Journal of Natural Medicines最新文献

{"title":"Theobromine as a molecular switch: targeting Nrf2 pathway in invasive and non-invasive bladder cancer","authors":"Beyza Ecem Oz-Bedir,&nbsp;Elif Ercan,&nbsp;Emine Terzi,&nbsp;Tuba Ozdemir-Sanci","doi":"10.1007/s11418-025-01961-z","DOIUrl":"10.1007/s11418-025-01961-z","url":null,"abstract":"<div><p>Naturally occurring compounds like Theobromine, found in tea, coffee, and cocoa, may have anticancer effects. This study explores how Theobromine induces cell death and apoptosis in bladder cancer cells and its impact on NRF2-related gene activity. Two human bladder cancer cell lines—RT112 (non-invasive) and HTB9 (invasive)—were employed. Cell viability was measured using the WST-1 assay, whereas apoptosis and caspase 3/7 activation were determined through flow cytometry. qPCR was performed to measure the expression of <i>NRF2, KEAP1</i>, and <i>P62</i> genes. Theobromine exhibited a dose-dependent reduction in cell viability in both RT112 and HTB9 bladder cancer cells, while also significantly enhancing apoptosis and caspase 3/7 activity (<i>p</i>&lt;0.0001). Flow cytometry analysis indicated G1-phase arrest in RT112 cells and S-phase accumulation in HTB9 cells following Theobromine treatment, while Cisplatin induced S-phase arrest in both cell lines. Theobromine suppressed <i>NRF2</i> and <i>P62</i> while increasing <i>KEAP1</i> levels in HTB9 cells, suggesting <i>NRF2</i> pathway inhibition. For RT112 cells, Theobromine upregulated <i>NRF2</i> and <i>P62</i> without altering <i>KEAP1</i> expression, highlighting cell type-specific modulation of the <i>NRF2</i> signaling pathway. This study shows that Theobromine differentially regulates the Nrf2-Keap1-p62 pathway in bladder cancer cells, inhibiting <i>NRF2</i> and <i>P62</i> expression in a cell-specific manner. These findings suggest its potential as a natural anticancer compound, warranting further <i>in vivo</i> studies to assess its therapeutic potential.</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 1","pages":"64 - 75"},"PeriodicalIF":2.5,"publicationDate":"2025-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534215","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":"Anti-inflammatory and UV-protective activities of isolated compounds from Calophyllum inophyllum L. in immune and skin cell models","authors":"Takayuki Ogi,&nbsp;Yasuhiro Kawano,&nbsp;Toru Usami,&nbsp;Idam Hermawan,&nbsp;Hiroto Yokaryo,&nbsp;Saori Yamamoto,&nbsp;Papawee Saiki","doi":"10.1007/s11418-025-01963-x","DOIUrl":"10.1007/s11418-025-01963-x","url":null,"abstract":"<div><p>High levels of UV radiation in Okinawa contribute to skin damage, photoaging, and inflammation. <i>Calophyllum inophyllum</i> L. (Tamanu) trees are frequently cultivated along roadways in Okinawa. The oil isolated from Tamanu nuts is renowned for antioxidants, antibacterial, and anti-inflammatory properties. However, the specific UV-absorbing compounds responsible for its anti-inflammatory activity remain unidentified. This study aimed to isolate, characterize, and evaluate the anti-inflammatory activity of UV-absorbing components from Okinawan Tamanu oil. Clinical tests confirmed the UV-protective effects of Tamanu oil, with SPF and PA values of 6.3 ± 0.4 and 2.9 ± 0.6, respectively. UV-absorbing compounds were isolated based on absorbance at 300 nm and structurally characterized by mass spectrometry and NMR. The anti-inflammatory effects of calophyllolide (CAL), inocalophyllin A (ICA), and inocalophyllin B (ICB) were evaluated in LPS-stimulated RAW 264 macrophages and UVB-induced HaCaT keratinocytes. The specific absorbance at 300 nm of CAL, ICA, and ICB isolated from Tamanu oil (300 nm specific absorbance <span>(E_{1cm}^{1% })</span> = 28) were <span>(E_{1cm}^{1% })</span> = 695, 285, and 378, respectively. All three compounds significantly inhibited nitric oxide production in LPS-induced RAW 264 cells. CAL downregulated TNF-α, IL-1β, IL-6, and IL-1α, while ICA and ICB suppressed IL-1β, IL-6, and IL-1α. In UVB-stimulated HaCaT cells, all compounds reduced IL-1α production. ICA also suppressed TNF-α, HMGB1, and HDAC2, while ICB downregulated CASP1, BAX, NLRP3, HDAC1, and HDAC2 significantly. These findings suggest that CAL, ICA, and ICB have strong anti-inflammatory properties, with ICA and ICB providing additional protection against UVB-induced skin damage via inhibition of necroptosis and inflammatory signaling.</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 1","pages":"179 - 191"},"PeriodicalIF":2.5,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145494225","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":"Digoxin targets BHLHE40 to inhibit epithelial-mesenchymal transition in cervical cancer cells via downregulation of ANGPTL3","authors":"Canyi Li,&nbsp;Penghua Luo,&nbsp;Lin Tang,&nbsp;Yongqiang Yang,&nbsp;Long Rao,&nbsp;Lijun Zhong","doi":"10.1007/s11418-025-01947-x","DOIUrl":"10.1007/s11418-025-01947-x","url":null,"abstract":"<div><p>This study aims to investigate the mechanism of action of BHLHE40 and its targeted drug, digoxin, in cervical cancer. The clinical significance of BHLHE40 was evaluated in cervical cancer samples using the UALCAN and Human Protein Atlas databases. The effects of BHLHE40 on proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) were then assessed through loss- and gain-of-function experiments coupled with CCK-8, wound healing, Transwell and Western blot analysis. A murine lung-metastasis model was further established to `validate the pro-metastatic role of BHLHE40 in vivo. JASPAR-based motif prediction, chromatin immunoprecipitation-qPCR (ChIP-qPCR), and luciferase reporter assays were employed to elucidate the transcriptional regulation of ANGPTL3 by BHLHE40. Molecular docking and cellular thermal shift assay (CETSA) were used to clarify the molecular interaction between digoxin and BHLHE40. BHLHE40 was markedly up-regulated in cervical cancer tissues and positively correlated with advanced tumor stage, lymph node metastasis, and poor prognosis. Knockdown of BHLHE40 suppressed proliferation, colony formation, migration, invasion, and attenuated EMT. Consistently, silencing BHLHE40 reduced the number of pulmonary metastatic nodules in nude mice. Mechanistically, BHLHE40 bound directly to the ANGPTL3 promoter and enhanced its transcriptional activity. Knock-down ANGPTL3 reversed BHLHE40-induced increases in migratory and invasive capacities as well as EMT-related phenotypic changes. Digoxin bound to the conserved domain of BHLHE40, down-regulated both BHLHE40 and ANGPTL3, and suppressed EMT and cell motility. Overexpression of BHLHE40 rescued these inhibitory effects of digoxin. Collectively, our findings demonstrate that BHLHE40 promotes EMT and metastasis in cervical cancer by transcriptionally activating ANGPTL3, whereas digoxin exerts anti-EMT effects by targeting this axis. These data highlight the critical role of the BHLHE40-ANGPTL3 axis in cervical cancer progression and suggest that repurposing digoxin offers a novel therapeutic strategy for suppressing EMT in this disease.</p><h3>Graphical Abstract</h3><p>Schematic diagram of BHLHE40/ANGPTL3in CESC. BHLHE40promotes the epithelial-mesenchymal transition of CESCthrough ANGPTL3, andDigoxincan blockthis process by specifically binding to BHLHE40</p>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"80 1","pages":"38 - 53"},"PeriodicalIF":2.5,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145450517","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":"Rice-derived glucosylceramides activate innate immune responses in myeloid lineage differentiated dendritic cells via toll-like receptors 2 and 4","authors":"Kenchi Miyasaka,&nbsp;Shogo Takeda,&nbsp;Ong Guang,&nbsp;Kiyoe Itoi,&nbsp;Kazuo Miyazaki,&nbsp;Yoshiaki Manse,&nbsp;Toshio Morikawa,&nbsp;Hiroshi Shimoda","doi":"10.1007/s11418-025-01951-1","DOIUrl":"10.1007/s11418-025-01951-1","url":null,"abstract":"<div><p>Rice-derived glucosylceramides (GlcCer) consist of multiple molecules that comprise different types of sphingoid bases and saturated fatty acids. These GlcCer are critical for epidermal barrier function and exert anti-melanogenic effects. Regarding their effects on the immune system, a dead cell-derived GlcCer [d18:2/24:1] was shown to enhance the activation of antigen-presenting cells via Mincle receptors. However, the immunomodulatory effects of rice-derived GlcCer have yet to be examined. Therefore, we herein investigated the effects of rice-derived GlcCer on dendritic cell (DC) activation. Among rice-derived GlcCer, GlcCer[d18:2(4<i>E</i>,8<i>Z</i>)/18:0] (10 μM) significantly enhanced IL-6 production by iMylc DC established from induced pluripotent stem cells. CD40 and CD80 expression was significantly upregulated by GlcCer[d18:2(4<i>E</i>,8<i>Z</i>)/18:0] in aMylc DC derived from human peripheral blood mononuclear cells. In a toll-like receptor (TLR) competitive binding assay using TLR antagonists, GlcCer[d18:2(4<i>E</i>,8<i>Z</i>)/18:0] bound to TLR2 and 4. The antigen-presenting abilities of GlcCer[d18:2(4<i>E</i>,8<i>Z</i>)/18:0] and GlcCer[d18:2(4<i>E</i>,8<i>Z</i>)/26:0] were confirmed by the mixed lymphocyte reaction test, which showed a significant T-cell proliferative effect. These results indicate that GlcCer[d18:2(4<i>E</i>,8<i>Z</i>)/18:0] activated DC being sensed by TLR2 and 4 and induced T-cell responses through the expression of CD40 and CD80. Therefore, the limited GlcCer molecules in rice appear to promote innate immune responses on DC.</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 1","pages":"54 - 63"},"PeriodicalIF":2.5,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367340","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 prunasin derivatives, bachmasides A and B, with α-glucosidase inhibitory activity from the leaves of Elaeocarpus bachmaensis","authors":"Phan Thi Diem Tran,&nbsp;Vu Thi Thanh Tam,&nbsp;Tran Phuong Ha,&nbsp;Le Tuan Anh,&nbsp;Le Trung Hieu,&nbsp;Ton That Huu Dat,&nbsp;Le Canh Viet Cuong","doi":"10.1007/s11418-025-01962-y","DOIUrl":"10.1007/s11418-025-01962-y","url":null,"abstract":"<div><p>Two new prunasines, bachmasides A and B (<b>1–2</b>), together with five known compounds, methyl 6-<i>O</i>-<i>p</i>-<i>trans</i>-coumaroyl-<i>β</i>-<span>d</span>-glucopyranoside (<b>3</b>), methyl 6-<i>O</i>-feruloyl-<i>β</i>-<span>d</span>-glucopyranoside (<b>4</b>), polystachyol (<b>5</b>), ethyl (6-<i>O</i>-<i>p</i>-hydroxybenzoyl)-<i>β</i>-<span>d</span>-glucopyranoside (<b>6</b>), and prunasin (<b>7</b>) were isolated from leaves of <i>Elaeocarpus bachmaensis</i>. The structures of isolated compounds (<b>1</b>–<b>7</b>) were elucidated by 1D-NMR, 2D-NMR, and HRMS spectra. The inhibition assays showed that compound <b>5</b> significantly inhibited α-amylase with IC₅₀ value of 90.2 ± 11.5 µg/ml, whereas compounds <b>1</b>,<b> 2</b>, <b>4</b> and <b>6</b> significantly inhibited α-glucosidase with IC₅₀ values ranging from 42.4 ± 5.4 to 75.4 ± 5.6 µg/ml, considerably lower than those of acarbose (IC₅₀ of 112.1 ± 3.1 and 133.0 ± 4.4 µg/ml, respectively). These findings suggest that <i>E. bachmaensis</i> may be a promising source of antidiabetic agents.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><img></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"80 1","pages":"172 - 178"},"PeriodicalIF":2.5,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312297","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":"Selective α-glucosidase inhibitory activity of (+)-eupenoxide and 3-ketone derivatives produced by the endophytic fungus of Aspergillus sp.","authors":"Shoji Maehara,&nbsp;Sachi Shibata,&nbsp;Chiho Takahara,&nbsp;Moeka Kumamoto,&nbsp;Yuhzo Hieda,&nbsp;Shogo Nakajima,&nbsp;Koichi Watashi,&nbsp;Toshiyuki Hata","doi":"10.1007/s11418-025-01964-w","DOIUrl":"10.1007/s11418-025-01964-w","url":null,"abstract":"<div><p><i>α</i>-Glucosidase and <i>α</i>-amylase are two important glycosidases involved in carbohydrate metabolism. Inhibitors of these enzymes are considered crucial therapeutic agents for carbohydrate absorption disorders such as diabetes and obesity. However, the inhibition of salivary amylase can result in undigested starch reaching the stomach, causing indigestion and potentially leading to gastric and duodenal ulcers as well as gastritis. Selective inhibitors that possess <i>α</i>-glucosidase inhibitory activity without affecting <i>α</i>-amylase are needed to address this issue. It has been revealed that (+)-eupenoxide and its 3-ketone derivative, produced by the endophytic fungus of <i>Aspergillus</i> sp. C-1-1 strain associated with <i>Catharanthus roseus</i>, selectively inhibits <i>α</i>-glucosidase. Additionally, from the <i>α</i>-glucosidase inhibitory activity of related compounds, we have successfully deduced the chemical structure feature necessary for <i>α</i>-glucosidase inhibition.</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 1","pages":"192 - 198"},"PeriodicalIF":2.5,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145297980","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":"Antiproliferative activity against glioblastoma-derived cancer stem cells and blood–brain-barrier permeability of carbazole derivatives from Murraya plants and related synthetic compounds","authors":"Kouta Ugawa,&nbsp;Raiki Yamamura,&nbsp;Kaori Yajima,&nbsp;Tomoe Ohta,&nbsp;Seikou Nakamura","doi":"10.1007/s11418-025-01956-w","DOIUrl":"10.1007/s11418-025-01956-w","url":null,"abstract":"<div><p>Carbazoles exhibit various pharmacological activities, including antitumor activity. Eustifoline-B is a carbazole from <i>Murraya</i> (Rutaceae) plants that exhibited strong antiproliferative activity against cancer stem cells (CSCs) that were established from a human glioblastoma (GBM) cell line (U-251 MG). This activity was stronger than that against GBM cells (non-CSCs), indicating that the activity was CSCs-selective. In this study, the efficacy of carbazole derivatives against GBM was evaluated, their structure–activity relationships were examined, and their blood–brain-barrier (BBB) permeability was investigated in vitro. First, 26 carbazole derivatives, two indole derivatives, and two quinoline derivatives were synthesized, including 12 new compounds. Next, 34 compounds, including the synthesized carbazole derivatives, were evaluated for their antiproliferative activities against U-251 MG CSCs and non-CSCs. Carbazoles with prenyl groups, including eustifoline-B, showed concentration-dependent antiproliferative activity against U-251 MG CSCs (IC₅₀ = 3.5–19.8 µM). Among the prenyl groups, carbazole derivatives with geranyl groups, such as eustifoline-B and eustifoline-C, tended to have stronger activity against CSCs (IC₅₀ = 6.2 µM and 3.5 µM) than that against non-CSCs (IC₅₀ &gt; 25 µM and IC₅₀ = 6.6 µM), indicating that they are CSCs-selective. Finally, in vitro BBB permeability studies were performed using six carbazoles; most carbazoles, including eustifoline-C, exhibited BBB permeability. These results suggest the promising potential of carbazoles as new pharmaceutical agents for the treatment of GBM.</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":"79 6","pages":"1361 - 1371"},"PeriodicalIF":2.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298065","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":"Role of the gut microbiota in the pharmacological effects of traditional Kampo medicine and natural products","authors":"Nobutomo Ikarashi,&nbsp;Risako Kon,&nbsp;Hiroyasu Sakai,&nbsp;Tomoo Hosoe","doi":"10.1007/s11418-025-01959-7","DOIUrl":"10.1007/s11418-025-01959-7","url":null,"abstract":"<div><p>The human gastrointestinal tract harbors over a thousand coexisting bacterial species that together constitute a highly complex intestinal microbiome. Dysbiosis of this microbial ecosystem has been implicated in the pathogenesis of disorders such as ulcerative colitis and obesity and has driven the development of microbiota-targeted prevention and treatment strategies. Traditional Kampo medicines are used with the aim of restoring the balance of the whole body, having been developed and established uniquely in Japan based on traditional Chinese medicine with a history of over two millennia. Recent evidence has revealed that the gut microbiota plays critical roles in the pharmacological effects of traditional Kampo medicines. For example, the anti-obesity activity of Bofutsushosan has been linked to an increase in <i>Akkermansia muciniphila</i>. The laxative effect of Daiokanzoto is related to rheinanthrone, which is produced from sennoside A through the gut microbiota, and drugs and foods that can alter the gut microbiota change the laxative activity of Daiokanzoto. In recent years, clinical trials have been conducted to examine the relationship between changes in the gut microbiota and the pharmacological effects of Kampo medicines, and this relationship has come to the forefront. This review discusses the findings of basic and clinical research on the role of the gut microbiota in the pharmacological action of traditional Kampo medicines, focusing on Bofutsushosan, Daiokanzoto, Daikenchuto, and Hangeshashinto, and discusses future issues and prospects for research into these interactions.</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":"79 6","pages":"1447 - 1454"},"PeriodicalIF":2.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273326","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":"Development of a low-cost, simple, and rapid identification method for Glycyrrhiza uralensis using PCR–RFLP and evaluation of seeds distributed on the market","authors":"Tomoyo Nishida,&nbsp;Shinichiro Sawa,&nbsp;Koji Sugimura","doi":"10.1007/s11418-025-01950-2","DOIUrl":"10.1007/s11418-025-01950-2","url":null,"abstract":"<div><p>Glycyrrhiza is a crude drug used worldwide, especially in China and Japan. <i>Glycyrrhiza uralensis</i> Fischer and <i>Glycyrrhiza glabra</i> L. are listed as original plants in the 18th revised Japanese Pharmacopoeia; however, <i>G. uralensis</i> is considered the most important <i>Glycyrrhiza</i> species because it has traditionally been used medicinally. Most <i>G. uralensis</i> used in Japan is imported from China, but export restrictions in recent years have raised concerns about stable supply. Therefore, domestic cultivation in Japan is expected to prevent price increases of raw materials and ensure a stable supply. Accurate species identification is an important step in quality control. In recent years, a method for identifying species using molecular markers has been evaluated for the <i>Glycyrrhiza</i> genus; however, in this study, we found that a simpler method, PCR–RFLP, using two types of restriction enzymes, can be used to identify <i>G. uralensis</i> more cheaply and easily than conventional methods. When applied to the <i>ITS</i>1-5.8S-<i>ITS</i>2 region, the analysis of seeds distributed in the market showed that only four of the 190 seeds surveyed were <i>G. uralensis</i>, while most were <i>G. glabra</i>, <i>G. inflata</i>, or their hybrids. Therefore, to appropriately use commercially available <i>G. uralensis</i> seeds, it is important to correctly identify the species at an early stage. Quick identification using PCR–RFLP is thought to be a useful method for ensuring the adequate supply of <i>G. uralensis</i>.</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":"79 6","pages":"1419 - 1432"},"PeriodicalIF":2.5,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11418-025-01950-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237641","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":"Calycosin ameliorates inflammation and M1 macrophage polarization via Spon2 in LPS-triggered MH-S alveolar macrophages","authors":"Gaoyan Chen,&nbsp;Xiaogang Li,&nbsp;Jingyi Zhang,&nbsp;Jiangli Ding,&nbsp;Yongchao Jiang,&nbsp;Rui Pan","doi":"10.1007/s11418-025-01944-0","DOIUrl":"10.1007/s11418-025-01944-0","url":null,"abstract":"<div><p>Acute lung injury (ALI) remains a critical inflammatory condition with limited therapeutic interventions. This study explores the anti-inflammatory potential of calycosin (CAL), a bioactive flavonoid, in lipopolysaccharide (LPS)-induced MH-S alveolar macrophages cell line, with particular focus on macrophage polarization mechanisms. Through CCK-8 cytotoxicity assessment and subsequent experimental grouping (control, LPS, and LPS + CAL), we demonstrated CAL’s ability to significantly suppress LPS-triggered inflammatory mediators including IL-1β, TNF-α, and IL-6 at both transcriptional and protein levels. Flow cytometric analysis revealed CAL’s dual regulatory effect on macrophage polarization markers, downregulating M1-associated CD86 while enhancing M2-related CD206 expression. Transcriptomic profiling identified 5,944 differentially expressed genes in LPS-stimulated cells enriched in TNF signaling pathways, while CAL treatment specifically modulated 83 genes predominantly involved in TGF-β signaling. Mechanistic investigations identified Spon2 as a critical mediator, where CAL-induced Spon2 downregulation attenuated inflammation and promoted M2 polarization, effects corroborated through Spon2-shRNA knockdown and overexpression experiments. Notably, we newly demonstrate that Spon2 overexpression abolishes CAL-mediated suppression of TNF-α and activation of TGF-β/Smad2 signaling. These findings collectively establish CAL as a promising therapeutic candidate for ALI through its Spon2-mediated modulation of macrophage polarization dynamics.</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 6","pages":"1389 - 1403"},"PeriodicalIF":2.5,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237714","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}