PhytomedicinePub Date : 2026-09-01Epub Date: 2026-07-21DOI: 10.1016/j.phymed.2026.158624
Su Bu, Xinrui Zhou, Deyi Li, Fei Lu, Xingxing Huo, Chao Tian, Chijing Zuo, Hang Song
{"title":"Polysaccharides-mediated mitochondrial remodeling: role in chemotherapy resistance of gastrointestinal tumors.","authors":"Su Bu, Xinrui Zhou, Deyi Li, Fei Lu, Xingxing Huo, Chao Tian, Chijing Zuo, Hang Song","doi":"10.1016/j.phymed.2026.158624","DOIUrl":"10.1016/j.phymed.2026.158624","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy resistance remains a major clinical challenge in the treatment of gastrointestinal (GI) cancers. Mitochondrial remodeling contributes to chemoresistance through several interconnected functional modules, including metabolic reprogramming, elevation of the apoptotic threshold, adjustment of the reactive oxygen species setpoint, and mitophagy-mediated mitochondrial quality control. Polysaccharides and polysaccharide-based systems may represent promising candidates for modulating mitochondria-associated dysfunctions because of their structural diversity, biological activity, and generally favorable biocompatibility in specific experimental settings.</p><p><strong>Purpose: </strong>This review aimed to systematically summarize the molecular mechanisms by which mitochondrial remodeling contributes to chemotherapy resistance in GI tumors and to evaluate the potential of polysaccharides and polysaccharide-based systems as therapeutic candidates for modulating these mitochondrial abnormalities.</p><p><strong>Methods: </strong>This PRISMA-guided systematic review with qualitative evidence synthesis searched PubMed and Web of Science from database inception to July 4, 2026. The search strategy covered terms related to polysaccharides and polysaccharide-based delivery systems, GI tumors, chemoresistance or chemosensitization, and mitochondria-related mechanisms. Records were deduplicated and screened according to predefined eligibility criteria. Core eligible studies were original experimental studies that investigated polysaccharide or polysaccharide-based interventions in GI tumor models, reported chemotherapy-related outcomes, and included endpoints related to mitochondria, redox regulation, apoptosis, autophagy, metabolism, or the tumor microenvironment. Because of substantial heterogeneity in polysaccharide sources, tumor models, chemotherapeutic agents, intervention formats, and mechanistic endpoints, the evidence was synthesized qualitatively rather than by meta-analysis.</p><p><strong>Results: </strong>The search identified 652 records, including 322 from PubMed and 330 from Web of Science. After removal of 174 duplicate records, 478 records were screened. Full texts were sought for 75 reports, of which 20 could not be retrieved. Ultimately, 55 reports were assessed for eligibility; one retracted article and 34 reports that did not meet the core eligibility criteria were excluded. In total, 20 studies were included in the core evidence synthesis. These studies supported the involvement of polysaccharides or polysaccharide-based systems in modulating chemotherapy responses in GI tumors through several mitochondria-related mechanisms, including metabolic remodeling, regulation of the apoptotic threshold, modulation of redox status, and autophagy/mitophagy-associated adaptation. Additional mechanistic and contextual evidence suggested that polysaccharide-based delivery platforms and gut microenvironment modu","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"159 ","pages":"158624"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592982","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}
PhytomedicinePub Date : 2026-09-01Epub Date: 2026-07-09DOI: 10.1016/j.phymed.2026.158570
Mengyao Shi, Lu Zhang, Siyu Tang, Yi Wang, Huanzhang Ding, Di Wu, Xiao Ma, Chuanbo Wang, Mengxiang Liu, Lin Lu, Chen Yang, Jiabing Tong, Zegeng Li, Jie Zhu
{"title":"Qibai Pingfei Capsule ameliorates NK‑cell dysfunction in COPD: Insights from single‑cell sequencing in a randomized multicenter double‑blinded placebo‑controlled trial.","authors":"Mengyao Shi, Lu Zhang, Siyu Tang, Yi Wang, Huanzhang Ding, Di Wu, Xiao Ma, Chuanbo Wang, Mengxiang Liu, Lin Lu, Chen Yang, Jiabing Tong, Zegeng Li, Jie Zhu","doi":"10.1016/j.phymed.2026.158570","DOIUrl":"10.1016/j.phymed.2026.158570","url":null,"abstract":"<p><strong>Background: </strong>Chronic inflammation in chronic obstructive pulmonary disease (COPD) arises from prolonged interactions among immune cells, functional cells, and inflammatory cytokines. The Qibai Pingfei Capsule (QBPF), a traditional Chinese medicine (TCM), has been utilized clinically for over two decades to treat COPD. However, robust evidence is required to validate its clinical effectiveness. Single-cell RNA sequencing (scRNA-seq) technology offers comprehensive insights into the immune-inflammatory microenvironment of COPD at the single-cell level, providing valuable strategies for integrating TCM into COPD management.</p><p><strong>Purpose: </strong>To clarify the mechanism of QBPF in treating COPD through scRNA-seq.</p><p><strong>Methods: </strong>A randomized, double-blind, placebo-controlled, multicenter study performed to investigate the QBPF efficacy in COPD patients. PBMCs from these patients were subjected to scRNA-seq, and lung tissue scRNA-seq data were obtained from the public database (GEO: GSE162610). The regulatory mechanism of QBPF was confirmed using a COPD rat model.</p><p><strong>Results: </strong>Acute exacerbation frequency was significantly decreased (p = 0.042), and CAT scores improved (p = 0.008) following QBPF treatment. Nevertheless, no significant changes were recorded in lung function, the 6-minute walk test (6MWT), or the mMRC scale. Within the QBPF group, the 6MWT (p < 0.01) and FEV₁/FVC% (p < 0.01) significantly improved from baseline to 3 months. ScRNA-seq confirmed immune dysfunction, especially the depleted NK cells and impaired activation. QBPF altered the expression of functional markers in NK cells of COPD patients, and animal studies confirmed that QBPF enhanced NK cell activity by modulating the expression of hepatitis A virus cellular receptor 2 (HAVCR2) and killer cell lectin-like receptor C2 (KLRC2). Additionally, scRNA-seq analysis revealed impaired immune function in COPD patients, specifically NK cell exhaustion and dysfunction.</p><p><strong>Conclusion: </strong>These findings demonstrated that QBPF can ameliorate and alleviate COPD symptoms, and its therapeutic effects have been linked to its potential to modulate NK cell function. This study provides some evidence that QBPF can improve NK cell activity in COPD.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"159 ","pages":"158570"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536733","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}
PhytomedicinePub Date : 2026-09-01Epub Date: 2026-06-27DOI: 10.1016/j.phymed.2026.158438
Siwen Fan, Hongying Du, Yixin Yao, Huanyi Wang, Min Zhang, Xuliu Shi, Jiankun Yan, Li Peng, Guangxu Xiao, Shuang He, Ming Lyu, Yan Zhu
{"title":"Corrigendum to \"Protection of Stroke-induced Blood-Brain Barrier Disruption by Guanxinning Injection and Its Active-component Combination via TLR4/NF-κB/MMP9-mediated Neuroinflammation\" [Phytomedicine. 2025 Nov; 147:157162].","authors":"Siwen Fan, Hongying Du, Yixin Yao, Huanyi Wang, Min Zhang, Xuliu Shi, Jiankun Yan, Li Peng, Guangxu Xiao, Shuang He, Ming Lyu, Yan Zhu","doi":"10.1016/j.phymed.2026.158438","DOIUrl":"10.1016/j.phymed.2026.158438","url":null,"abstract":"","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":" ","pages":"158438"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148339792","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":"Targeting cystathionine-β-synthase (CBS)-mediated cell stemness and gut microbiome homeostasis: mechanism and clinical study of combined resveratrol-curcumin treatment for ulcerative colitis.","authors":"Shuai Su, Lingyu Ren, Shixing Wang, Zhifang Zhang, Keyao Yang, Deying Zhou, Meiyan Wang, Xiaonan Xi, Weilong Zhong","doi":"10.1016/j.phymed.2026.158625","DOIUrl":"10.1016/j.phymed.2026.158625","url":null,"abstract":"<p><strong>Background: </strong>Durable mucosal healing is the primary therapeutic goal in ulcerative colitis (UC). Intestinal epithelial stemness and microbiota homeostasis drive this healing process. Cystathionine-β-synthase (CBS) is a key enzyme in endogenous sulfur metabolism. Sulfur metabolism is essential for mitochondrial energy production and mucosal integrity. However, the precise role of CBS in UC pathogenesis remains unclear. Single plant-derived polyphenols, such as resveratrol or curcumin, show limited clinical efficacy due to low bioavailability. The combined effect of these botanical agents on CBS-mediated gut homeostasis requires further investigation.</p><p><strong>Purpose: </strong>This study aimed to define the molecular function of CBS in colitis and to evaluate the therapeutic mechanism and clinical translational potential of a combined plant-derived resveratrol-curcumin treatment for UC.</p><p><strong>Study design: </strong>A comprehensive bench-to-bedside translational approach was employed. The study integrated human clinical sample analysis, in vivo animal experiments using transgenic models, in silico molecular docking, and a pilot clinical trial.</p><p><strong>Methods: </strong>CBS expression was quantified in colonic biopsies from UC patients and healthy controls. Dextran sulfate sodium (DSS) was used to induce colitis in wild-type (WT) and CBS knockout (Cbs<sup>-/-</sup>) mice. Clinical phenotypes, mucosal protein expression, microbiota composition, and short-chain fatty acid (SCFA) profiles were systematically assessed. Molecular docking evaluated the binding affinity between the CBS protein and the resveratrol-curcumin combination. The in vivo efficacy of this combination was tested in both WT and Cbs<sup>-/-</sup> mice. Finally, a pilot clinical trial assessed the combination therapy alongside mesalamine in UC patients.</p><p><strong>Results: </strong>Colonic CBS expression was downregulated in both UC patients and colitis mice. CBS deficiency worsened DSS-induced clinical damage. It disrupted intestinal barrier homeostasis and severely impaired SCFA production. Molecular docking demonstrated strong binding affinity between the resveratrol-curcumin combination and the CBS protein. In vivo, this combined treatment effectively alleviated colitis symptoms. It reduced pro-inflammatory cytokines, upregulated mucosal proteins via CBS activation, and restored microbiota structure. Notably, these mucosal protective effects were completely abolished in Cbs<sup>-/-</sup> mice, confirming CBS as the essential target for this combined protective effect. In the pilot trial, the addition of resveratrol and curcumin to mesalamine improved clinical outcomes in UC patients.</p><p><strong>Conclusion: </strong>CBS acts as a crucial endogenous protector in the colon. It maintains epithelial stemness and microbiota metabolic homeostasis. The plant-derived resveratrol-curcumin combination specifically targets and restores CBS expression","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"159 ","pages":"158625"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584863","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}
PhytomedicinePub Date : 2026-09-01Epub Date: 2026-07-20DOI: 10.1016/j.phymed.2026.158609
Wei Zou, Tianle Li, Jacek Plewka, Xiaoxiong Song, Xueting Wan, Xin Luo, Mengyuan Gao, Suyun Yu, Yuanyuan Wu, Xiaoman Li, Aiyun Wang, Katarzyna Magiera-Mularz, Bogdan Musielak, William Fenical, Yang Zhao, Zhonghong Wei, Yin Lu
{"title":"Discovery of natural product-derived rosavin as a programmed death-ligand 1 inhibitor for cancer immunotherapy.","authors":"Wei Zou, Tianle Li, Jacek Plewka, Xiaoxiong Song, Xueting Wan, Xin Luo, Mengyuan Gao, Suyun Yu, Yuanyuan Wu, Xiaoman Li, Aiyun Wang, Katarzyna Magiera-Mularz, Bogdan Musielak, William Fenical, Yang Zhao, Zhonghong Wei, Yin Lu","doi":"10.1016/j.phymed.2026.158609","DOIUrl":"10.1016/j.phymed.2026.158609","url":null,"abstract":"<p><strong>Background: </strong>Given the limitations of the existing monoclonal antibody (mAb)-based therapies, more efficient and safer small-molecule-based checkpoint therapies targeting the programmed cell death-1 (PD-1) / programmed cell death ligand-1 (PD-L1) axis are gaining growing attention and urgently required.</p><p><strong>Objective: </strong>To identify a novel PD-L1 small-molecule inhibitor from natural products and systematically evaluate its antitumor activity, mechanism of action, and potential biomarkers.</p><p><strong>Methods: </strong>Based on the co-crystal structure of PD-L1 with BMS-202 (PDB ID: 5J89), molecular docking was employed for high-throughput virtual screening of 16,563 natural products. The binding affinity of candidate compounds to PD-L1 protein was validated through microscale thermophoresis (MST), cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) assays and nuclear magnetic resonance (NMR). The blockade of PD-1/PD-L1 interaction was assessed using homogeneous time-resolved fluorescence (HTRF), NFAT-Luc luciferase reporter gene system, and cell membrane PD-1 binding assays. In vivo antitumor efficacy was systematically assessed in humanized PD-L1 knock-in B16F10 and MC38 tumor-bearing mouse models. The mechanism of action was investigated using RNA-seq transcriptomics, flow cytometry, and immunofluorescence staining. Finally, response mechanisms and potential biomarkers were systematically analyzed by comparing differential responses across distinct tumor models.</p><p><strong>Results: </strong>Through high-throughput virtual screening, we identified rosavin as a small molecule with a novel scaffold that targets PD-L1, exhibiting the unusual small-molecule property of inhibiting PD-L1 without inducing its dimerization. Rosavin demonstrated significant antitumor activity in vivo by promoting antitumor immunity through enhancing CD8<sup>+</sup> T cell activation, consistent with the effects of PD-L1/PD-1 blockade. Notably, rosavin was particularly effective for fighting against tumor progression in microsatellite instability-high (MSI-H) solid tumors and robustly strengthened the expression levels of CXCL9 and CXCL10 in tumors, which may serve as potential biomarkers for predicting responsiveness to rosavin-mediated PD-1/PD-L1 blockade.</p><p><strong>Conclusion: </strong>Rosavin serves as a privileged novel and unexpected scaffold for designing potent PD-1/PD-L1 modulators, offering promising candidates for cancer immunotherapy.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"159 ","pages":"158609"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148585105","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":"Quercetin as tigecycline adjuvant reverses multidrug-resistant Acinetobacter baumannii infection.","authors":"Zhigang Sun, Ziwen Cai, Yangyang Bian, Caelinn James, Jing Wang, Zhuo Li, Wenjing Zhang, Tingting Wan, Zhao Liu, Yuting Zhang, Jiahua He, Lingzhao Fang, Bingjie Li, Xiaoye Liu","doi":"10.1016/j.phymed.2026.158621","DOIUrl":"10.1016/j.phymed.2026.158621","url":null,"abstract":"<p><p>The rise and global dissemination of multidrug-resistant (MDR) Acinetobacter baumannii has become a major public health threat. However, the constant emergence of drug-resistant mutants has resulted in increasingly limited therapeutic options. Tigecycline (TGC) continues to be one of the few antibiotics still effective against many A. baumannii strains. Herein, we discovered that quercetin (Qu) synergizes with TGC, enhancing its therapeutic efficacy against MDR A. baumannii by reducing the minimum inhibitory concentration (MIC) by 4- to 32-fold. Mechanistic analysis revealed that the synergistic effect arises from enhanced bacterial membrane permeation and concurrent inhibition of the resistance-nodulation-division (RND) efflux pump by quercetin, which lead in the increase in intracellular TGC levels by high‑performance liquid chromatography (HPLC) detection. Furthermore, metabolomics revealed significant perturbations in aminoacyl-tRNA biosynthesis along with significant perturbations in amino acid metabolism, consistent with TGC-induced translational arrest and elevated intracellular drug accumulation. In murine models of pulmonary infection, the TGC and Qu combination exhibited antibacterial efficacy. Collectively, our findings reveal a promising alternative therapeutic strategy for combating MDR A. baumannii infections.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"159 ","pages":"158621"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592975","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":"Lonicera trichosantha alleviates LPS-induced endometritis in mice by modulating the gut microbiota and host metabolism.","authors":"Zhikang Chen, Wenjing Li, Mingyu Wang, Yanan Li, Jia Gao, Zeyu Xie, Tashi Tsering, Jingming Jia, Anhua Wang","doi":"10.1016/j.phymed.2026.158577","DOIUrl":"10.1016/j.phymed.2026.158577","url":null,"abstract":"<p><strong>Background: </strong>Endometritis is an inflammatory disorder of the endometrial lining. Conventional antibiotic therapy often fails to control the accompanying disruptive inflammation. The 95 % ethanol-eluted fraction of Lonicera trichosantha (95 %-LT), exhibits potent anti-inflammatory activity in vitro. Nevertheless, its efficacy in vivo and the mechanisms underlying its potential therapeutic effect on endometritis are largely unknown.</p><p><strong>Purpose: </strong>This study aimed to elucidate the protective effects of 95 %-LT against endometritis and to define its mechanism of action, specifically through the gut microbiota-metabolite axis.</p><p><strong>Methods: </strong>The chemical profile of the 95 %-LT fraction was characterized using high-performance liquid chromatography (HPLC) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The therapeutic effects of 95 %-LT were systematically investigated using in vitro cellular inflammation models, a murine endometritis model, 16S ribosomal RNA (16S rRNA) gene sequencing, untargeted metabolomics, pseudo-germ-free (PGF) models, fecal microbiota transplantation (FMT), and in vivo supplementation with key bacterial strains and metabolites.</p><p><strong>Results: </strong>Three primary chemical constituents were identified in the 95 %-LT. Dose-dependent mitigation of endometrial pathological injury was achieved following intervention with 95 %-LT. Gut flora reconstruction induced by 95 %-LT was validated through 16S rRNA gene sequencing, among which the commensal beneficial bacterium Lactobacillus murinus exhibited the most remarkable enrichment. Concurrently, untargeted metabolomics showed that 95 %-LT enhanced the production of kynurenic acid (KYNA), a tryptophan-derived metabolite. FMT and PGF model experiments confirmed that the gut microbiota is indispensable for this therapeutic effect. Finally, in vivo supplementation verified that both L. murinus and KYNA function as key mediators underlying the efficacy of 95 %-LT.</p><p><strong>Conclusion: </strong>Our results demonstrate that 95 %-LT alleviates endometritis by orchestrating a gut microbiota-dependent mechanism, specifically through the \"L. murinus-KYNA axis\". This study provides a mechanistic foundation for exploiting Tibetan medicine-derived compounds in endometritis therapy.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"159 ","pages":"158577"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497994","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}