Natural Products and Bioprospecting最新文献

{"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}

{"title":"Artificial intelligence-based screening of phytochemicals for targeted cancer therapy","authors":"Livia Ramos Santiago,&nbsp;Estéfani Alves Asevedo,&nbsp;Maria Eduarda Jeunon de Oliveira,&nbsp;Karen Cota Pereira,&nbsp;Maria Fernanda da Silva Trindade,&nbsp;Ana Gabriela Silva Oliveira,&nbsp;Marina Andrade Rocha,&nbsp;Sojin Kang,&nbsp;Amama Rani,&nbsp;Moon Nyeo Park,&nbsp;Michel William Tan,&nbsp;Rony Abdi Syahputra,&nbsp;Bonglee Kim,&nbsp;Rosy Iara Maciel de Azambuja Ribeiro","doi":"10.1007/s13659-026-00599-y","DOIUrl":"10.1007/s13659-026-00599-y","url":null,"abstract":"<div><p>Cancer remains one of the leading causes of death worldwide and continues to pose a serious public health challenge. The limited success of many current treatments—often due to toxicity, poor selectivity, and the development of drug resistance—highlights the need for new and more effective therapeutic options. Phytochemicals have emerged as a valuable source of anticancer agents, offering rich structural diversity and a wide range of biological activities. However, identifying promising compounds from the vast chemical space of natural products remains difficult using conventional screening methods, which are typically slow, costly, and inefficient. In recent years, artificial intelligence (AI) has begun to transform phytochemical-based drug discovery. Machine learning and deep learning approaches are now used to support key steps in the discovery process, including metabolite identification, virtual screening, target prediction, and toxicity assessment. By integrating chemical, biological, and multi-omics data, AI enables a more systematic and data-driven exploration of natural product diversity. Despite these advances, challenges persist, particularly the scarcity of high-quality experimental data, the structural complexity of phytochemicals, and their limited representation in public databases. This review critically examines current AI applications in phytochemical-based anticancer drug discovery and discusses emerging strategies aimed at overcoming these limitations. Overall, AI-driven phytochemical screening represents a promising path toward accelerating the development of next-generation cancer therapies.</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":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00599-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147738077","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":"Sophflarines F–K: matrine-based alkaloids with a rare aromatic system from Sophora flavescens and their anti-inflammatory and synergistic antibacterial effects","authors":"Ding Luo,&nbsp;Le-Yan Wang,&nbsp;Xiang-Feng Zhao,&nbsp;Xiao-Lin Huang,&nbsp;Yang-Yi Hu,&nbsp;Qiong-Yun Jing,&nbsp;Yan-Jun Chen,&nbsp;He Tian,&nbsp;Si-Yan Chen,&nbsp;Yu-Yan Wang,&nbsp;Xian-Hui Huang,&nbsp;Zhen-Ling Zeng,&nbsp;Xiao-Ping Liao","doi":"10.1007/s13659-026-00595-2","DOIUrl":"10.1007/s13659-026-00595-2","url":null,"abstract":"<div><p>Six new matrine-based alkaloids, sophflarines F–K <b>(1–6)</b>, featuring a rare aromatic system, were obtained from the water-soluble alkaloid fractions of <i>Sophora flavescens</i> by UV-guided separation. Their structures were elucidated by the interpretation of spectroscopic analyses, quantum chemical calculation, and X-ray diffraction data. Compounds <b>1</b> and <b>2</b> represent highly modified 15,16-<i>seco</i>-17-<i>nor</i>-matrine derivatives incorporating a rare 4,5-dihydro-3<i>H</i>-pyrrolo[2,3,4-ij]quinolizine moiety, while compound <b>5</b> possesses an unusual 6/6/6–5 tetracyclic skeleton. A copper sulfate-induced zebrafish assay revealed that compounds <b>1</b>, <b>4</b>, and <b>5</b> exhibited moderate anti-inflammatory activity at non-toxic concentrations. Checkerboard assays demonstrated that compounds <b>5</b> and <b>6</b> potentiated colistin activity against <i>Escherichia coli</i> ATCC25922 and BW25113-<i>mcr</i>-1, reducing colistin MIC values by 16- and 32-fold, respectively. These findings expand the structural diversity of aromatic matrine-type alkaloids and highlight their potential as anti-inflammatory agents and antibacterial adjuvants.</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":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13076842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669498","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":"Tropical psychotria plants are a rich source for peptide inhibitors of human prolyl oligopeptidase","authors":"Roland Hellinger,&nbsp;Paula Schwarz,&nbsp;Jonathan Dieringer,&nbsp;Carina Ebermann,&nbsp;Kirtikumar B. Jadhav,&nbsp;Markus Muttenthaler,&nbsp;Christian W. Gruber","doi":"10.1007/s13659-026-00598-z","DOIUrl":"10.1007/s13659-026-00598-z","url":null,"abstract":"<div><p>Peptides from natural sources have often served as valuable leads in drug discovery. Plant-derived protease inhibitors are a notable class, yet their distribution, diversity, and targets remain underexplored. Here, eleven tropical Psychotria species were screened for cyclic cysteine-rich peptides, with extracts showing concentration-dependent inhibition of human prolyl oligopeptidase (POP). Peptidomics combining mass spectrometry and transcriptome mining revealed multiple inhibitory peptides. From <i>Psychotria solitudinum</i>, which contained 37 peptides, a novel peptide (psysol 3) was purified and sequenced. Its synthetic analogue inhibited POP with an IC₅₀ of ~ 1.3 µM. Sequence analysis and synthetic probes identified loop 3 as the inhibitory motif. Psysol 3 is a new probe for POP pharmacology and future structure–activity studies.</p></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13076805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669487","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}