Natural Products and Bioprospecting最新文献

Bioactive compounds from food-compatible medicinal herbs have shown promise as preventive agents against age-related neurodegenerative conditions, particularly Alzheimer’s disease (AD). The present work aimed to find Lobetyolin as a new suppressor of Aβ aggregation and its interventions on abnormal metabolism in AD. Aβ-expressing Caenorhabditis elegans (strain CL4176) and wild-type worms were employed to evaluate paralysis onset, lifespan, cerebral Aβ deposition, and intracellular reactive oxygen species (ROS) after Lobetyolin administration. Untargeted ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) metabolomics coupled with RNA-seq transcriptomics was carried out to profile systemic metabolic and gene-expression changes. Differential metabolites and transcripts were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and pathway-impact analyses; hub targets were prioritized by integrating enrichment scores with in-silico docking. Lobetyolin (12.5–50 µM) markedly protected C. elegans from Aβ-driven toxicity and oxidative stress. In CL2006 worms, β-amyloid deposits fell by 54.8 ± 9.4%, while paralysis in CL4176 was delayed by 20.9 ± 4.5%. Lifespan increased by up to 18.2% in CL4176 and 25.0% in wild-type N2 worms. Concomitantly, intracellular ROS declined maximally by 28.1 ± 8.9% (N2) and 22.4 ± 3.8% (CL4176). Integrative metabolomic–transcriptomic analyses, validated by RT-qPCR, revealed selective remodeling of glutathione metabolism: gst-38 expression was suppressed, whereas gst-1 was elevated. Lobetyolin confers neuroprotective and geroprotective benefits in vivo, primarily through reprogramming glutathione-centered redox metabolism and selectively modulating glutathione-S-transferases (GST) isoforms. These findings position Lobetyolin as a promising dietary lead compound for AD prevention and healthy aging interventions.

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Nidulin is a secondary metabolite of the depsidone family produced by Aspergillus spp., and has shown promises in pharmacological applications. This study aimed to investigate the effect of nidulin on glucose metabolism in skeletal muscle, the primary site of physiological glucose disposal, and its underlying mechanisms. Using a 2-[³H]-deoxy-glucose (2-DG) uptake assay, nidulin stimulated 2-DG in L6 myotubes in a dose- and time-dependent manner. This effect of nidulin was additive to insulin and metformin, and remained effective under palmitic acid-induced insulin resistance. At the molecular level, nidulin upregulated the mRNA expression and promoted membrane translocation of glucose transporters, GLUT4 and GLUT1. Although nidulin activated AMPK and p38 signaling, pharmacological inhibition of this pathway had minimal effect on nidulin-enhanced 2-DG uptake activity. Notably, nidulin activated key insulin signaling proteins, including IRS1, AKT, and p44/42, and its effect was attenuated by an AKT inhibitor. This study further compared the upstream mechanism of nidulin with that of insulin. While nidulin did not directly activate the insulin receptor β-subunit, it modulated redox homeostasis and intracellular calcium, evidenced by increased cytosolic H₂O₂ and Ca²⁺ levels. The 2-DG uptake-enhancing effect of nidulin and its activation of AKT were suppressed by either an antioxidant or calcium chelator treatment. These findings position nidulin as a promising insulin-sensitizing agent, offering mechanistic insights and therapeutic potential for improving glucose homeostasis in type 2 diabetes.

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Five new heterodimers, chalasoergodimers A–E (1–5), and three known heterodimers (6–8), along with four chaetoglobosin monomers (9–12), were isolated from a marine-derived Chaetomium sp. fungus. The structures of new compounds 1–5 were elucidated by HRESIMS, NMR, chemical calculated ¹³C NMR and ECD methods. Among them, compound 1 was derived from C-2′ substitution of chaetoglobosin Fex (9) with ergosta-4,6,8(14),22-tetraen-3β-ol, representing a new dimerization mode among chaetoglobosin-ergosterol derivative hybrids. Compound 2 featured substitution at NH-1′ and constituted the first example of this dimeric type bearing an R-configuration at C-3′′. Compounds 3–5 were formed via a Diels–Alder cycloaddition between chaetoglobosins and 14-dehydroergosterol. Furthermore, it was revealed that compound 9–12 exhibited the significant cytotoxic activity against the human non-small cell lung cancer cell (A549), with compound 12 showing the most potent effect at an IC₅₀ of 5.14 μM.

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Propolis, consisting of plant-derived materials, wax, and bee secretions, is abundant in bioactive constituents like flavonoids, phenolic compounds, and terpenes, which enhance its various biological functions. These encompass antioxidant, anti-inflammatory, antibacterial, anticancer, antidiabetic, and immunomodulatory properties. Propolis has demonstrated effectiveness in the prevention and treatment of multiple illnesses, including cardiovascular disease, atherosclerosis, infections, diabetes, wound healing, and burns. Its extensive health benefits endorse its application in medications, nutritional supplements, and cosmetics, where it is acknowledged as a safe and efficacious natural product. Propolis, whether utilized in its raw state, as extracts, or in conjunction with other products, exhibits considerable promise in alternative medicine and nutritional health. Propolis extracts are crucial to examine as a key component in health and wellness, offering prospective applications in disease prevention and therapeutic support Further research is necessary to clarify its molecular mechanisms, examine potential allergic reactions, and determine ideal dosages for various ages. This article provides a comprehensive comparative examination of various propolis types, emphasizing their distinct phytochemical contents and varying biological effects concurrently. It integrates results from both in vitro and in vivo investigations, enhancing the comprehension of health applications and mechanisms of action, grounded comparisons in pertinent prior studies.

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Polysaccharides are the primary active constituents of Polygonatum kingianum Coll. et Hemsl. However, the comprehensive characterization of P. kingianum polysaccharides (PKP) remains scarce, impeding investigations into the structure–activity relationship. In this study, a novel polysaccharide, PKP1, was purified using Cellulose DE-52 and Sephadex G-50 column chromatography, and its complete structure was elucidated through monosaccharide composition analysis, methylation analysis, as well as 1D and 2D NMR analysis. The results revealed that PKP1 primarily comprised Fru and Glc, exhibiting a molecular weight of 5.3 × 10³ Da and a polymer dispersity index of 1.20. The completed structure of PKP1 consisted of β-D-Fruf-(2 → , → 1,2)-β-D-Fruf-(6 → , → 1)-β-D-Fruf-(2 → and → 1)-α-D-Glcp-(6 → as the main chain sugar residues, with β-D-Fruf-(2 → and → 2)-β-D-Fruf-(6 → serving as the side chains sugar residues. The detailed structure of PKP1 suggested it is a novel Fru-dominated neutral polysaccharide. Biological assays indicated that PKP1 significantly reduced the levels of NO, IL-6, and TNF-α in RAW264.7 macrophages, while also exerting regulatory effects on the gut microbiota structure and its metabolites in vitro. Our findings enriched the understanding of the structural characteristics of P. kingianum polysaccharides and laid a solid foundation for considering P. kingianum as a potential functional food supplement.

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Two pairs of undescribed alkaloid enantiomers, (+)-/(−)-ormohenins A (1) and B (2), were isolated from the seeds of Ormosia henryi Prain, along with four undescribed alkaloids (3, 4, 7 and 8) and seven known ones (5, 6, 9–13). Compounds 1–6 belong to the ormosanine-type alkaloids, compounds 7, 9, and 11 are of the lupinine-type, compounds 8 and 10 are classified as anagyrine-type alkaloids, 12 and 13 are cytisine-type alkaloids. The chemical structures of 1–13 were elucidated through comprehensive NMR and MS data analyses. Furthermore, the racemates (±)-1 and (±)-2 were successfully resolved into their respective optically pure enantiomers using a chiral HPLC system. The absolute configurations of compounds 1–3 were determined using single-crystal X-ray diffraction and corroborated by DFT calculations of specific rotations. The absolute configurations of 4, 7, and 8 were assigned by the experimental electronic circular dichroism (ECD) with those predicted using TDDFT calculations. Compound 12 exhibited significant acetylcholinesterase (AChE) inhibitory activity with the IC₅₀ value of 6.581 ± 1.203 μM. The neuroprotective effects of these compounds against Aβ_25-35 induced cell damage in PC12 cells were investigated, and compounds 3, 9, and 12 exhibited significant neuroprotective effects against Aβ_25-35 induced PC12 cell damage, with the EC₅₀ values of 7.99–15.49 μM, respectively.

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Modern pharmacology has found that both Realgar and Coptis chinensis can induce apoptosis in tumor cells, and traditional Chinese medicine theory suggests the possibility of combining the two, however, the specific mechanisms involved have not been elucidated. This study investigated the therapeutic mechanism of the Realgar-Coptis chinensis drug pair (RCCD) against hepatocellular carcinoma (HCC) by identifying its key active compounds and targets. Through integrated LC–MS analysis, transcriptomics, network pharmacology, and bioinformatics, we identified the mechanism of action, key bioactive compounds, and core targets. Molecular docking, molecular dynamics simulations, and microscale thermophoresis (MST) validated the binding affinity between key compounds and core targets. TIMER2.0 database was used to analyze the relationship between the core targets and HCC. H22 tumor xenograft mouse model and immunohistochemistry and pathology analyses were performed to validate the antitumor efficacy of the active compounds. RCCD has a high degree of selectivity of lipid metabolism pathway, 4-Methylumbelliferone (4-MU) was the key active compound with strong binding activity to the core target fatty acid synthase (FAS), and 4-MU down-regulated the expression of FASN in tumor tissues and induced apoptosis in HCC cells. In addition, as a hyaluronan synthase (HAS2/3) inhibitor, 4-MU interfered with the HA-dependent tumor microenvironment and fibrosis process by inhibiting HAS2/3. Thus, 4-MU may inhibit tumor progression by inhibiting FAS and HAS2/3. 4-MU extracted from RCCD exerts anti-HCC effects by modulating the activities of FAS and HAS2/3, thereby reprogramming lipid metabolism and regulating hyaluronan synthesis.

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Background

Depression promotes breast cancer progression. Given the lack of specific targets for depression-associated breast cancer, there are currently no therapeutic drugs for this type of breast cancer.

Methods

Transcriptomic analysis was conducted to identify and functionally annotate genes with differential expression in breast cancer patients exhibiting depressive symptoms. Subsequently, Mendelian randomization was employed to investigate the causal associations between these pivotal genes and breast cancer, thereby validating their potential roles as therapeutic targets. Furthermore, molecular docking techniques were utilized to screen for candidate compounds that may exert therapeutic effects on depression-associated breast cancer. The efficacy of the selected compounds was further assessed using both in vitro cellular experiments and in vivo animal models.

Results

We identified IL-8 as a key gene involved in depression-mediated breast cancer progression using transcriptomics. Mendelian randomized analysis suggested that high IL-8 expression promoted breast cancer progression. Further studies demonstrated that IL-8 mediated the breast cancer-promoting effect of depression through the receptor CXCR2. Evidence from both in vitro and in vivo experiments indicates that senkyunolide H may exert its therapeutic effect by regulating CXCR2, thereby counteracting the protumor effects associated with depression in breast cancer.

Conclusion

Depression activates CXCR2-mediated breast cancer cell proliferation through IL-8, and senkyunolide H regulates CXCR2 and inhibits its ability to block the cancer-promoting effects of depression, ultimately inhibiting the growth of breast cancer in the context of depression.

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