Natural Products and Bioprospecting最新文献

{"title":"Distribution and bioactivities of tirucallane-type triterpenoids from Meliaceae family","authors":"Fajar Fauzi Abdullah,&nbsp;Sabrina Aisyah Putri,&nbsp;Noor Aishah Najihah,&nbsp; Nurlelasari,&nbsp;Wahyu Safriansyah,&nbsp;Khalijah Awang,&nbsp;Unang Supratman","doi":"10.1007/s13659-026-00631-1","DOIUrl":"10.1007/s13659-026-00631-1","url":null,"abstract":"<div><p>Tirucallane-type triterpenoids are one of the most structurally diverse classes of secondary metabolites in Meliaceae family, which is predominantly distributed across tropical and subtropical regions. A total of 373 tirucallane derivatives have been reported between 1967 and 2025, from 48 species belonging to 17 genera. These compounds were isolated from different plant parts, including bark, stem bark, roots, leaves, fruits, twigs, seeds, and aerial tissues. Therefore, this review aims to integrate current reports on tirucallane-type triterpenoids from 17 Meliaceae genera, emphasizing structural complexity, taxonomic occurrence, and pharmacological relevance to guide future chemotaxonomic and drug discovery efforts. Literature collection was performed through Google Scholar, Reaxys, PubMed, and SciFinder. The results showed that based on the structural characteristics, tirucallane derivatives were categorized into intact, seco, heteroatom-substituted, degraded, and highly rearranged, with the intact subgroup being the most abundant. Furthermore, tirucallane derivatives have a broad spectrum of biological properties, including cytotoxic, antimicrobial, antiplasmodial, antidiabetic, anti-inflammatory, immunomodulatory, FXR agonistic, and insecticidal effects, indicating significant potential therapeutic value. Among the reported compounds, laxiracemosin E (<b>361</b>) showed the strongest anticancer potential with IC₅₀ = 1.5 µM, while aphanamgrandin C (<b>372</b>), aphanamgrandin D (<b>373</b>), and dubione B (<b>227</b>) demonstrated potent antibacterial activity (MIC = 1.57–3.13 µg/mL). Hispidol A (<b>2</b>) indicated remarkable antiplasmodial activity (IC₅₀ = 2.45 µM), while meliasenin G (<b>64</b>), phellochin (<b>66</b>), and methyl angolensate (<b>343</b>) were identified as promising α-glucosidase inhibitors (IC₅₀ = 6.1 µM). In conclusion, tirucallane triterpenoids from Meliaceae offer an outstanding structural platform for future drug discovery and bioactivity optimization.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13216417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148040394","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":"New patchoulol- and guaiane-type sesquiterpenoids from Sanguisorba officinalis with anti-melanogenic activity","authors":"Long-Long Wu,&nbsp;Jia-Rui Wu,&nbsp;Kai-Xian Chen,&nbsp;Liu-Qiang Zhang,&nbsp;Yi-Ming Li","doi":"10.1007/s13659-026-00616-0","DOIUrl":"10.1007/s13659-026-00616-0","url":null,"abstract":"<div><p>Twelve new sesquiterpenoids, sanguisorbaols A–L (<b>1–12</b>), along with twenty-five known compounds (<b>13–37</b>), were isolated from the roots of <i>Sanguisorba officinalis</i>. Structures were determined through comprehensive analysis of HRESIMS, 1D and 2D NMR spectroscopic data, ECD and NMR calculations, and X-ray crystallographic analysis. Among them, compounds <b>1–6</b> were identified as new patchoulol-type sesquiterpenoids bearing hydroxyl groups at different positions, the further structural elucidation revealed that compounds <b>5</b> and <b>6</b> are nor-patchoulol-type sesquiterpenoids due to the absence of the C-11 carbon atom. Compounds <b>7–11</b> were characterized as guaiane-type sesquiterpenoids incorporating a [5,7]-bicyclic framework, among which <b>7</b> and <b>8</b> constitute a pair of C-11 epimers. Notably, compound <b>12</b> possesses a rare bicyclo[4.3.1]decane core scaffold. All the patchoulol-type sesquiterpenoids reported here were obtained for the first time from the genus <i>Sanguisorba</i>, and a plausible biosynthetic pathway was proposed. Furthermore, the anti-melanogenic bioactivity of all isolates was assessed using IBMX-stimulated B16F10 melanoma cells. Compounds <b>3–5</b>, <b>8–10</b>, <b>12–14</b>, <b>17</b>, <b>19</b>, <b>21</b>, <b>22</b>, <b>25–27</b>, <b>29</b>, <b>31</b>, <b>32</b> and <b>34</b> demonstrated significant inhibitory activity against melanogenesis at concentrations ranging from 6.25 to 50 μM. These results highlighted the potential of <i>S. officinalis</i> as a natural anti-melanogenesis agent for skin-whitening or for the treatment of hyperpigmentation disorders.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13161421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147873039","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":"Four new Cyclohexenone with antibacterial activity from the coral-derived fungus Aspergillus flavus","authors":"Cili Wang,&nbsp;Jiarui Zhang,&nbsp;Lei Li,&nbsp;Sen Wang,&nbsp;Kai Li,&nbsp;Hu Hou,&nbsp;Pinglin Li","doi":"10.1007/s13659-026-00618-y","DOIUrl":"10.1007/s13659-026-00618-y","url":null,"abstract":"<div><p>Marine fungus-derived natural products are an important source of new drugs and lead compounds. In this study, guided by the Global Natural Products Social (GNPS) molecular networking strategy, four new cyclohexenone derivatives, aspergiflones A–D (<b>1</b>–<b>4</b>), together with three known analogues (<b>5</b>–<b>7</b>), were isolated from the coral-derived fungus <i>Aspergillus flavus.</i> The structures of these compounds were elucidated through extensive spectroscopic analyses, comparison with literature data, hydrolysis reactions, quantum chemical calculations, and TDDFT-ECD calculations. Structurally, aspergiflone A (<b>1</b>) is a novel cyclohexenone dimer featuring an unprecedented skeleton in which two cyclohexenone units are connected at C-15 via a C−C single bond. Compound <b>1</b> exhibited potent antibacterial activity against <i>Escherichia coli</i>. Mechanism studies revealed that compound <b>1</b> disrupts bacterial cell morphology, increases cell membrane permeability, and decreases intracellular K⁺ ion levels. Additionally, transcriptome analysis revealed that the differentially expressed genes (DEGs) were mainly associated with cellular process regulation, stimulus response, catalytic, and binding functions. Several pathways were also significantly affected in <i>Escherichia coli</i>, including ABC transporters, cofactor biosynthesis, energy metabolism, and arginine biosynthesis. The finding indicated that aspergiflone A has considerable potential in food safety.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13161379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147872977","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":"Mechanistic insights into polyphenolic constituents from traditional Chinese medicines in inhibiting colorectal cancer metastasis","authors":"Ming-Hong Li,&nbsp;Lu Liu","doi":"10.1007/s13659-026-00622-2","DOIUrl":"10.1007/s13659-026-00622-2","url":null,"abstract":"<div><p>Colorectal cancer (CRC) is the third most predominant cancer caused by genetic, environmental and nutritional factors and is the world’s second most significant cause of cancer-related mortality. During the process of tumor metastasis, firstly, cancer cell increases its proliferative capacity by reducing autophagy and apoptosis, and then the cancer cell capacity is stimulated by increasing the ability of tumors to absorb nutrients from the outside through angiogenesis. Both of the two steps can increase tumor migration and invasion. Finally, the purpose of tumor metastasis is achieved. By inducing autophagy and apoptosis of tumor cells, blocking the angiogenesis and inhibiting EMT outside the tumor can reduce the invasion and migration of cancer, and consequently achieve the purpose of inhibiting tumor metastasis. Traditional Chinese Medicine (TCM) has the characteristics of multiple targets, slight side effects and good therapeutic effects. Research of the anticancer effect of Polyphenolic in TCM has made considerable progress in recent years. This review explores the research achievements of Polyphenolic in TCM on CRC metastasis in the past ten years, summarizes the development direction of Polyphenolic in TCM on CRC metastasis research in the past ten years and makes a prospect for the future.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00622-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829736","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":"First total synthesis of (±)-spirobroussonin B via electromediated oxidative coupling for constructing spirodienone ring","authors":"Hong-Ji Shi,&nbsp;Xing-Ping Zhang,&nbsp;Cong-Xi Gao,&nbsp;Kun Xie,&nbsp;Wu-Yan Chen,&nbsp;Ming-Ming Li,&nbsp;Kou Wang","doi":"10.1007/s13659-026-00630-2","DOIUrl":"10.1007/s13659-026-00630-2","url":null,"abstract":"<div><p>An electromediated oxidative coupling strategy for constructing spirodienone fragment has been developed and applied as the key step for the total synthesis of (±)-spirobroussonin B. This concise route was accomplished in only four steps, 41.6% overall yield and the key coupling reaction was demonstrated on a gram scale. The absolute configurations of the enantiomers were unambiguously determined by chiral resolution and ECD calculations. This work establishes a solid foundation for developing practical and efficient syntheses of spirobroussonin B and related analogues.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><img></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00630-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829734","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":"Facile synthesis and biological evaluation of glomuferrin and rhizoferrin as ferroptosis inhibitors in rice blast disease","authors":"Anna Fusetti,&nbsp;Francesca Annunziata,&nbsp;Michael S. Christodoulou,&nbsp;Andrea Pinto,&nbsp;Andrea Kunova,&nbsp;Salvatore Princiotto,&nbsp;Sabrina Dallavalle","doi":"10.1007/s13659-026-00619-x","DOIUrl":"10.1007/s13659-026-00619-x","url":null,"abstract":"<div><p>Iron homeostasis has recently emerged as a key determinant in the early stages of plant–pathogen interactions, particularly in phytopathogens that exploit iron-dependent cell death (known as ferroptosis) to initiate host invasion. In <i>Pyricularia oryzae</i>, the causal agent of rice blast disease, appressorium formation is tightly linked to ferroptotic events in germinating conidia. Accumulation of intracellular Fe³⁺ and reactive oxygen species (ROS) promotes lipid peroxidation, ultimately triggering conidial cell death and, consequently, appressorium maturation. Therefore, inhibition of ferroptosis by targeting fungal iron homeostasis represents a promising strategy to suppress appressorium development and block subsequent host infection. Rhizoferrin, an α-hydroxy carboxylate siderophore secreted by <i>Rhizopus microspora</i>, was identified as a suitable precursor of its ring-closed derivative glomuferrin. The obtainment of an unexpected succinimide intermediate within the synthetic pathway enabled the access to both rhizoferrin and, to our knowledge for the first time, glomuferrin. Chelation evaluation revealed that rhizoferrin exhibits significantly higher affinity for iron than glomuferrin. The effects of these siderophores on conidial germination and appressorium formation were evaluated in wild-type and strobilurin-resistant <i>P. oryzae</i> strains, at concentrations ranging from 5 mM to 200 μM. The promising activity observed, especially for rhizoferrin, highlights the potential of α-hydroxy carboxylate siderophores as ferroptosis inhibitors and offers new perspectives for their development in crop protection.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00619-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809477","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":"Cytotoxic trichothecene derivatives from Trichothecium sp. DWS815","authors":"Peng-Ju Xu,&nbsp;Ai-Lin Liang,&nbsp;Wen-Yu Lu,&nbsp;Hong-Ping Long,&nbsp;Qing-Hui Xiao,&nbsp;Qi-An Chen,&nbsp;Meng-Lan Hu,&nbsp;Ngoc Nhu Thao Nguyen,&nbsp;Shao Liu,&nbsp;Jing Li,&nbsp;Wen-Xuan Wang","doi":"10.1007/s13659-026-00613-3","DOIUrl":"10.1007/s13659-026-00613-3","url":null,"abstract":"<div><p>Ten novel trichothecene sesquiterpenoids including two new <i>seco</i>-trichothecenes, trichotheciumones A (<b>1</b>) and B (<b>2</b>), a new trichothecene sesquiterpenoid glycoside, trichothecinoside A (<b>3</b>), and seven new trichothecene sesquiterpenoids, trichothecrotocins T−Z (<b>4</b>−<b>10</b>), together with three new natural products (<b>11</b>−<b>13</b>) and thirteen known compounds (<b>14</b>−<b>26</b>), were isolated from the soil fungus <i>Trichothecium</i> sp. DWS815. The structures and absolute configurations of the new compounds were elucidated by extensive spectroscopic analyses and quantum chemistry ECD calculations. Given the notable anticancer properties of known trichothecenes, the isolated compounds were evaluated for the cytotoxic activities against three cancer cell lines (HCT116, 4T1, MHCC97H) and one normal cell line (GES-1). Cell cycle analysis revealed new compounds <b>7</b> and <b>8</b> induced G2/M phase arrest in HCT116 cancer cells, which resulted to cell proliferation inhibition activity.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00613-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809451","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":"Diversity of oligosaccharides in lipooligosaccharides of Akkermansia muciniphila and its anti-atherosclerotic activity","authors":"Yuting Zhang,&nbsp;Wang Dong,&nbsp;Jinghan Lin,&nbsp;Jingzu Sun,&nbsp;Ruopeng Yin,&nbsp;Xun Lv,&nbsp;Wenzhao Wang,&nbsp;Tao Wang,&nbsp;Hongwei Liu","doi":"10.1007/s13659-026-00612-4","DOIUrl":"10.1007/s13659-026-00612-4","url":null,"abstract":"<div><p>As an important and beneficial gut commensal, <i>Akkermansia muciniphila</i> plays a crucial role in regulating host metabolism and immunity. Lipooligosaccharides from <i>A. muciniphila</i> (ALOS) show anti-obesity effects in high-fat diet-fed mice. Herein, we investigated the chemical characteristics of core oligosaccharides of ALOS and explored its anti-atherosclerotic efficacy. The LC-Q-TOF-MS analysis indicated a high structural diversity of core oligosaccharides in ALOS, comprising fourteen distinct oligosaccharide species with different degrees of phosphorylation. Functionally, administration of ALOS significantly attenuated hyperlipidemia and reduced atherosclerotic plaque burden in high-fat diet-fed <i>ApoE</i>^{<i>−/−</i>} mice. The improvement of these metabolic symptoms was related to the restoration of intestinal barrier integrity. Mechanistically, ALOS upregulated the IL-23/IL-22 immune axis, which in turn promoted intestinal epithelial repair and modulates the microbiota. ALOS intervention reshaped the gut microbiota composition by enriching beneficial genera such as <i>Bifidobacterium longum</i>, <i>Roseburia intestinalis</i>, and <i>Oscillibacter sp.</i>, while suppressing potential pathobionts. Our findings highlight the structural diversity and anti-atherosclerotic effect of lipooligosaccharides from <i>A. muciniphila</i>.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00612-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147796924","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":"Prenylated acylphloroglucinols from the fruits of Hypericum patulum","authors":"Yu-Feng Qiu,&nbsp;Yi Zhou,&nbsp;Cheng Chen,&nbsp;Juan Huang,&nbsp;Xing-Wei Yang","doi":"10.1007/s13659-026-00629-9","DOIUrl":"10.1007/s13659-026-00629-9","url":null,"abstract":"<div><p>Twenty-eight prenylated acylphloroglucinols, including the new hypulatones C–F (<b>1</b>–<b>4</b>), have been isolated from the fruits of <i>Hypericum patulum</i> and structurally characterized. Compound <b>1</b> represents a rare meroterpenoid formed through the addition of a prenylated acylphloroglucinol unit and a sesquiterpenoid moiety. Spirocyclic polycyclic polyprenylated acylphloroglucinol <b>2</b> contains six chiral centers, and its relative configuration was established based on ¹H–¹H coupling constants, conformational analysis, and NOE correlations. The cytotoxic activities of all isolates against two human carcinoma cell lines (Huh-7 and Panc-1) were evaluated using the CCK-8 assay. Bioassay results indicated that compounds <b>6</b>, <b>8</b>, and <b>15</b> exhibited moderate antiproliferative activity.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00629-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147738065","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":"Natural monoterpenoid geraniol promotes antioxidant defense and stress tolerance via SKN-1/Nrf2 activation in Caenorhabditis elegans","authors":"Stéfano Romussi,&nbsp;Ailin Lacour,&nbsp;Diego Rayes,&nbsp;María José De Rosa","doi":"10.1007/s13659-026-00604-4","DOIUrl":"10.1007/s13659-026-00604-4","url":null,"abstract":"<div><p>Oxidative stress (OS) is a major contributor to aging and the pathogenesis of numerous conditions, including diabetes, neurodegenerative, cardiovascular, and autoimmune disorders. Consequently, therapeutic strategies aimed at enhancing endogenous cytoprotective pathways have gained significant interest. Plant-derived essential oils represent attractive sources for such interventions due to their natural origin and low toxicity; specifically, the monoterpenoid geraniol, a principal component of rose oil, has demonstrated promising antioxidant properties in vitro. In this study, we utilized <i>Caenorhabditis elegans</i> to investigate the in vivo efficacy and molecular mechanisms of geraniol effect. Our results show that geraniol significantly reduces intracellular reactive oxygen species and enhances resistance to acute OS induced by juglone. Mechanistic characterization using GFP-reporter strains revealed that geraniol activates the DAF-16/FOXO and SKN-1/Nrf2 transcription factors, while surprisingly causing a slight but consistent downregulation of the HSF-1-mediated heat-shock response. Crucially, genetic epistasis analysis using null/hypomorphic mutants demonstrated that only SKN-1 is strictly essential for geraniol-mediated protection against induced OS. In conclusion, this study underscores the utility of <i>C. elegans</i> as a robust and accessible platform for the pharmacological screening of natural products. Our findings establish geraniol, a key constituent of rose oil, as a multifunctional modulator of cellular defenses that orchestrates multiple cytoprotective pathways, identifying the SKN-1-dependent response as a critical driver of its antioxidant efficacy in <i>C. elegans</i>. By delineating this specific genetic requirement, these results provide a mechanistic foundation that supports the therapeutic potential of geraniol in mitigating aging and pathophysiology driven by OS.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00604-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147738049","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}