Phytomedicine最新文献

{"title":"Cannabidiolic acid (CBDA) and CBDA-rich extracts modulatory effects on voltage-dependent NaV1.2 sodium channels.","authors":"Agustín Manzur De Nardi, Pedro Martin, Daniela Sedan, Cristina Daniela Bugvila, Lucas Pinto Alman, Dario Andrinolo, Verónica Milesi, Nicolás Enrique","doi":"10.1016/j.phymed.2026.158491","DOIUrl":"10.1016/j.phymed.2026.158491","url":null,"abstract":"<p><strong>Background and purpose: </strong>Cannabidiolic acid (CBDA), the acidic precursor of cannabidiol (CBD), is increasingly recognized for its therapeutic potential, particularly within full-spectrum Cannabis sativa extracts. However, the molecular mechanisms underlying its biological activity remain poorly characterized.</p><p><strong>Methods: </strong>In this study we investigated the electrophysiological effects of purified CBDA and a CBDA-rich ethanolic extract on human voltage-gated sodium channels (NaV1.2), a clinically relevant molecular target in epilepsy.</p><p><strong>Results: </strong>CBDA significantly reduced NaV1.2 currents with a low-micromolar IC₅₀ of 1.4 ± 0.3 µM, without altering activation voltage-dependence. CBDA also stabilized the channel's inactivated state, evidenced by a hyperpolarizing shift in steady-state inactivation, slowing recovery from inactivation, and inducing a pronounced use-dependent blockade. Notably, the CBDA-rich extract reproduced these effects but elicited markedly stronger inhibition than purified CBDA. To identify contributors to this enhanced activity, we evaluated two main components of the extract: the essential oil fraction and neutral CBD. Neither fraction altered channel activation, and only the low CBD concentration present in the extract induced a significant shift in inactivation.</p><p><strong>Conclusion: </strong>These findings establish NaV1.2 as a molecular target for CBDA-mediated pharmacology, provide a biophysical rationale for the enhanced anticonvulsant activity reported for CBDA-enriched cannabis preparations relative to isolated constituents, and support the further preclinical evaluation of defined cannabis chemotypes as multi-component pharmacological agents for neuronal sodium channelopathies.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"159 ","pages":"158491"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polygonatum sibiricum polysaccharide ameliorates intestinal barrier dysfunction in aging mice via gut microbiota-metabolite modulation and TLR4/NF-κB pathway inhibition.","authors":"Peiyao Guan, Xin Zeng, Ziye Li, Qian Wang, Han Ding, Tingting Wang, Jiayun Wang, Yansong Fu, Lizhang Chen, Hong Qin","doi":"10.1016/j.phymed.2026.158551","DOIUrl":"10.1016/j.phymed.2026.158551","url":null,"abstract":"<p><strong>Background: </strong>Intestinal barrier dysfunction is a critical pathological feature of aging-related diseases. Polygonatum sibiricum polysaccharide (PSP), a natural bioactive compound, has been reported to possess microbiota-regulatory and immunomodulatory properties; however, its protective effects against aging-induced intestinal barrier injury and the underlying mechanisms remain unclear.</p><p><strong>Purpose: </strong>This study aimed to investigate the protective effects of PSP on age-related intestinal barrier dysfunction and to elucidate the underlying mechanisms, with a particular focus on the microbiota-metabolism-immunity axis.</p><p><strong>Study design: </strong>A combination of in vivo and in vitro experiments, together with multi-omics analyses and network pharmacology, was employed to systematically evaluate the effects and mechanisms of PSP in aging-associated intestinal barrier injury.</p><p><strong>Methods: </strong>Ultraviolet (UV) spectroscopy, gel permeation chromatography (GPC), high-performance liquid chromatography-mass spectrometry (HPLC-MS), and Fourier-transform infrared spectroscopy (FT-IR) were adopted to comprehensively characterize the purity and detailed structural profiles of PSP. Naturally aged mice were orally administered PSP (400 mg/kg) to assess intestinal barrier integrity, permeability, inflammatory responses, and gut microbiota composition. In vitro, D-galactose (D-gal)-induced senescent Caco-2 cells were treated with PSP (100, 200, and 400 μg/ml) to evaluate cellular senescence, tight junction protein expression, and pro-inflammatory cytokine production. Network pharmacology analysis was conducted to predict key signaling pathways involved, followed by experimental validation and reverse confirmation using a TLR4 agonist.</p><p><strong>Results: </strong>Characterization by UV spectroscopy and GPC confirmed the purity and molecular weight distribution of PSP, respectively; monosaccharide analysis revealed it was mainly composed of glucose, mannose, and galactose, and FT-IR identified its characteristic functional groups. In naturally aged mice, PSP administration significantly improved intestinal barrier integrity, reduced intestinal permeability, alleviated inflammatory responses, and reshaped gut microbiota composition. In Caco-2 cells, PSP dose-dependently attenuated D-gal-induced cellular senescence, restored tight junction protein expression, and suppressed pro-inflammatory cytokine production. Network pharmacology analysis identified the TLR4/NF-κB signaling pathway as a potential key target of PSP, which was further confirmed by both in vivo and in vitro experiments.</p><p><strong>Conclusions: </strong>Collectively, these findings demonstrate that PSP alleviates aging-associated intestinal barrier dysfunction through multi-level regulation involving the microbiota-metabolism-immunity axis and supports its potential as a natural therapeutic candidate for anti-aging interventions.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"159 ","pages":"158551"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratrol exerts stage- and sex-specific anti-aging and multigenerational effects via epigenetic and metabolic pathways in Drosophila.","authors":"Quanyong Wu, Boya Ouyang, Wanning Ma, Yuxuan Zhao, Jingyimei Liang, Yi Yuan, Hui Cao, Jesus Simal-Gandara, Shaoping Nie, Jianbo Xiao","doi":"10.1016/j.phymed.2026.158531","DOIUrl":"10.1016/j.phymed.2026.158531","url":null,"abstract":"<p><strong>Background: </strong>Resveratrol is a polyphenolic compound with reported anti-aging properties that exhibit complex and context-dependent biological effects, while its potential multigenerational influence remains unclear.</p><p><strong>Objectives: </strong>To investigate the stage-specific effects of resveratrol on development and lifespan in Drosophila melanogaster and to determine whether resveratrol-associated longevity benefits can extend across generations through metabolic and epigenetic regulation.</p><p><strong>Methods: </strong>Drosophila melanogaster were exposed to 50 μg/ml resveratrol (ER50) either during embryonic development or during adulthood. Developmental timing, lifespan, hormonal and nutrient-sensing signaling pathways, stress-response and autophagy pathways, mTOR signaling, metabolomic profiles, histone modifications, histone-modifying enzyme expression, and multigenerational lifespan effects were evaluated.</p><p><strong>Results: </strong>Embryonic exposure to ER50 accelerated pupation and adult emergence but shortened adult lifespan. These effects were accompanied by activation of the juvenile hormone-insulin/IGF signaling axis and impaired antioxidant capacity. In contrast, adult ER50 supplementation extended lifespan in female flies and was associated with enhanced stress-response and autophagy pathways together with suppression of mTOR signaling. Mechanistically, longevity-promoting effects in adults coincided with increased glycolysis and pentose phosphate pathway activity, citrate accumulation, and remodeling of one-carbon metabolism, indicating broad reprogramming of energy and redox metabolism. These metabolic changes were accompanied by increased H3K9 acetylation (H3K9ac), upregulation of the histone acetyltransferase-related factor nej, and downregulation of Ash1, suggesting that resveratrol promotes lifespan extension through coordinated regulation of metabolic state and chromatin remodeling. Notably, maternal adult exposure to ER50 was associated with lifespan extension in female offspring across two subsequent generations, together with persistent metabolic alterations and chromatin changes.</p><p><strong>Conclusions: </strong>Resveratrol exhibits stage- and sex-dependent effects in Drosophila and functions as a metabolic-epigenetic modulator. Adult supplementation is associated with extended female lifespan and multigenerational longevity effects, potentially mediated through coordinated regulation of energy metabolism and chromatin homeostasis.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"159 ","pages":"158531"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of anti-fibrotic components of Bofutsushosan under conditions of age-associated obesity in mice.","authors":"Ayano Onishi, Toshiharu Onodera, Shu Sugaya, Tetsuya Matsushita, Masahiko Komorisono, Jihoon Shin, Shigeki Nishitani, Atsunori Fukuhara, Iichiro Shimomura","doi":"10.1016/j.phymed.2026.158522","DOIUrl":"10.1016/j.phymed.2026.158522","url":null,"abstract":"<p><strong>Background: </strong>Bofutsushosan (BTS) is a traditional herbal medicine used to reduce body weight, edema, and constipation. Aged individuals often present pro-fibrotic comorbidities such as metabolic dysfunction-associated steatohepatitis (MASH), chronic kidney disease, and heart failure with preserved ejection fraction. Although the weight-reducing effect of BTS is well recognized, its effects under aged conditions remain uncharacterized.</p><p><strong>Purpose: </strong>To characterize the anti-fibrotic effects of BTS under age-associated obesity and identify the components responsible.</p><p><strong>Study design: </strong>An aged diet-induced obese mouse model combined with an in vitro TGFβ-induced fibrosis model in 3T3-L1 preadipocytes, followed by component-resolved screening and reformulation of BTS.</p><p><strong>Methods: </strong>63-week-old mice were fed a high-fat diet containing 2% BTS for 2 months, and tissues were analyzed by histology and qPCR. In 3T3-L1 preadipocytes, pro-fibrotic gene expression and SMAD2/3 phosphorylation were assessed following treatment with whole BTS, single-component-depleted BTS, or individual components.</p><p><strong>Results: </strong>BTS reduced body weight by 14.8% with decreased food intake, reduced adipose tissue size, and ameliorated hepatic steatosis. Pro-fibrotic genes were reduced in adipose tissue and liver, including 60.6% and 46.2% reductions of Col1a1. BTS suppressed TGFβ-mediated pro-fibrotic gene expression and SMAD2/3 phosphorylation in 3T3-L1 preadipocytes. Among the 18 components, Sal Mirabilis was the primary pro-fibrotic constituent, whereas Forsythiae Fructus, Zingiberis Rhizoma, Rhei Rhizoma, and Scutellariae Radix were anti-fibrotic. A modified formula lacking Sal Mirabilis and supplemented with these four ingredients exerted a stronger anti-fibrotic effect.</p><p><strong>Conclusion: </strong>BTS exerts anti-fibrotic effects under age-associated obesity, and its therapeutic potential can be enhanced by removing pro-fibrotic and increasing anti-fibrotic components.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"159 ","pages":"158522"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148423253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Target pathway validation for Compound Kushen Injection active against cancer cells.","authors":"Hanyuan Shen, Saeed Nourmohammadi, Yan Zhou, Yuka Harata-Lee, Zhipeng Qu, Wei Wang, Andrea J Yool, David L Adelson","doi":"10.1016/j.phymed.2026.158598","DOIUrl":"10.1016/j.phymed.2026.158598","url":null,"abstract":"<p><strong>Background: </strong>Traditional Chinese medicines are based on complex mixtures of natural products and their multi-target mechanism of action. Therefore the discovery and validation of targets and mechanisms have always been challenging. In previous studies, using transcriptomic methods and Compound Kushen Injection (CKI) as a model drug, we identified multiple pathways and candidate target genes for validation, through which CKI exerts its pharmacological effects.</p><p><strong>Purpose: </strong>This study aimed to demonstrate the involvement of multiple genetic targets in different pharmacological activities for natural products in Compound Kushen Injection.</p><p><strong>Methods: </strong>In this study, we selected eight key genes from four candidate pathways and used CRISPR/CAS technology to knock out these genes in four cell lines, validating their role in CKI activity.</p><p><strong>Results: </strong>Although the sensitivity of different cell lines to gene knockout varied, overall, it led to reductions in various cellular activities. After the addition of CKI, we observed that, except for the minor impact of CDKN1A gene knockout on the effect of CKI, knocking out the other genes significantly affected the pharmacological efficacy of CKI in different assays. Among them, knockout of MYD88 and NFkB genes enhanced the efficacy of CKI. At the same time, we found that the genes IL24 and CYP1B1 play a crucial role in CKI inhibition of tumour cell migration, and the CYP1A1 gene is critical for the cell cycle arrest induced by CKI.</p><p><strong>Conclusions: </strong>These findings validate the results of our previous transcriptomic analysis and further demonstrate the complexity of pharmacological mechanisms of multi-target synergistic action of natural product mixtures.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"159 ","pages":"158598"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dihydrobaicalein suppresses osteoclast differentiation and mitochondrial transfer to prevent postmenopausal osteoporosis.","authors":"Wei Deng, Junxi Pan, Kai Tang, Tianzhao Tian, Yingfeng Cai, Liye Chen, Peijie Luo, Zhongquan Fu, Zhida Zhang","doi":"10.1016/j.phymed.2026.158564","DOIUrl":"10.1016/j.phymed.2026.158564","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Postmenopausal osteoporosis (PMOP) is a prevalent metabolic bone disorder driven primarily by excessive osteoclast (OC) activation and enhanced bone resorption. The current therapeutic agents for PMOP remain limited by adverse effects associated with long-term use, underscoring the need for novel pharmacological alternatives with favorable safety profiles. Dihydrobaicalein (DIH), a polyhydroxylated flavanone compound, has demonstrated promising anti-inflammatory, antioxidant, and immunomodulatory activities,yet its therapeutic potential and mechanisms of action in PMOP treatment remain largely unexplored.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;This study aimed to evaluate the therapeutic efficacy of DIH against PMOP and elucidate the underlying mechanisms from multiple perspectives, including multitarget signaling pathway regulation, modulation of energy metabolism, and inhibition of tunneling nanotube (TNT)-mediated intercellular mitochondrial transfer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design: &lt;/strong&gt;An integrative approach combining in vivo pharmacological evaluation in an ovariectomized (OVX) mouse model with comprehensive in vitro mechanistic studies using receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis was employed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;For in vivo experiments, OVX mice were randomized into sham, OVX vehicle, estradiol (E₂) positive control, and low- and high-dose DIH (5 and 10 mg/kg) groups, and were treated by intragastric administration for 8 weeks. Bone microarchitecture, histomorphology, mechanical properties, bone metabolic markers, and systemic safety were evaluated. For in vitro experiments, bone marrow-derived macrophages were stimulated with RANKL to induce osteoclast differentiation. The effects of DIH on osteoclast differentiation, bone-resorptive function, and osteogenic differentiation were assessed using cytochemical staining, functional assays, RT-qPCR, Western blotting, and RNA sequencing. Direct molecular targets of DIH were identified through surface plasmon resonance, cellular thermal shift assay, biolayer interferometry, and molecular docking/dynamics simulations. Osteoclast energy metabolism and mitochondrial function were evaluated using a Seahorse extracellular flux analyzer, metabolite quantification, and mitochondrial membrane potential detection. Finally, a coculture system of Mito-DsRed-labeled BMSCs and Mito-EGFP-labeled RAW264.7 cells, together with a Transwell model, was established to investigate the effect of DIH on TNT-mediated intercellular mitochondrial transfer and apoptosis-related signaling.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In vivo, DIH dose-dependently improved bone microarchitecture, restored mechanical properties, and normalized bone metabolic markers in OVX mice, with high-dose DIH (10 mg/kg) achieving efficacy comparable to that of E₂ and showing no evident systemic toxicity. Histological and Western blot analyses confirmed reduced oste","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"159 ","pages":"158564"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"The protective effect of blueberry anthocyanins on the intestinal barrier in pup and adult mice via the TLR4 signaling pathway\" [Phytomedicine 155 (2026) 158076].","authors":"Yakun Xing, Xingyu Zhao, Jiawei Zheng, Xinyu Li, Wuyang Huang","doi":"10.1016/j.phymed.2026.158458","DOIUrl":"10.1016/j.phymed.2026.158458","url":null,"abstract":"","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":" ","pages":"158458"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Xanthoxylin alleviates dextran sulfate sodium (DSS)-induced colitis by targeting macrophage infiltration via the tumor necrosis factor (TNF)/nuclear factor-kappa B (NF-κB) signaling pathway\" [Phytomedicine 153:157971 (2026) PMID: 41720014].","authors":"Yuxin Chen, Ziyan Chen, Jiacheng Li, Rui Zhao, Qiwen Chen, Chuyue Zhong, Mengmeng Lu, Yuzhe Shi, Lushuang Wang, Lishimeng Bao, Zhigui Zuo, Xinli Mao, Fang Wu","doi":"10.1016/j.phymed.2026.158555","DOIUrl":"10.1016/j.phymed.2026.158555","url":null,"abstract":"","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":" ","pages":"158555"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cinnamon polysaccharides reshape gut microbiota and enrich Alloprevotella rava to promote acetate-dependent choline metabolism and delay mammary aging.","authors":"Meng Zhang, Yu Cao, Kefei Li, Dewei He, Xuanting Liu, Xian Dong, Junlong Bi, Wenjin Guo, Shoupeng Fu","doi":"10.1016/j.phymed.2026.158597","DOIUrl":"10.1016/j.phymed.2026.158597","url":null,"abstract":"<p><strong>Background: </strong>Aging disrupts choline metabolism, impairs mitochondrial function, and accelerates tissue degeneration. As gut microbes critically influence host nutrient handling, microbiota-targeted interventions may provide a promising strategy to delay mammary senescence.</p><p><strong>Purpose: </strong>This study aimed to determine whether cinnamon polysaccharides (CP) and the commensal bacterium, Alloprevotella rava, could remodel host gut microbiota, enhance host choline utilisation, improve mitochondrial function, and thereby delay mammary senescence.</p><p><strong>Study design: </strong>An experimental study was conducted using mouse models, maternal intervention experiments, microbiota and metabolite analyses, and complementary cellular assays to evaluate the effects of CP and A. rava on choline metabolism, mitochondrial function, mammary senescence, and offspring development.</p><p><strong>Methods: </strong>Mice were treated with CP to assess its effects on mammary senescence and gut microbiota composition. The enrichment and supplementation of A. rava were further examined for their capacity to regulate serum and mammary choline levels, as well as the expression of host choline transporters, phosphatidylcholine biosynthetic enzymes, and microbial choline-trimethylamine (TMA) lyases (cutA and cutC). Cell-based experiments were performed to evaluate the direct effects of A. rava culture supernatant on epithelial choline uptake and biosynthesis. Metabolite analyses were used to identify the major microbial effector involved, and maternal intervention studies were conducted to assess systemic and offspring-related outcomes.</p><p><strong>Results: </strong>CP alleviated mammary senescence in mice by reshaping the gut microbiota and enriching A. rava. Supplementation with A. rava increased choline levels in serum and mammary tissue, upregulated the expression of host choline transporters and phosphatidylcholine biosynthetic enzymes, and reduced microbial choline-TMA lyase expression, thereby improving host choline utilisation. The A. rava culture supernatant directly stimulated epithelial choline uptake and biosynthesis, and metabolite analyses identified acetate, rather than succinate, as the principal effector. These alterations reinforced choline-dependent phospholipid synthesis, improved mitochondrial function, and protected against cellular aging. In addition, cellular assays and maternal intervention experiments showed that A. rava enhanced epithelial metabolic resilience and supported offspring brain development.</p><p><strong>Conclusion: </strong>Supplementation with A. rava establishes a gut-mammary axis that promotes choline metabolism, strengthens mitochondrial function, and delays mammary senescence. Targeting specific gut microbes or their acetate-driven metabolites may represent a feasible strategy to improve maternal tissue health and support progeny neurodevelopment.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"159 ","pages":"158597"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rhubarb extract attenuates periodontitis by modulating an MMP3-associated inflammatory-ferroptotic axis: Integrated multi-omics analysis and experimental validation.","authors":"Yifei Hou, Chongzheng Yan, Hongxu Zhao, Zihan Yang, Yijing Li, Xiamei Lu, Aohua Yang, Xinrui Xu, Xinhui Wu, Xuan Song, Jianing Zhang, Yi Liu","doi":"10.1016/j.phymed.2026.158632","DOIUrl":"10.1016/j.phymed.2026.158632","url":null,"abstract":"<p><strong>Background: </strong>Periodontitis is a chronic inflammatory disease characterized by dysregulated host immunity, oxidative injury, connective tissue breakdown, and alveolar bone loss. Rhubarb (Rhei Radix et Rhizoma) has anti-inflammatory and redox-modulating properties, but its therapeutic mechanism in periodontitis remains unclear.</p><p><strong>Purpose: </strong>This study investigated whether rhubarb extract alleviates periodontal inflammatory injury and explored the role of matrix metalloproteinase 3 (MMP3) in periodontitis and ferroptosis.</p><p><strong>Methods: </strong>The rhubarb extract was profiled by UPLC-Q-TOF-MS. Network pharmacology, transcriptomics, and untargeted metabolomics were integrated to identify targets and pathways. LPS-stimulated human gingival fibroblasts (HGFs), MMP3 knockdown and overexpression, molecular docking, molecular dynamics simulation, surface plasmon resonance (SPR), and a rat periodontitis model were used for mechanistic validation.</p><p><strong>Results: </strong>The rhubarb extract contained anthraquinone derivatives. Integrated multiomics identified MMP3 as a rhubarb-responsive hub linked to inflammatory activation and ferroptosis-related metabolic disruption. Rhubarb extract inhibited LPS-induced NF-κB activation and cytokine production, restored the SLC7A11/GPX4 antioxidant defense axis, and suppressed ACSL4/LPCAT3-associated lipid remodeling. These effects were accompanied by reduced ROS generation, Fe²⁺ accumulation, lipid peroxidation, and mitochondrial damage. MMP3 silencing partially mimicked the anti-ferroptotic effects of rhubarb extract, whereas MMP3 overexpression weakened its cytoprotective activity. Molecular docking, molecular dynamics simulation, and SPR analyses supported direct interactions between representative rhubarb constituents and MMP3. In vivo, rhubarb extract reduced periodontal inflammation, collagen degradation, iron deposition, osteoclast formation, and alveolar bone loss.</p><p><strong>Conclusion: </strong>Rhubarb extract attenuates experimental periodontitis by suppressing inflammation, ferroptosis-related lipid peroxidation, and osteoclast-mediated bone resorption, partly through the modulation of an MMP3-associated inflammatory-ferroptotic axis.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"159 ","pages":"158632"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}