Natural Products and Bioprospecting最新文献

{"title":"Clerodane diterpenoid glycosides from the tuberous roots of Paratinospora sagittata: targeted isolation, structure characterization and immunomodulatory properties","authors":"Jun-Sheng Zhang,&nbsp;Rui Ao,&nbsp;Yin-Bo Pan,&nbsp;Xin-Cheng Zhuang,&nbsp;Yi-Ke Yin,&nbsp;Jie Bao,&nbsp;Hua Zhang","doi":"10.1007/s13659-025-00555-2","DOIUrl":"10.1007/s13659-025-00555-2","url":null,"abstract":"<div><p>Guided by the MS/MS-based molecular networking, eight previously undescribed clerodane diterpenoid glycosides, designated tinospinosides F–M (<b>1</b>−<b>8</b>), along with 12 known analogues (<b>9</b>−<b>20</b>), were isolated from the tuberous roots of <i>Paratinospora sagittata</i>. Structural elucidation of the undescribed compounds was achieved through comprehensive spectroscopic analyses (NMR, HRESIMS), with their absolute configurations confirmed via single-crystal X-ray diffraction, TD-DFT/ECD computational analyses, and chemical degradation. Immunomodulation evaluation on all the isolates revealed that compounds <b>6</b> and <b>7</b> exerted significant promoting effect toward NO production in RAW264.7 macrophages. Further study demonstrated that <b>6</b> could enhance the release of immune cytokines (e.g., TNF-<i>α</i>) and upregulate the protein expression of iNOS and COX-2, which was potentially mediated through the activation of NF-κB signaling pathway.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12862036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cortinarius mapuveronicae from South America, a chemical and morphological link between European and Australian dermocyboid Cortinarii","authors":"Josefine Lange,&nbsp;Lesley Huymann,&nbsp;Sophie Schwarzkopf,&nbsp;Dilara Balci,&nbsp;Mehdi D. Davari,&nbsp;Arijana Turanovic,&nbsp;Clemens Gotsis,&nbsp;Götz Palfner,&nbsp;Bianka Siewert,&nbsp;Ursula Peintner,&nbsp;Norbert Arnold","doi":"10.1007/s13659-025-00552-5","DOIUrl":"10.1007/s13659-025-00552-5","url":null,"abstract":"<div><p>The new species <i>Cortinarius mapuveronicae</i> from Andean-Patagonian <i>Nothofagus</i>-forests is described in a polythetic approach combining chemical analysis of the anthraquinonoid secondary metabolites, microscopical and morphological characteristics, as well as molecular phylogeny. <i>C. mapuveronicae</i> exhibits an intense red color reaction of the basidiomata by treatment with KOH, whereas the basidiospores are turning purplish brown. As responsible compound, the new anthraquinonoid pigment clavorubin-8-<i>O</i>-methylether (<b>1</b>), together with the known monomeric and dimeric anthraquinones (+)-7,7-emodinphyscion (<b>2</b>), emodin (<b>3</b>), emodin-6,8-di-<i>O</i>-methylether (<b>4</b>), questin (<b>5</b>), (+)-(<i>S</i>)-skyrin (<b>6</b>), (+)-(<i>S</i>)-aurantioskyrin (<b>7</b>), hypericin (<b>8</b>), dermolutein (<b>9</b>), and endocrocin (<b>10</b>) could be identified, showing also remarkable activity in a (photo)antimicrobial and (photo)cytotoxic assay. Phylogenetic analysis (ITS, LSU, rpb1) demonstrates a sister group relationship with the holotype of <i>C. rubrobasalis</i>.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12862044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of pyridomycin derivatives as InhA inhibitors from actinomycetes through molecular networking and an In-House tandem mass library","authors":"Byeongsan Lee,&nbsp;Gwi Ja Hwang,&nbsp;Jun-Pil Jang,&nbsp;Beomcheol Park,&nbsp;Juhee Won,&nbsp;Sun Young Kim,&nbsp;Minjeong Woo,&nbsp;Connor Wood,&nbsp;Bang Yeon Hwang,&nbsp;Jae-Hyuk Jang,&nbsp;Young-Soo Hong","doi":"10.1007/s13659-025-00576-x","DOIUrl":"10.1007/s13659-025-00576-x","url":null,"abstract":"<div><p>A screen of ~ 4000 actinomycetes strains identified <i>Streptomyces</i> sp. W3009 as a producer of the antituberculosis agent pyridomycin. Using a mass spectrometry-based metabolomics approach coupled with molecular networking, we identified seven pyridomycin derivatives, six of which were novel. Three of these novel compounds were linear, featuring a unique 3-hydroxypicolinic acid–<span>l</span>-threonine–3-(3-pyridyl)-<span>l</span>-alanine (3HP–T–3PA) scaffold. Their structures were elucidated via detailed NMR studies. While two cyclic derivatives (<b>4</b> and <b>5</b>) showed modest antitubercular activity, the three linear derivatives, despite possessing the key 3HP–T–3PA moiety, exhibited no inhibitory activity. This intensive MS-based approach demonstrates the important role of such techniques in the discovery of novel biologically active core structures and their natural derivatives.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12862043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary ellagic acid inhibiting gastrointestinal pathogens by modulation of microbiome-metabolite-immune axis","authors":"Li-Na Mei,&nbsp;Jia-Shan Shen,&nbsp;Yu Duan,&nbsp;Zhuo-Qi Shi,&nbsp;Hui-Zhen Peng,&nbsp;Xiao-Dong Luo","doi":"10.1007/s13659-025-00584-x","DOIUrl":"10.1007/s13659-025-00584-x","url":null,"abstract":"<div><p>Antibiotic-induced depletion of the gut microbiota facilitated the colonization of vancomycin-resistant <i>Enterococci</i> (VRE) in the gastrointestinal tract, and then increased patients' susceptibility to secondary infections. Ellagic acid, a major constituent of fruits and nuts, showed various bioactivities except for antibacterial. Interestingly, it promoted the recovery of gut microbiota, enhanced microbial diversity and stimulated the proliferation of probiotic gut microbes, and then ameliorated the overgrowth of pathogens in vivo in our experiment. Moreover, ellagic acid activated <i>Gpr41</i> and <i>Gpr43</i> mainly by promoting the production of short chain fatty acids (SCFAs) such as acetic acid and propionic acid to inhibit the NF-ĸB signaling pathway. Then the dietary supplement with ellagic acid might treat infected gut to avoid antibiotic-associated intestinal diseases, and the finding also provided a novel strategy for exploring antibacterial agent besides screening in vitro.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12860781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146096745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monoterpene indole alkaloids from the aerial parts of Ophiorrhiza brevidentata and their immunological activities","authors":"Fan Xu,&nbsp;Zheng-Hui Li,&nbsp;Meng-Lin Feng,&nbsp;Jia-Yu Jin,&nbsp;Bao-Bao Shi,&nbsp;Ji-Kai Liu","doi":"10.1007/s13659-025-00575-y","DOIUrl":"10.1007/s13659-025-00575-y","url":null,"abstract":"<div><p>Phytochemical study of the EtOAc extract of <i>Ophiorrhiza brevidentata</i> resulted in the discovery of 10 new monoterpene indole alkaloids (<b>1–10</b>), along with 13 known compounds (<b>11 − 23</b>). Compound <b>1</b> possess an unprecedented skeleton consisting of fused 6/5/6/7/6 polycyclic systems. The structural characterization of these compounds was achieved using Nuclear Magnetic Resonance, Mass Spectrometry and Quantum Chemical Calculations. Compounds <b>3–5</b> and <b>9</b> exhibited strong inhibition on lipopolysaccharide-induced B cell proliferation with IC₅₀ values ranging from 3.6–9.1 µM with excellent selectivity indices (SI &gt; 10).</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12790544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing detection of low‑abundance metabolites in proton NMR through band‑selective suppression and presaturation","authors":"Upendra Singh,&nbsp;Renad Z. Al Ahmadi,&nbsp;Ruba Al‑Nemi,&nbsp;Manel Dhahri,&nbsp;Mohammed S. Alarawi,&nbsp;Abdul Aziz,&nbsp;Faisal Abdulaziz Bushulaybi,&nbsp;Tamer Abdalla Mashtoly,&nbsp;Abdul‑Hamid Emwas,&nbsp;Lukasz Jaremko,&nbsp;Mariusz Jaremko","doi":"10.1007/s13659-025-00570-3","DOIUrl":"10.1007/s13659-025-00570-3","url":null,"abstract":"<div><p>Metabolomics provides powerful means to analyze metabolite profiles in biological samples, enabling insights into biochemical changes under genetic, environmental, or pathological conditions. Nuclear Magnetic Resonance (NMR) spectroscopy is central to metabolomics, but its utility is often constrained by the strong and overlapping resonances of abundant components, such as sugars in plant‑ and food‑derived materials, which obscure signals of lower‑abundance metabolites. Here, we introduce a modified NMR acquisition method that increases sensitivity and specificity by selectively suppressing dominant signals, while enhancing weaker metabolite signals across the spectrum. The method integrates water presaturation with excitation sculpting (ES), yielding a robust 1D presat‑¹H‑ES pulse sequence. Validation on a range of sugar-rich samples demonstrated 2–fourfold signal enhancement for low‑abundance metabolites compared with conventional ¹H‑ES. Multivariate analyses show the method improves reproducibility and discrimination, enabling detection and comparison of low‑abundance metabolites not accessible with conventional approaches’. Beyond sugar‑rich systems, the method is broadly applicable to other spectral regions where dominant metabolite classes obscure lower‑concentration compounds, including primary metabolites and structurally diverse natural products. Overall, the 1D presat‑¹H‑ES significantly enhances resolution and sensitivity of NMR‑based metabolomics, shortens analysis time, and supports more precise profiling for both fundamental studies and translational applications in metabolomics and natural‑products discovery.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12790556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harziachalasins A–G, polycyclic-fused cytochalasins from the endophytic fungus Trichoderma harzianum MLJ-4 with HIV latency reversal activity","authors":"Yan-Jiang Zhang,&nbsp;Xian-Yuan Yang,&nbsp;Yi-Fan Fu,&nbsp;Qiong Liao,&nbsp;Jia-Qian Chen,&nbsp;Xian-An Chen,&nbsp;Dong Huang,&nbsp;Tao Yuan,&nbsp;Xin Chen,&nbsp;Sheng Yin,&nbsp;Gui-Hua Tang","doi":"10.1007/s13659-025-00572-1","DOIUrl":"10.1007/s13659-025-00572-1","url":null,"abstract":"<div><p>Seven new polycyclic-fused cytochalasins (CYTs), harziachalasins A–G (<b>1</b>–<b>7</b>), together with three known analogues (<b>8</b>–<b>10</b>) were isolated from the solid culture of the endophytic fungus <i>Trichoderma harzianum</i> MLJ-4, which was originally isolated from the leaves of <i>Asclepias curassavica</i>. The planar and absolute structures of all new compounds were determined on the basis of extensive spectroscopic data (1D, 2D NMR and HR-ESI–MS), NMR calculations with DP4 + probability analysis, and theoretical simulations of ECD spectra. Compound <b>1</b> represents the first example of 5/6/6 tricyclic CYT featuring a 2-methyl-4-oxopentyl side chain at the C-14 position. This novel architecture originates from a 5/6/6/7 tetracyclic CYT precursor through sequential oxidative cleavage of the C-19–C-20 bond followed by decarboxylative elimination of C-19. Compound <b>2</b> features an unprecedented 5/6/6/6/7 pentacyclic scaffold incorporating a 1,3-dioxane moiety, may be constructed by the acetalization of the 7-OH and 13-OH on a 5/6/6/7 tetracyclic CYT with acetaldehyde. Compounds <b>1</b>–<b>10</b> were screened for HIV latency reversal activity using J-Lat A72 and J-Lat 10.6 cell models. Compound <b>4</b> showed strong activity, with half-maximal effective concentrations (EC₅₀) values of 2.68 μM (J-Lat A72 cells) and 2.99 μM (J-Lat 10.6 cells), demonstrating consistent potency. Mechanistic studies revealed <b>4</b> activated the NF-<i>κ</i>B pathway to reverse HIV latency, offering insights for new therapeutic strategies targeting this pathway.</p><h3>Graphic Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12790558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xylanins A–P, sixteen new guaiane-type dimers from the branches and leaves of Xylopia vielana with anti-proliferative activity against PANC-1 cell line","authors":"Xianglian Jiang,&nbsp;Ting Zhang,&nbsp;Fancheng Meng,&nbsp;Min Chen,&nbsp;Guowei Wang","doi":"10.1007/s13659-025-00574-z","DOIUrl":"10.1007/s13659-025-00574-z","url":null,"abstract":"<div><p>Sixteen previously undiscovered guaiane-type sesquiterpene dimers, xylanins A–P (<b>1–16</b>), along with six known analogues (<b>17–22</b>), were isolated from the branches and leaves of <i>Xylopia vielana</i> with chromatographic techniques. Their structures including absolute configurations were determined by high-resolution electrospray ionization mass spectrometry (HR-ESI–MS), nuclear magnetic resonance (NMR) data, electron circular dichroism (ECD) spectra, as well as X-ray crystallographic analysis. In cytotoxicity test, we found that five compounds (<b>6</b>, <b>7</b>, <b>8</b>, <b>9</b> and <b>12</b>) had cytotoxic activities in vitro against the human pancreatic cancer (PANC-1) and human prostate cancer (PC-3) cell lines. Of these compounds, compound <b>8</b> showed a relatively greater cytotoxic effect against PANC-1 cell lines with half maximal inhibitory concentration (IC₅₀) value of 1.06 μM. Flow cytometry analysis showed that the apoptosis rate of PANC-1 cells increased with increasing concentrations of compound <b>8</b>, and also demonstrated that the cell cycle of PANC-1 cells was arrested at S phase by the treatment of compound <b>8</b>. By the invasion test, compound <b>8</b> was found to restrain the invasion of PANC-1 cells. In autophagy assay, we observed increased microtubule-associated protein 1 light chain 3 <b>(</b>LC3) by immunofluorescence in the compound <b>8</b>-treated group.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12790548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome mining reveals the unique function of UbiA-type prenyltransferase in Laetiporus sulphureus","authors":"Yue Wang,&nbsp;Qian Wang,&nbsp;Chunlei Wang,&nbsp;Pengchao Wang,&nbsp;Ran Wang,&nbsp;Jing Wu,&nbsp;Hirokazu Kawagishi,&nbsp;Chengwei Liu","doi":"10.1007/s13659-025-00571-2","DOIUrl":"10.1007/s13659-025-00571-2","url":null,"abstract":"<div><p>Eight UbiA-type prenyltransferases were mined in <i>Laetiporus sulphureus</i> by bioinformatic analysis, and phylogenetic analysis showed that they have unique functions. Through heterologous expression in <i>Aspergillus oryzae</i> and addition of exogenous hydroquinone (HYQ, <b>2</b>) substrate, it was found that <i>LaPT3</i> could transfer isoprenyl groups on <b>2</b>. Substrate specificity studies revealed that <i>LaPT3</i> was substrate specific and could only transfer dimethylallyl diphosphate (DMAPP) using <b>2</b> as substrate to produce the product 2-(3-methylbut-2-en-1-yl) benzene-1,4-diol (<b>1</b>). The key active sites of LaPT3 were analyzed and two key amino acid sites near the conserved motifs were targeted for mutation, and the product yields were reduced to 60% and 29% respectively by mutating N100 to S and G208 to A. Molecular docking and site-directed mutagenesis results indicate that these two amino acid sites play a crucial role in the catalytic generation of <b>2</b> by LaPT3 to produce <b>1</b>.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12790560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The ethyl acetate extract from Trichoderma viride fermentation acts by downregulating the leukocyte transendothelial migration signaling pathway to induce ferroptosis in triple-negative breast cancer cells","authors":"Yu Kuang,&nbsp;Bai-Hui Lu,&nbsp;Jia-Yi Wu,&nbsp;Song-Yu Wu,&nbsp;Hai-Yan Fu,&nbsp;Qing-Yan Nan,&nbsp;Jing Li,&nbsp;Xiao-Long Yang","doi":"10.1007/s13659-025-00569-w","DOIUrl":"10.1007/s13659-025-00569-w","url":null,"abstract":"<div><h3>Purpose</h3><p>Triple-negative breast cancer (TNBC), characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression, remains clinically challenging due to the lack of effective targeted therapies. This investigation revealed the anti-TNBC potential of <i>Trichoderma viride</i> ethyl acetate extract (TVEAE) from the endophytic fungus <i>Trichoderma viride</i> isolated from <i>Coreopsis basalis</i>.</p><h3>Methods</h3><p>Pharmacological validation of TVEAE's anti-TNBC efficacy was conducted through in vitro and in vivo pharmacological models. The cell death mechanisms were systematically investigated using Hoechst staining, reactive oxygen species (ROS) detection, and lipid peroxidation assays. Potential therapeutic targets and signaling pathways were identified by integrating network pharmacology, transcriptomics, and weighted gene co-expression network analysis (WGCNA). Furthermore, this study validated key tumor-related proteins involved in tumor progression and cell death pathways via Western blotting. Finally, chemical constituents were characterized through molecular network coupled with Global Natural Products Social Molecular Networking (GNPS) analysis.</p><h3>Results</h3><p>Both in vitro and in vivo models established TVEAE's significant anti-TNBC efficacy. Mechanistic interrogation established TVEAE-mediated ferroptosis induction via selective modulation of leukocyte transendothelial migration (TEM) signaling cascades. Integrative analysis combining transcriptomics, WGCNA, and network pharmacology identified IL-6/TNF-<i>α</i>/HSP90AA1 as core therapeutic targets regulating TEM pathway dynamics. GNPS-assisted molecular networking uncovered six structurally novel anti-TNBC metabolites, including N-lauryldiethanolamine, erucamide, and Gliotoxin.</p><h3>Conclusion</h3><p>This study provides the first evidence of TVEAE's anti-TNBC activity through multi-target engagement along the leukocyte TEM signaling axis, effectively triggering ferroptosis. The mechanistic elucidation advances TNBC therapeutic development, offering a multi-dimensional targeting strategy against this recalcitrant malignancy.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-025-00569-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145930400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}