Journal of Natural Medicines最新文献

{"title":"Ginsenoside Rg1 attenuates arsenic-induced nephrotoxicity in mice by suppressing inflammation, fibrosis, and EMT via multiple signalling pathways","authors":"Ye Li,&nbsp;Yurong Ren,&nbsp;Lingye Liu,&nbsp;Xiaoming Zhang,&nbsp;Xueyuan Zhi","doi":"10.1007/s11418-026-02051-4","DOIUrl":"10.1007/s11418-026-02051-4","url":null,"abstract":"<div><p>Arsenic-induced nephrotoxicity, characterized by inflammation and fibrosis, represents a critical yet inadequately addressed health concern. This study investigated the potential of ginsenoside Rg₁, a bioactive component from <i>Panax ginseng</i>, to counteract arsenic-triggered renal impairment and explored the involved molecular pathways. Male C57BL/6J mice were exposed to arsenic via drinking water for 12 weeks, with a subset receiving concomitant Rg₁ intervention. Assessments included renal function biomarkers, histopathological evaluation of inflammation and fibrosis, and analysis of epithelial-mesenchymal transition (EMT) markers. Our findings indicated that Rg₁ treatment significantly ameliorated arsenic-induced renal dysfunction and pathological injury. This protection was mechanistically linked to the suppression of inflammatory responses, inhibition of fibrotic deposition and EMT process, and concomitant modulation of key pro-fibrotic signaling cascades (TGF-β1/Smad2/3, PI3K/AKT, MAPK, and AHR). In conclusion, our results demonstrated that the substantial therapeutic potential of ginsenoside Rg₁ against arsenic-induced kidney injury, providing a novel pharmacological perspective for intervention.</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":"1253 - 1266"},"PeriodicalIF":2.6,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148057","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 ameliorates deficits in self-care behaviors in a polyinosinic-polycytidylic acid-induced fatigue model via dopamine D2 receptor activation","authors":"Chihiro Yamada,&nbsp;Sachiko Mogami,&nbsp;Yoshiaki Sato,&nbsp;Hayato Baba,&nbsp;Tsutomu Fujii","doi":"10.1007/s11418-026-02035-4","DOIUrl":"10.1007/s11418-026-02035-4","url":null,"abstract":"<div><p>Fatigue is induced by physical and mental overload and decreases activity, motivation, and judgment, interfering with daily life. An association between fatigue and prolonged activation of the immune system has been suggested. However, the detailed underlying mechanisms are unknown, and effective treatments for fatigue have not been established. Ninjin’yoeito, a Kampo medicine, reportedly improves anorexia and fatigue scores. In this study, we examined the anti-fatigue effects of Ninjin’yoeito extract powder (NYT) in a polyinosinic-polycytidylic acid (poly[I:C])-induced mouse model of inflammatory fatigue. C57BL/6 male mice were intraperitoneally injected with poly(I:C) (12 mg/kg) to assess locomotive activity and nesting and grooming behaviors. NYT was orally administered to mice. NYT showed no effect on the reduction of locomotive and wheel-running activities following poly(I:C) administration. The enhanced rectal temperature and peripheral and hypothalamic levels of inflammatory cytokines also remained unaffected by NYT. In contrast, NYT significantly restored the nesting and grooming behaviors impaired by poly(I:C) administration. The restorative effect of NYT was abolished by cotreatment with a dopamine D2 receptor (D2R) antagonist. Furthermore, the impaired grooming behavior following poly(I:C) administration was restored by the dopamine-metabolizing enzyme monoamine oxidase (MAO)-B inhibitor, but not by the MAO-A inhibitor. Ingredients of NYT, such as formononetin derived from the astragalus root, paeonol from the peony root, heptamethoxyflavone and nobiletin from citrus unshiu peel, demonstrated inhibitory activities against MAO-B. These findings suggest that NYT improves fatigue-like self-care deficits potentially by inhibiting dopamine metabolism, likely via MAO-B, leading to enhanced D2R 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 4","pages":"1026 - 1036"},"PeriodicalIF":2.6,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11418-026-02035-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148038","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":"Sappanone A exerted promising therapeutic effects in vitiligo through Wnt5a-mediated noncanonical Wnt signaling","authors":"Mingming Xu,&nbsp;Meilin Ding,&nbsp;Rui Li,&nbsp;Hejuan Zhang,&nbsp;Feifei Ren,&nbsp;Hongyang Li,&nbsp;Wei Zhang","doi":"10.1007/s11418-026-02050-5","DOIUrl":"10.1007/s11418-026-02050-5","url":null,"abstract":"<div><p>Vitiligo is a skin disease characterized by the loss of skin melanocytes, featuring the dual pathology of melanocyte damage due to oxidative stress and immune-mediated inflammation, which ultimately classifies it as an autoimmune condition. Sappanone A (SA), isolated from <i>Caesalpinia sappan </i>L., exhibits notable anti-oxidative stress and anti-inflammatory activity in various diseases. However, its potential effects and mechanisms in vitiligo remain uninvestigated. This study was designed to investigate the effects of SA on melanocytes and keratinocytes under oxidative stress and to evaluate its therapeutic potential in the monobenzone-induced vitiligo model. In vitro, SA protected PIG1 cells from H₂O₂-induced cytotoxicity and suppressed HMGB1 expression, nuclear export, and extracellular release. Furthermore, SA reduced HMGB1-induced overexpression of inflammatory cytokines in HaCaT cells, including <i>CXCL8</i>, <i>CXCL9</i>, <i>CXCL10</i>, <i>CXCL11</i>, and <i>TNF-α</i>. In vivo, SA administration alleviated monobenzone-induced depigmentation and CD8⁺ T-cell infiltration in C57BL/6 mice. Transcriptomic analysis, protein–protein interaction network construction, and molecular docking revealed that Wnt5a may be a potential target of SA, and SA significantly reversed monobenzone-induced <i>Wnt5a</i> expression and activation of noncanonical Wnt signaling. Overall, SA effectively attenuated the HMGB1-mediated inflammatory response in keratinocytes. Furthermore, it exerted repigmentation effects in monobenzone-induced vitiligo mice via inhibiting the Wnt5a-mediated noncanonical Wnt signaling pathway. These results suggest that SA is a promising therapeutic candidate for vitiligo.</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":"1152 - 1167"},"PeriodicalIF":2.6,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148011","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":"Differential analysis of lipid profiles in natural Calculus Bovis and Bovis Calculus Sativus by UHPLC-MS/MS","authors":"Qiang Mao,&nbsp;Huan Zhong,&nbsp;Wan-Li Liang,&nbsp;Jin Dai,&nbsp;Rui-Ting Huang,&nbsp;Yi-Di Wang,&nbsp;Di-Yang Sun,&nbsp;Kai Tang,&nbsp;Long-Fei Xia,&nbsp;Hai-Biao Gong,&nbsp;Yi-Fang Li,&nbsp;Wan-Yang Sun,&nbsp;Qiong-Yi Zhang,&nbsp;Li Zeng,&nbsp;Li-Li Yu,&nbsp;You-Hua Xu,&nbsp;Qi-Biao Wu,&nbsp;Yi-Zhun Zhu,&nbsp;Hong-Li Tan,&nbsp;Shu-Hua Ouyang,&nbsp;Rong-Rong He","doi":"10.1007/s11418-026-02043-4","DOIUrl":"10.1007/s11418-026-02043-4","url":null,"abstract":"<div><p>Natural <i>Calculus Bovis</i> (NCB) and <i>Bovis Calculus Sativus</i> (BCS) are both used clinically but exhibit different therapeutic effects, the material basis of which remains unclear. Lipid-soluble components are hypothesized to contribute to these differences, however the compositional variations at the lipid level have not been fully characterized. In this study, untargeted UHPLC-MS/MS lipidomics was employed to compare the lipid profiles of NCB and BCS. The results indicated that both samples contained fatty acyls, glycerolipids (GL), glycerophospholipids (GP), sphingolipids (SP), and sterol lipids (ST), indicating a conserved core lipid framework. However, NCB showed higher lipid complexity and abundance. NCB contained higher levels and greater molecular diversity of intact GP (phosphatidylcholines and phosphatidylethanolamines), SP (ceramides), fatty acid-derived lipids (polyunsaturated <i>N</i>-acylethanolamines, PU-NAE), and sterol esters. In comparison, BCS exhibited a simplified profile dominated by GL, with reduced GP, SP and ST species, enrichment of lysophospholipids and bile acid-related sterols, and lower overall lipid abundance. These differences may result from distinct formation processes: prolonged<i> in vivo</i> maturation for NCB versus time-limited <i>in vitro</i> culturing for BCS. This study expands the current understanding of the material basis of NCB and BCS, from a lipidomic perspective, offering molecular insights into its pharmacological properties and providing a scientific foundation for the material basis, quality control, standardization and rational clinical application of <i>Calculus Bovis</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":"80 4","pages":"1079 - 1092"},"PeriodicalIF":2.6,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148022","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":"Berberine is a key active component underlying the anti-allergic actions of orengedokuto in a murine model of contact hypersensitivity","authors":"Mitsuhiko Nose,&nbsp;Atsushi Tsuge,&nbsp;Meika Mizuno,&nbsp;Yuki Kodama,&nbsp;Atsuki Watanabe,&nbsp;Masato Kishi,&nbsp;Fumiaki Ohashi,&nbsp;Shinsuke Hisaka","doi":"10.1007/s11418-026-02047-0","DOIUrl":"10.1007/s11418-026-02047-0","url":null,"abstract":"<div><p>Orengedokuto (OGT) is used to treat atopic dermatitis. We previously reported that OGT exerts anti-allergic effects by inhibiting effector T cell activation in a murine model of contact hypersensitivity (CHS). However, the active crude drugs and ingredients responsible for these effects remain unknown. Here, we evaluated the effects of hot water extracts of four crude drugs (Scutellaria radix, Coptidis rhizome, Phellodendri cortex and Gardenia fructus) constituted in OGT. The results showed that Phellodendri cortex is an active crude drug of OGT. As berberine-baicalin and berberine-wogonoside complexes precipitate in OGT decoction, we prepared the supernatant and precipitate fractions of OGT and then compared their anti-allergic effects on a 2,4,6-trinitrichlorobenzene-induced CHS mouse model. Interestingly, the precipitated fraction of OGT exhibited anti-allergic effects. Liquid chromatography-tandem mass spectrometry analysis of the serum concentration of berberine after oral administration of OGT or its fractions suggested that berberine is an active ingredient in OGT. Adoptive transfer experiments and ex vivo and in vitro studies demonstrated that berberine exerts anti-allergic effects via inhibiting effector T cell activation in a murine CHS model. In conclusion, Phellodendri cortex in OGT appears to be an active crude drug with anti-allergic action in a murine 2,4,6-trinitrichlorobenzene-induced CHS model, and berberine may be the active ingredient. The detailed molecular mechanism by which berberine inhibits T cell receptor stimulation and interferon-γ production in effector T cells remains unclear.</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":"1142 - 1151"},"PeriodicalIF":2.6,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148040166","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":"Efficacy of the combined method of chloroplast atpF–atpA and genome-wide SNP analysis using MIG-seq for identifying hybrids between A. acutiloba and A. acutiloba var. sugiyamae","authors":"Motoyasu Minami,&nbsp;Takako Mori,&nbsp;Taichi Fujii,&nbsp;Tomoyasu Shirako,&nbsp;Toshiyuki Atsumi,&nbsp;Takashi Tsuchida,&nbsp;Toshiro Shibata,&nbsp;Shigeki Hayashi","doi":"10.1007/s11418-026-02048-z","DOIUrl":"10.1007/s11418-026-02048-z","url":null,"abstract":"<div><p>Angelicae acutilobae radix, which has traditionally been used to treat gynecological disorders, is listed in the Japanese Pharmacopoeia Eighteenth Edition as the root of <i>Angelica acutiloba</i> or <i>A. acutiloba</i> var<i>. sugiyamae</i>. There are constituent differences in the roots of these varieties, and the quality of the crude drug processed from the roots of <i>A. acutiloba</i> is considered to be superior to that processed from <i>A. acutiloba</i> var<i>. sugiyamae</i> based on traditional pharmacognostical evaluations. Although <i>A. acutiloba</i> and <i>A. acutiloba</i> var<i>. sugiyamae</i> have different botanical characteristics, interbreeding of these varieties easily produces hybrids. The presence of hybrids within cultivated <i>A. acutiloba</i> populations or the same lot can result in variability of this crude drug. In order to identify their hybrids, we developed a combined method for the analysis of DNA polymorphisms in the <i>atp</i>F–<i>atp</i>A intergenic region of chloroplast DNA using direct sequencing to identify the maternal lineage and genomic components using genome-wide SNP analysis by MIG-seq. Mixtures of hybrids found in cultivated <i>A. acutiloba</i> plants and processed Angelicae acutilobae radices in Japan and China could be identified by the combined method. This combined method is expected to be useful for accurately identifying hybrids in a wide variety of plant-derived medicines globally, both in cultivated fresh medicinal plant populations and in dried herbal materials.</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":"1243 - 1252"},"PeriodicalIF":2.6,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147969419","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":"A comprehensive review on the chemical composition, pharmacological effects and quality evaluation of Gentiana straminea Maxim.","authors":"Yuan-Wen Zhuang,&nbsp;Min Wang,&nbsp;Jian-Tao Zhao,&nbsp;Yu-Qing Wang,&nbsp;Run-Qian Yu,&nbsp;Huan Xia,&nbsp;Xiao-Hong Wei,&nbsp;Peng-Cheng Lin,&nbsp;Gui-Yang Xia,&nbsp;Sheng Lin","doi":"10.1007/s11418-026-02033-6","DOIUrl":"10.1007/s11418-026-02033-6","url":null,"abstract":"<div><p><i>Gentiana straminea</i> Maxim. (GSM), a cornerstone medicinal plant in Tibetan ethnopharmacology, has been utilized for over two millennia. This species exhibits a wide distribution across China, predominantly in the northwest. Its roots and flowers characterized by bitter, pungent taste and neutral properties are used medicinally. Traditional applications include treating rheumatoid arthritis, icteric hepatitis, leprosy, and “toxic heat” syndromes. Recent research has identified critical bioactive constituents: secoiridoids (gentiopicroside, swertiamarin, sweroside), loganic acid, flavonoids (vitexin, isovitexin), volatile compounds, and saccharides. GSM demonstrates significant pharmacological activities, including anti-inflammatory, analgesic, antioxidant, hepatoprotective, cardioprotective, anti-hypoxic, anti-bacterial, and insecticidal effects. By systematically reviewing domestic and international literature from the past two decades, this study summarizes the morphological characteristics, resource distribution, breeding practices, cultivation methods, chemical composition, and pharmacological actions of GSM. The aim is to provide a scientific basis for its cultivation, identification, rational clinical application, and to promote its development and utilization.</p><h3>Graphic Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div><p>Botany, pharmacological effects, and chemical composition of <i>Gentiana straminea</i> Maxim.</p></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"80 4","pages":"899 - 920"},"PeriodicalIF":2.6,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147969436","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 interplay of Ashwagandha with hormonal dynamics and gut microbiota in women with breast cancer: a tri-axial perspective","authors":"Rawan R. Kawaf,&nbsp;Ayah M. Alkherat,&nbsp;Yasmin Shareef,&nbsp;Loulia Khalid Jandali,&nbsp;Rand Salamalek,&nbsp;Sarra B. Shakartalla,&nbsp;Sama S. Soliman,&nbsp;Nashwa Ahmed Mohamed,&nbsp;Sameh S. M. Soliman","doi":"10.1007/s11418-026-02026-5","DOIUrl":"10.1007/s11418-026-02026-5","url":null,"abstract":"<div><p>Ashwagandha (<i>Withania somnifera</i>), a traditional Ayurvedic adaptogen, is increasingly investigated in hormone-sensitive malignancies such as breast cancer. Its bioactive constituents, particularly withaferin A, exhibit diverse effects relevant to hormonal regulation, tumor suppression, and systemic balance. This review explores Ashwagandha’s tri-axial roles in hormonal modulation, gut microbiota interaction, and direct anticancer activity across breast cancer subtypes. Preclinical findings show that withaferin A suppresses estrogen receptor alpha (ERα), inhibits STAT3 and NF-κB signaling, induces ROS-mediated apoptosis, and alters epigenetic regulators. In HER2-positive and triple-negative models, it reduces cancer stem cell activity, epithelial-to-mesenchymal transition (EMT), and pro-inflammatory mediators. Ashwagandha also influences the hypothalamic–pituitary–gonadal axis, raising LH, FSH, estrogen, and progesterone, while lowering cortisol and normalizing thyroid function. Immunologically, it enhances CD8⁺ T cell activity, reduces myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), and may synergize with checkpoint inhibitors. Effects on gut microbiota suggest additional roles in estrogen metabolism and inflammatory regulation. Toxicity data indicate high tolerability (LD₅₀ &gt; 2000 mg/kg), though rare hepatic and thyroid adverse events occur. Regulatory oversight remains inconsistent, with limited phytochemical standardization. Ashwagandha shows multidimensional promise but requires rigorous, standardized clinical validation.</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":"1278 - 1300"},"PeriodicalIF":2.6,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147925532","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 pentandralactams from Vietnamese Ceiba pentandra (L.) Gaertn. and their anti-inflammatory activity via NO production inhibition","authors":"Chuong Nguyen Ngoc,&nbsp;Manh Hung Tran,&nbsp;Thuy Mi Pham Lam,&nbsp;Hieu Thi Hong Nguyen,&nbsp;Minh-Anh Nguyen Ngo Le,&nbsp;Trong Tuan Vo","doi":"10.1007/s11418-026-02031-8","DOIUrl":"10.1007/s11418-026-02031-8","url":null,"abstract":"<div><p>A phytochemical study on the 70% ethanol extract of the stem bark of Vietnamese <i>Ceiba pentandra</i> (L.) Gaertn led to the isolation of the three new sesquiterpene alkaloids pentandralactams A (<b>1</b>), B (<b>2</b>), and C (<b>3</b>), along with the six known compounds thespesilactam (<b>4</b>), isohemigossylic acid lactone-2-methyl ether (<b>5</b>), alanense H (<b>6</b>), hibiscolactone A (<b>7</b>), 11-hydroxy-2-O-methylhibiscolactone A (<b>8</b>), and vavain 3′-O-<i>β</i>-D-glucoside (<b>9</b>). Their structures were elucidated through extensive spectroscopic analyses, including HR-ESI-MS, and 1D and 2D NMR. All isolates were tested for their ability to inhibit NO production in LPS-induced RAW 264.7 cells. The sesquiterpene alkaloids pentandralactams A–C (<b>1 − 3</b>) exhibited potent NO inhibition with IC₅₀ values of 8.03, 9.79, and 11.28 µM, respectively. In silico, compound <b>1</b> demonstrated the strongest binding affinity with iNOS enzyme with extensive π-π stacking, hydrophobic interactions, and a key hydrogen bond, without any unfavorable contacts. Compound <b>2</b> formed multiple hydrogen bonds in addition to π-π interactions, contributing to stable binding, though its broader interaction distribution may slightly affect its specificity. Compound <b>3</b> also engaged in essential π-π and hydrophobic contacts but exhibited an unfavorable acceptor-acceptor interaction with ASN370, potentially reducing its efficacy. These results highlight the potential of <i>C. pentandra</i>-derived compounds for further development as anti-inflammatory agents.</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":"1222 - 1231"},"PeriodicalIF":2.6,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147925545","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":"Asarinin attenuates ferroptosis resistance by inhibiting the activity of S-adenosyl homocysteine hydrolase in lung cancer","authors":"Zibo Li,&nbsp;Yuanyuan Wang,&nbsp;Ziyang Huang,&nbsp;Zhiyi Wang,&nbsp;Zhenzhen Guo,&nbsp;Erping Xu,&nbsp;Yaqiu Zheng","doi":"10.1007/s11418-026-02029-2","DOIUrl":"10.1007/s11418-026-02029-2","url":null,"abstract":"<div><p>As a critical rate-limiting enzyme in the methionine cycle, S-adenosylhomocysteine hydrolase (AHCY) participates in intracellular cysteine synthesis. Its overexpression has been shown to induce ferroptosis resistance in lung cancer. However, naturally derived inhibitors of AHCY remain understudied. Here, we demonstrated that AHCY overexpression attenuates the ferroptosis-promoting effect of erastin by generating homocysteine (Hcy) and glutathione (GSH) in A549 cells. Virtual screening of Traditional Chinese Medicine Active Compound Library and subsequent experimental validation identified asarinin (Ar) as a bioactive natural product that enhances the efficacy of erastin by targeting AHCY. Ar potentiates erastin-induced lipid peroxidation and ROS production by suppressing Hcy and GSH synthesis. Consistently, the ferroptosis-sensitizing effect of Ar is abolished upon supplementation with Hcy and GSH. Biochemical assays revealed that Ar exhibits high binding affinity for AHCY, inhibits AHCY activity with an IC₅₀ of 22.1 µM, and increases AHCY protein stability. Molecular dynamics simulations indicated that Ar interacts with the H353 residue of AHCY. In lung cancer xenograft model, Ar alone showed minimal antitumor effects but significantly enhanced the anti-tumor activity of erastin, demonstrating promising combination therapy potential. Our findings identify Ar as a naturally derived AHCY inhibitor with potential pharmacological effects in sensitizing ferroptosis.</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":"1012 - 1025"},"PeriodicalIF":2.6,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147925560","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}