Phytomedicine最新文献

{"title":"L-theanine ameliorates traumatic-brain-injury-induced hippocampal neuronal death in rats","authors":"Min Kyu Park ,&nbsp;Bo Young Choi ,&nbsp;A Ra Kho ,&nbsp;Song Hee Lee ,&nbsp;Dae Ki Hong ,&nbsp;Beom Seok Kang ,&nbsp;Chang Jun Lee ,&nbsp;Hyun Wook Yang ,&nbsp;Seo Young Woo ,&nbsp;Se Wan Park ,&nbsp;Dong Yeon Kim ,&nbsp;Hyun Ho Jung ,&nbsp;Won il Yang ,&nbsp;Sang Won Suh","doi":"10.1016/j.phymed.2025.156457","DOIUrl":"10.1016/j.phymed.2025.156457","url":null,"abstract":"<div><h3>Background</h3><div>Traumatic brain injury (TBI) is a major health concern, often resulting in significant brain damage and functional impairments. A key contributing factor to TBI-induced neuronal injury is the overactivation of AMPA glutamate receptors, leading to an increased influx of calcium and zinc ions. This study investigates the neuroprotective potential of l-theanine, known for its antioxidant potential and ability to enhance glutathione synthesis, against hippocampal damage in a TBI rat model.</div></div><div><h3>Methods</h3><div>Rats subjected to TBIs were treated with two dosages of l-theanine (100 and 200 mg/kg) and an AMPA receptor inhibitor, NBQX (30 mg/kg). The neuronal damage assessment, conducted 24 h post-injury, involved a histological analysis, focusing on the factors of neuronal death, oxidative damage, and glial cell activation. The statistical analysis included the performance of an ANOVA followed by a Bonferroni post hoc test, with the data presented as mean ± SEM values and the significance determined at <em>p</em> &lt; 0.05.</div></div><div><h3>Results</h3><div>Treatment with l-theanine was observed to significantly mitigate the zinc accumulation, neuronal death, and cognitive impairments associated with TBI. These benefits are likely attributed to the inhibition of AMPA receptor activity and reduction in neuroinflammation, possibly enhanced as a result of increased glutathione production.</div></div><div><h3>Conclusion</h3><div>This study suggests that l-theanine can perform a neuroprotective role in TBI, modulating AMPA receptor activation and diminishing neuroinflammation. Its antioxidant and anti-inflammatory properties further enhance the material's potential use as a therapeutic agent for reducing hippocampal damage caused as a result of a TBI.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156457"},"PeriodicalIF":6.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guizhi Shaoyao Zhimu Decoction alleviates rheumatoid arthritis by inhibiting inflammation by targeting SLPI","authors":"Dongmei Pan ,&nbsp;Yu Guo ,&nbsp;Yi Liu ,&nbsp;Haixin Yang ,&nbsp;Zhaohui Gong ,&nbsp;Yanyi Du ,&nbsp;Ruotong Xu ,&nbsp;Li Gao ,&nbsp;Qiang Xu ,&nbsp;Nan Li","doi":"10.1016/j.phymed.2025.156471","DOIUrl":"10.1016/j.phymed.2025.156471","url":null,"abstract":"<div><h3>Background</h3><div>Guizhi Shaoyao Zhimu decoction (GSZD) is a recognised herbal formula that has demonstrated efficacy in the treatment of rheumatoid arthritis (RA). Despite its recognised clinical benefits and widespread use, the precise mechanisms by which this decoction exerts its therapeutic effects are not fully understood.</div></div><div><h3>Purpose</h3><div>To determine the impact of GSZD on collagen-induced arthritis (CIA) mice and MH7A cells and to explore the molecular mechanisms through which GSZD operates in RA.</div></div><div><h3>Methods</h3><div>The in vivo effects of GSZD were evaluated in a CIA model. Network pharmacology and bioinformatics approaches were employed to identify GSZD targets. Protein expression was measured by western blotting. Matrix metalloproteinases (MMPs) expression was detected using ELISA and quantitative RT-PCR. Cell migration and invasion were determined using the Boyden chamber assay.</div></div><div><h3>Results</h3><div>The arthritis score was significantly lowered by GSZD, which also alleviated joint swelling and bone damage, reduced the pathological score, and lowered the serum levels of MMPs in CIA mice. From a mechanistic perspective, we discovered that SLPI serves as a novel target gene of GSZD in MH7A cells. The findings indicated that GSZD treatment significantly suppressed the expression of SLPI, as well as the PI3K/AKT/NF-κB signalling pathway. Additionally, GSZD treatment decreased both the migration and invasion of MH7A cells, as well as MMPs expression. Further investigations of molecular mechanisms revealed that GSZD effectively inhibited SLPI expression and PI3K/AKT/NF-κB pathway activity in TNF-α-stimulated MH7A cells.</div></div><div><h3>Conclusion</h3><div>The findings indicate that GSZD markedly reduced the severity of arthritis in CIA mice and restricted the migration, invasion, and expression of MMPs in MH7A cells by interfering with the SLPI and PI3K/AKT/NF-κB signalling pathways. Our research further elucidated the underlying mechanism by which GSZD exerts its therapeutic effects in the treatment of RA and showed for the first time that SLPI could serve as a novel therapeutic target for RA, offering potential avenues for more effective treatment strategies.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156471"},"PeriodicalIF":6.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143377964","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":"Exploring trends in natural product-based treatments to skin burn: A comprehensive review","authors":"José Adão Carvalho Nascimento Júnior ,&nbsp;Ana Maria Santos Oliveira ,&nbsp;Karen Dayana Lancheros Porras ,&nbsp;Paula dos Passos Menezes ,&nbsp;Adriano Antunes de Souza Araujo ,&nbsp;Paula Santos Nunes ,&nbsp;Diana Marcela Aragón ,&nbsp;Mairim Russo Serafini","doi":"10.1016/j.phymed.2025.156481","DOIUrl":"10.1016/j.phymed.2025.156481","url":null,"abstract":"<div><h3>Background</h3><div>Burns are traumatic injuries caused by thermal, chemical, or other external factor, significantly impacting organic tissue. They are among the most common and severe types of trauma worldwide, often resulting in considerable morbidity and mortality. Natural products, owing to their pharmacological properties, present promising avenues for burn management and treatment.</div></div><div><h3>Purpose</h3><div>This study aims to provide a comprehensive review of patented pharmaceutical formulations containing natural products for burn treatment and to define trends in the market.</div></div><div><h3>Methods</h3><div>Patent documents were identified through searches in the World Intellectual Property Organization (WIPO) and European Patent Office (EPO) databases using “burn*” as a keyword in the title and/or abstract and International Patent Classification (IPC) code A61K36/00. The review also examines clinical trials and SWOT analyses to evaluate strengths, weaknesses, opportunities, and threats in this field.</div></div><div><h3>Results</h3><div>A total of 82 patents were selected, highlighting the use of natural products, such as <em>Aloe vera, Coptis chinensis,</em> borneol, menthol, and propolis, predominantly derived from Traditional Chinese Medicine. These findings are supplemented with clinical trial data and market insights. The results underscore both the therapeutic efficacy and challenges, such as standardization and regulatory hurdles, of using natural products.</div></div><div><h3>Conclusion</h3><div>This patent review highlights the potential of natural-origin formulations in addressing the limitations of conventional burn treatments. Continued research is essential to overcome existing barriers, ensuring broader accessibility and enhanced therapeutic outcomes.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156481"},"PeriodicalIF":6.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143394831","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":"Dual role of Baimao-Longdan-Congrong-Fang in inhibiting Staphylococcus aureus virulence factors and regulating TNF-α/TNFR1/NF-κB/MMP9 axis","authors":"Tao Jiang,&nbsp;Xiujing Zhu,&nbsp;Zixin Yin,&nbsp;Rui Gao,&nbsp;Yufen Li,&nbsp;Chenhao Li,&nbsp;Qianting Meng,&nbsp;Xiaojuan Zhu,&nbsp;Wu Song,&nbsp;Xin Su","doi":"10.1016/j.phymed.2025.156477","DOIUrl":"10.1016/j.phymed.2025.156477","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Baimao-Longdan-Congrong-Fang (BLCF), a traditional Chinese herbal formula described in the &lt;em&gt;Taiping Shenghui Fang&lt;/em&gt; (998 AD), consists of medicinal plants with heat-clearing and tonifying properties. BLCF has a promise as a treatment for &lt;em&gt;Staphylococcus aureus&lt;/em&gt; (&lt;em&gt;S. aureus&lt;/em&gt;) pneumonia, according to its historical use and current pharmacological research.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;In this study, the inhibitory effects of BLCF on &lt;em&gt;S. aureus&lt;/em&gt; virulence factors were evaluated &lt;em&gt;in vitro&lt;/em&gt;, and its mechanisms of action were investigated in a methicillin-resistant &lt;em&gt;S. aureus&lt;/em&gt; (MRSA) pneumonia mouse model.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The inhibitory effect of BLCF on &lt;em&gt;S. aureus&lt;/em&gt; virulence factors, including sortase A (SrtA) and α-hemolysin (Hla), was investigated by fluorescence resonance energy transfer (FRET) and hemolysis assays. A C57BL/6J mouse model of MRSA pneumonia was employed to evaluate its therapeutic efficacy. Accordingly, an integrated strategy of medicinal chemistry, network pharmacology analysis, GEO database analysis, bioinformatics, molecular docking, molecular dynamics simulation, GeneMANIA-based functional association (GMFA), and GSEA was used to identify and illustrate potential therapeutic targets and mechanisms. Subsequently, the mechanistic results were confirmed by Western blot analysis and RT-qPCR.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;While BLCF exhibited weak inhibitory activity against &lt;em&gt;S. aureus&lt;/em&gt; USA300, Newman, and SA37 strains, it significantly suppressed SrtA-related virulence functions without affecting bacterial growth. FRET and hemolysis assays confirmed that BLCF inhibited SrtA activity (IC&lt;sub&gt;50&lt;/sub&gt; = 1.25 mg/mL) while decreasing hemolytic activity. Furthermore, BLCF protected mice from MRSA infection, increasing their survival rates. Bioinformatics analysis identified 26 active compounds and 2 hub genes (&lt;em&gt;Tnf&lt;/em&gt; and &lt;em&gt;Mmp9&lt;/em&gt;) that were associated with 5 types of immune cell, including activated CD4 T cells, myeloid-derived suppressor cells, activated dendritic cells, macrophages, and mast cells. Molecular docking revealed 3 active compounds (isoacteoside, verbascoside, and echinacoside) that exhibited strong binding affinities to TNF, MMP9, and SrtA. Molecular dynamics simulations validated the stable interactions between isoacteoside and the target proteins, yielding binding energies of −136.76 ± 8.83 kJ/mol, −174.98 ± 14.89 kJ/mol, and −186.34 ± 9.06 kJ/mol, respectively. The therapeutic effect of BLCF was closely linked to the NF-κB signaling pathway, as revealed by GMFA and GSEA analyses. &lt;em&gt;In vivo&lt;/em&gt;, BLCF reduced lung bacterial load, improved the wet/dry ratio, and decreased inflammatory cytokines, thereby enhancing lung histopathology through modulation of the TNF-α/TNFR1/NF-κB/MMP9 axis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;BLCF can effectively treat MRSA pneumonia in mice by inhibiting S","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156477"},"PeriodicalIF":6.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387626","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":"Curcuma wenyujin extract alleviates cognitive deficits and restrains pyroptosis through PINK1/Parkin mediated autophagy in Alzheimer's disease","authors":"Yu Qi ,&nbsp;Jingwen Zhang ,&nbsp;Yuanlong Zhang ,&nbsp;Haoyun Zhu ,&nbsp;Jiabao Wang ,&nbsp;Xiao Xu ,&nbsp;Shengjie Jin ,&nbsp;Chunlai Wang ,&nbsp;Fang Zhang ,&nbsp;Min Zhao ,&nbsp;Zhigang Wu ,&nbsp;Haoru Zhu ,&nbsp;Pengcheng Yan","doi":"10.1016/j.phymed.2025.156482","DOIUrl":"10.1016/j.phymed.2025.156482","url":null,"abstract":"<div><h3>Background</h3><div>Pyroptosis and mitophagy have gained significant attention in Alzheimer's disease (AD) treatment. Curcumae Radix (CR), the dried radix of <em>Curcuma wenyujin</em> Y. H. Chen et C. Ling, is a traditional Chinese medicine (TCM) extensively utilized for neurological disorders. Yet, its impact and mechanistic role in AD remain unclear.</div></div><div><h3>Purpose</h3><div>This study aims to explore the active fraction of CR in AD treatment and its potential mechanisms.</div></div><div><h3>Methods</h3><div>CR extracts were qualitatively analyzed using UHPLC-Triple-TOF/MS. Aβ_1–42-induced mice received daily intragastric drug treatments for three weeks. Cognitive abilities of AD model mice were assessed through Y maze, novel object recognition, and eight-arm maze tests. Therapeutic targets of CR extracts were identified using quantitative proteomics. In both <em>in vivo</em> and <em>in vitro</em> settings, effects on pyroptosis and mitophagy were examined by Western blot (WB), immunofluorescence (IF) staining, and ELISA assays.</div></div><div><h3>Results</h3><div>The ethyl acetate (EAC) fraction of CR extract exhibited optimal anti-AD effects. CR extracts enhanced memory and cognition in Aβ_1–42-induced mice, improved neuronal morphology, and reduced Aβ accumulation in the brain. Proteomics analysis suggested the anti-AD properties of CR might involve inflammation reduction, cell survival enhancement, and mitophagy modulation. CR treatments in both AD mice and Aβ-induced SH-SY5Y cells resulted in reduced pyroptosis, increased LC3 and Beclin1 levels, and activation of the PINK1/Parkin pathway.</div></div><div><h3>Conclusion</h3><div>The EAC fraction of CR is effective in AD treatment by mitigating pyroptosis, reducing neuroinflammation, and promoting mitophagy, actions facilitated through the PINK1/Parkin pathway.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156482"},"PeriodicalIF":6.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403242","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":"Erianin triggers ferroptosis in colorectal cancer cells by facilitating the ubiquitination and degradation of GPX4","authors":"Yuting Zheng ,&nbsp;Yinli Zheng ,&nbsp;Haipeng Chen ,&nbsp;Xuanjing Tan ,&nbsp;Guiyu Zhang ,&nbsp;Muyan Kong ,&nbsp;Ruidi Jiang ,&nbsp;Hong Yu ,&nbsp;Keyao Shan ,&nbsp;Jiyao Liu ,&nbsp;Rong Zhang ,&nbsp;Zhongqiu Liu ,&nbsp;Jinjun Wu","doi":"10.1016/j.phymed.2025.156465","DOIUrl":"10.1016/j.phymed.2025.156465","url":null,"abstract":"<div><h3>Background</h3><div>Colorectal cancer (CRC) continues to represent a significant global public health challenge. Ferroptosis, a novel form of cell death dependent on iron and involving lipid peroxidation, has emerged as an effective strategy for treating various cancers with great potential for application.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the therapeutic potential of erianin, a novel dibenzyl compound isolated from the well-known herbal medicine Dendrobium chrysotoxum Lindl, in the treatment of CRC through induction of ferroptosis.</div></div><div><h3>Methods</h3><div>Human CRC HCT116 and SW480 cells were employed for in vitro investigations, while an AOM/DSS CRC animal model was established for in vivo experiments.</div></div><div><h3>Results</h3><div>The results demonstrated that erianin effectively inhibited the growth of CRC cells and suppressed tumorigenesis in the AOM/DSS CRC animal model. Erianin induced ferroptosis in CRC cells as evidenced by a significant increase in intracellular Fe²⁺ levels and lipid peroxides, along with a decrease in glutathione. Additionally, ferroptosis inhibitors reversed the cytotoxicity of erianin against CRC cells as well as its induction of ferroptosis. Notably, novel glutathione peroxidase 4 (GPX4), a core regulatory factor of ferroptosis, was found to be overexpressed in human primary colon adenocarcinoma tissues compared with normal tissues. However, erianin significantly reduced GPX4 expression by facilitating its ubiquitination and degradation. Furthermore, the overexpression of GPX4 mitigated erianin-induced ferroptotic cell death; conversely, the silencing of GPX4 amplified these effects.</div></div><div><h3>Conclusion</h3><div>Erianin demonstrates the potential to inhibit CRC by inducing ferroptosis through accelerating the ubiquitination and degradation of GPX4, indicating its promise as a therapeutic candidate against CRC.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156465"},"PeriodicalIF":6.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387627","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":"Exploring the mechanism by which Zexie Tang regulates Alzheimer's disease: Insights from multi-omics analysis","authors":"Shijie Su ,&nbsp;Kongli Huang ,&nbsp;Han Cai ,&nbsp;Dongyun Wei ,&nbsp;Haixia Ding ,&nbsp;Liejie Lin ,&nbsp;Yuting Wang ,&nbsp;Jihong Gu ,&nbsp;Qi Wang","doi":"10.1016/j.phymed.2025.156453","DOIUrl":"10.1016/j.phymed.2025.156453","url":null,"abstract":"<div><h3>Background</h3><div>Neurodegenerative disorders, such as Alzheimer's disease (AD), are characterized by a progressive decline in cognitive function. Modulating microglial metabolic reprogramming presents a promising therapeutic avenue for AD. Previous studies have shown that Zexie Tang (ZXT) possesses neuroprotective properties and can ameliorate cognitive impairment, but the underlying mechanisms remain unclear.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the efficacy of ZXT in improving cognitive function in AD mice using a multi-omics approach and to explore its potential role in modulating microglial metabolic reprogramming.</div></div><div><h3>Methods</h3><div>Behavioral assessments were conducted to evaluate the effects of ZXT on cognitive function in APP/PS1 mice. H&amp;E, Nissl, and Thioflavin S staining were performed to assess the impact of ZXT on brain pathology. A multi-omics approach, including transcriptomics, gut microbiota analysis, and metabolomics, was employed to elucidate the mechanisms of action of ZXT. RT-qPCR, immunoblotting, and immunofluorescence were used to validate the effects of ZXT on glycolipid metabolism, neuroinflammation, and the AMPK-mTOR-HIF1α pathway.</div></div><div><h3>Results</h3><div>ZXT effectively protected against cognitive deficits, reduced hippocampal neuronal apoptosis, and decreased Aβ plaque deposition. Transcriptomics analysis revealed that ZXT was involved in immune system processes and metabolic processes and had a specific cellular response with microglia. Additionally, ZXT regulated the composition and functions of brain metabolites and gut microbiota. Our study demonstrated that ZXT positively influenced glucolipid metabolism and attenuated neuroinflammation, which were linked to the AMPK-mTOR-HIF1α pathway in the brain.</div></div><div><h3>Conclusion</h3><div>Our findings suggested that ZXT may mitigate cognitive deficits in APP/PS1 mice by modulating gut microbiota and enhancing brain energy metabolism. ZXT regulated glucolipid metabolism and neuroinflammation by modulating microglial metabolic reprogramming involving the AMPK-mTOR-HIF1α pathway.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156453"},"PeriodicalIF":6.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422134","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":"Tetrandrine alleviates macrophage activation syndrome after CAR-T cell therapy","authors":"Youming Wang ,&nbsp;Li Ding ,&nbsp;Yingxiang Wang ,&nbsp;Hui Li ,&nbsp;Miaomiao Wu ,&nbsp;Sujun Li ,&nbsp;Qianwen Xu ,&nbsp;Yuanli Chen ,&nbsp;Xingbing Wang","doi":"10.1016/j.phymed.2025.156483","DOIUrl":"10.1016/j.phymed.2025.156483","url":null,"abstract":"<div><h3>Background</h3><div>Cytokine release syndrome (CRS) and secondary hemophagocytic lymphohistiocytosis (sHLH) are severe and potentially life-threatening complications after chimeric antigen receptor T (CAR-T) cell therapy, driven by excessive cytokine release from macrophages. The traditional Chinese herbal remedy <span>d</span>-tetrandrine (tetrandrine) exhibits anti-inflammatory properties in various diseases; however, its efficacy in mitigating CRS and sHLH remains underexplored.</div></div><div><h3>Methods</h3><div>To establish an <em>in vitro</em> CRS model, supernatants from co-cultures of CAR-T and Raji cells were used to stimulate mTHP-1 macrophages. To model CRS and lymphoma <em>in vivo</em>, CAR-T and Raji cells were infused into the tail vein of NCG mice. An sHLH model was established in C57BL/6 J mice through intraperitoneal administration of Poly I:C and LPS.</div></div><div><h3>Results</h3><div>Results demonstrated that tetrandrine markedly reduced the secretion of IL-6 and IL-1β from macrophages, alone with IL-2, TNF-α, GM-CSF, IL-8, and IFN-γ from CAR-T cells, while preserving the cytotoxic functions exhibited by CAR-T cells. In mouse models, tetrandrine treatment effectively decreased the concentrations of mouse IL-6 and human IFN-γ in mice serum, while maintaining the therapeutic efficacy exhibited by CAR-T cells. Mechanistically, tetrandrine enhances autophagy through the restraint of the AKT/mTOR signaling pathway, which is dysregulated in macrophages during CRS. Notably, lysosomal injury observed in macrophages during CRS was ameliorated by tetrandrine, which restored lysosomal pH and increased lysosome numbers, thereby positively influencing autophagy. In the sHLH model, tetrandrine treatment extended survival and alleviated pathological features, highlighting its protective role in mitigating the adverse effects of CRS and sHLH.</div></div><div><h3>Conclusion</h3><div>This study identified tetrandrine as a promising therapeutic candidate for attenuating macrophage activation associated with CAR-T cell therapy and LPS/Poly I:C-induced stimulation. These findings underscore the potential of tetrandrine to mitigate toxicities after CAR-T cell therapy while ensuring its therapeutic efficacy.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156483"},"PeriodicalIF":6.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143394834","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":"6-C-methylquercetin in Baeckea frutescens exerts anti-prostate cancer effect via ErbB/PI3K/AKT pathway","authors":"Beixi Jia ,&nbsp;Mengyao Zhang ,&nbsp;Xinyue Jiang ,&nbsp;Siyuan Zhou ,&nbsp;Ke Han ,&nbsp;Ruyi Deng ,&nbsp;Haixia Cai ,&nbsp;Yuefeng Bi","doi":"10.1016/j.phymed.2025.156463","DOIUrl":"10.1016/j.phymed.2025.156463","url":null,"abstract":"<div><h3>Background</h3><div>Prostate cancer (PCa) is one of the malignant tumors that seriously affect the health of middle-aged and older men. Chinese medicinal herbs have great potential in tumor therapy with less toxic side effects. 6-C-methylquercetin in the folk medicine <em>Baeckea frutescens</em>, has a good inhibitory effect on human prostate cancer cells (PC3), but its effect and mechanism of anti-PCa have not been elucidated.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the antitumor effect of 6-C-methylquercetin on PCa and its molecular mechanism.</div></div><div><h3>Methods</h3><div>Network pharmacology was employed to predict the potential targets and pathways of 6-C-methylquercetin acting on PCa, and molecular docking and molecular dynamics simulations were used to analyze the interactions between 6-C-methylquercetin and key target proteins. CCK8, flow cytometry, wound healing, transwell, RT-qPCR, and western blot assay were performed to elucidate the effect of 6-C-methylquercetin on the proliferation, apoptosis, cycle, migration and invasion of PC3 cells, and revealed its regulations on the ErbB/PI3K/AKT pathway. For <em>in vivo</em> experiments, the nude mouse PC3 xenograft model was used, H&amp;E staining, TUNEL, and immunofluorescence assay were performed on tumor tissues, and the biosafety was evaluated by blood routine examination and liver and kidney function tests.</div></div><div><h3>Results</h3><div>Network pharmacological analysis and computational simulations revealed that 6-C-methylquercetin acted on PCa through the ErbBs and PI3K/AKT pathway, and 6-C-methylquercetin had a strong binding affinity for these key node proteins. <em>In vitro</em> experiments demonstrated that 6-C-methylquercetin inhibited the proliferation, migration and invasion of PC3 cells, affected the cell cycle, and induced apoptosis, by suppressing the ErbB/PI3K/AKT pathway activity. Animal experiments showed that 6-C-methylquercetin inhibited the progression of prostate cancer in tumor xenograft mice with a good <em>in vivo</em> biosafety.</div></div><div><h3>Conclusion</h3><div>The study first revealed the anti-PCa potential of 6-C-methylquercetin, which may involve the regulation of the ErbB/PI3K/AKT pathway, but its direct targets and specific therapeutic mechanism need to be further explored. These findings suggested that 6-C-methylquercetin had the potential to suppress the development of PCa, and provided a scientific basis for the development and utilization of C-methylated flavonoid compounds from <em>B. frutescens</em>.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156463"},"PeriodicalIF":6.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349128","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":"Integrated transcriptomics and network pharmacology to reveal the mechanism of Physochlainae Radix in the treatment of asthma","authors":"Jinyan Tan ,&nbsp;Jianing Zhang ,&nbsp;Weidong Yang ,&nbsp;Jianli Li ,&nbsp;Yun Zang ,&nbsp;Siqi Yang ,&nbsp;Yan Liu ,&nbsp;Rui Mao ,&nbsp;Leilei Xie ,&nbsp;Bingyou Yang ,&nbsp;Yingli Wang ,&nbsp;Yangang Cheng","doi":"10.1016/j.phymed.2025.156470","DOIUrl":"10.1016/j.phymed.2025.156470","url":null,"abstract":"<div><h3>Background</h3><div>Physochlainae Radix (PR), a valuable traditional Chinese medicine, has been historically applied for the treatment of bronchitis and asthma in clinic, yet its mechanisms have not been clearly elucidated.</div></div><div><h3>Purpose</h3><div>This study aims to reveal the underlying mechanisms of PR in treating asthma, employing transcriptomics and network pharmacology approaches.</div></div><div><h3>Methods</h3><div>To evaluate the therapeutic effects of PR on asthma, we established the asthmatic model in ICR mice by using OVA. Firstly, we employed LC-MS and GNPS to analyze the major chemical constituents in PR. Subsequently, the effects of PR in asthma treatment were assessed through histology, biochemical analysis, and immunofluorescence (IF) assay. Further, an integrated approach of transcriptomics and network pharmacology was applied to identify the target proteins and related pathways of PR against asthma. IF, immunohistochemical (IHC), enzyme-linked immunosorbent assay (ELISA), and western blotting (WB) were utilized for experimental validation and mechanistic studies.</div></div><div><h3>Results</h3><div>Using UPLC/Q-Orbitrap-MS and GNPS, we eventually identified 23 potential active components from PR. It was discovered for the first time that PR contains a large number of steroidal saponins. PR treatment has been shown to improve lung function, histomorphological changes, and inflammation in the OVA-induced asthma model. According to the results of the transcriptomics and network pharmacology research, PR targeted CXCR2, CCR1, MMP3, MMP9, and IL-17 as crucial elements for treating asthma through the TLR4/MyD88/NF-κB, MAPK, and IL-17 pathways. The key proteins of these pathways were validated by IF and/or WB. Additionally, it was verified that the therapeutic effect of PR on asthmatic mice was related to the inhibition of the activation of the TLR4/MyD88 pathway by introducing TAK-242, an inhibitor of TLR4.</div></div><div><h3>Conclusions</h3><div>This research revealed that PR improves asthma through the TLR4/MyD88/NF-κB, MAPK, and IL-17 pathways. It is worth noting that this is the first time that transcriptomics and network pharmacology have been comprehensively used to explore the mechanism of PR in treating asthma. This finding advances our understanding of the pharmacological mechanisms underlying PR and lends support to its usage as a treatment agent for asthma.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156470"},"PeriodicalIF":6.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387628","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}