Phytomedicine最新文献

{"title":"Gastrodin prevents stress-induced synaptic plasticity impairment and behavioral dysfunction via cAMP/PKA/CREB signaling pathway","authors":"Zhihuang Zhao ,&nbsp;Pei Liu ,&nbsp;Haili Zhang ,&nbsp;Meidan Wang ,&nbsp;Yue Liu ,&nbsp;Lulu Wang ,&nbsp;Hui He ,&nbsp;Yangyan Ge ,&nbsp;Tao Zhou ,&nbsp;Chenghong Xiao ,&nbsp;Zili You ,&nbsp;Jinqiang Zhang","doi":"10.1016/j.phymed.2025.156661","DOIUrl":"10.1016/j.phymed.2025.156661","url":null,"abstract":"<div><h3>Background</h3><div>Chronic stress is widely recognized as a critical factor that impairs synaptic plasticity dependent brain function and behavior, contributing to the onset of depression and anxiety disorders, which subsequently undermine learning and memory processes. Gastrodin (GAS), a prominent bioactive constituent of Gastrodiae Rhizoma exhibiting notable neuroprotective properties, holds significant potential for the prevention and treatment of stress-induced neurological dysfunction. However, the protective effects of GAS on stress-induced synaptic plasticity impairment and the underlying mechanisms have yet to be fully elucidated.</div></div><div><h3>Objectives</h3><div>To investigate the potential of GAS in protecting synaptic plasticity from chronic stress and its underlying cellular and molecular mechanisms.</div></div><div><h3>Method</h3><div>A chronic stress model was constructed in C57BL/6J mice, and the effects of GAS on synaptic plasticity were examined using Golgi staining and immunohistochemistry. Systematic behavioral analysis was employed to assess the impact of GAS on depressive- and anxiety-like behaviors and cognitive function of mice. Metabolomics, transcriptomics, Western blotting, immunolocalization, enzyme-linked immunosorbent assay, and the administration of signal blockers were utilized to investigate the cellular and molecular pathways via which GAS safeguards synaptic plasticity.</div></div><div><h3>Results</h3><div>The results showed that chronic stress exposure reduces the dendritic arbor complexity, density of dendritic spines, proportion of mushroom spines of hippocampal neurons, as well as disrupts synaptic function, impairs cognitive function and induces depressive-like behaviors. Importantly, impairment of hippocampal synaptic plasticity, anxiety- and depressive-like behaviors, and cognitive decline induced by chronic stress were significantly ameliorated following GAS treatment. Moreover, we identified the cAMP/PKA/CREB signaling in hippocampal neurons as a potential mechanism through which GAS prevents synaptic plasticity impairment from chronic stress exposure. Blockade of cAMP/PKA/CREB signaling abolished the protective effects of GAS on synaptic plasticity of hippocampal neurons and behaviors in stress-exposed mice.</div></div><div><h3>Conclusion</h3><div>This study is the first to identify GAS as a potential natural compound for alleviating stress-induced synaptic plasticity impairment and behavioral dysfunction by activating the cAMP/PKA/CREB signaling pathway in hippocampal neurons, offering a promising strategy for stress-induced neurological disorders.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156661"},"PeriodicalIF":6.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697245","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":"Eupalinolide B targets DEK and PANoptosis through E3 ubiquitin ligases RNF149 and RNF170 to negatively regulate asthma","authors":"Qiaoyun Bai ,&nbsp;Chongyang Wang ,&nbsp;Ningpo Ding ,&nbsp;Zhiguang Wang ,&nbsp;Ruobai Liu ,&nbsp;Liangchang Li ,&nbsp;Hongmei Piao ,&nbsp;Yilan Song ,&nbsp;Guanghai Yan","doi":"10.1016/j.phymed.2025.156657","DOIUrl":"10.1016/j.phymed.2025.156657","url":null,"abstract":"<div><h3>Purpose</h3><div>We investigated the mechanism by which eupalinolide B (EB) regulates DEK protein ubiquitination and degradation, and its impact on DEK-mediated receptor-interacting protein kinase 1 (RIPK)-PANoptosis pathway in allergic asthma.</div></div><div><h3>Study Design and Methods</h3><div><em>In vitro</em> studies were conducted on human bronchial epithelial cells (BEAS-2B) treated with EB and human-recombinant DEK. Mass spectrometry analysis, RNA sequencing, molecular docking, and functional assays were used to assess the interactions and effects of EB, DEK, and ring finger protein 149 and 170 (RNF149 and RNF170). <em>In vivo</em> experiments involved a house dust mite-induced asthma model in mice and evaluation of airway inflammation, DEK expression, and PANoptosis markers.</div></div><div><h3>Results</h3><div><em>In vitro</em>, EB could bind to DEK. RNF149 and RNF170 were identified as regulatory factors of DEK, polyubiquitinating the K349 site in the DEK coding DNA sequence region 270–350 through K48 linkages and leading to its degradation. RNA sequencing showed that DEK overexpression upregulated the expression of genes such as RIPK1, FADD, and Caspase 8. Treatment with DEK siRNA or EB reduced the activation of the RIPK1-PANoptosis pathway in BEAS-2B-DEK cells. <em>In vivo</em>, EB significantly reduced the levels of DEK in house dust mite-induced mice and alleviated pulmonary inflammatory cell infiltration, goblet cell hyperplasia, collagen fiber deposition, and eosinophil proportion in BALF. Knocking out the DEK gene reduced RIPK1-induced PANoptosis, and inhibited airway inflammation and cell apoptosis.</div></div><div><h3>Conclusion</h3><div>EB promotes the degradation of DEK by RNF149 and RNF170, inhibits the RIPK1-PANoptosis pathway, and may effectively suppress asthma. EB may become a potential drug for treating airway inflammation in asthma.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156657"},"PeriodicalIF":6.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683111","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":"Traditional Chinese medicine in chronic rhinosinusitis: Mechanisms and postoperative recovery","authors":"Xi-he Zhang ,&nbsp;Qing-Jia Sun ,&nbsp;Li-chun Zhao ,&nbsp;Long Chen ,&nbsp;Wei Li","doi":"10.1016/j.phymed.2025.156658","DOIUrl":"10.1016/j.phymed.2025.156658","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Chronic rhinosinusitis (CRS) is inflammation of the sinuses and nasal passages that lasts for &gt;3 months. Its pathogenesis is complex, treatment is difficult, and it has multiple effects on patients. Although surgical treatment can effectively relieve the symptoms, the recurrence rate is high, and there are postoperative complications such as infection. At present, nasal spray hormone, antibiotics and other western drugs are used in clinical treatment, but there are drug dependence and toxic side effects. However, traditional Chinese medicine (TCM) has made remarkable progress in the treatment and promotion of postoperative recovery, guided by its unique TCM theory, and has little toxic and side effects, providing more treatment options for patients.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;The review aims to elucidate the mechanism of CRS from the aspects of traditional medicine and modern medicine, and evaluate the influence of TCM compound, components of TCM, TCM nasal irrigation, TCM fumigation and other auxiliary treatment methods on CRS, providing a new perspective for the application of TCM in CRS.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We conducted the literature retrieval with PubMed, Web of Science, Google Scholar and CNKI databases in a systematic manner (up to July 2024). The keywords included \"sinusitis\", \"chronic rhinosinusitis\", \"nasal polyps\", \"herbal medicine\", \"medicinal plants\", \"traditional Chinese medicine\", \"oxidative stress\", \"pathogenic microbial\", \"anatomic structure\" and so on. The obtained literatures were comprehensively sorted out. For image creation, Figdraw 2.0 was methodically employed.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The pathogenesis of CRS involves various interaction mechanisms such as bacterial biofilm formation, oxidative stress injury and impaired ciliary mucosa clearance. It is worth noting that TCM exerts therapeutic effects by targeting the above-mentioned pathological processes. Clinical studies have confirmed that TCM comprehensive therapy can significantly improve sinus symptom score, accelerate postoperative mucosal epithelialization, and promote postoperative rehabilitation of CRS. We also discussed the toxic side effects and clinical applications of related drugs.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;In TCM, CRS is classified under the diagnostic category of Bi Yuan. Its pathogenesis is attributed to exogenous invasion of the six climatic pathogens (Liu Yin: wind, cold, summer heat, dampness, dryness, and fire), spleen-stomach qi deficiency, internal damp-heat accumulation, and &lt;em&gt;qi&lt;/em&gt;-blood stasis. Guided by TCM principles, therapeutic strategies are individualized through syndrome differentiation, which tailors interventions to the patient's unique clinical manifestations. Therapeutic modalities include oral herbal formulations (e.g., decoctions or granules), acupuncture, and acupoint application. These approaches aim to restore physiological balance by harmoniz","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156658"},"PeriodicalIF":6.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697244","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":"Structural and functional properties of common natural organic cations","authors":"Zipeng Zheng ,&nbsp;Jun Hu ,&nbsp;Dawei Sun ,&nbsp;Kuanchen Huang ,&nbsp;Xusheng Li ,&nbsp;Jianxia Sun ,&nbsp;Weibin Bai","doi":"10.1016/j.phymed.2025.156662","DOIUrl":"10.1016/j.phymed.2025.156662","url":null,"abstract":"<div><h3>Background</h3><div>Natural products have emerged as a critical focus in modern scientific research due to their structural diversity and therapeutic potential. Among these are natural organic cations—a distinct class of nitrogen- and oxygen-containing compounds. Despite their pharmacological relevance, the literature lacks a systematic synthesis of structure-activity relationships for natural organic cations (NOC). This gap hinders the rational development of NOC-based therapies as sustainable alternatives to synthetic compounds.</div></div><div><h3>Methods</h3><div>Literature was searched and collected using databases, including PubMed, Science Direct, and Web of Science. The search terms used included \"natural organic cation\", \"alkaloid\", \"anthocyanin\", \"structure-activity relationship\", \"charge interaction\", \"π-cation interaction\", \"biological activity\", \"antimicrobial\", \"antioxidant\", \"anticancer\", \"neuroprotection\", \"anti-inflammatory\", “berberine\", \"coptisine\", \"palmatine\", “cyanidin\", \"delphinidin\", \"pelargonidin\", \"free radical scavenging\", \"gut microbiota metabolism\", \"NF-κB pathway”, \"G-quadruplex DNA\", \"isoquinoline alkaloid\", \"protoberberine\", \"benzophenanthridine\", \"planar conjugated system\", \"charge delocalization\", \"methylenedioxy group\", and several combinations of these words.</div></div><div><h3>Results</h3><div>The bioactivity of NOC is underestimated. This review uncovers the structure-activity relationships of NOC. Firstly, planar conjugated systems and substituents control target binding: N⁺ in alkaloids enhances DNA/protein affinity, while O⁺ in anthocyanins enables free radical scavenging and enzyme inhibition. Secondly, cationic species outperform neutral analogs in antimicrobial potency, antioxidant capacity, and target selectivity. NOC bind to biomolecules via π-cation/π-π stacking and electrostatic binding. Charge localization in conjugated systems enhances stability and bioactivity.</div></div><div><h3>Conclusion</h3><div>This review consolidates evidence that NOC represent promising candidates for replacing synthetic compounds in therapies for cancer, neurodegeneration, metabolic disorders, etc. Key findings highlight the superiority of cationic species in target engagement and bioactivity, driven by planar conjugated systems and substituent effects. However, clinical translation requires addressing gaps in bioavailability and long-term safety. Future research must prioritize structural optimization and mechanistic validation. By bridging these gaps, NOC could advance as sustainable, low-toxicity agents in precision medicine and functional nutrition.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156662"},"PeriodicalIF":6.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697735","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":"Revealing the gastric protective mechanism of Physochlaina physaloides (L) G. Don. with clinical orientation: PPAR/NF-κB signalling pathway activation","authors":"Siqi Li ,&nbsp;Wanze Feng ,&nbsp;Dongxue Chen ,&nbsp;Lan Yu ,&nbsp;Hongwei Cui ,&nbsp;Minhui Li","doi":"10.1016/j.phymed.2025.156642","DOIUrl":"10.1016/j.phymed.2025.156642","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Gastrointestinal diseases are global health issues. Current drugs for gastrointestinal diseases cause discomfort and toxicity; consequently, the use of traditional medicines and their extracts has gained attention in recent years. &lt;em&gt;Physochlaina physaloides&lt;/em&gt; (L) G. Don. (&lt;em&gt;P. physaloides&lt;/em&gt;) is traditionally used for diarrhoea and gastroenteritis; however, its material basis and mechanism of action for gastric injury have not been fully studied.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This study aims to explore &lt;em&gt;P. physaloides&lt;/em&gt; and their protective effects on gastric injury, together with the potential mechanisms.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Study design and methods&lt;/h3&gt;&lt;div&gt;We constructed chronic gastritis and gastric ulcer models in rats using 56 % ethanol and anhydrous ethanol, respectively. Additionally, we screened gastric injury pathways via transcriptomics and the gene expression omnibus (GEO) database. Subsequently, we constructed an ethanol-stimulated GES-1 cell model and screened the active fraction of &lt;em&gt;P. physaloides&lt;/em&gt; based on the cell survival rate and antioxidant activity. The effect of the active fraction of &lt;em&gt;P. physaloides&lt;/em&gt; was investigated via tissue structure (HE staining), mucus secretion (PAS staining), anti-inflammatory activity, antioxidant activity, and gastric acid secretion levels. We employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine the active components of &lt;em&gt;P. physaloides&lt;/em&gt; and the drug components in blood, before investigating the mechanisms via immunofluorescence, transcriptomic, metabolomics, network pharmacology, molecular docking, qRT-PCR, western blotting, and flow cytometry.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The occurrence of gastritis, gastric ulcer, and gastric cancer is related to the PPAR/NF-κB signalling pathway, with decreased expression of FABP3 and PPARγ, and increased expression of Bcl-2 and TNF-α. The n-butanol fraction of &lt;em&gt;P. physaloides&lt;/em&gt; (BPP) showed significant improvement in cell survival and antioxidant activity &lt;em&gt;in vitro&lt;/em&gt;. BPP also alleviated inflammation and oxidative stress in rat models, including by upregulating CAT, GSH, SOD, IL-10, PGE&lt;sub&gt;2&lt;/sub&gt;; downregulating VEGFA, IL-6, IL-8, TNF-α, and NO; improving pathological damage; restoring mucus levels; and reducing gastric acid secretion and macrophage expression. BPP and its active components, anisodamine and hyoscyamine, upregulated the expression of PPARα, PPARγ, CPT1, and FABP3, and downregulated NF-κB p65, thereby regulating the PPAR/NF-κB signalling pathway for gastroprotection. The BPP and its active components did not significantly increase the expression of GPX4 and SLC7A11, nor did they reduce the production of ROS. Therefore, their effects are unrelated to ferroptosis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;This study provides the first evidence of the effectiveness of BPP in the prevention of gastric ulcers and treatment of chronic","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156642"},"PeriodicalIF":6.7,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683116","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":"4-Hydroxyderricin attenuates ischemic brain injury and neuroinflammation by upregulating haptoglobin expression in microglia","authors":"Biying Ma ,&nbsp;Wenqi Wang ,&nbsp;Zhongxia Li ,&nbsp;Chao Zhong ,&nbsp;Jing Zhou ,&nbsp;Bo Yang ,&nbsp;Liying Liu ,&nbsp;Zhanqiu Wang ,&nbsp;Xiangjiao Yi ,&nbsp;Yanrong Zheng ,&nbsp;Yiqi Wang","doi":"10.1016/j.phymed.2025.156649","DOIUrl":"10.1016/j.phymed.2025.156649","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;&lt;em&gt;Angelica keiskei&lt;/em&gt; (Miq.) Koidz. is a traditional plant that is widely used in Asian countries because of its tonic, diuretic, and galactagogue properties. The chalcone compound 4-hydroxyderricin (4-HD), uniquely present in &lt;em&gt;A. keiskei&lt;/em&gt;, has demonstrated inhibitory effects on inflammation in peripheral tissues. Nonetheless, its efficacy in central neuroinflammation and ischemic brain injury remains unclear.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This study aims to assess the ability of 4-HD to alleviate acute ischemic brain injury and the associated inflammatory response, and to elucidate the underlying mechanisms.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Mice underwent middle cerebral artery occlusion (MCAO) surgery to induce acute cerebral ischemic injury. The extent of brain injury was evaluated by TTC staining and neurological function scoring. Immunofluorescence was employed to observe glial cell activation, whereas ELISA and RT-PCR were used to quantify inflammatory cytokine expression in ischemic brain tissues. Oxygen-glucose deprivation (OGD) and lipopolysaccharide (LPS) stimulation of BV2 microglial cells were conducted in vitro to examine the direct impact of 4-HD on microglial inflammation. ELISA and RT-PCR were carried out to quantify inflammatory cytokine expression in BV2 cells. Western blotting and immunofluorescence techniques were used to detect protein expression and localization, respectively. Additionally, alterations in gene expression were measured using RNA-seq analysis profiling following 4-HD treatment of BV2 cells. A short hairpin RNA (shRNA) was used to silence the &lt;em&gt;Haptoglobin&lt;/em&gt; (&lt;em&gt;Hp&lt;/em&gt;) gene to elucidate the relationship between drug effects and Hp protein levels.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;4-HD effectively reduced the infarct area and enhanced neurological function 24 h post-MCAO surgery by lowering inflammatory cytokine levels and inhibiting microglia activation in ischemic brain tissues. In OGD and LPS-stimulated BV2 microglia, 4-HD decreased the levels of inflammatory cytokines. Mechanistic research indicated that 4-HD enhanced Hp and reduced HMGB1 expression in BV2 cells. Moreover, the activation of the NF-κB and MAPK signaling pathways, two key pro-inflammatory pathways downstream of HMGB1, was inhibited by 4-HD treatment. In BV2 cells with &lt;em&gt;Hp&lt;/em&gt; gene knockdown, the inhibitory effect of HMGB1 disappeared, and its anti-inflammatory effect was also significantly weakened.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;4-HD has the potential to mitigate brain injury and neuroinflammation resulting from MCAO-induced acute ischemic damage. This neuroprotective effect is linked to the suppression of microglial activation and the inhibition of HMGB1 pro-inflammatory signaling, facilitated by the increased expression of the Hp protein. This study revealed, for the first time, the protective effects and mechanisms of 4-HD on ischemic brain injury. Additionally, we ","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156649"},"PeriodicalIF":6.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674441","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":"Renshen Zhuye decoction ameliorates high-fat diet-induced obesity and insulin resistance by modulating gut microbiota and metabolic homeostasis","authors":"Fei Luo ,&nbsp;Jie Yang ,&nbsp;Zhiping Song ,&nbsp;Yuan Zhao ,&nbsp;Panpan Wang ,&nbsp;Kaiyuan Liu ,&nbsp;Xin Mou ,&nbsp;Wenhong Liu ,&nbsp;Wei Li","doi":"10.1016/j.phymed.2025.156655","DOIUrl":"10.1016/j.phymed.2025.156655","url":null,"abstract":"<div><h3>Background</h3><div>Obesity, characterized by excessive adipose tissue accumulation, has become a global health challenge with rapidly increasing prevalence. It contributes significantly to metabolic disorders including insulin resistance (IR). Renshen-zhuye decoction (RZD), a traditional Chinese medicine formula historically used for diabetes, shows potential for improving metabolic parameters, but its effects and mechanisms in obesity and insulin resistance remain unclear.</div></div><div><h3>Purpose</h3><div>This study aimed to evaluate the therapeutic benefits of RZD on obesity and insulin resistance, and to elucidate the underlying mechanisms through which it improves glucose and lipid metabolism.</div></div><div><h3>Methods</h3><div>The role of RZD was evaluated in a high-fat diet (HFD) mouse model. The formula was characterized using UPLC-MS. Comprehensive analyses including histopathological staining, immunofluorescence, biochemical assays, 16S rRNA gene sequencing of gut microbiota, and non-targeted metabolomic analysis were performed. To validate the role of gut microbiota, we employed antibiotic treatment (ABX) to deplete intestinal flora and conducted fecal microbiota transplantation (FMT) experiments.</div></div><div><h3>Results</h3><div>RZD treatment dose-dependently alleviated HFD-induced dyslipidemia and insulin resistance, improving glucose tolerance, insulin sensitivity, and energy expenditure. Gut microbiota analysis revealed that RZD significantly modulated the composition of intestinal flora and their metabolic profiles. Additionally, RZD reduced intestinal and systemic inflammation by enhancing intestinal barrier integrity, particularly through increased expression of tight junction proteins such as Occludin. Importantly, the beneficial effects of RZD on weight management and glucose homeostasis were antagonized by antibiotic intervention, while FMT experiments confirmed that these improvements were mediated through gut microbiota modulation.</div></div><div><h3>Conclusion</h3><div>This study provides new insights into RZD's modulatory effects on gut microbiota and subsequent improvements in obesity-related metabolic parameters. RZD alleviates HFD-induced obesity and insulin resistance in mice by modulating gut microbiota composition and function, which subsequently improves intestinal barrier integrity, reduces inflammation, and enhances metabolic homeostasis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156655"},"PeriodicalIF":6.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683161","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":"Xerophenone H, a naturally-derived proteasome inhibitor, triggers apoptosis and paraptosis in lung cancer","authors":"Wen-Yu Lyu ,&nbsp;Jun Cao ,&nbsp;Wei-Qing Deng ,&nbsp;Mu-Yang Huang ,&nbsp;Hongwei Guo ,&nbsp;Ting Li ,&nbsp;Li-Gen Lin ,&nbsp;Jin-Jian Lu","doi":"10.1016/j.phymed.2025.156647","DOIUrl":"10.1016/j.phymed.2025.156647","url":null,"abstract":"<div><h3>Background</h3><div>Polycyclic polyprenylated acylphloroglucinols (PPAPs) characterized by unique chemical architectures, exhibit diverse pharmacological activities. Xerophenone H (XeH) is a PPAP extracted from the plant <em>Garcinia multiflora</em> Champ. ex Benth. (Clusiaceae) with a novel and unique chemical structure. Although <em>in vitro</em> screening has revealed the anti-cancer activity of XeH, whose <em>in vivo</em> effectiveness and mechanistic basis required systematic investigation.</div></div><div><h3>Methods</h3><div>Cytotoxic effects were evaluated through MTT and colony formation assays. A subcutaneous xenograft model was established to assess <em>in vivo</em> anti-cancer efficacy. To elucidate the underlying mechanism of the anti-cancer effect of XeH, RNA-sequencing and western blotting were performed. A proteasome activity assay was conducted to quantify the effect of XeH. Molecular docking and cellular thermal shift assays were conducted to identify the potential molecular target for XeH.</div></div><div><h3>Results</h3><div>XeH demonstrated concentration-dependent cytotoxicity in A549 cells (IC₅₀ = 12.16 μM at 48 h). Intratumoral administration (10 mg/kg triweekly) achieved 38.6 % tumor growth inhibition. XeH simultaneously triggered apoptosis and paraptosis in A549 and H460 cells. Mechanistically, XeH promoted the formation of protein aggregates and induced significant endoplasmic reticulum stress in lung cancer cells by directly interacting with PSMB5 and inhibiting proteasome activity.</div></div><div><h3>Conclusions</h3><div>XeH, a novel PPAP, was identified as a novel proteasome inhibitor. It effectively downregulated proteasome activity, and induced both apoptosis and paraptosis in lung cancer cells.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156647"},"PeriodicalIF":6.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670813","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":"Embelin improves alcoholic steatohepatitis in alcohol-associated liver disease via ATF6-mediated P2X7r-NLRP3 signaling pathway","authors":"Jin-Jin Zhang ,&nbsp;Jiang-Tao Zhong ,&nbsp;Wan-Ling Wang ,&nbsp;Si-Ying Wang ,&nbsp;Xin Guo ,&nbsp;Hai-Ming Sun ,&nbsp;Jian Song","doi":"10.1016/j.phymed.2025.156638","DOIUrl":"10.1016/j.phymed.2025.156638","url":null,"abstract":"<div><h3>Background</h3><div>Alcohol-associated liver disease (ALD) manifests with impaired lipid metabolism and inflammation within the liver. Embelin (EB), a natural para-benzoquinone compound derived from the <em>Embelia ribes Burm.f.</em> has several pharmacological properties.</div></div><div><h3>Objective</h3><div>This research examines how EB influences the inflammatory milieu of the liver in ALD.</div></div><div><h3>Methods</h3><div><em>In vivo</em>, we created an ALD model by subjecting mice to the Lieber–DeCarli diet for ten days, supplemented by a solitary binge, and subsequent ATF6 silencing. We employed RNA sequencing to analyze the ALD-related signaling pathways. <em>In vitro</em> experiments involved treating AML12 with EB and ethanol, and administering a siRNA-ATF6 to HepG2 cells. We investigated the ATF6 and P2 × 7r promoter interaction through a dual-luciferase assay. Mouse bone marrow-derived macrophages (BMDMs) were also treated with lipopolysaccharide/adenosine triphosphate (LPS/ATP) and EB to produce a conditioned medium.</div></div><div><h3>Results</h3><div>EB effectively mitigated lipid synthesis and the formation of neutrophil extracellular traps (NETs) during ALD. RNA sequencing revealed significant alterations in the ATF6/NOD-like receptor pathway in alcohol-induced mice. EB up-regulated ATF6 while down-regulating P2 × 7r-NLRP3 and its target genes. shRNA-mediated ATF6 knockdown markedly increased P2 × 7r protein and mRNA levels in mouse livers and exacerbated lipid accumulation. The absence of ATF6 in hepatocytes impaired the inhibitory effect of EB on the P2 × 7r-NLRP3 pathway. It was demonstrated that ATF6 directly binds to the P2 × 7r promoter. Moreover, EB reduced pyroptosis in BMDMs, thereby diminishing the inflammatory response.</div></div><div><h3>Conclusions</h3><div>These findings suggest that EB ameliorates alcoholic steatohepatitis (ASH) by modulating the ATF6-P2 × 7r/NLRP3 signaling pathway in ALD. EB might be a prospective therapeutic candidate, and its mechanism would be a new direction or strategy for alcoholic liver disease.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156638"},"PeriodicalIF":6.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642322","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":"TaoHeChengQi Decotion alleviate chronic renal failure via regulation of PHD2/UCP1 and RIPK3/AKT/TGF-β pathway","authors":"Wei Liu ,&nbsp;Cheng Hu ,&nbsp;Xiaojing Qian ,&nbsp;Chunfeng He ,&nbsp;Renze Gu ,&nbsp;Zhenglei Meng ,&nbsp;Dongmei Li ,&nbsp;Qingchuan Zhang","doi":"10.1016/j.phymed.2025.156548","DOIUrl":"10.1016/j.phymed.2025.156548","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Chronic renal failure (CRF) is a late stage in the development of chronic kidney disease (CKD). Currently, there are no specific clinical drugs available. Traditional Chinese medicine (TCM), as a holistic therapeutic approach, may provide new strategies to improve the clinical management of CRF.</div></div><div><h3>Aim of the study</h3><div>This study aimed to investigate the ameliorative effect of TaoHeChengQi Decoction (THCQD) on CRF and to elucidate its potential mechanism.</div></div><div><h3>Materials and methods</h3><div>Animal experiments were performed using 5/6 nephrectomy to establish a model of renal failure in rats, and serum, urine, and kidney samples were collected for study after low, medium, and high doses of (2, 4, and 8 g/kg) of THCQD were given by gavage for 8 consecutive weeks. Cellular experiments were performed using Ang II or TGF-β to stimulate HK-2 cells to produce symptoms similar to those of renal failure in vivo to evaluate the ameliorative effect and mechanism of THCQD. After clarifying the chemical composition of THCQD Tang, this study explored the pathogenesis of the disease by mass spectrometry-based proteomics technology, and used affinity ultrafiltration mass spectrometry, surface plasmon resonance, DARTS, and CETSA to investigate the pharmacological material basis of the compound, which was verified by immunoblotting and and immunofluorescence staining experiments.</div></div><div><h3>Results</h3><div>THCQD attenuated renal injury, renal fibrosis and oxidative stress indices in serum (urine or kidney tissue) of CRF rats. Cellular experiments confirmed that THCQD also protected HK-2 cells from Ang II or TGF-β-induced injury. The mechanism of action was found to be related to the PHD2/UCP1 and RIPK3/AKT/TGF-β pathways by proteomic studies and verified by immunoblotting experiments. In addition, the pharmacodynamic material bases of PHD2/UCP1 and RIPK3/AKT/TGF-β pathways were confirmed to be amygdalin (Amy) and rhein (Rhe), respectively, by AUF-MS, SPR, CETSA and DARTS.</div></div><div><h3>Conclusion</h3><div>THCQD synergistically ameliorates 5/6 nephrectomy-induced CRF by activating PHD2/UCP2-mediated autophagy and targeting RIPK3 and its downstream TGF-β pathway. The basis of the synergistic effects of the above signaling pathways are Amy and Rhe, respectively.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156548"},"PeriodicalIF":6.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670846","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}