Journal of Natural Medicines最新文献

{"title":"Exploring the biological tissue toxicity and related toxic components of Euodiae Fructus through the multi-tissue spectrum-toxicity relationship.","authors":"Hao Li, Liansheng Yang, Wenwen Wang, Siying Xue, Yanhong Wang, Zhixin Yang","doi":"10.1007/s11418-025-01955-x","DOIUrl":"https://doi.org/10.1007/s11418-025-01955-x","url":null,"abstract":"<p><p>Euodiae Fructus is recorded in ancient Chinese herbal texts as having \"small toxicity\", with \"soup washing\" noted as a detoxification method. However, the specific organs affected and the conditions required for detoxification remain unclear. This study systematically evaluated the toxicity of Euodiae Fructus on serum and various organs (liver, heart, spleen, lung, kidney, and brain) and clarified the parameters of hot-water washing. Decoction components were analyzed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), with the fingerprint peak areas from various decoctions constituting the spectral profile. The total relative levels of the serum toxicity index and tissue injury indices were defined as \"toxicity.\" A spectral-toxicity relationship was established using partial least squares regression, from which regression equations, coefficients, and variable importance in projection were obtained. Toxicity analysis indicated that Euodiae Fructus primarily affects the liver, spleen, lung, kidney, and brain. Moreover, rapid hot-water washing performed three times significantly reduced its toxicity. A total of 32 toxic compounds were identified, predominantly including alkaloids, triterpenes, organic acids, volatile oils, and flavonoids. These findings provide an experimental basis for the rational use of Euodiae Fructus and offer methodological insights for the pharmacological investigation of traditional Chinese medicine.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205303","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":"Optimizing blood-brain barrier permeability: the effect of wine processing on alkaloids in Phellodendri Chinensis Cortex.","authors":"Shuo Zhang, Jiahui Zhao, Wenjing Ren, Yue Zhou, Yang Chen, Shiru Jiang, Gui Xu, Xiutong Ge, Hui Gao, Fan Zhang","doi":"10.1007/s11418-025-01952-0","DOIUrl":"https://doi.org/10.1007/s11418-025-01952-0","url":null,"abstract":"<p><p>This study investigated the modification of blood-brain barrier (BBB) permeability of alkaloids from Phellodendri Chinensis Cortex (PC) by wine processing. Phytochemical analysis using UPLC-QqQ-MS compared raw PC (RPC) and wine-processed PC (WPC), identifying significant changes in four major alkaloids (phellodendrine, magnoflorine, berberrubine, and berberine). Subsequent in vivo experiments demonstrated enhanced brain distribution of these alkaloids in WPC-treated mice. An in vitro BBB model was established using bEnd.3 endothelial cells and astrocytes to evaluate the permeability of four major alkaloids from RPC and WPC using UPLC-QqQ-MS. Tight junction protein expression and transporter interactions were analyzed through Western blotting and ligand fishing assays. Results showed WPC treatment significantly enhanced alkaloid transport across the BBB model, with mechanistic studies demonstrating downregulation of tight junction proteins (ZO-1 and Occludin), reduced P-glycoprotein expression, and increased binding to the absorptive transporter TfRc. These findings reveal that wine processing enhances BBB penetration of PC alkaloids by coordinately modulating both paracellular and transcellular transport pathways, providing scientific validation for traditional processing methods of Chinese Materia Medica and insights for developing brain-targeted herbal medicines.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147398","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":"Two novel resveratrol dimers from Vatica albiramis: structural elucidation and UV-induced formation.","authors":"Masashi Fukaya, Kakeru Sugiyama, Kaori Ryu, Daiki Ito, Munekazu Iinuma, Tetsuro Ito","doi":"10.1007/s11418-025-01953-z","DOIUrl":"https://doi.org/10.1007/s11418-025-01953-z","url":null,"abstract":"<p><p>Two novel resveratrol dimers, vaticanols O (1) and P (2), were isolated from the bark and stem wood of Vatica albiramis (Dipterocarpaceae), a genus rich in highly oligomerized stilbenoids. Along with seven known constituents, their structures were elucidated by comprehensive spectroscopic analyses, including 1D and 2D NMR, HR-ESI-MS, and ECD measurements. Compound 1 possesses a rare fused ring skeleton comprising a 1,2-dihydrobenzo[1, 2-b:4,3-b'] difuran unit, while 2 features a 6,10b-dihydro-1H-anthra[1, 9-bc] furan skeleton with an additional C₁ unit. Absolute configurations were assigned from NOESY correlations and electronic circular dichroism (ECD) data, supported by molecular modeling. Importantly, both dimers can be generated from ( -)-(E)-ε-viniferin under UV irradiation, as verified by LC-ESI-QTOF-MS, providing experimental support for plausible non-enzymatic biosynthetic pathways. These UV-induced transformations, monitored by LC-ESI-QTOF-MS, represent the first report of photo-triggered structural diversification of ( -)-(E)-ε-viniferin.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147361","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":"New protostane triterpenoids and their bioactivities from the fruits of Schinus terebinthifolius.","authors":"Le-Thuy-Thuy-Trang Hoang, Hoang-Vinh-Truong Phan, Phan-Si-Nguyen Dong, Vo Thi Minh Thao, Thapakorn Chumphon, Van-Kieu Nguyen, Jirapast Sichaem","doi":"10.1007/s11418-025-01948-w","DOIUrl":"https://doi.org/10.1007/s11418-025-01948-w","url":null,"abstract":"<p><p>Two new protostane triterpenoids, schifoliusterpenes A and B (1 and 2), were isolated from the fruits of Schinus terebinthifolius. Their structures were elucidated by NMR, HRESIMS, DP4 probability analysis, and comparison with previously reported data. These new compounds were evaluated for α-glucosidase and acetylcholinesterase (AChE) inhibition, nitric oxide (NO) suppression, and antioxidant, antimicrobial, and cytotoxic activities. Compound 1 was identified as an effective AChE inhibitor (IC₅₀ 31.3 μM), and 2 exhibited a significant effect in decreasing NO production (IC₅₀ 26.4 μM). Moderate cytotoxicity of 1 was recorded against KB, HepG2, A549, and MCF7 cancer cell lines, with IC₅₀ values ranging from 65.3 to 71.6 μM, while 2 exhibited a selective effect against KB (IC₅₀ 92.5 μM). Significant susceptibility to gram-positive bacteria rather than gram-negative bacteria and fungi was observed for both compounds, particularly against Bacillus subtilis (IC₅₀ 5.4-5.5 μM, MIC 8.8-35.0 μM) and Staphylococcus aureus (IC₅₀ 77.9-93.8 μM). In contrast, compounds 1 and 2 demonstrated weak activity in both α-glucosidase inhibitory and antioxidant assays. Further molecular docking simulation on 1 and 2 proposed the determinant role of the C-26 carboxyl and C-3 ketone groups in their structures for the positive bioactivities, providing stable binding interactions with the target proteins via effective hydrogen-bond formation.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147369","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":"New ferrichrome-type siderophores produced by Fusarium lateritium cultured on sodium nitrate-supplemented rice medium.","authors":"Yuki Hitora, Kensuke Iwakiri, Yusaku Sadahiro, Tokuya Teshima, Haru Shinotsuka, Sachiko Tsukamoto","doi":"10.1007/s11418-025-01954-y","DOIUrl":"https://doi.org/10.1007/s11418-025-01954-y","url":null,"abstract":"<p><p>Iron is an essential element for all living organisms, and various microorganisms, such as fungi and bacteria, produce siderophores that chelate iron and facilitate its uptake from the environment. Certain fungi produce ferrichrome-type cyclic hexapeptides containing three N^δ-acetyl-N^δ-hydroxyornithine residues as siderophores. In this study, we found that adding sodium nitrate to solid rice culture medium induced the production of several new ferrichrome-type siderophores in Fusarium lateritium (18F04506), isolated from tidal flat soil in Kumamoto, Japan. LC-MS-guided fractionation of the culture extract afforded two new metabolites, named fusariferins A and B. Their planar structures were determined by detailed analysis of 1D and 2D NMR spectra, and the absolute configurations of the amino acids were determined using Marfey's method. Furthermore, we demonstrated that these compounds were produced by the fungus only when cultured on rice medium supplemented with sodium nitrate, but not on medium supplemented with ammonium chloride, ammonium sulfate, or ammonium nitrate. These findings not only expand the structural diversity of fungal siderophores through the discovery of new ferrichrome-type compounds but also provide new insights into the nitrogen-dependent regulatory mechanism of siderophore biosynthesis in fungi.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129758","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":"Rapid determination of heavy metals and arsenic in herbal medicines using energy-dispersive X-ray fluorescence spectrometry.","authors":"Ryoko Arai, Hiroyuki Kamakura, Naoko Masumoto, Michiho Ito","doi":"10.1007/s11418-025-01949-9","DOIUrl":"https://doi.org/10.1007/s11418-025-01949-9","url":null,"abstract":"<p><p>The Heavy Metals Limit Test in the Japanese Pharmacopoeia is a chemical method used to detect the total amount of heavy metals based on Pb contents. However, determining the amounts of particular metals has become popular since the ICH-Q3D Guideline for Elemental Impurities was adopted. This is effectively performed using energy-dispersive X-ray fluorescence (EDXRF) analysis, an analytical method used to detect elements. In this study, we determined six elements (Cr, Cu, As, Cd, Hg, and Pb) in 25 herbal medicines using EDXRF and compared the quantitative values to those obtained using inductively coupled plasma-mass spectrometry (ICP-MS). The 25 herbal medicines used included 20 plants, two animals, and three minerals. EDXRF quantitative values for Cr, Cu, As, and Pb were obtained through calibration curve methods, whereas Cd and Hg were all below the limit of quantitation (10σ). Comparison of the quantitative values obtained via EDXRF and ICP-MS revealed ratios of 65-198%. The results for both methods were similar, with slightly larger differences observed for minerals between the EDXRF and ICP-MS quantitative values than those observed for plants. Some differences in quantitative values were observed in the comparison of six herbal medicines among different collection sites, owing to the environments in which Coptis rhizome and Mentha herb were grown. Furthermore, Longgu revealed significant elemental variations among the samples during simultaneous multi-elemental analysis. EDXRF enabled the easy and convenient determination of heavy metals in herbal medicines. Thus, it has potential applications in the quality control and evaluation of herbal medicines.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079442","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":"Yatiaroic acids A-C, three novel seco-serratane triterpenoids from Myrica gale var. tomentosa.","authors":"Yusuke Hirasawa, Yuuka Seiya, Erika Koyama, Nahoko Uchiyama, Mayu Nagamura, Daishi Endo, Hiroshi Morita","doi":"10.1007/s11418-025-01943-1","DOIUrl":"https://doi.org/10.1007/s11418-025-01943-1","url":null,"abstract":"<p><p>Three novel triterpenoids, yatiaroic acids A-C (1-3) with an unprecedented seco-serratane skeleton were isolated from branches of Myrica gale var. tomentosa. The relative and absolute stereochemistry of 1-3 were determined on the basis of the 2D NMR data, chemical transformation, and CD calculation.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063137","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":"New pterosins from Hypolepis punctata.","authors":"Liang Shen, Wenhao Mu, Peixin Wang, Maoni Ren, Yating Jia, Xiaoran Min, Jiajia He, Guozheng Huang, Hui Shen, Jianguo Cao","doi":"10.1007/s11418-025-01945-z","DOIUrl":"https://doi.org/10.1007/s11418-025-01945-z","url":null,"abstract":"<p><p>Two new (1-2) and eight known pterosins (3-10) were obtained from the aerial parts of Hypolepis punctata. One compound (11) was synthesized from compound 4. Their structures were established by spectroscopic methods and the absolute configuration was further determined by single-crystal X-ray diffraction analysis for compounds 1, 3 and 4. Notably, compound 1 showed low toxicity while significantly inhibiting lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022570","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":"Unintended metabolites in Monascus pilosus (beni-koji) cultures resulting from Penicillium adametzioides contamination.","authors":"Seiji Tanaka, Tomoya Yoshinari, Naoko Masumoto, Michiho Ito","doi":"10.1007/s11418-025-01946-y","DOIUrl":"https://doi.org/10.1007/s11418-025-01946-y","url":null,"abstract":"<p><p>The health hazards, including kidney damage, were reported following the ingestion of a health food product, so-called \"foods with functional claims (FFC)'', containing beni-koji (red yeast rice), a product of Monascus pilosus very recently in Japan. Puberulic acid (PA) was detected as an unexpected compound in FFC products, and further investigation was required to identify additional unintended compounds and determine the route of PA contamination. To date, we have reported the possibility contamination of FFC products by Penicillium adametzioides in a manufacturing facility, and the presence of two novel unintended compounds, designated as compounds 1 and 2. However, the mechanism underlying the formation of compounds 1 and 2 in FFC products remains unclear. To investigate this mechanism, culture extracts of M. pilosus, P. adametzioides, and their co-cultures were analyzed. Two unintended metabolites were detected in the co-culture samples of M. pilosus and P. adametzioides.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938239","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":"Chemical and pharmaceutical evaluation of roasted Ephedra herba and elucidation of the health hazards caused by white smoke generated during processing","authors":"Koki Matsuda,&nbsp;Makio Shibano","doi":"10.1007/s11418-025-01938-y","DOIUrl":"10.1007/s11418-025-01938-y","url":null,"abstract":"<div><p>In traditional Chinese medicine and traditional Japanese medicine (Kampo medicine), crude drugs are processed to obtain different efficacy, potentially improving the efficacy from the same sample or reducing its adverse effects. Honey-roasted Ephedra herba (EH) and roasted EH are often processed to reduce its sweating inducing effects and enhance its antitussive effects. We attempted to standardize roasted EH based on changes in ephedrine alkaloid content by optimizing the heating temperature and roasting color using a spectrophotometer. Additionally, the volatile oil content of the standardized roasted EH as well as its inhibition of adipose differentiation and change in thermogenesis-related gene expression were assessed using mouse preadipocytes and rat brown adipocytes. As the processing temperature increased, the contents of (1<i>R</i>, 2<i>S</i>)-(−)-ephedrine, (1<i>S</i>, 2<i>S</i>)-(+)-pseudoephedrine, (1<i>R</i>, 2<i>S</i>)-(−)-<i>N</i>-methylephedrine, (1<i>R</i>, 2<i>S</i>)-(−)-norephedrine, and (1<i>S</i>, 2<i>S</i>)-(+)-norpseudoephedrine decreased, with significant decreases recorded at temperatures &gt; 250 °C for the five alkaloids. <i>L</i>* and <i>b</i>* decreased with increasing temperature, whereas <i>a</i>* increased. <i>C</i>* <span>(left( {C* , = sqrt {left( {a*} right)^{2} + (b*)^{2} } } right))</span> of 22.28 (processing temperature: 280 °C), which was linked to 20% and 40% reductions in total ephedrine alkaloid and phenylpropanolamine ((1<i>R</i>, 2<i>S</i>)-(−)-norephedrine + (1<i>S</i>, 2<i>S</i>)-(+)-norpseudoephedrine) content, respectively, was similar to the characteristics of roasted EH used in Japan. Conversely, heat processing significantly increased the levels of volatile oils, including <i>p</i>-cymene, limonene, dehydro-<i>p</i>-cymene, <i>β</i>-terpineol, <i>γ</i>-terpinene, <i>α</i>-terpinolene, benzoic acid, and benzaldehyde. Moreover, EH had significantly reduced lipid droplet accumulation compared with negative control and roasted EH (both, <i>P</i> &lt; 0.001). These changes were accompanied by decreased expression of, peroxisome proliferator-activated receptor gamma genne (<i>Pparg</i>), ligand-activated nuclear receptor, which is implicated to regulate fat-specific gene expression and activate adipocyte differentiation. EH, roasted EH (280 °C and 300 °C), ephedrine, and norephedrine significantly increased the expression of <i>Ucp1</i> in rat brown adipocytes. However, no significant difference was observed between EH and roasted EH. We determined how heat processing of EH alters its alkaloid content and pharmacological effects. In addition, we found that the white smoke produced when EH is roasted in pharmacies poses health risks, as it contains ephedrine alkaloids and compounds such as furfural and furfuryl alcohol.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 5","pages":"1106 - 1121"},"PeriodicalIF":2.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815538","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}