrima J.L. Steward Ex Brandis via PI3K, AKT1, and KRAS for Lung Cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of mortality worldwide and remains a major therapeutic challenge due to high metastasis, drug resistance and limited treatments. Pistacia integerrima J.L. Steward Ex Brandis (PI) consists of flavonoids, steroids, terpenoids and phenolic compounds reported for pharmacological activities. The efficacy of potent bioactives from P. integerrima may be ascertained employing cytotoxic, antiproliferative, anti-migratory, and anti-metastatic evaluations in A549 NSCLC cells with proteomic profiling, molecular docking, and dynamics simulation study. METHODS AND RESULTS: PI EtAc produced significant dose-dependent cytotoxicity in A549 cells (100&#xa0;&#xb5;g/mL, p&#x2009;<&#x2009;0.0001 in the MTT assay. There was a pronounced decrease in colony formation after treatment with EtAc, with 18.41% (p&#x2009;<&#x2009;0.002), and markedly. Furthermore. PI EtAC markedly inhibited cell migration emphasized by wound healing and Transwell migration (p&#x2009;<&#x2009;0.01) assays, indicating reduced metastatic migratory potential. Proteomic analysis demonstrated significant downregulation of Endoglin (CD105), KLK5 and MMP-2, indicating suppression of angiogenic and metastatic signalling pathways in the Human XL Oncology protein array. The interaction of major PI phytochemicals with key NSCLC-associated targets was recorded in Molecular docking, revealing favourable binding affinities of kaempferol, &#x3b2;- sitosterol, luteolin, and quercetin towards several oncogenic targets, including AKT1(-&#x2009;7.6&#xa0;kcal/mol), PI3K(-&#x2009;9.4&#xa0;kcal/mol), KRAS (-&#x2009;8.5&#xa0;kcal/mol) and MMP9 (-&#x2009;8.1&#xa0;kcal/mol). Molecular dynamics simulation confirmed the structural stability of the kaempferol -AKT1 complex throughout the 100 ns simulation. CONCLUSION: Pistacia integerrima bioactives exhibited significant anti-proliferative, anti-migratory, and anti-metastatic activities in vitro, which may provide scientific rationale identifying newer promising candidates for NSCLC.

Humans

Polyphenol-Rich Opuntia ficus-indica Cladodes: An Integrated Metabolomic, In Vivo and In Silico Study Supporting Their Hypolipidemic and Hepatoprotective Effects.

Background: Hyperlipidemia is a major risk factor for cardiometabolic disorders, including non-alcoholic fatty liver disease (NAFLD), and is closely associated with oxidative stress. Opuntia ficus-indica (OFI) cladodes are recognized as a rich source of bioactive phytochemicals; however, the molecular mechanisms underlying their metabolic benefits remain incompletely understood. Objectives: This study aimed to comprehensively evaluate the hypolipidemic and hepatoprotective potential of a polyphenol-rich O. ficus-indica cladode extract (OCE) using an integrated approach combining in vivo evaluation, untargeted metabolomics (UHPLC-Orbitrap-MS/MS), molecular docking, and ADMET prediction. Methods: Hyperlipidemic mice fed a high-fat diet (HFD) were treated with OCE, while molecular docking was performed on ten major annotated phytochemicals against twelve key proteins involved in lipid metabolism and cholesterol homeostasis, including HMGCR, FAS, PPAR&#x3b1;, PCSK9, and NPC1L1, using simvastatin as the reference compound. Results: OCE treatment significantly improved plasma and hepatic lipid profiles, improved glucose homeostasis, and markedly reduced hepatic malondialdehyde (MDA) levels, indicating attenuation of oxidative stress. Histopathological analysis further supported a pronounced hepatoprotective effect, with a substantial reduction in hepatic steatosis. Untargeted metabolomics enabled the annotation of 102 metabolites, putatively identifying piscidic acid as the predominant phenolic constituent together with a diverse profile of flavonoids and phenolic acids. Molecular docking supported the potential contribution of these phytochemicals to the regulation of lipid metabolism through favorable interactions with multiple therapeutic targets, while ADMET prediction suggested an overall favorable pharmacokinetic and toxicity profile despite the lower intestinal permeability predicted for glycosylated derivatives. Conclusions: Overall, these findings support O. ficus-indica cladodes as a promising source of dietary bioactive compounds with potential applications in the nutritional management and prevention of hyperlipidemia and related cardiometabolic disorders.

Animals

An Arabidopsis Protein-Flavonoid Interactome Identifies Peroxiredoxin A as a Candidate for Flavonoid Action in Chloroplasts.

The ability of phytochemicals to act as small molecule effectors of protein function is a largely overlooked dimension of plant biochemistry. This is particularly true for the ubiquitous flavonoids where, despite abundant examples of functional interactions with human proteins, biological activities in plants are primarily attributed to ROS scavenging. We used affinity capture to explore the protein interactome of the flavonoid glycoside, rutin, in Arabidopsis seedlings. Unexpectedly, the 397 high-confidence candidates included numerous proteins associated with chloroplasts, where flavonoids are present at exceedingly low levels. Intriguingly, several identified targets are conserved with known flavonoid-interacting proteins in mammals, where the bioavailability of flavonoids is similarly low. Using one of these, the Arabidopsis plastidial 2-cys peroxiredoxin A, as a test case, this study substantiated the potential of affinity proteomics for identifying novel protein targets of phytochemicals and suggests that flavonoids modulate protein function in plants to a larger extent than previously suspected.

Arabidopsis

Cis-regulatory evolution of CsANS1 drives cultivar variation in anthocyanin accumulation in tea plants.

Anthocyanins, a ubiquitous class of water-soluble phytochemicals renowned for their chromatic diversity and potent bioactivity, are integral to the phenotypic and metabolic plasticity of higher plants. Using an integrative multi-omics approach that combines transcriptomic and metabolomic profiling, we identified anthocyanin synthase (CsANS1) as the key genetic determinant responsible for interspecific variation in anthocyanin accumulation among tea plants. Architectural comparison of promoter regions revealed a 192-bp variation insertion in the CsANS1 cis-regulatory region with potential functional significance. This insertion was strictly conserved in anthocyanin-rich (purple-leaf) cultivars, including both natural and hybrid genotypes, but entirely missing in anthocyanin-deficient (green-leaf) cultivars. Dual-luciferase assays confirmed that this insertion enhances promoter activity. Additionally, we delineated a tripartite regulatory axis comprising CsmiR156b, CsSPL9, and CsMYB75 which orchestrates the spatiotemporal modulation of CsANS1 expression and, consequently, anthocyanin biosynthesis. Collectively, these findings provide a mechanistic paradigm for anthocyanin polymorphism in tea plants, implicating both cis-regulatory evolution and transcriptional network synergy as pivotal drivers of phytochemical diversification.

Anthocyanins

QTLs associated with phenolic acid accumulation and antioxidant activity in tropical maize.

Maize represents a significant source of phytochemicals, with phenolic acids standing out as one of the most extensively studied functional compound families. These bioactive molecules have gained attention for their potent antioxidant properties and potential contributions to human health improvement. To evaluate the segregation of phenolic compounds in maize and its genetic basis, this study was conducted to identify quantitative trait loci (QTLs) associated with major phenolic compounds and their antioxidant capacity. The mapping population comprised 100 recombinant inbred lines (RILs) derived from the cross between P84 and Kilima. Twelve traits were analyzed: free and cell wall-bound antioxidant capacity, total phenolic content, and contents of p-coumaric acid, ferulic acid, three isomers of di-ferulic acid, and three isomers of tri-ferulic acid. The RILs exhibited substantial diversity in phenolic compound profiles. In total, 19 QTLs were identified for nine traits, with the number of associated regions ranging from 1 to 5 and explaining between 2.95% and 37.48% of the phenotypic variation. This research provides substantial evidence for the co-localization of major QTLs for principal phenolic acids in maize with genomic regions harboring genes putatively related to their biosynthesis and biotic resistance. This is the first study to report QTLs associated with triferulic acids in maize. The identified regions co-localizing with biotic stress resistance genes represent targets for marker-assisted selection toward the improvement of phenolic acid accumulation in maize breeding programs.

QTLs

A python based automated computational framework to classify and comparative genomics analysis of the global diversity of chili leaf curl virus (ChiLCV) strains to understand virus host interactions.

Chili leaf curl virus (ChiLCV) is a Begomovirus chillicapsici that is one of the most devastating viruses impacted on the production of chili in the world, especially in South Asia. In the present study, we combined high-throughput computational genomics with experimental analysis of global diversity. A workflow was created using automated Python scripts to download, curate and process ChiLCV genomes from public database. About 410 complete ChiLCV genomes download from public databases. Using a phylogenetic approach, these isolates were subdivided into 34 strains, belonging to 10 major clades, showing significant genetic diversity. Geographic analysis revealed that Pakistan (207 isolates) and India (148 isolates) were the main sources of ChiLCV diversity and the remainder of the isolates were from Oman, Bangladesh, Iran, Saudi Arabia and Sri Lanka. Recombination was observed as a major evolutionary force as more than twenty recombination events were detected. Analysis of cis-regulatory elements showed a complex structure of the viral promoter, including multiple binding sites for transcription factors, hormone-response elements, light-responsive elements, and stress-responsive elements, indicating a high number of interactions between viral regulatory elements and host signaling pathways. Pangenome analysis showed the presence of a highly dynamic open pangenome made up of strain-specific orthologous groups (species-specific orthogroups). Experimental inoculation of chili plants was also carried out to assess the biological effects of infection, along with phytochemical, FTIR, HPLC, and qPCR analyses.

Begomovirus

Molecular mechanisms underlying low glycemic index in rice: Insights from Indian landrace diversity.

The rising prevalence of diabetes mellitus, especially among populations with high rice consumption, underscores the need for functional staple crops with a low glycemic index (GI). This review examines the molecular and genetic factors influencing low-GI traits in rice, highlighting the importance of diversity within Indian landraces. Traditional cultivars like Mappillai Samba, Karuppu Kavuni and Kattuyanam contains high level of Resistant starch, dietary fiber and bioactive phytochemicals. The Waxy (Wx) gene, which codes for granule-bound starch synthase I (GBSSI), is very important for controlling the production of amylose. For example, functional alleles like Wxa and Wxlv are linked to higher amylose levels and lower starch digestibility. Moreover, secondary metabolites, such as anthocyanins and phytosterols like stigmasterol, play a role in regulating blood sugar levels by stopping the activities of &#x3b1;-amylase and &#x3b1;-glucosidase. Interactions within the starch-dietary matrix, including starch-protein, starch-lipid, and starch-polyphenol complexes, further influence enzymatic hydrolysis and glucose release kinetics. Recent advancements in genomics, encompassing QTL mapping and gene editing techniques, offer innovative prospects for the creation of biofortified, low-GI rice cultivars. The integration of these molecular insights into rice breeding programs can facilitate the development of low-glycemic, nutritionally enhanced rice cultivars that contribute to improved metabolic health and food security.

Oryza

Resistance of Populus davidiana&#x2009;&#xd7;&#x2009;P. bolleana overexpressing cinnamoyl-CoA reductase gene to Lymantria dispar larvae.

Lignin is a crucial defense phytochemical against phytophagous insects. Cinnamoyl-CoA reductase (CCR) is a key enzyme in lignin biosynthesis. In this study, transgenic Populus davidiana&#x2009;&#xd7;&#x2009;P. bolleana overexpressing the PdbCCR gene were generated via Agrobacterium-mediated transformation. Successful integration of PdbCCR into the poplar genome was confirmed by PCR amplification and quantitative reverse transcription PCR (qRT-PCR). The lignin content in the transgenic poplar leaves was significantly higher than that in the wild poplar, and after L. dispar larvae fed on the transgenic poplar, the CCR activity was clearly induced. The L. dispar larvae grew slowly after feeding on transgenic poplar and the laccase, cellulase and three detoxifying enzymes were induced compared with larvae after feeding on wild-type poplar. The bioassay further revealed that transgenic poplar plants overexpressing PdbCCR showed a high level of resistance to L. dispar larvae. These results confirmed that PdbCCR is a candidate gene for breeding insect resistant poplar.

Populus