Journal of Natural Medicines最新文献

{"title":"A novel mechanism for treating acute lung injury with ligustilide: elucidation via network pharmacology and in vitro validation","authors":"Yi Yu,&nbsp;Zhennan Wang,&nbsp;Chentong Pan,&nbsp;Keyao Zhu,&nbsp;Liying Xu","doi":"10.1007/s11418-026-02011-y","DOIUrl":"10.1007/s11418-026-02011-y","url":null,"abstract":"<div><p>Ligustilide inhibits the release of multiple inflammatory factors and alleviates acute lung injury (ALI), although its underlying mechanisms require further investigation. This study combined network pharmacology and in vitro experiments to systematically elucidate the therapeutic mechanism of ligustilide against lipopolysaccharide (LPS)-induced ALI. Potential targets of ligustilide and ALI-related genes were screened from public databases, identifying 227 overlapping targets. Protein-protein interaction (PPI) network analysis revealed PIK3R1 as core targets. KEGG pathway enrichment analysis highlighted the PI3K/Akt/mTOR signaling axis as one of the most significantly enriched pathway (<i>P</i> &lt; 0.001). Molecular docking confirmed a strong binding affinity between ligustilide and the PIK3R1 protein. In vitro, LPS exposure (10 µg/ml, 48 h) suppressed autophagy in HPAEpiCs, evidenced by reduced Beclin-1 and LC3 protein levels and a decrease in autophagic vesicles, while concurrently activating the PI3K/Akt/mTOR signaling pathway (<i>P</i> &lt; 0.01) and elevating the levels of IL-17 A, IL-6, and TNF-α. Treatment with ligustilide (25 µg/ml) significantly reversed these effects by modulating autophagy-related markers and suppressing the release of these inflammatory cytokines (<i>P</i> &lt; 0.05). Furthermore, co-treatment with anti-IL-17 A neutralizing antibodies amplified these protective effects through enhanced inhibition of the PI3K/Akt/mTOR pathway (<i>P</i> &lt; 0.01). These findings suggest that ligustilide alleviates ALI by modulating autophagy-related markers and inhibiting inflammatory responses via the IL-17 A-mediated PI3K/Akt/mTOR signaling pathway. The integration of network pharmacology with experimental validation provides a robust mechanistic framework for understanding ligustilide’s therapeutic potential against ALI.</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":"639 - 656"},"PeriodicalIF":2.5,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11418-026-02011-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147493379","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":"Neoflavonoids and a megastigmane glycoside from Dalbergia cultrata: structural elucidation and biological evaluation","authors":"Wiriya Yaosanit,&nbsp;Paratchata Batsomboon,&nbsp;Phanruethai Pailee,&nbsp;Theerawat Thananthaisong,&nbsp;Poonsakdi Ploypradith,&nbsp;Somkid Sitthimonchai,&nbsp;Wansuda Sutinan,&nbsp;Panita Khlaychan,&nbsp;Chulabhorn Mahidol,&nbsp;Supanna Techasakul,&nbsp;Somsak Ruchirawat,&nbsp;Vilailak Prachyawarakorn","doi":"10.1007/s11418-025-02001-6","DOIUrl":"10.1007/s11418-025-02001-6","url":null,"abstract":"<div><p>A phytochemical investigation of the twigs and stems of <i>Dalbergia cultrata</i> yielded fourteen secondary metabolites, including three novel compounds: two neoflavonoids and a megastigmane glycoside. Structures were elucidated using spectroscopic methods and ECD calculations. Biological evaluation showed weak to moderate antibacterial and antioxidant activities, whereas aromatase inhibition was more pronounced. Two coumarins, dalbergin (<b>11</b>) and stevenin (<b>12</b>), were the most potent inhibitors, with IC₅₀ values of 1.23 and 1.61 µM, respectively. In contrast, the selected neoflavonoids showed only moderate activity. Neoflavonoid <b>7</b> exhibited both growth-inhibitory and fungicidal activity against <i>Candida albicans</i> and <i>C. tropicalis</i>. These results highlight <i>D. cultrata</i> as a source of structurally diverse and biologically active secondary metabolites.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><img></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"80 3","pages":"797 - 808"},"PeriodicalIF":2.5,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147466351","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":"Inhibitory effects of three genuine resin glycosides from Calystegia hederacea on in vitro porcine lipase assay and in silico docking simulation analysis","authors":"Hirotaka Nishikawa,&nbsp;Masashi Hirano,&nbsp;Hideki Kinoshita,&nbsp;Kazunari Yoneda,&nbsp;Masateru Ono,&nbsp;Shin Yasuda","doi":"10.1007/s11418-026-02017-6","DOIUrl":"10.1007/s11418-026-02017-6","url":null,"abstract":"<div><p>Resin glycosides are characteristically present in Convolvulaceae plants. We recently demonstrated that three genuine resin glycosides, muricatins V, VI, and IX, from the seeds of <i>Ipomoea muricata</i>, inhibit lipase. This study investigated whether the resin glycoside fraction (CHRG Fr.) obtained from the whole plants of <i>Calystegia hederacea</i> and three resin glycosides, calyhedins II (1), III (2), and VIII (3), from the rhizomes of this plant, can inhibit porcine lipase <i>in vitro</i>. The results indicated the inhibitory effects of CHRG Fr. (IC₅₀; 33.1 µg/mL) and 1–3 (IC₅₀; 4.5–23.7 µM). <i>In silico</i> molecular docking simulations revealed that 1–3 bind stably to the catalytic sites of porcine (PDB ID: 1ETH) and human (PDB ID: 1LPB) pancreatic lipases. Using data from 1 to 3 and three muricatins that we had previously determined, we observed a high correlation (R² = 0.817, log₁₀ (<i>a</i>; IC₅₀ value) = 0.472799 x (<i>b</i>; docking score) + 5.9412, <i>n</i> = 6) between <i>in vitro</i> IC₅₀ values and <i>in silico</i> binding scores for porcine lipase. By a leave-one-out cross-validation approach, we confirmed that this equation is a useful model with moderate predictive performance. There was also a high correlation (R² = 0.928) in binding scores between porcine and human lipases. In conclusion, this study is the first to demonstrate that 1–3 from <i>C. hederacea</i> can inhibit porcine lipase <i>in vitro</i> and bind stably to lipase catalytic sites <i>in silico</i>. Therefore, it is suggested that resin glycosides from <i>C. hederacea</i> may serve as unique lipase inhibitors. (246 words)</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":"680 - 690"},"PeriodicalIF":2.5,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11418-026-02017-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388984","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":"A plant alkaloid lycorine inhibits non-small cell lung cancer cell proliferation, metastasis, glycolysis and promotes ferroptosis through the ZNF143/SPC25 axis","authors":"Meng Lv,&nbsp;Xiangrui Chen,&nbsp;Yaqiong Wang,&nbsp;Qiting Yang,&nbsp;Yongbiao Lv,&nbsp;Wei Xie,&nbsp;Junxiang Cai","doi":"10.1007/s11418-025-01966-8","DOIUrl":"10.1007/s11418-025-01966-8","url":null,"abstract":"<div><p>Lycorine has been shown to have anti-tumor activity in many cancers, including non-small cell lung cancer (NSCLC). However, its underlying molecular mechanisms still need to be further revealed. The expression levels of spindle component 25 (SPC25) and zinc finger protein 143 (ZNF143) were examined by qRT-PCR and western blot. Cell proliferation, migration and invasion were determined by colony formation assay and transwell assay. Glucose uptake, lactate production and ATP level were evaluated to assess cell glycolysis. The levels of ROS, MDA, GSH and Fe²⁺ were examined to evaluate ferroptosis. Animal experiments were performed to explore the role of SPC25 and lycorine in vivo. The interaction between ZNF143 and SPC25 promoter was confirmed by ChIP and dual-luciferase reporter assays. SPC25 was overexpressed in NSCLC tissues and cells. Lycorine could reduce SPC25 expression. SPC25 overexpression promoted NSCLC cell proliferation, metastasis, glycolysis, suppressed ferroptosis, and enhanced tumorigenesis, while lycorine reversed these effects. ZNF143 could bind to SPC25 promoter region to increase its expression. SPC25 knockdown reversed the promoting effect of ZNF143 on NSCLC cell proliferation, metastasis and glycolysis, as well as the inhibitory effect on ferroptosis, and these effects could be aggravated by lycorine. In conclusion, lycorine may suppress ZNF143/SPC25 axis to inhibit NSCLC malignant progression, providing new evidence that lycorine can be used as an adjuvant therapy for NSCLC.</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><p>Lycorine May suppress ZNF143-medaited transcriptional activation of SPC25 to inhibit NSCLC cell proliferation, metastasis, Glycolysis and promote ferroptosis</p></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"80 3","pages":"530 - 540"},"PeriodicalIF":2.5,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388975","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":"Suppression LIF with 8-Gingerol blockades colorectal cancer tumorigenesis by reversing M2-type macrophage polarization","authors":"Yingying Shao,&nbsp;Yiman Liu,&nbsp;Ranran Su,&nbsp;Zewen Zhang,&nbsp;Yu Wang,&nbsp;Xiaomei Bao,&nbsp;Chunze Zhang,&nbsp;Haiyang Yu","doi":"10.1007/s11418-025-01971-x","DOIUrl":"10.1007/s11418-025-01971-x","url":null,"abstract":"<div><p>Colorectal cancer (CRC) remains a formidable therapeutic challenge, with persistent difficulties in developing therapies that simultaneously target tumor cell proliferation and the tumor immune microenvironment (TIME). 8-Gingerol (8-G), a bioactive natural compound, has shown anti-tumor potential; however, its mechanisms in the evolution of CRC and TIME are yet unknown. Through comprehensive investigation using multiple CRC cell lines and in vivo models, experiments conducted both in vitro and in vivo verified that 8-G markedly inhibited CRC cell tumorigenesis. Mechanistically, 8-G exerted dual anti-tumor effects: it directly induced a coordinated cell death program known as PANoptosis in CRC cells, characterized by concurrent activation of apoptotic, pyroptotic, and necroptotic pathways, and simultaneously reprogrammed tumor-associated macrophages (TAMs) toward the anti-tumor M1-type by downregulating LIF. We further established LIF as a key immunosuppressive mediator in CRC, where its expression correlates with poor patient prognosis and promotes M2-TAMs polarization. Further analyses showed 8-G blocked LIF-triggered pyroptosis during CRC cell-TAMs crosstalk, while promoting interferon-γ (IFN-γ) expression and secretion in TAMs via LIF suppression—key changes that remodel the TIME toward anti-tumor immunity. Our findings unveil the dual action of 8-G that not only inhibits CRC cells directly but also remodels the immunosuppressive TIME by targeting LIF, thereby promoting anti-tumor immunity. This study highlights the therapeutic potential of 8-G and identifies LIF as a promising target for CRC immunotherapy.</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":"541 - 554"},"PeriodicalIF":2.5,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147389046","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":"Olive (Olea europaea) phenolics for the control of psoriasis via targeting SMYD2 and IL-17A protein–protein interaction networks","authors":"Md Ashiq Mahmud,&nbsp;Mohamed M. Mohyeldin,&nbsp;Md Towhidul Islam Tarun,&nbsp;Abu Bakar Siddique,&nbsp;Sitanshu S. Singh,&nbsp;Khalid A. El Sayed","doi":"10.1007/s11418-026-02015-8","DOIUrl":"10.1007/s11418-026-02015-8","url":null,"abstract":"<div><p>Psoriasis is a chronic immune-mediated skin disease characterized by keratinocyte hyperproliferation and persistent inflammation driven by cytokines signaling. This study aimed to identify novel anti-psoriasis natural products and evaluate their potential molecular attributes. Transcriptomics analysis of psoriatic lesions (GSE54456) and in vitro IL-17A-stimulated HaCaT keratinocytes demonstrated significant upregulation of the lysine methyltransferase SMYD2, suggesting its possible involvement in psoriasis pathology. Treatments of HaCaT cells in vitro with the olive tree (<i>Olea europaea</i>) fruit oil phenolics <i>S</i>-(–)-oleocanthal (OC), <i>S</i>-(–)-hydroxy-oleocanthal (HOC, oleacein), and <i>S</i>-(–)-ligstroside aglycone (LA) at a single 10 µM treatment concentration significantly suppressed the SMYD2 expression and reduced markers of psoriatic inflammation, validated by quantitative PCR and Western blot analysis. The RAW 264.7 macrophages stimulated with LPS and IFN-γ exhibited diminished expression of the pro-inflammatory cytokines, including iNOS, IL-6, and TNF-α, following OC, HOC, and LA treatments. Molecular and protein-protein interaction modeling identified the IL-17A dimer selective binding pocket where OC displayed near-benchmark complementarity binding to the co-crystallized ligand (PubChem CID 153616520), engaging key residues Gln94, Trp67, and Leu97. OC induced the largest pocket expansion (1.52-fold) among all ligands, suggesting strong allosteric interference with IL-17RA binding. Consistently, AlphaLISA assays confirmed the OC ability to effectively inhibit the IL-17A–IL-17RA interaction, unlike LA, which showed modest inhibition. Further, surface plasmon resonance demonstrated dose-dependent blockade of IL-17A–IL-17F binding by OC, validating its IL-17A-IL-17F protein-protein heterodimerization interaction inhibitory capacity. Collectively, findings identify OC as a potent natural modulator for the IL-17 signaling that downregulates SMYD2 and disrupts IL-17A protein-protein interactions, evidencing its anti-psoriatic therapeutic potential.</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":"657 - 679"},"PeriodicalIF":2.5,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147375739","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 meroterpenoids from Sargassum macrocarpum as inhibitors of amyloid β aggregation","authors":"Mitsuhiro Sekiguchi,&nbsp;Mafumi Horiuchi,&nbsp;Seiya Shinoda,&nbsp;Joh Yamanaka,&nbsp;Yuta Tozawa,&nbsp;Yasuki Higashimura,&nbsp;Yusaku Miyamae,&nbsp;Hideyuki Shigemori","doi":"10.1007/s11418-026-02006-9","DOIUrl":"10.1007/s11418-026-02006-9","url":null,"abstract":"<div><p>Three new meroterpenoids, macrocarquinoids J(<b>1</b>)–L(<b>3</b>) were isolated from brown alga, <i>Sargassum macrocarpum</i>, along with sargahydroquinoic acid. The structures of <b>1</b>–<b>3</b> were elucidated with 2D NMR spectral data. The inhibitory activities of these compounds against Aβ42 aggregation were evaluated using thioflavin T assay and transmission electron microscopy. All three new meroterpenoids were found to be active, and macrocarquinoid L was the strongest among the three compounds. Furthermore, sargahydroquinoic acid significantly delayed the onset of paralysis in transgenic <i>Caenorhabditis elegans</i>, suggesting its potential inhibitory effect on amyloid aggregation.</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":"809 - 816"},"PeriodicalIF":2.5,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147389025","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":"Betulinic acid increases brain-derived neurotrophic factor expression via the PKA, NMDA receptor, and calcineurin pathways in cultured cortical neurons","authors":"Mamoru Fukuchi,&nbsp;Natsumi Maeda,&nbsp;Sachie Hoshino,&nbsp;Gegentuya Huanood,&nbsp;Kazuki Watanabe","doi":"10.1007/s11418-026-02025-6","DOIUrl":"10.1007/s11418-026-02025-6","url":null,"abstract":"<div><p>Brain-derived neurotrophic factor (BDNF) is a crucial neurotrophin that plays a vital role in neuronal survival, synaptic plasticity, and cognitive function. Reduced BDNF expression has been implicated in neurodegenerative and neuropsychiatric disorders. Thus, compounds that enhance <i>Bdnf</i> expression may have therapeutic potential for these disorders. In this study, we screened 48 compounds, including those from <i>Morus alba</i> L. (Moraceae) branches and structurally similar compounds, for their ability to induce <i>Bdnf</i> expression in primary cultured cortical neurons derived from <i>Bdnf-Luciferase</i> transgenic mice. <i>M. alba</i>-derived compounds failed to increase <i>Bdnf</i> expression; however, among the structurally similar compounds, betulinic acid (BA), moronic acid, and oleanolic acid elevated <i>Bdnf</i> mRNA levels. Further mechanistic analysis, particularly focusing on BA, revealed that the BA-induced <i>Bdnf</i> expression was inhibited by the protein kinase A (PKA) inhibitor H89, <i>N</i>-methyl-<span>d</span>-aspartate receptor (NMDAR) antagonist APV, and the calcineurin inhibitor FK506. Furthermore, BA promoted the nuclear translocation of cAMP-response element-binding protein (CREB)-regulated transcriptional coactivator 1 (CRTC1), which translocates to the nucleus upon dephosphorylation by calcineurin. The BA-induced nuclear translocation of CRTC1 was completely inhibited by H89, APV, and FK506. Although BA also increased CREB phosphorylation, the phosphorylation was prevented by H89 and APV, but not by FK506. These results suggest that CREB phosphorylation and CRTC1 nuclear translocation contribute to BA-induced <i>Bdnf</i> expression. Our findings indicate that BA enhances <i>Bdnf</i> expression in a manner dependent on PKA, NMDAR, and calcineurin signaling pathways, highlighting its potential as a modulator of activity-dependent BDNF transcription.</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":"735 - 747"},"PeriodicalIF":2.5,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147389019","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":"Chemistry and bioactivities of erinacines from Hericium fungi","authors":"Yhiya Amen,&nbsp;Ahmed Othman ,&nbsp;Kuniyoshi Shimizu","doi":"10.1007/s11418-026-02005-w","DOIUrl":"10.1007/s11418-026-02005-w","url":null,"abstract":"<div><p>Erinacines are a class of cyathane diterpenoids predominantly biosynthesized in the mycelia of the medicinal mushroom <i>Hericium erinaceus</i>, commonly known as Lion’s Mane or Yamabushitake. Recognized as the main constituents responsible for the neurological effects of <i>Hericium</i> species, erinacines exhibit a range of biological properties, including anti-inflammatory, neurotrophic, neurogenic, antidepressant, and anticancer activities, as well as κ-opioid receptor agonist activity. This review provides a detailed analysis of the pharmacological potential of the twenty-three erinacines reported to date, along with their comprehensive nuclear magnetic resonance (NMR) characterization. This work underscores the promise of erinacines as valuable lead compounds for the development of therapeutic agents.</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":"493 - 512"},"PeriodicalIF":2.5,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388959","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":"Isoliquiritigenin combined with gemcitabine inhibited lung cancer by suppressing JAK2/STAT3 signaling via lncRNA-p21/miRNA-4534 axis","authors":"Chenyue Xu,&nbsp;Cancan Gong,&nbsp;Cheng Wang,&nbsp;Meiping Xie,&nbsp;Mianhua Wu,&nbsp;Dengfeng Ge,&nbsp;Hao Ren,&nbsp;Bin Zhang,&nbsp;Zequn Jiang,&nbsp;Wenting Li","doi":"10.1007/s11418-025-01990-8","DOIUrl":"10.1007/s11418-025-01990-8","url":null,"abstract":"<div><p>Isoliquiritigenin (2’-4’-4-trihydroxychalcone, ISL), a flavonoid from the herbal medicine <i>Glycyrrhiza uralensis Fisch</i>, has promising antitumor effects. While ISL has demonstrated anti-cancer potential, its comprehensive molecular mechanism of action in lung cancer remains inadequately explored, particularly in the context of combination therapy with gemcitabine (Gem). This study conducted in vivo and in vitro experiments to investigate the anti-lung cancer effect of ISL (50 mg/kg/d), in combination with Gem (50 mg/kg/3d) (ISL + Gem) and elucidate the molecular mechanism of ISL (25 µM) combined with Gem (1 µM) (ISL + Gem) in inducing apoptosis and inhibiting proliferation of lung cancer cells. The results revealed that ISL + Gem exerted its antitumor effects by promoting apoptosis and inhibiting the proliferation of lung cancer cells as well as their ability to invade and metastasize. It was discovered that long non-coding RNA (lncRNA) -p21 was differentially lowly expressed in human non-small cell lung cancer (NSCLC) tissues. In vitro studies confirmed that combined ISL and Gem treatment increased lncRNA-p21 expression in NSCLC cell lines. Inhibitory effects of proliferation, invasion and migration as well as induction of apoptosis by ISL + Gem can be enhanced by the overexpression of lncRNA-p21 and eliminated by knock-down of lncRNA-p21. Luciferase assays revealed that lncRNA-p21 acts as a competing endogenous RNA (ceRNA) for miR-4534, which was significantly upregulated in NSCLC tissues compared to normal controls. Treatment with ISL, Gem, or their combination effectively suppressed miR-4534 expression in H460 cells. Further studies revealed that ISL + Gem, overexpression of lncRNA-p21 or silencing of miR-4534 inhibited the expression of CXC chemokine ligand-12 (CXCL12), as well as janus kinase 2 and signal transducer activator of transcription 3 (JAK2/STAT3) pathway-related proteins. In contrast, knock-down of lncRNA-p21 or overexpression of miR-4534 reversed the above effects of ISL + Gem. In conclusion, this study showed that ISL combined with Gem could effectively impede the progression of lung cancer partially through inactivating JAK2/STAT3 signaling pathway via lncRNA-p21/miRNA-4534 axis.</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":"583 - 602"},"PeriodicalIF":2.5,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147281286","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}