Journal of Natural Medicines最新文献

{"title":"Pharmacological regulation of airway ciliary motility: endogenous mediators, pharmaceutical agents, and natural compounds with a focus on ginsenoside Rd","authors":"Kouta Noriyama,&nbsp;Eishi Ashihara","doi":"10.1007/s11418-026-02039-0","DOIUrl":"10.1007/s11418-026-02039-0","url":null,"abstract":"<div><p>Mucociliary clearance (MCC) is a central component of airway innate defense, and its impairment contributes to respiratory morbidity in chronic obstructive pulmonary disease, asthma, primary ciliary dyskinesia, and chemotherapy-induced ciliary dysfunction. Reduced ciliary motility increases susceptibility to infection, making pharmacological enhancement of airway cilia an attractive yet underexplored strategy. Ciliary activity is regulated by intracellular signaling pathways including cAMP-, Ca²⁺-, nitric oxide-, and Cl⁻- signaling, which converge on axonemal dynein to control ciliary beat frequency, bend angle, and bend distance. Although numerous endogenous mediators, pharmaceutical agents, and natural compounds stimulate ciliary motility, these findings remain fragmented and lack systematic integration. This review classifies airway ciliary activators by signaling mechanism and discusses their translational relevance in diseases characterized by impaired MCC. Particular emphasis is placed on ginsenoside Rd as a representative natural compound that enhances ciliary motility through activation of estrogen receptor β and potentiation of the P2 X 7 receptor and ameliorates chemotherapy-induced ciliary motility disturbance. Its preferential lung accumulation supports translational potential. By integrating intracellular signaling mechanisms with translational perspectives, this review highlights pharmacological activation of airway cilia, including strategies derived from natural compounds and herbal medicines, as a meaningful and underexplored approach to enhancing MCC, and outlines key knowledge gaps and future research directions.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"80 4","pages":"921 - 934"},"PeriodicalIF":2.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11418-026-02039-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Auricularia auricula polysaccharides alleviate Propionibacterium acnes-induced lung sarcoidosis-like granulomatosis in mice via the gut-lung axis","authors":"Meng-Qi Zhao,&nbsp;Ju-Fang Jia,&nbsp;Tian-Bo Liu,&nbsp;Wen-Jie Wang,&nbsp;Xue-Qing Liu,&nbsp;Wen-Fei Wang,&nbsp;Hai-Xue Kuang,&nbsp;Jun Liang,&nbsp;Yong-Gang Xia","doi":"10.1007/s11418-025-01987-3","DOIUrl":"10.1007/s11418-025-01987-3","url":null,"abstract":"<div><p>The main aim of this study was to explore the potential of <i>Auricularia auricula</i> polysaccharides (AAP) in treating lung sarcoidosis-like granulomatosis and its regulatory impact on gut microbiota and short-chain fatty acids (SCFAs). A mouse model of the disease was established, and AAP’s therapeutic effect was evaluated using HE staining and PCR. To explore the underlying regulatory mechanisms, 16S rRNA sequencing was used to profile differences in gut microbiota, while untargeted metabolomics and quantitative SCFA analysis were employed to identify key metabolic pathways. Finally, Western blotting of lung tissues was performed to verify the molecular mechanism. Our study revealed that AAP significantly ameliorated pathological changes in lung tissue, decreased mRNA levels of TNF-<i>α</i>, IL-1<i>β</i>, IL-6, and IL-8, modulated gut microbiota composition, regulated the distribution of serum and fecal metabolites to significantly enrich them in the butanoate metabolism pathway, and elevated SCFAs content. These alterations were critical to its protective effects against <i>Propionibacterium acnes</i> (PA)-induced lung sarcoidosis-like granulomatosis. Mechanistically, we found that AAP mediated the enrichment of the beneficial bacteria <i>Bifidobacterium</i> within the gut and enhanced the production of SCFAs, especially butyric acid. This may lead to the suppression of the TLR4/MyD88 inflammatory signaling pathway in the lungs, and thereby effectively combating PA-induced lung sarcoidosis-like granulomatosis inflammation. These findings provided a scientific basis for AAP to alleviate inflammation in experimental lung sarcoidosis-like granulomatosis by modulating gut microbiota and SCFAs production, suggesting that AAP may be a potential drug for the improvement of lung sarcoidosis-like granulomatosis.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"80 4","pages":"953 - 973"},"PeriodicalIF":2.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of chemical compositional profiles and immunomodulatory activity of ginseng in different habitats","authors":"Chen-Yue Zeng,&nbsp;Quan-Kuan Dai,&nbsp;Hua-Ze Wu,&nbsp;Ao Li,&nbsp;Yong-Lin Chen,&nbsp;Qing-Hui He,&nbsp;Dan Tang,&nbsp;Hong-Yan Ma","doi":"10.1007/s11418-026-02034-5","DOIUrl":"10.1007/s11418-026-02034-5","url":null,"abstract":"<div><p>This study aims to clarify the differences in quality and immunomodulatory effects among the three ecological cultivation variants of ginseng: cultivated ginseng (CG), transplanted ginseng (TG), and mountain-cultivated ginseng (MCG). Despite ecological distinctions, these variants are prone to mislabeling, and comparative research is limited. We collected 30 batches of samples and conducted an initial assessment of their morphological and sensory characteristics. Subsequently, untargeted plant metabolomics analysis was performed using UPLC-Q-Orbitrap HRMS/MS. Multivariate statistical strategies, including principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), were applied to screen for key differential metabolites. Through KEGG analysis, we further investigated the manifestation of these differences in metabolic pathways. A cyclophosphamide (CTX)-immunocompromised mouse model was established. The immunomodulatory capacity of CG and MCG was evaluated based on hematological parameters, inflammatory markers, and splenic T lymphocyte subsets in the mice. Our findings indicate that 20(S)-ginsenoside Rg₃, ginsenoside V, ginsenoside I, levan, ginsenoside Rs₂, quinquenoside I, and L-arginine can function as discriminatory biomarkers for MCG, TG, and CG. According to the results of the immunomodulatory evaluation, both CG and MCG demonstrated immunomodulatory effects. However, MCG showed significantly higher efficacy compared to CG in regulating the spleen index, T-lymphocyte subsets, serum IgG levels, and IL-4 concentration. This study establishes a scientific foundation for precise ginseng classification, quality control, and clinical application by demonstrating significant phenotypic, metabolic, and functional differences among CG, TG, and MCG.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"80 4","pages":"1037 - 1063"},"PeriodicalIF":2.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of human and mouse transient receptor potential vanilloid 1 by enantiomeric evodiamine and rutaecarpine","authors":"Shunsuke Nakamori,&nbsp;Tatsuya Shirahata,&nbsp;Anju Soda,&nbsp;Marie Kashiwazaki,&nbsp;Takahiro Hirota,&nbsp;Yusuke Kawabata,&nbsp;Atsuko Okamura,&nbsp;Yoshihisa Asada,&nbsp;Susumu Ohkawara,&nbsp;Toshiko Tanaka-Kagawa,&nbsp;Hideto Jinno,&nbsp;Yoshinori Kobayashi","doi":"10.1007/s11418-026-02028-3","DOIUrl":"10.1007/s11418-026-02028-3","url":null,"abstract":"<div><p>(+)-Evodiamine and rutaecarpine are the primary alkaloidal components of Euodia Fruit (EF; dried fruits of <i>Euodia ruticarpa</i> Bentham, Rutaceae) known to activate the transient receptor potential vanilloid 1 (TRPV1). Although evodiamine and rutaecarpine share similar chemical structures, their three-dimensional conformations differ due to the presence or absence of a carbon-nitrogen double bond in the five-membered ring. Furthermore, the enantiomer (−)-evodiamine does not naturally occur and exhibits a stereochemical configuration opposite to that of (+)-evodiamine. Therefore, elucidating the relationship between TRPV1 activity and these alkaloidal structures is essential. In this study, we evaluated the activation of human and mouse TRPV1 (hTRPV1 and mTRPV1, respectively) by (+)-evodiamine, (−)-evodiamine, (±)-evodiamine, and rutaecarpine using TRPV1-expressing cells. Evodiamine isolated from EF exhibited 89% enantiomeric excess (e.e.), and half-maximal effective concentrations (EC₅₀) of 0.34 and 0.031 µM for hTRPV1 and mTRPV1, respectively. Rutaecarpine activated mTRPV1 in a concentration-dependent manner up to 0.625 µM, but did not significantly activate hTRPV1. Furthermore, we synthesized high optical purity (+)-evodiamine and (−)-evodiamine and compared their effects on TRPV1 activation. The EC₅₀ value of (+)-evodiamine was 12 times lower than that of (−)-evodiamine for hTRPV1 activation; in contrast, the EC₅₀ of (+)-evodiamine was 7 times lower than that of (−)-evodiamine for mTRPV1 activation. These results suggest that the stereochemistry of Euodia alkaloids is crucial for TRPV1 activation.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"80 4","pages":"1000 - 1011"},"PeriodicalIF":2.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Piperlongumine A attenuates RANKL-induced osteoclastogenesis by targeting MAPK signaling and downregulating c-Fos and NFATc1","authors":"Tran Thi Thu Phuong,&nbsp;Le Hoang Long,&nbsp;Phan Thi Tu Uyen,&nbsp;Nguyen Xuan Nhiem,&nbsp;Jeong-Hyung Lee,&nbsp;Nguyen Hai Dang","doi":"10.1007/s11418-026-02010-z","DOIUrl":"10.1007/s11418-026-02010-z","url":null,"abstract":"<div><p>Bone homeostasis is tightly regulated by the equilibrium between osteoclasts and osteoblasts. Inhibiting osteoclast development with natural compounds presents a valuable approach to osteoporosis prevention and therapy. <i>Piper longum</i> L. (PL), traditionally employed in culinary and herbal medicine practices, has been reported to exhibit multiple bioactive properties, notably anti-inflammatory and antioxidant effects. However, its potential role in regulating bone metabolism remains largely unexplored. In this study, we isolated several compounds from PL extract (PLE) and evaluated their impact on osteoclast differentiation both in vitro and ex vivo. Using TRAP staining, western blotting, immunofluorescence staining, and real-time qPCR, we assessed the inhibitory effects of potential candidates on RANKL-induced osteoclast formation. Our results demonstrated that eight compounds exhibited significant inhibitory effects on RANKL-induced osteoclast differentiation in vitro, with piperlongumine A (PL-A) exhibiting the strongest activity. Moreover, PL-A suppressed RANKL-induced formation of TRAP-positive multinucleated osteoclasts in a dose-dependent manner and concurrently downregulated the mRNA expression of ATP6V0D2, CTSK, MMP-9, TRAP, and DC-STAMP. Additionally, PL-A significantly downregulated c-Fos and NFATc1, key regulators of osteoclastogenesis, in both RAW 264.7 cells and BMDMs stimulated with RANKL. These findings identify piperlongumine A (PL-A) as a potent inhibitor of RANKL-induced osteoclastogenesis, acting through downregulation of osteoclast-related genes and key transcription factors via the MAPK signaling pathway. PL-A shows strong potential as a natural therapeutic candidate for preventing bone loss and treating osteoclast-related diseases.</p></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"80 4","pages":"987 - 999"},"PeriodicalIF":2.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Components with potential anti-inflammatory effect from the seeds of Dolichos lablab","authors":"Wei Zhang,&nbsp;Yijin Wu,&nbsp;Jiaming Cheng,&nbsp;Jingya Ruan,&nbsp;Yingying Wang,&nbsp;Lequan Yu,&nbsp;Dan Wang,&nbsp;Yi Zhang,&nbsp;Tao Wang","doi":"10.1007/s11418-026-02038-1","DOIUrl":"10.1007/s11418-026-02038-1","url":null,"abstract":"<div><p>Four new nitrogenous compounds, designated as dolilabnitrogenousols A₁−A₃, B (<b>1</b>−<b>4</b>), and six new others, namely dolilabnosides A−C, D₁, D₂ (<b>5</b>−<b>9</b>), and (2<i>S</i>)-[[(3-furanyl)carbonyl]oxy]butanedioic acid (<b>10</b>), along with ten known compounds (<b>11</b>–<b>20</b>), which were initially isolated from <i>Lablab</i> genus, were obtained from the seeds <i>Dolichos lablab</i> L., a plant with medicine food homology. Their structures were determined based on high resolution electrospray ionization MS (HR-ESI-MS) data, various NMR spectroscopic analyses, electronic circular dichroism (ECD) calculations, as well as chemical reactions. Moreover, the expression level of nitric oxide (NO) was measured using a lipopolysaccharide (LPS)-induced RAW264.7 cell model to evaluate the anti-inflammatory activity of the obtained compounds. The results of bioactive assay indicated that compounds <b>1</b>–<b>4</b>, <b>6</b>, <b>7</b>, <b>10</b>–<b>13</b>, <b>16</b>, <b>17</b>, and <b>20</b> displayed significant inhibitory activity on NO release in RAW264.7 cells in a dose-dependent manner. Additionally, the structure-activity relationships were summarized. These findings highlight the potential of the ingredients from <i>D. lablab</i> seeds in the treatment of inflammation-related disorders.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"80 4","pages":"1064 - 1078"},"PeriodicalIF":2.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ninjin’yoeito Kampo medicine enhances zebrafish endurance under forced-swimming conditions via muscle hypertrophy","authors":"Kaita Hirano,&nbsp;Jihwan Eum,&nbsp;Haruri Nagata,&nbsp;Yuko Kamada-Futagami,&nbsp;Toshiki Hyodo,&nbsp;Momoko Kawabe,&nbsp;Seiwa Michihara,&nbsp;Shigeki Chiba,&nbsp;Akio Inui,&nbsp;Kazuhiro Shiozaki","doi":"10.1007/s11418-026-02020-x","DOIUrl":"10.1007/s11418-026-02020-x","url":null,"abstract":"<div><p>Maintaining skeletal muscle mass and function is essential for extending healthy life expectancy in aging populations. While exercise and nutritional support are primary strategies to counteract sarcopenia and frailty, their effectiveness is often limited in the elderly. Thus, pharmacological and dietary interventions that directly enhance muscle formation have attracted increasing attention. Ninjin’yoeito (NYT), a traditional Japanese Kampo medicine composed of 12 medicinal herbs, has recently been highlighted for its antifrailty potential. In this study, we examined the effects of NYT dietary supplementation on muscle hypertrophy and endurance in zebrafish. NYT administration did not alter food intake or spontaneous locomotion under standard conditions, but it markedly improved endurance performance in a forced swimming test. NYT-fed zebrafish displayed prolonged upstream swimming times and delayed fatigue onset. Histological analysis revealed hypertrophy of fast-twitch muscle fibers, and gene expression profiling demonstrated upregulation of <i>myhz2</i>, <i>actn3</i>, and <i>myod</i>, which are key regulators of fast muscle development and differentiation. In contrast, genes associated with slow-twitch fibers and canonical protein synthesis pathways were unaffected. Furthermore, <i>ldh</i>, a pivotal enzyme in anaerobic glycolysis, was significantly upregulated in NYT-treated fish following exercise, suggesting enhanced energy metabolism. Collectively, these findings indicate that NYT promotes fast-twitch muscle hypertrophy and enhances physical performance, supporting its potential as a functional intervention to prevent or attenuate age-related decline in muscle health.</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":654,"journal":{"name":"Journal of Natural Medicines","volume":"80 3","pages":"709 - 719"},"PeriodicalIF":2.5,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11418-026-02020-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antioxidative effects of diarylheptanoids","authors":"Sae Miyagishi,&nbsp;Yohei Saito,&nbsp;Masuo Goto,&nbsp;Kyoko Nakagawa-Goto","doi":"10.1007/s11418-026-02040-7","DOIUrl":"10.1007/s11418-026-02040-7","url":null,"abstract":"<div><p>Twenty-one diarylheptanoid derivatives including five symmetric and sixteen asymmetric, which were synthesized previously, evaluated for their antioxidant and antiproliferative activities. Among these, asymmetric diarylheptanoid <b>22</b> exhibited the most potent antioxidant effects. Compound <b>22</b> demonstrated a DPPH radical scavenging of 8.6 µM and, at a concentration of 100 µM, achieved 78.2% scavenging and 46.5% ferrous ion chelating activity. Combined with its relatively low toxicity against tested cell lines, <b>22</b> is a promising candidate for the treatment of diseases driven by oxidative stress.</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":654,"journal":{"name":"Journal of Natural Medicines","volume":"80 3","pages":"876 - 880"},"PeriodicalIF":2.5,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pistaciaphenols A–E: novel chalcone-based biflavonoids from the branches of Pistacia chinensis","authors":"Tomoki Mizoguchi,&nbsp;Naohito Abe,&nbsp;Satoshi Endo,&nbsp;Satoshi Okubo,&nbsp;Takao Yamaura,&nbsp;Masayoshi Oyama,&nbsp;Ken-ichi Nakashima","doi":"10.1007/s11418-026-02023-8","DOIUrl":"10.1007/s11418-026-02023-8","url":null,"abstract":"<div><p><i>Pistacia chinensis</i> (Anacardiaceae) is a deciduous tree widely distributed in East Asia. Despite its long-standing use for ornamental, timber, and medicinal purposes, its secondary-metabolite profile remains only partially characterized. In this study, branches of <i>P. chinensis</i> were extracted with methanol, and the ethyl acetate-soluble fraction was subjected to repeated chromatographic separation, yielding five previously undescribed chalcone-containing biflavonoids, pistaciaphenols A–E (<b>1</b>–<b>5</b>), along with the known biflavonoid pauferrol B (<b>6</b>) and two flavanones, (2<i>S</i>,3<i>S</i>)-aromadendrin (<b>7</b>) and (2<i>S</i>,3<i>S</i>)-taxifolin (<b>8</b>). Comprehensive spectroscopic analyses, including 1D and 2D NMR (HMQC, HMBC, and double quantum filtered COSY) and high-resolution electrospray ionization mass spectrometry, established the structures of <b>1</b>–<b>5</b> as dimers composed of either isoliquiritigenin- or dihydroisoliquiritigenin-derived units linked to flavanone or flavone counterparts. Pistaciaphenols A (<b>1</b>) and C (<b>3</b>) possessed a liquiritigenin-derived flavanone moiety, whereas pistaciaphenol B (<b>2</b>) contained a flavone unit. Pistaciaphenols D (<b>4</b>) and E (<b>5</b>) featured a rare spiro-structure, a structural motif previously reported only from several <i>Daphne</i> species. The absolute configurations of <b>1</b> and <b>3</b> (2′′<i>R</i>,3′′<i>S</i>) were determined via analysis of electronic circular dichroism (ECD) spectra in conjunction with empirical correlations reported for C-3-substituted flavanones. For <b>4</b> and <b>5</b>, GIAO-based ¹³C NMR chemical-shift calculations with DP4 + and CP3 analysis, together with experimental and time-dependent DFT-calculated ECD data, established <b>4</b> as 2′′<i>R</i>,3′′<i>R</i> and supported assignment of <b>5</b> as most plausibly 2′′<i>R</i>,3′′<i>S</i>. These findings expand the structural diversity of chalcone-based biflavonoids in Anacardiaceae and provide new scaffolds for future biological evaluation.</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":654,"journal":{"name":"Journal of Natural Medicines","volume":"80 3","pages":"748 - 757"},"PeriodicalIF":2.5,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The root bark of Paeonia suffruticosa alleviates Staphylococcus aureus-induced pneumonia in mice by modulating toxin secretion and function","authors":"Xibo Xue,&nbsp;Yijiu Gao,&nbsp;Ying-Jian Sun","doi":"10.1007/s11418-026-02012-x","DOIUrl":"10.1007/s11418-026-02012-x","url":null,"abstract":"<div>\u0000 \u0000 <p><i>Staphylococcus aureus</i>, which is a major zoonotic pathogen, can cause various tissues infection and the prevalence of multidrug-resistant <i>S. aureus</i> causes more difficulty in treating the infectious diseases. Moutan Cortex (MC), tree peony root-bark, derived from the root bark of <i>Paeonia suffruticosa</i> Andrews, a key component in traditional Chinese herbal medicine for infections, inhibits α-hemolysin (Hlα) hemolytic activity of <i>S. aureus</i>. This study aimed to elucidate the characteristics of Hlα inhibition and the anti-inflammatory mechanisms of the herb Moutan Cortex decoction (MCD, the aqueous extract of MC). LC-MS identified active components including paeonol, paeoniflorin, glabrone, and ellagic acid. Network pharmacology predicted anti-inflammatory effects via modulation of MAPK-NF-κB and IL-1β signaling pathways. Animal studies demonstrated that MCD significantly reduced Hlα accumulation in lung tissue, suppressed NF-κB signaling-mediated inflammation, attenuated alveolar damage, and improved lung function in a murine model of <i>S. aureus</i> pneumonia. Bacterial proteomic analysis revealed that MCD, at a non-bactericidal concentration, downregulated the toxin synthesis-associated agr and SarA regulatory pathways, inhibited toxin secretion, and induced oxidative stress in <i>S. aureus</i>. Furthermore, MCD directly interacted with Hlα, inhibiting its oligomerization and blocking its hemolytic activity. These findings demonstrate that MCD exerts multi-targeted regulatory effects against <i>S. aureus</i> infection. At a sub-inhibitory concentration, it reduces bacterial pathogenicity both by interfering with the agr/SarA regulatory systems to diminish toxin secretion and by directly neutralizing secreted Hlα toxin, while concurrently alleviating lung injury by suppressing NF-κB signaling-mediated inflammation.</p>\u0000 <span>AbstractSection</span>\u0000 Graphical Abstract\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>\u0000 \u0000 </div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"80 3","pages":"625 - 638"},"PeriodicalIF":2.5,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}