Search Results (133)

Background/Objectives: Metabolic syndrome (MetS) is a pressing global health challenge comprising obesity, hyperglycemia, hypertension, and hyperlipidemia. Conventional polypharmacy often presents long-term compliance issues and side effects. Eucommia ulmoides Oliv., a traditional medicinal and edible plant rich in iridoids, lignans, flavonoids, and polysaccharides, has emerged as a promising natural intervention. This review aims to systematically summarize the bioavailability and multifaceted pharmacological mechanisms of E. ulmoides and its bioactive components in alleviating MetS. Methods: We comprehensively reviewed the recent in vitro and in vivo literature to map the functional evidence, specific signaling pathways, and gut microbiota–host interactions associated with E. ulmoides extracts and its key phytochemicals (e.g., asperuloside) against various metabolic dysfunctions. Results: Current evidence indicates that E. ulmoides operates through a “multi-component, multi-target, and multi-pathway” paradigm. For hyperlipidemia and obesity, it activates hepatic lipid metabolism (PPARα/CPT1A, FXR/CYP7A1) and mitigates oxidative stress (Nrf2/ARE). Furthermore, it dose-dependently reshapes the gut microbiota by enriching beneficial bacteria like Akkermansia and increasing butyrate production, exerting profound gut–liver axis regulation. It also ameliorates hypertension by activating the ACE2-Ang-(1–7)-Mas axis, improves insulin resistance via the AMPK/PI3K/Akt cascade, and manages hyperuricemia by modulating XOD and renal transporters. Notably, the low oral bioavailability of its glycosides highlights the crucial role of gut microbial hydrolysis in its efficacy. Conclusions: E. ulmoides holds substantial therapeutic potential as a multi-target natural supplement for MetS. However, future translational applications necessitate large-scale randomized clinical trials, multi-omics studies to further clarify host–microbiome interactions, and the development of standardized formulations to ensure clinical efficacy. Full article

Highlighting its pivotal role in modern pharmacology, the gut microbiome is emerging as a key determinant of drug efficacy, toxicity, and bioavailability. This review proposes the Gut Microbiome Dependency Continuum, a four-layer framework describing progressively deeper levels of microbiome involvement in drug discovery and therapeutic function. The first layer, intact functional microbiome-dependent therapeutics and includes interventions such as faecal microbiota transplantation and defined microbial consortia. The second layer, microbiome-modulated approved drugs include widely used therapeutics whose pharmacokinetics or pharmacodynamics are strongly influenced by microbial metabolism. Examples include metformin, irinotecan, levodopa, and digoxin, where gut microbial interactions influence efficacy, toxicity, and inter-individual variability in treatment outcomes. The third layer, microbiota-transformable natural products, encompasses dietary and plant-derived compounds such as polyphenols, ginsenosides, alkaloids, fibres, isoflavones, lignans, and glucosinolates. Their biological activity depends on microbial biotransformation into bioactive metabolites. The fourth layer, engineered microbiome therapeutics, includes synthetic biology approaches such as programmable microbial systems, engineered probiotics, CRISPR-based microbiome editing, and microbiome-responsive drug delivery systems. It also includes synthetic microbial consortia, enabling targeted sensing, therapeutic delivery, and ecological reprogramming of gut microbial communities. Altogether, these layers define a continuum in which the gut microbiome evolves from a passive modulator to an essential metabolic organ and ultimately a programmable therapeutic platform. The article provides an integrated framework for microbiome-informed drug discovery. It also supports the development of precision, ecology-aware, and engineered microbial therapeutics. Full article

The composition, differences, and metabolic mechanisms of phenolic compounds in fruits and peels of three different varieties (including Clausena lansium ‘Jixin’, ‘Seedless’ and ‘Bingtang’) were investigated. The results showed that the total phenolic content in the fruits followed the order CLB (2080.14 mg/kg) > CLS > CLJ, while in peels it followed CLSp (2457.56 mg/kg) > CLJp > CLBp. Significant differences were observed in flavanols, flavonols, lignans, and phenolic acids among samples. A total of 12 (in fruits) and 9 (in peels) differential phenolic compounds (VIP > 1) were screened. Compared with CLB, several antioxidants and antibacterial phenolics were significantly up-regulated in CLS and CLJ. Pathway analysis revealed that fruit differences were mainly enriched in phenylpropanoid biosynthesis and flavone/flavonol biosynthesis pathways, whereas peel differences were mainly enriched in flavonoid biosynthesis and flavone/flavonol biosynthesis pathways. These findings provided a theoretical basis for wampee variety identification, improvement, and functional evaluation. Full article

Background/Objectives: Schisandrin B (Sch B), a bioactive lignan of Schisandra chinensis has been commonly investigated for its antitumor activities, yet its radiosensitizing effect and mechanism remain unclear. This study was conducted to investigate the radiosensitizing effects of Sch B in breast cancer (BC) and elucidate its molecular mechanisms, with a specific focus on the gut microbiota–immune axis. Methods: In vitro, CCK-8, colony formation, and 3D spheroid assays were used to evaluate the effects of Sch B on proliferation inhibition and radiosensitization, flow cytometry and immunofluorescence were used to elucidate the mechanisms involved. In vivo, 4T1 tumor-bearing mice were treated with Sch B, and 16S rDNA sequencing and LC-MS/MS were used to analyze the gut microbiota and short-chain fatty acid (SCFA) metabolism. IHC and qPCR detected antitumor immune responses. Results: Sch B inhibited the proliferation of BC cells in a time- and dose-dependent manner with negligible toxicity to the mammary epithelial cell line MCF-10A. Furthermore, Sch B enhanced the radiosensitivity (sensitization enhancement ratio: 1.20~1.77) of BC by inducing G1 phase cell cycle arrest and delaying radiation-induced DNA double-strand break repair. In vivo, Sch B suppressed BC growth in BALB/c mice without causing obvious systemic toxicity. Sch B reversed tumor-induced gut microbiota dysbiosis (restoring species abundance and the Firmicutes/Bacteroidetes ratio, enriching beneficial genera such as Lactobacillus and Butyrobacter) and normalized SCFA profiles (correlative evidence). Furthermore, Sch B modulated systemic immune responses by increasing the expression of Ifng, Cxcl10, Ddx58 and promoting CD3⁺ and CD8⁺ T-cell infiltration in tumors. Conclusions: Sch B exerts BC radiosensitization through dual mechanisms, direct regulation of the cell cycle and DNA repair, and indirect modulation of the gut microbiota-immune axis (correlative evidence), highlighting it as a safe and effective candidate for improving the efficacy of BC radiotherapy. Full article

Background: The artificial cultivation of Dendropanax dentiger under forest understory conditions offers a sustainable alternative to wild harvesting, yet the metabolic adaptations underlying transplantation stress and recovery remain poorly understood. Objectives: In this study, we performed a comparative metabolomics analysis of different organs (leaves, current-year stems, three-year-old stems, and roots) from wild D. dentiger plants and those transplanted to the understory. Methods and Results: Metabolite annotation and classification revealed that over 60% of the metabolites fell into the categories of lipids and lipid-like molecules, organoheterocyclic compounds, phenylpropanoids, and polyketides. Further differential analysis of metabolites showed that understory transplantation significantly altered the metabolic profiles of all organs, exhibiting organ-specific response patterns. For the metabolite components in the organs of transplanted and wild D. dentiger, these metabolites were mainly classified into eight categories: alkaloids and derivatives; benzenoids; lignans, neolignans and related compounds; lipids and lipid-like molecules; organic acids and derivatives; organoheterocyclic compounds; phenylpropanoids and polyketides; and organic oxygen compounds. Notably, the contents of (-)-asarinin, (Z)-1-(methylthio)-5-phenyl-1-penten-3-yne, and stearidonic acid (SDA, 18:4n-3) were higher in transplanted plants than in wild plants, indicating the potential of understory cultivation for the targeted extraction of these bioactive compounds. Conclusion: These findings provide a metabolomics basis for optimizing the artificial cultivation and quality control of D. dentiger. This study highlights the value of metabolomics in understanding the metabolic composition of D. dentiger and offers a reference for its artificial cultivation. Full article

Phytoestrogens are plant-derived phenolic compounds that structurally resemble endogenous estrogens and can exert both estrogenic and anti-estrogenic effects in animals. In ruminant nutrition, the main classes of phytoestrogens (isoflavones, lignans, stilbenes, coumestans and selected flavonoids) are supplied predominantly by legume forages and soybean-based feeds, in which concentrations can reach several mg/g of dry matter. After ingestion, these compounds are extensively metabolized by the rumen microbiota to derivatives with altered biological potency, such as equol and p-ethyl-phenol, which influence endocrine, immune and metabolic pathways. Experimental and field studies in cattle, sheep and goats indicate that dietary phytoestrogens may improve nitrogen utilization, immune competence, growth performance, antioxidant status and milk yield. However, they can also impair fertility, modify hormone profiles and compromise embryo survival in a compound-, dose-, and species-dependent manner. In this review, we summarize current knowledge on the botanical and nutritional sources, ruminal metabolism and transfer of phytoestrogens in ruminants, and critically examine their effects on blood metabolites, immune responses, growth and carcass traits and lactational performance and reproductive function. A structured literature search based on PRISMA principles was used to identify and appraise experimental and observational studies in both grazing and intensive production systems up to 2025. Remaining knowledge gaps and practical implications for the safe use of phytoestrogen-rich feeds in livestock production are highlighted. Full article

Camphora officinarum (syn. Cinnamomum camphora) is an ecologically, medicinally, and economically important tree species widely known for its essential oils (EOs), timber, and long history of use in traditional medicine. In recent years, renewed interest in this species has been driven by taxonomic revision, the discovery of chemically distinct chemotypes, and advances in genomics, metabolomics, and biotechnological processing. This review summarizes current knowledge on the botany, distribution, phytochemistry, biological properties, agro-industrial value, and biotechnological potential of C. officinarum. Particular attention is given to the genetic and metabolic basis of terpene diversity, especially the role of terpene synthase (TPS) gene expansion in the formation of camphor-, linalool-, borneol-, cineole-, and citral-type profiles. We also discuss developments in essential oil extraction, the utilization of non-volatile constituents such as flavonoids and lignans, and the nutritional value of seed kernel oil rich in medium-chain fatty acids (MCFAs). In addition, recent progress in tissue culture, multi-omics analysis, metabolic engineering, and nano-enabled delivery systems is reviewed. The paper also considers important safety and ecological issues, including the dose-dependent toxicity of camphor and the contrasting status of the species as a protected native resource in East Asia and an invasive plant in some introduced regions. Overall, this review provides an updated and balanced overview of C. officinarum, identifies key knowledge gaps, and highlights future prospects for sustainable utilization, conservation of native genetic resources, and exploitative control of invasive populations. Full article

Secondary plant metabolites such as polyphenols (flavonoids, phenolic acids, stilbenes, and lignans) are valued for their numerous benefits and commonly associated with antioxidants, anti-inflammatory, anticancer, neuroprotective, and antidiabetic effects. Comprehensive profiling facilitates their identification and quantification, with metabolomics emerging as an increasingly valuable tool. This current work provides an overview of recent application of metabolomics for investigating polyphenols with nutraceutical potential. It also highlights the influence of plant species and environmental stressors (both biotics and abiotic) inducing metabolic shifts that promote the production and accumulation of these bioactive compounds (BACs). While various analytical tools including mass spectrometry (MS) coupled with liquid chromatography (LC-MS) or gas chromatography (GC-MS), as well as nuclear magnetic resonance (NMR) spectroscopy have been utilized to identify the diverse group of polyphenol metabolites, LC-MS has been predominantly used due to its superior sensitivity and wider metabolite coverage, with flavonoids being the main compounds identified. The integration of bioinformatic tools and pathway enrichment analysis in metabolomics is providing expansive insight into the pool of polyphenols, and their bio-functional interpretation and metabolic variations beyond the narrow scope of chromatographic separation alone. This overview also identifies limitations of current methods and suggests directions for future research, aimed at facilitating the development of nutraceuticals. Full article

To explore the seasonal variation patterns of the skin microecology of Altay sheep under transhumant grazing conditions, skin swabs were collected from 60 free-grazing Altay sheep at seasonal transition nodes in the Altay region. Metagenomic sequencing combined with untargeted metabolomics was used to characterize their bacterial community structure, functional pathways, and metabolite profiles. The results showed that the skin microecology of Altay sheep presented obvious seasonal variation patterns. In spring, 35 of the 39 highly abundant bacteria were environmentally derived, five proliferation-related pathways were significantly enriched, and the levels of five metabolites associated with microbial community regulation and skin barrier defense were elevated. In summer, the abundance of three skin symbiotic bacteria increased, the activities of eight pathways mainly related to biofilm formation were significantly enhanced, and the contents of five metabolites primarily associated with membrane lipid homeostasis and selective bacteriostasis increased. In autumn, the abundances of nine radiation-resistant and cold-tolerant strains increased, together with the elevated abundance of two opportunistic pathogens; five repair-related pathways were active, and the levels of four anti-inflammatory and repair-associated metabolites were synchronously increased. In winter, the abundance of two cold-tolerant strains increased, the activities of pathways related to nitrogen metabolism and energy synthesis were enhanced, and one lignan compound was identified as the key metabolite. These findings elucidate the seasonal dynamic patterns of the skin microecology of Altay sheep and provide a theoretical basis for research on the adaptive mechanisms and seasonal health management of Altay sheep and other sheep in alpine regions. Full article

Pinoresinol diglucoside (PDG), one of the major lignans isolated from E. ulmoides Oliver bark, has various pharmacological functions, including antihypertension and prevention of osteoporosis. However, the glycosyltransferase-encoding gene (GT) involved in regulating the glycosylation of pinoresinol to form PDG has not been reported in E. ulmoides. In this study, we screened and cloned the EuGT8 gene from E. ulmoides based on our transcriptome data. The expression pattern of the EuGT8 gene exhibited a strong positive correlation with dynamic changes in the PDG contents in three different organs of E. ulmoides. The expression level of the EuGT8 gene and PDG content were significantly decreased in asODN-EuGT8-treated shoot tips in comparison with the control group. Prokaryotic expression of the EuGT8 gene revealed that the purified EuGT8 protein could catalyze the conversion of pinoresinol into PDG. In addition, we performed transcriptional and metabolomic analyses to compare the differences between transgenic Arabidopsis and WT plants. A total of 1799 DEGs and 294 DEMs were identified in transgenic and WT plants. KEGG enrichment analysis showed that the DEGs were mainly enriched in phenylpropanoid biosynthesis, secondary metabolite biosynthesis, and starch/sucrose metabolism pathways. The DEMs were mainly enriched in ABC transporters, aminoacyl-tRNA biosynthesis, biosynthesis of amino acids, phenylpropanoid biosynthesis, and flavone and flavonol biosynthesis pathways. Correlation analysis between DEGs and DEMs identified a total of 231 DEGs associated with 38 DEMs, which were mainly distributed in multiple metabolic pathways. This finding provides both theoretical insights and genetic resources for breeding high-PDG E. ulmoides varieties, facilitating marker-assisted selection (MAS) and promoting sustainable E. ulmoides production in Guizhou. Full article

Background/Objectives: Eudesmin is a tetrahydrofurofuranoid lignan known for its diverse pharmacological activities, including anti-tumor, anti-inflammatory, and neuroprotective effects. However, its metabolism has not been well characterized. Methods: This study examined the in vitro metabolism of eudesmin using human and mouse hepatocytes, human liver microsomes, and recombinant drug-metabolizing enzymes. Liquid chromatography–high-resolution mass spectrometry combined with ion identity molecular networking enabled the comprehensive visualization and annotation of eudesmin metabolites. Results: Eudesmin exhibited moderate metabolic stability in human and mouse hepatocytes, with half-lives of 181.0 min and 132.9 min, and intrinsic clearance values of 27.7 mL/min/kg and 154.0 mL/min/kg, respectively. Incubation of eudesmin with human hepatocytes resulted in the formation of 13 metabolites, including five phase I metabolites (M1–M5) and eight phase II conjugates. Phase I metabolism was dominated by O-demethylation of the 3,4-dimethoxyphenyl moieties, yielding mono-O-demethylated (M1 and M2) and di-O-demethylated metabolites (M3 and M4), as well as a hydroxylated metabolite (M5). Enzyme phenotyping, kinetic analyses, and chemical inhibition experiments identified cytochrome P450 2C9 (CYP2C9) as the major contributor to O-demethylation, with additional contributions from CYP2C19, CYP2C8, CYP3A4, and CYP3A5, whereas hydroxylation was mediated primarily by CYP3A4 and CYP3A5. The O-demethylated metabolites subsequently underwent phase II metabolism, forming glucuronide conjugates of M1–M4 and sulfate conjugates of M1–M3, including a disulfate of M3. Uridine 5′-diphospho-glucuronosyltransferase and sulfotransferase screening revealed the involvement of multiple conjugative enzymes, indicating extensive and distributed phase II metabolism. Specifically, di-O-demethylated metabolites and their conjugates were detected in human hepatocytes but not in mouse hepatocytes, suggesting that the sequential O-demethylation pathway is limited in mice. Conclusions: This study characterizes eudesmin metabolism, with CYP2C9-mediated O-demethylation and significant species differences between humans and mice, and provides a basis for its further pharmaceutical development. Full article

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome driven by systemic inflammation, persistent oxidative stress, endothelial dysfunction, and impaired mitochondrial bioenergetics. Despite recent therapeutic advances, the management of these specific pathophysiological mechanisms remains a challenge. Polyphenols, bioactive compounds found in plants, have emerged as potential modulators of these pathways. Objective: This review critically summarizes the pathophysiological and molecular evidence supporting the role of polyphenols—specifically phenolic acids, flavonoids, and lignans—in attenuating key pathways implicated in the progression of HFpEF, while also addressing the current limitations in clinical translation. Results: Preclinical evidence indicates that polyphenols regulate cellular homeostasis by activating the Keap1/Nrf2 antioxidant axis and AMPK/SIRT1 metabolic pathways, while inhibiting NF-κB-mediated pro-inflammatory signals and TGF-β fibrotic pathways. These molecular actions collectively preserve endothelial function via PI3K/Akt/eNOS, reduce interstitial fibrosis, and improve myocardial metabolic efficiency. Furthermore, the modulation of gut microbiota amplifies these systemic effects, particularly in obesity-related phenotypes. However, direct clinical application is currently hindered by low bioavailability and a scarcity of randomized trials specifically in HFpEF populations. Polyphenols represent a promising and biologically plausible nutritional therapeutic axis for the multidimensional management of HFpEF. While the molecular rationale is strong, future research should focus on improving bioavailability and conducting high-quality clinical trials to validate efficacy as an adjuvant therapy. Full article

Background/Objectives: Commiphora gileadensis (Balm of Gilead) is an aromatic medicinal plant with a history of traditional use in ancient and Arabic medicine. It has been used traditionally to treat inflammation, infections, and wounds. Despite its long-standing cultural and economic importance, modern pharmacological validation requires a comprehensive synthesis of current scientific data. This review aims to provide a thorough comparative summary of the phytochemical composition and biological activities of its diverse products. Methods: An updated literature search was conducted using databases such as ScienceDirect, PubMed, Scopus, and Google Scholar, covering publications from approximately 2000 to 2025. The review included English-language peer-reviewed articles, books, and reports providing phytochemical analyses or biological evaluations. Data were manually extracted and categorized by plant parts (resin, leaves, bark, stems), major constituents, and specific pharmacological activities. Results: The review identified ten diverse chemical groups, mainly terpenoids (mono-, sesqui-, di-, and triterpenes) and flavonoids. Other remarkable classes included phenolic acids, phytosterols, lignans, coumarins, and fatty acids. However, the essential oil chemical profile is highly variable, influenced by geographical origin and preparation technique. Pharmacological studies demonstrated a wide spectrum of bioactivities, in particular antioxidant, anti-inflammatory, antimicrobial, anticancer, antidiabetic, and wound-healing properties. Toxicological studies classified the plant as generally non-toxic; however, there is a notable lack of clinical and pharmacokinetic data. Conclusions:C. gileadensis possesses a rich and diverse secondary metabolite profile, validating its traditional ethnobotanical applications. Future research should prioritize pre-clinical and clinical trials to establish its safety, bioavailability, and metabolic fate for its successful integration into modern medicine. Full article

Rosmarinus officinalis L. is known for its drought tolerance; however, its growth is adversely affected by both mild and severe water stress. This study investigates the potential of rhizomicrobiome (RM) transplantation to strengthen water stress resilience. Three RMs derived from native plants—R. officinalis (RO), Pistacia lentiscus L. (PL), and Juniperus phoenicea L. (JP)—collected from a semi-arid Mediterranean garrigue were inoculated into R. officinalis subjected to severe drought stress for 30 days. Although RM transplantation did not result in an increase in biomass, it led to the accumulation of intermediates within the phenylpropanoid/coumarin pathway and significant source-specific alterations in other leaf metabolites. Specifically, PL-RM increased the abundance of lignans and stress signaling metabolites. JP-RM improved the root-to-shoot ratio and the sugar and sugar-alcohol accumulation in leaves. Both JP-RM and RO-RM treatments reduced the abundance of abscisic acid, cyclic GMP, and purine recycling pathways. Additionally, RO-RM decreased the abundance of fifteen defense-related metabolites, indicating a direct interference of the inoculum with the plant immune system. In conclusion, these findings suggest that targeted RM manipulation can be an effective strategy to modulate R. officinalis leaf metabolism. Full article

Background/Objectives: Propolis is a complex bee product with a composition that varies according to local vegetation, environmental conditions, and bee foraging behaviours. Recently, gas chromatography–mass spectrometry (GC–MS) has been employed in Uganda to analyse its volatile components. This study examined Ugandan propolis non-volatile metabolites to determine chemotypes and identify antibacterial compounds. Methods: Ethanolic extracts were analysed using liquid chromatography–high-resolution quadrupole time-of-flight mass spectrometry (LC-HR-QTOF-MS) in an untargeted MS/MS mode. Data processing was carried out using MZmine, then annotated with Global Natural Products Social Molecular Networking (GNPS) and SIRIUS. Chemometric methods assisted in identifying regional chemical signatures. Metabolites highlighted by the heatmap were evaluated for antibacterial activity using molecular docking against bacterial targets, followed by ADMET (absorption, distribution, metabolism, excretion, and toxicity) assessments. Results: Out of 3252 features, 234 and 52 putative compounds were annotated in GNPS and SIRIUS, respectively, as indicated by molecular networking, suggesting high chemical complexity. The chemical space mainly comprises flavonoids (including glycosides, aglycones, methylated, and prenylated derivatives), phenolic acids, amides, hydroxycinnamate derivatives, lignans, megastigmanes, and various diterpenoid skeletons. Multivariate analyses clearly distinguish geographical chemotypes, separating flavonoid-rich regions from diterpenoid-rich regions. Docking studies revealed flavonoids, diterpenoids, and lignans with strong predicted antibacterial activities and favourable ADMET profiles. Conclusions: This study provides the first LC–MS characterisation of the non-volatile metabolome of Ugandan propolis, thereby expanding its chemical diversity. Metabolomics and computational approaches lay a foundation for future ecological, chemotaxonomic, and pharmacological research. Full article