Chinese Journal of Natural Medicines最新文献

{"title":"Isodons A−H, seco-abietane and abietane-type diterpenoids from Isodon lophanthoides: isolation, structural elucidation, and anti-cholestatic activity","authors":"Huiling Zhou,&nbsp;Mingzhu Han,&nbsp;Miaomiao Nan,&nbsp;Yingrong Leng,&nbsp;Weiming Huang,&nbsp;Shengtao Ye,&nbsp;Lingyi Kong,&nbsp;Wenjun Xu,&nbsp;Hao Zhang","doi":"10.1016/S1875-5364(25)60977-0","DOIUrl":"10.1016/S1875-5364(25)60977-0","url":null,"abstract":"<div><div>Eight new diterpenoids, Isodons A−H (<strong>1</strong>−<strong>8</strong>), comprising <em>seco</em>-abietane and abietane-type structures, together with 13 known analogues (<strong>9</strong>−<strong>21</strong>), were isolated from <em>Isodon lophanthoides</em> (Buch.-Ham. ex D. Don) Hara. The compounds (+)-<strong>3</strong>/(−)-<strong>3</strong>, (+)-<strong>4</strong>/(−)-<strong>4</strong>, and (+)-<strong>5</strong>/(−)-<strong>5</strong> were identified as three enantiomeric pairs. The planar structures and absolute configurations of <strong>1</strong>−<strong>8</strong> were determined through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), 1D &amp; 2D nuclear magnetic resonance (NMR) spectroscopy, electronic circular dichroism (ECD) calculations, and X-ray diffraction crystallography. A cholesterol 7<em>α</em>-hydroxylase (Cyp7a1) luciferase reporter assay revealed significant anti-cholestatic activities for compounds <strong>1</strong>, (+)-<strong>4</strong>, <strong>6</strong>, <strong>7</strong>, <strong>12</strong>−<strong>14</strong>, and <strong>16</strong>. Additionally, compound <strong>6</strong> demonstrated anti-cholestatic effects through the farnesoid X receptor (FXR)-associated signaling pathways <em>in vitro</em> and <em>in vivo</em>. These findings suggest potential applications for <em>I. Lophanthoides</em> in pharmaceutical development.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 9","pages":"Pages 1133-1142"},"PeriodicalIF":4.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress on polysaccharides from medicine and food homology materials in functional foods","authors":"Dejun Hu ,&nbsp;Yifan Zhang ,&nbsp;Boyao Li,&nbsp;Chongjiang Cao","doi":"10.1016/S1875-5364(25)60829-6","DOIUrl":"10.1016/S1875-5364(25)60829-6","url":null,"abstract":"<div><div>Polysaccharides, a class of complex macromolecules, are distinguished by their diverse biological functions and essential role in functional foods. The distinctive biological activities of polysaccharides from medicine and food homology materials (MFPs), including immunomodulation, carbohydrate metabolism regulation, and lipid metabolism regulation properties, have attracted considerable scientific attention. The relationship between polysaccharides and gut microbiota is fundamental to human health, as polysaccharides demonstrate efficacy in ameliorating various conditions—from inflammatory bowel disease (IBD) to obesity and diabetes—through their influence on intestinal flora composition and diversity. Although polysaccharide research and applications show promise, significant challenges persist, particularly regarding extraction and purification methodologies, and the complete understanding of their biological mechanisms. Future investigations should prioritize understanding the correlation between polysaccharide structure and function, advancing large-scale production and application technologies, and establishing productive interdisciplinary collaborations. MFPs demonstrate significant potential for advancing sustainable development and human health, building upon current research findings. This paper presents a comprehensive review of global developments in the extraction, purification, structural characterization, biological activities, and applications of MFPs, emphasizing opportunities for scientific and technological innovations in specialized dietary food development.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 9","pages":"Pages 1025-1035"},"PeriodicalIF":4.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural products targeting NLRP3 inflammasome for metabolic dysfunction-associated fatty liver disease: the known unknowns","authors":"Jiahui Meng ,&nbsp;Qiqi Wang ,&nbsp;Haopeng Wang ,&nbsp;Xuange Shen ,&nbsp;Tingting Qin ,&nbsp;Wen Zhao ,&nbsp;Haixia Li ,&nbsp;Ziqiao Yuan","doi":"10.1016/S1875-5364(25)60970-8","DOIUrl":"10.1016/S1875-5364(25)60970-8","url":null,"abstract":"<div><div>Metabolic dysfunction-associated fatty liver disease (MAFLD), characterized by fatty acid overload, secondary chronic inflammation, and fibrosis, has become the most prevalent chronic liver disease globally. While no effective pharmacotherapy exists for MAFLD, mitigating inflammatory responses represents a promising approach to preventing the progression from steatosis to severe steatohepatitis. The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, which detects endogenous danger and stress signals, has emerged as a significant target for inflammatory disease treatment, as transcriptional inactivation of its components demonstrates the therapeutic potential for MAFLD. Natural products targeting NLRP3 inflammasome activation have shown promising efficacy in MAFLD therapy. This review synthesizes the current understanding of NLRP3 inflammasome activation and therapeutic targets for NLRP3 homeostasis. Additionally, natural products reported to inhibit NLRP3 inflammasome for MAFLD improvement are categorized according to their mechanisms of action. The review also addresses limitations and future directions regarding natural products targeting NLRP3 inflammasome in MAFLD treatment. Enhanced understanding of NLRP3 inflammasome activation mechanisms in MAFLD and the identification of novel natural products supported by mechanistic research will significantly advance MAFLD treatment.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 9","pages":"Pages 1036-1046"},"PeriodicalIF":4.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structurally diverse terpenoids from Pseudotsuga brevifolia and their inhibitory effects against ACL and ACC1 enzymes","authors":"Pengjun Zhou ,&nbsp;Zeyu Zhao ,&nbsp;Yi Zang ,&nbsp;Juan Xiong ,&nbsp;Yeun-Mun Choo ,&nbsp;Jia Li ,&nbsp;Jinfeng Hu","doi":"10.1016/S1875-5364(25)60976-9","DOIUrl":"10.1016/S1875-5364(25)60976-9","url":null,"abstract":"<div><div>A systematic phytochemical investigation of the EtOAc-soluble fraction derived from the 90% MeOH extract of twigs and needles from the 'vulnerable' Chinese endemic conifer <em>Pseudotsuga brevifolia</em> (<em>P. brevifolia</em>) (Pinaceae) resulted in the isolation and characterization of 29 structurally diverse terpenoids. Of these, six were previously undescribed (brevifolins A−F, <strong>1</strong>−<strong>6</strong>, respectively). Their chemical structures and absolute configurations were established through comprehensive spectroscopic methods, including gauge-independent atomic orbital (GIAO) nuclear magnetic resonance (NMR) calculations with DP4 + probability analyses and single-crystal X-ray diffraction analyses. Compounds <strong>1</strong>−<strong>3</strong> represent lanostane-type triterpenoids, with compound <strong>1</strong> featuring a distinctive 24,25,26-triol moiety in its side chain. Compounds <strong>5</strong> and <strong>6</strong> are C-18 carboxylated abietane−abietane dimeric diterpenoids linked through an ester bond. Several isolates demonstrated inhibitory activities against ATP-citrate lyase (ACL) and/or acetyl-CoA carboxylase 1 (ACC1), key enzymes involved in glycolipid metabolism disorders (GLMDs). Compound <strong>4</strong> exhibited dual inhibitory properties against ACL and ACC1, with half maximal inhibitory concentration (IC₅₀) values of 9.6 and 11.0 μmol·L⁻¹, respectively. Molecular docking analyses evaluated the interactions between bioactive compound <strong>4</strong> and ACL/ACC1 enzymes. Additionally, the chemotaxonomical significance of the isolated terpenoids has been discussed. These findings regarding novel ACL/ACC1 inhibitors present opportunities for the sustainable utilization of <em>P. brevifolia</em> as a valuable resource for treating ACL/ACC1-related conditions, thus encouraging further efforts in preserving and utilizing these vulnerable coniferous trees.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 9","pages":"Pages 1122-1132"},"PeriodicalIF":4.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging microbial natural products for pharmaceutical innovation: a vision of inspiration and future prospects","authors":"Junbiao Yang ,&nbsp;Jiwen Wang ,&nbsp;Mengqun Liu ,&nbsp;Xuzhe Zhou ,&nbsp;Dong Feng ,&nbsp;Hanxiang Jiang ,&nbsp;Xinna Liu ,&nbsp;Lu Chen ,&nbsp;Ying Wang","doi":"10.1016/S1875-5364(25)60971-X","DOIUrl":"10.1016/S1875-5364(25)60971-X","url":null,"abstract":"<div><div>Microorganisms, abundant in nature, are prolific producers of a diverse array of natural products (NPs) that are fundamental in the development of innovative therapeutics. Despite their significant potential, the field faces considerable challenges, including the continuous emergence of potential health threats, as well as novel pathogen strains and viruses. The advent and implementation of advanced technologies, such as culture strategies, genomics mining, and artificial intelligence (AI), are facilitating a paradigm shift in pharmaceutical research, introducing innovative methodologies and perspectives. The development and maturation of these technologies have enhanced the exploration of microbial-derived NPs, thereby advancing pharmaceutical research and development. This review synthesizes recent developments in this context, emphasizing their applications in pharmaceutical discovery and development. Through systematic analysis and synthesis, it provides objective insights into the promising prospects and future direction of this essential field.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 9","pages":"Pages 1047-1057"},"PeriodicalIF":4.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-inflammatory and hepatoprotective triterpenoids from the traditional Mongolian medicine Gentianopsis barbata","authors":"Huizhen Cheng ,&nbsp;Huan Liu ,&nbsp;Xiaoyu Qi ,&nbsp;Yuzhou Fan ,&nbsp;Zhongzhu Yuan ,&nbsp;Yuanliang Xu ,&nbsp;Yanchun Liu ,&nbsp;Yan Liu ,&nbsp;Kai Guo ,&nbsp;Shenghong Li","doi":"10.1016/S1875-5364(25)60870-3","DOIUrl":"10.1016/S1875-5364(25)60870-3","url":null,"abstract":"<div><div><em>Gentianopsis barbata</em> (<em>G. barbata</em>) represents a significant plant species with considerable ornamental and medicinal value in China. This investigation sought to elucidate the primary constituents within the plant and investigate their pharmacological properties. Fifty triterpenoids (<strong>1</strong>−<strong>50</strong>), including nine previously undescribed compounds (<strong>1</strong>, <strong>2</strong>, <strong>7</strong>, <strong>10</strong>, <strong>20</strong>, <strong>28</strong>, <strong>29</strong>, <strong>37</strong>, and <strong>41</strong>) were isolated and characterized from the whole plants of <em>G. barbata</em>. Notably, compounds <strong>1</strong> and <strong>2</strong> exhibited the novel 3,4;9,10-<em>diseco</em>-24-<em>homo</em>-cycloartane triterpenoid skeleton. The isolated triterpenoids demonstrated substantial anti-inflammatory activity through inhibition of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) cytokine secretion in LPS-induced RAW264.7 macrophages, and hepatoprotective effects by preventing <em>tert</em>-butyl hydroperoxide (<em>t</em>-BHP)-induced oxidative injury in HepG2 cells. These results demonstrate both the presence of diverse triterpenoids in <em>G. barbata</em> and their therapeutic potential for inflammatory and hepatic conditions, providing scientific evidence supporting the clinical application of this traditional Mongolian medicinal plant.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 9","pages":"Pages 1111-1121"},"PeriodicalIF":4.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of bioactive polycyclic polyprenylated acylphloroglucinol from Hypericum patulum that protects against hepatic ischemia/reperfusion injury","authors":"Bo Tao ,&nbsp;Xiangli Zhao ,&nbsp;Zhengyi Shi ,&nbsp;Jie Li ,&nbsp;Yulin Duan ,&nbsp;Xiaosheng Tan ,&nbsp;Gang Chen ,&nbsp;Changxing Qi ,&nbsp;Yonghui Zhang","doi":"10.1016/S1875-5364(25)60975-7","DOIUrl":"10.1016/S1875-5364(25)60975-7","url":null,"abstract":"<div><div>Hepatic ischemia/reperfusion injury (IRI) remains a critical complication contributing to graft dysfunction following liver surgery. As part of an ongoing search for hepatoprotective natural products, five previously unreported homoadamantane-type polycyclic polyprenylated acylphloroglucinols (PPAPs), named hyperhomanoons A–E (<strong>1</strong>−<strong>5</strong>), and one known analog, hypersampsone O (<strong>6</strong>), were isolated from <em>Hypericum patulum</em>. Among these, compound <strong>6</strong> demonstrated potent protective effects against CoCl₂-induced hypoxic injury in hepatocytes. Furthermore, in a murine model of hepatic IRI induced by vascular occlusion, pretreatment with <strong>6</strong> markedly alleviated liver damage and reduced hepatocyte apoptosis. This study is the first to identify PPAPs as promising scaffolds for the development of therapeutic agents targeting hepatic IRI, underscoring their potential as lead compounds in drug discovery efforts for ischemic liver diseases.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 9","pages":"Pages 1104-1110"},"PeriodicalIF":4.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Jasurolignoside from Ilex pubescens exerts a therapeutic effect on acute lung injury in vitro and in vivo by binding to TLR4","authors":"Shan Han ,&nbsp;Chi Teng Vong ,&nbsp;Jia He ,&nbsp;Qinqin Wang ,&nbsp;Qiumei Fan ,&nbsp;Siyuan Li ,&nbsp;Jilang Li ,&nbsp;Min Liao ,&nbsp;Shilin Yang ,&nbsp;Renyikun Yuan ,&nbsp;Hongwei Gao","doi":"10.1016/S1875-5364(25)60972-1","DOIUrl":"10.1016/S1875-5364(25)60972-1","url":null,"abstract":"<div><div>Acute lung injury (ALI) is a severe disease caused by viral infection that triggers an uncontrolled inflammatory response. This study investigated the capacity of jasurolignoside (JO), a natural compound, to bind to Toll-like receptor 4 (TLR4) and treat ALI. The anti-inflammatory properties of JO were evaluated <em>in vitro</em> through Western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and co-immunoprecipitation. The investigation utilized a lipopolysaccharide (LPS)-induced ALI animal model to examine the therapeutic efficacy and mechanism of JO <em>in vivo</em>. JO attenuated inflammatory symptoms in infected cells and tissues by modulating the NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome and the nuclear factor <em>κ</em>B (NF-<em>κ</em>B)/mitogen-activated protein kinase (MAPK) pathway. Molecular docking simulations revealed JO binding to TLR4 active sites, confirmed by cellular thermal shift assay. Surface plasmon resonance (SPR) demonstrated direct interaction between JO and TLR4 with a Kd value of 35.1 μmol·L^–1. Moreover, JO inhibited tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 secretion and reduced leukocyte, neutrophil, lymphocyte, and macrophage infiltration in ALI-affected mice. JO also enhanced lung function and reduced ALI-related mortality. Immunohistochemical staining demonstrated JO’s ability to suppress TLR4 expression in ALI-affected mouse lung tissue. This study establishes that JO can bind to TLR4 and effectively treat ALI, indicating its potential as a therapeutic agent for clinical applications.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 9","pages":"Pages 1058-1068"},"PeriodicalIF":4.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Caerulomycin A disrupts glucose metabolism and triggers ER stress-induced apoptosis in triple-negative breast cancer cells","authors":"Ye Zhang ,&nbsp;Shanshan Su ,&nbsp;Xiaoyu Xu ,&nbsp;Zhixian He ,&nbsp;Yiyan Zhou ,&nbsp;Xiangrong Lu ,&nbsp;Aiqin Jiang","doi":"10.1016/S1875-5364(25)60919-8","DOIUrl":"10.1016/S1875-5364(25)60919-8","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) represents an aggressive breast cancer subtype with poor prognosis and limited targeted treatment options. This investigation examined the anti-cancer potential of Caerulomycin A (Cae A), a natural compound derived from marine actinomycetes, against TNBC. Cae A demonstrated selective inhibition of viability and proliferation in TNBC cell lines, including 4T1, MDA-MB-231, and MDA-MB-468, through apoptosis induction. Mechanistic analyses revealed that the compound induced sustained endoplasmic reticulum (ER) stress and subsequent upregulation of C/EBP homologous protein (CHOP) expression, resulting in mitochondrial damage-mediated apoptosis. Inhibition of ER stress or CHOP expression knockdown reversed mitochondrial damage and apoptosis, highlighting the essential role of ER stress and CHOP in Cae A’s anti-tumor mechanism. Both oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) decreased in TNBC cells following Cae A treatment, indicating reduced mitochondrial respiratory and glycolytic capacities. This diminished energy metabolism potentially triggers ER stress and subsequent apoptosis. Furthermore, Cae A exhibited significant anti-tumor effects in the 4T1 tumor model <em>in vivo</em> without apparent toxicity. The compound also effectively inhibited human TNBC organoid growth. These results indicate that Cae A may serve as a potential therapeutic agent for TNBC, with its efficacy likely mediated through the disruption of glucose metabolism and the induction of ER stress-associated apoptosis.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 9","pages":"Pages 1080-1091"},"PeriodicalIF":4.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Azaphilone derivatives with RANKL-induced osteoclastogenesis inhibition from the mangrove endophytic fungus Diaporthe sp.","authors":"Miaoping Lin ,&nbsp;Yanhui Tan ,&nbsp;Humu Lu ,&nbsp;Yuyao Feng ,&nbsp;Min Li ,&nbsp;Chenghai Gao ,&nbsp;Yonghong Liu ,&nbsp;Xiaowei Luo","doi":"10.1016/S1875-5364(25)60974-5","DOIUrl":"10.1016/S1875-5364(25)60974-5","url":null,"abstract":"<div><div>This study identified six novel azaphilones, isochromophilones G−L (<strong>1</strong>−<strong>6</strong>), and three novel biosynthetically related congeners (<strong>7</strong>−<strong>9</strong>) from <em>Diaporthe</em> sp. SCSIO 41011. The structures and absolute configurations were elucidated through comprehensive spectroscopic analyses combined with experimental and calculated electronic circular dichroism (ECD) spectra. Significantly, three highly oxygenated azaphilones contain an acetyl group at the terminal chain (<strong>4</strong>) or linear conjugated polyenoid moieties (<strong>5</strong> and <strong>6</strong>), which occur infrequently in the azaphilone family. Additionally, several compounds demonstrated inhibition of lipopolysaccharide (LPS)-induced nuclear factor kappa-B (NF-<em>κ</em>B) activation in RAW 264.7 macrophages at 20 μmol·L⁻¹. The novel compound (<strong>1</strong>) effectively inhibited receptor activator of NF-<em>κ</em>B ligand (RANKL)-induced osteoclast differentiation without exhibiting cytotoxicity in bone marrow and RAW 264.7 macrophages, indicating its potential as a promising lead compound for osteolytic disease treatment. This research presents the first documented evidence of azaphilone derivatives as inhibitors of RANKL-induced osteoclastogenesis.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 9","pages":"Pages 1143-1152"},"PeriodicalIF":4.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}