Phytomedicine最新文献

{"title":"Network pharmacology and experimental validation of inflammation inhibition by ChuanKeZhi Injection in treating asthma","authors":"Jiaying Yuan ,&nbsp;Yuhan Wang ,&nbsp;Bingxian Sha ,&nbsp;Yunfeng Zhang ,&nbsp;Ondo Osie Eloina Margarita Mokuy ,&nbsp;Mingming Jin ,&nbsp;Li Yu ,&nbsp;Xianghuai Xu","doi":"10.1016/j.phymed.2025.156891","DOIUrl":"10.1016/j.phymed.2025.156891","url":null,"abstract":"<div><h3>Background</h3><div>Chuankezhi injection (CKZ), derived from the traditional Chinese herbs Ying-Yang-Huo (<em>Epimedium brevicornu Maxim</em>) and Ba-Ji-Tian (<em>Morinda officinalis F.C. How</em>), has demonstrated remarkable clinical effects in the treatment of asthma. However, the underlying mechanisms remain unclear.</div></div><div><h3>Purpose</h3><div>This study aims to explore the mechanisms and molecular targets of CKZ in the treatment of asthma, utilizing network pharmacology and molecular biology experiments.</div></div><div><h3>Study Design</h3><div>A combination of network pharmacology and experimental validation was used to identify the specific targets and pathways through which CKZ exerts its effects on asthma. In vitro and in vivo experiments were conducted to further verify the findings.</div></div><div><h3>Methods</h3><div>Liquid chromatography-mass spectrometry (LC/MS) and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry were employed to identify the components of CKZ. GeneCards was used to gather asthma-related targets, and the STRING online database was utilized to construct protein-protein interaction (PPI) networks. Hub genes were identified from the PPI network and analyzed through Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. In vitro and in vivo experiments were conducted to validate the network pharmacology predictions.</div></div><div><h3>Results</h3><div>LC/MS and MALDI-TOF analysis revealed that CKZ is rich in flavonoid compounds. Network pharmacological analysis identified TNF, AKT1, IL-6, GAPDH, and SRC as the top five hub genes. GO and KEGG pathway analyses suggested that CKZ’s effect on asthma is closely associated with mitochondrial function and the mitogen-activated protein kinase (MAPK) signaling pathway. In vivo and in vitro experiments showed that CKZ treatment alleviated airway inflammation and collagen deposition in asthma mouse models, as demonstrated by HE, PAS, and Masson staining. CKZ also reduced the levels of inflammatory cytokines (IL-4, IL-5, IL-13, and TNF-α) in bronchoalveolar lavage fluid (BALF) and serum. Furthermore, CKZ improved mitochondrial damage and inhibited the activation of the MAPK signaling pathway, as confirmed by Western blotting analysis.</div></div><div><h3>Conclusion</h3><div>CKZ effectively alleviates airway inflammation and improves airway damage in asthma by inhibiting the MAPK signaling pathway. These findings suggest that CKZ is a promising therapeutic option for asthma treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156891"},"PeriodicalIF":6.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144185589","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":"Sophora compounds against non-small cell lung cancer: Research status and mechanisms","authors":"Baibai Ye ,&nbsp;Cheng Lin ,&nbsp;Hao Huang ,&nbsp;Ping Chen ,&nbsp;Xinyu Liu ,&nbsp;Keke Wang ,&nbsp;Han Zhang ,&nbsp;Jiahui Liu ,&nbsp;Chenning Zhang ,&nbsp;Linfu Li","doi":"10.1016/j.phymed.2025.156890","DOIUrl":"10.1016/j.phymed.2025.156890","url":null,"abstract":"<div><h3>Background</h3><div>Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer, characterized by dysregulated signaling pathways. Many Sophora compounds exhibit potential anti-NSCLC properties. However, the research status, particularly regarding the underlying mechanisms, remains fragmented.</div></div><div><h3>Purpose</h3><div>To review the research status as well as mechanisms of Sophora compounds against NSCLC.</div></div><div><h3>Methods</h3><div>A systematic review was conducted on publications retrieved from PubMed, Web of Science and CNKI. The retrieval keywords are paired in various forms of \"Sophora compound name\" and \"non-small cell lung cancer\" (including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma). Only experimental (at cell or animal level) or clinical studies demonstrating therapeutic effects of Sophora compounds were included.</div></div><div><h3>Results</h3><div>&gt;52 Sophora compounds have demonstrated potential anti-NSCLC effects through various signaling pathways, primarily targeting apoptosis induction, cell cycle arrest, and metastasis suppression. Investigated signaling pathways mainly include apoptosis, PI3K/Akt/mTOR, MAPK, STAT3/NF-κB, and EGFR signaling. The expression of apoptotic caspases, Bcl-2, Bax, Akt, mTOR, PI3K, Erk, Jnk, p38, STAT3 and NF-κB is frequently assayed. Notably, most researches have focused on cell models of A549 and H1299, primarily on aforementioned signaling pathways at the protein level.</div></div><div><h3>Conclusion</h3><div>Many Sophora compounds, particularly flavonoids, show promise as multi-target agents against NSCLC. However, animal experiments and clinical evidence remain limited, and future studies could prioritize investigations on deeper molecular mechanisms, and on little-explored toxicology.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156890"},"PeriodicalIF":6.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124771","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":"Icaritin induces paraptosis in hepatocellular carcinoma cells by targeting BHLHE40 via endoplasmic reticulum stress and mitochondrial dysfunction","authors":"Wencheng Wei ,&nbsp;Hao Wang ,&nbsp;Li Fu ,&nbsp;Hui Liu","doi":"10.1016/j.phymed.2025.156870","DOIUrl":"10.1016/j.phymed.2025.156870","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;Icaritin, a flavonoid derived from the traditional Chinese medicine &lt;em&gt;Epimedium&lt;/em&gt;, exhibits diverse biological activities; however, the mechanisms underlying its effects against hepatocellular carcinoma (HCC) remain unclear. This study aimed to investigate the anticancer properties of icaritin and elucidate the mechanisms of icaritin-induced cell death.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The effects of icaritin-induced paraptosis were assessed using CellTiter-Glo, EdU, and colony formation assays, and phenotypic observations. Transcriptome analysis was performed to identify the dysregulated genes associated with icaritin-induced paraptosis. Western blotting and qRT-PCR were used to analyze icaritin-induced changes in protein and mRNA levels, respectively. Mito-GFP, ROS, and MMP assays were conducted to monitor the mitochondrial status. IPA, molecular docking, CETSA, shRNA and cell-derived xenografts confirmed the role of &lt;em&gt;BHLHE40&lt;/em&gt; in icaritin-induced paraptosis &lt;em&gt;in vivo&lt;/em&gt; and &lt;em&gt;in vitro&lt;/em&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Icaritin induced paraptosis in HCC cells, which was characterized by cytoplasmic vacuolation and caspase-independent. Transcriptomic analysis indicated that icaritin triggered ER stress and mitochondrial dysfunction, validated by molecular and biochemical assays. IPA, molecular docking, and CETSA analyses identified &lt;em&gt;BHLHE40&lt;/em&gt; as a crucial mediator of this process. &lt;em&gt;BHLHE40&lt;/em&gt; knockdown inhibited ER stress and mitochondrial dysfunction, significantly reducing icaritin-induced paraptosis in HCC cells. Animal experiments demonstrated that silencing of &lt;em&gt;BHLHE40&lt;/em&gt; diminished the inhibitory effects of icaritin on tumor growth in xenograft models.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;These results highlight the potent anticancer effects of icaritin, particularly its ability to induce paraptosis by targeting &lt;em&gt;BHLHE40&lt;/em&gt;. This study provides a comprehensive understanding of the anticancer mechanisms of icaritin and suggests that targeting &lt;em&gt;BHLHE40&lt;/em&gt; represents a novel therapeutic strategy for enhancing the efficacy of cancer treatment.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Abbreviations&lt;/h3&gt;&lt;div&gt;HCC: Hepatocellular carcinoma; TCM: Traditional Chinese Medicine; ER: Endoplasmic Reticulum; MMP: Mitochondrial Membrane Potential; ROS: Reactive Oxygen Species; CTG: CellTiter-Glo; EdU: 5-ethynyl-2′-deoxyuridine; UPR: Unfolded Protein Response; BHLHE40: Basic helix-loop-helix family member E40; IPA: Ingenuity Pathway Analysis; CETSA: Cellular Thermal Shift Assay; PI: Propidium Iodide;PCR: Polymerase Chain Reaction; qRT-PCR: Quantitative Reverse Transcription PCR; GFP: Green Fluorescent Protein; JC-1: 5,5′,6,6′-Tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide; ATF4: Activating Transcription Factor 4; PERK: Protein kinase RNA-like ER kinase; DDIT3: DNA Damage Inducible Transcript 3; LMNA: Lamin A/C; IC50: Half Maximal Inhibitory Concentration; PEG300: Polyethyle","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156870"},"PeriodicalIF":6.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134408","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 attenuates prenatal X-ray-induced microcephaly and adult depression via SIRT1-mediated senescence suppression and TPH2/5-HT pathway restoration in mice","authors":"Yu Feng Zhang,&nbsp;Ze Lin Xu,&nbsp;Chen Wang,&nbsp;Jing Li,&nbsp;Meng Ying Wu,&nbsp;Yi Qi Yi,&nbsp;Ting Wang,&nbsp;Po Bian","doi":"10.1016/j.phymed.2025.156845","DOIUrl":"10.1016/j.phymed.2025.156845","url":null,"abstract":"<div><h3>Background</h3><div>With increasing use of medical imaging (e.g., CT scans) and environmental radiation sources, over 2 % of pregnancies worldwide are inadvertently exposed to low-dose ionizing radiation (IR), raising urgent concerns about fetal neuroprotection. While prenatal IR is implicated in microcephaly and lifelong neuropsychiatric risks, prior studies have not resolved whether sirtuin-mediated pathways, particularly SIRT1/TPH2 signaling, drive these deficits or whether dietary phytochemicals like resveratrol can mitigate them.</div></div><div><h3>Purpose</h3><div>To determine (1) the role of SIRT1/TPH2 signaling in IR-induced neurodevelopmental and psychiatric impairments, and (2) the therapeutic potential of maternal resveratrol supplementation to counteract these effects—a strategy not previously explored in prenatal radiation models.</div></div><div><h3>Study design</h3><div>Mouse cohorts received prenatal X-ray irradiation (0, 1.0 Gy, 2 Gy gestational day 8) with/without resveratrol supplementation, followed by longitudinal cortical and behavioral analyses.</div></div><div><h3>Methods</h3><div>RNA sequencing/Western blotting quantified SIRT1, TPH2, BDNF, and senescence markers (P16, P21 and SA-β-gal). 5-HT levels were assessed by ELISA. Depression-like behaviors were tested via forced swim and tail suspension.</div></div><div><h3>Results</h3><div>IR-exposed fetuses exhibited progressive microcephaly with reduced cortical thickness, accompanied by SIRT1 downregulation, BDNF suppression, and elevated cellular senescence. Adult offspring displayed depression-like behaviors, linked to TPH2 downregulation and diminished 5-HT levels. Resveratrol supplementation normalized SIRT1/TPH2 signaling, restored cortical neurotrophic factors, and attenuated both microcephaly and depressive phenotypes.</div></div><div><h3>Conclusion</h3><div>This study provides the first evidence that (1) SIRT1/TPH2 signaling is a central mediator of IR-induced neurodevelopmental and psychiatric impairments, and (2) maternal resveratrol supplementation prevents cortical damage and depression in offspring by rescuing this pathway. These findings position resveratrol as a novel, mechanism-driven intervention for fetal neuroprotection against environmental radiation.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156845"},"PeriodicalIF":6.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147800","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":"Protective effects of Ginkgo biloba supplementation on clinical outcomes in metabolic dysfunction-associated steatotic liver disease","authors":"Tom Ryu ,&nbsp;Beom Sun Chung ,&nbsp;Jaejun Lee ,&nbsp;Ji Won Han ,&nbsp;Hyun Yang ,&nbsp;Keungmo Yang","doi":"10.1016/j.phymed.2025.156889","DOIUrl":"10.1016/j.phymed.2025.156889","url":null,"abstract":"<div><h3>Background</h3><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health concern linked to increased risks of cardiovascular disease, chronic kidney disease (CKD), and premature mortality. Ginkgo biloba has shown potential therapeutic benefits in conditions characterized by metabolic dysfunction. This study aimed to evaluate the potential protective effects of Ginkgo biloba supplementation on overall survival (OS) and the incidence of cardiovascular and renal outcomes specifically in MASLD patients.</div></div><div><h3>Methods</h3><div>This cohort study included 402,476 participants from the UK Biobank, categorized into MASLD and No steatotic liver disease (SLD) cohorts. Ginkgo biloba users and non-users were compared using inverse probability of treatment weighting to balance baseline characteristics. Clinical outcomes were assessed using Cox proportional hazards models, with subgroup analyses.</div></div><div><h3>Results</h3><div>Ginkgo biloba supplementation was associated with significantly improved OS [hazard ratio (HR) = 0.79, 95 % confidence interval (CI): 0.64–0.98, <em>p</em> = 0.034) and reduced risks of cardiovascular events (HR = 0.82, 95 % CI: 0.66–1.00, <em>p</em> = 0.012) and CKD (HR = 0.73, 95 % CI: 0.56–0.96, <em>p</em> = 0.012) in the MASLD cohort, while no significant benefits were observed in the No SLD cohort. Subgroup analyses indicated enhanced benefits in older adults, males, individuals with BMI ≥ 25 kg/m², and diabetic patients. The beneficial effects were pronounced in patients with advanced fibrosis.</div></div><div><h3>Conclusion</h3><div>Ginkgo biloba supplementation is associated with improved survival and reduced cardiovascular and renal risks in MASLD patients, particularly in high-risk subgroups. These findings highlight the potential of Ginkgo biloba as an adjunctive therapy in MASLD management. This is the first large-scale study to examine the potential impact of Ginkgo biloba supplementation on clinical outcomes in MASLD, with fibrosis-stratified analyses providing insights into its differential effects across disease severity.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156889"},"PeriodicalIF":6.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144137960","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":"Terrestrosin D promotes autophagy and apoptosis of breast cancer cells through PSMD1-dependent activation of P53 pathway","authors":"Li-Ling Jia ,&nbsp;Chen-Jie Wu ,&nbsp;Pei-Wen Ye ,&nbsp;Qian Zhang ,&nbsp;Hua Liu ,&nbsp;Tu-Ping Li ,&nbsp;Xiao-Lei Hu","doi":"10.1016/j.phymed.2025.156883","DOIUrl":"10.1016/j.phymed.2025.156883","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Breast cancer, particularly triple-negative breast cancer (TNBC), poses a significant threat to women's health. In tumor cells, autophagy and apoptosis are double-edged swords, playing complex roles in cancer progression and treatment. This study aimed to investigate whether Terrestrosin D (TED) exerts antitumor effects on TNBC by modulating autophagy and apoptosis, and to elucidate the underlying molecular mechanisms.</div></div><div><h3>Methods</h3><div>The antiproliferative and pro-apoptotic effects of TED on TNBC cells were assessed using CCK-8, EdU assay, Live/Dead staining, and flow cytometry. Autophagy was monitored through immunofluorescence and confocal microscopy. RNA sequencing was performed to identify the pathways and molecular targets involved. The anti-TNBC effects of TED were further evaluated in vivo using tumor xenograft models. Western blotting was conducted to validate the relationship between PSMD1, P53, and TED-induced antitumor activity.</div></div><div><h3>Results</h3><div>TED exhibited significant antitumor effects both in vitro and in vivo. Cellular phenotypic analyses revealed that TED promoted autophagy and apoptosis. Transcriptomic analyses indicated that TED stabilizes P53 expression and activates the P53 signaling pathway by inhibiting the function of PSMD1.</div></div><div><h3>Conclusion</h3><div>TED exhibits potent antitumor effects on TNBC by promoting autophagy and apoptosis. It achieves this through PSMD1 inhibition, stabilizing P53 expression, and activating the P53 pathway. Notably, this study is the first to demonstrate that TED directly targets PSMD1, a key proteasomal regulator, thereby unveiling a novel mechanism for P53 stabilization in TNBC. These findings provide new insights into the therapeutic modulation of the PSMD1 - P53 axis by natural compounds and support the development of TED as a multi-functional agent for aggressive breast cancers.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156883"},"PeriodicalIF":6.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115060","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":"Erchen Decoction ameliorates the rat model of polycystic ovary syndrome by regulating the steroid biosynthesis pathway","authors":"Jinrong Zhang ,&nbsp;Hongming Huang ,&nbsp;Min Xiao ,&nbsp;Xiaocui Jiang ,&nbsp;Yong Yang ,&nbsp;Min Huang ,&nbsp;Shang Wang ,&nbsp;Biran Zhu ,&nbsp;Min Zhao","doi":"10.1016/j.phymed.2025.156852","DOIUrl":"10.1016/j.phymed.2025.156852","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;&lt;strong&gt;:&lt;/strong&gt; Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder associated with chronic inflammation and metabolic issues, including insulin resistance, weight gain, and lipid imbalance. It may cause infertility, menstrual irregularities, and increase the likelihood of developing type 2 diabetes, immune system disturbances, and cardiovascular conditions.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To identify the key components, underlying mechanisms, and therapeutic targets of Erchen decoction (ECD) for treating PCOS.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Abbreviations: Abi group, abiraterone group; AKR, aldo-keto reductase; AMH, anti-Müllerian hormone; BC, betweenness; BP, biological process; BSA, bovine serum albumin; CC, cellular component; CCK-8, cell counting kit-8; Con group, control group; DC, degree centrality; DDA, data-dependent acquisition; DHEA, dehydroepiandrosterone; DHEAS, DHEA sulfate; DHT, dihydrotestosterone; ECD, Erchen decoction; Ecd group, Erchen decoction group; ELISA, enzyme-linked immunosorbent assay; E2, estradiol; FSH, follicle-stimulating hormone; GO, gene ontology; HE, hematoxylin and eosin; H-Ecd group, high-dose Erchen decoction group; HFD, high-fat diet; HSD, hydroxysteroid dehydrogenases; KEGG, Kyoto encyclopedia of genes and genomes; KGN, human granulosa-like tumor cells; LAC, local average connectivity; l-Ecd group, low-dose Erchen decoction group; LH, luteinizing hormone; Met group, metformin (Glucophage) group; MF, molecular function; MIS, Müllerian inhibiting substance; MST, microscale thermophoresis; PCOS model group, PCOS group; PCA, principal component analysis; PCOS, polycystic ovary syndrome; PPI, protein–protein interaction; T, testosterone; TCM, traditional Chinese medicine; Tcm group, traditional Chinese medicine group; UHPLC, ultra-high-performance liquid chromatography Bioinformatics was used to predict the targets of ECD components for treating PCOS. Sprague–Dawley rats were assigned to control (Con) and PCOS model groups. The latter was induced via letrozole (Femara) gavage (1 mg/kg) combined with a high-fat diet. The PCOS group was then subdivided for 28 days of intervention. Body weight was recorded, ovarian morphology was assessed through hematoxylin and eosin staining, and serum hormones were quantified using enzyme-linked immunosorbent assay. Proteomic analyses were performed to examine the underlying mechanisms and potential targets, which were validated using immunofluorescence, western blotting, and RT-qPCR. The pharmacological effects of the key ECD components were confirmed in dihydrotestosterone (DHT)-treated human granulosa KGN cells.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The body weight of the rats in the Con and high-dose ECD (H-Ecd) groups decreased compared with that in the PCOS group. The H-Ecd and metformin (Glucophage) groups had significantly elevated levels of testosterone (T), luteinizing hormone, anti-Müllerian hormone (","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156852"},"PeriodicalIF":6.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144178122","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":"Ginsenoside Rg1 alleviates cognitive impairment in vascular dementia by modulating Adcy1/Kdr–mediated cholinergic synapse and PI3K–AKT pathway","authors":"Yuheng Wang ,&nbsp;Xiaolu Wei ,&nbsp;Huijun Wang ,&nbsp;Yan Zhang ,&nbsp;Pengyue Li ,&nbsp;Yawen Zhou ,&nbsp;Shan Jiang ,&nbsp;Yan Rong ,&nbsp;Lihua Chen ,&nbsp;Haiyu Zhao","doi":"10.1016/j.phymed.2025.156882","DOIUrl":"10.1016/j.phymed.2025.156882","url":null,"abstract":"<div><h3>Background</h3><div>Vascular dementia (VD), a prevalent neurodegenerative disorder that stems from chronic cerebral hypoperfusion, poses a substantial clinical challenge given the scarcity of efficacious treatment options. While ginsenoside Rg1 (Rg1) has demonstrated neuroprotective and antioxidative effects in various models of neurodegenerative disease, the mechanisms underlying its therapeutic potential in VD pathogenesis have yet to be systematically elucidated.</div></div><div><h3>Purpose</h3><div>This study investigate the therapeutic potential of Rg1 in VD using a bilateral common carotid artery occlusion (2–VO) rat model and simultaneously explored the molecular mechanisms underlying its pharmacological effects.</div></div><div><h3>Methods</h3><div>To systematically assess the therapeutic efficacy of Rg1 on VD, we employed a well–established rat model of 2–VO. Behavioral outcomes were evaluated using standardized tests, histopathological changes were analyzed following histologic staining, and oxidative stress markers were quantified through biochemical analyses. Additionally, untargeted metabolomic profiling of serum and brain tissues was performed using UPLC–LTQ–Orbitrap MS, followed by targeted metabolomics to quantify essential amino acids and neurotransmitters. Additionally, integrated network pharmacology, transcriptomics, molecular docking, microscale thermophoresis (MST), qRT–PCR and western blotting were performed to facilitate a detailed investigation of the therapeutic potential of Rg1 and its molecular mechanisms in VD.</div></div><div><h3>Results</h3><div>Rg1 significantly ameliorated cognitive deficits and neuronal damage in rats with VD. Metabolomics revealed its unique ability to restore amino acid homeostasis and rebalance key neurotransmitters, including acetylcholine and glutamate. Mechanistically, Rg1 activated Adcy1 and Kdr, in turn enhancing cholinergic synapse integrity, and modulating the PI3K–AKT pathway to attenuate oxidative stress. Notably, molecular docking simulations displayed robust binding interactions between Rg1 and target proteins (all binding energies &lt;–7 kcal/mol), and microscale thermophoresis (MST), qRT–PCR and western blotting findings revealed high consistency with multi–omics predictions.</div></div><div><h3>Conclusion</h3><div>Thie findings of this reveals novel evidence that Rg1 alleviates VD by restoring amino acid homeostasis and neurotransmitter equilibrium, thereby activating Adcy1/Kdr–mediated cholinergic synapse and PI3K–AKT signaling pathway. These results position Rg1 as a promising phototherapeutic candidate for VD treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156882"},"PeriodicalIF":6.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134407","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":"Hyperoside alleviates zearalenone-induced liver injury by regulating mitochondrial calcium overload mediated excessive autophagy","authors":"Tianyu Han ,&nbsp;Lulu Wang ,&nbsp;Yan jiang ,&nbsp;Shanshan Fei ,&nbsp;Yiding Liu ,&nbsp;Zhijun Liu ,&nbsp;Tong Wang ,&nbsp;Baiwen Guan ,&nbsp;Yu Yang ,&nbsp;Guangliang Shi","doi":"10.1016/j.phymed.2025.156880","DOIUrl":"10.1016/j.phymed.2025.156880","url":null,"abstract":"<div><h3>Background</h3><div>Zearalenone (ZEA), one of the most common mycotoxins in moldy plants, can cause ferroptosis in the liver. Hyperoside (Hyp) is mainly derived from <em>Hypericum perforatum</em> and exerts hepatoprotective, neuroprotective, and cardioprotective effects. It is not known whether Hyp alleviates ZEA-induced ferroptosis-related damage</div></div><div><h3>Aim</h3><div>The protective effect of Hyp on ZEA-induced liver injury was studied and its underlying mechanisms were elucidated.</div></div><div><h3>Methods</h3><div>The protective effect of Hyp on ZEA-induced liver injury was determined based on ALT and AST levels and by using H&amp;E staining and transmission electron microscopy. The protective effect of Hyp in attenuating ferroptosis was determined by measuring mitophagy- and ferroptosis-related indices. CETSA and siRNA transfection were used to determine the targeting of Hyp to MCU protein.</div></div><div><h3>Results</h3><div>Hyp attenuated ZEA-induced ferroptosis and excessive mitophagy in hepatocytes, and use of Hyp or FUNDC1 knockdown by siRNA decreased ferroptosis in AML12 cells. Furthermore, Hyp attenuated ZEA exposure–induced Gpx4 interaction with FUNDC1 and reversed the recruitment and degradation of glutathione peroxidase 4 to mitochondria. Hyp was found to target MCU protein to attenuate mitochondrial Ca²⁺ overload and mitophagy induced by upregulated ZEA exposure. MCU knockdown reversed ZEA-induced mitophagy. Hyp also reversed ZEA-induced excessive mitochondrial fission and impairment in mitochondrial function.</div></div><div><h3>Conclusion</h3><div>Our study demonstrated that Hyp could alleviate ZEA induced ferroptosis by targeting MCU to inhibit mitochondrial Ca²⁺overloaded mitophagy.Our findings provide evidence for Hyp as an effective treatment in alleviating ferroptosis-related liver injury.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156880"},"PeriodicalIF":6.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147799","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":"Neuroprotective effects of Gastrodia elata and its compounds in a Caenorhabditis elegans Alzheimer’s disease model","authors":"Yanqing Zhang ,&nbsp;Xiaotong Zhao ,&nbsp;Li Gong ,&nbsp;Changjiangsheng Lai ,&nbsp;Jing Liu ,&nbsp;Junbo Xie","doi":"10.1016/j.phymed.2025.156876","DOIUrl":"10.1016/j.phymed.2025.156876","url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by learning and memory impairments, primarily caused by excessive β-amyloid protein (Aβ) accumulation, which induces neurotoxicity and metabolic dysfunction. Gastrodia elata (GE), a medicinal herb, has demonstrated antioxidant, antidepressant, and neuroprotective properties, making it a promising candidate for treating neurological diseases. However, systematic studies on its active compounds improving learning and memory through targeted metabolomics remain limited.</div></div><div><h3>Purpose</h3><div>This study aimed to evaluate the neuroprotective effects of Gastrodia elata (GE) and its active compounds, with a specific focus on learning and memory impairments in Alzheimer’s disease.</div></div><div><h3>Methods</h3><div>Using Caenorhabditis elegans (<em>C. elegans</em>) models of AD, the effects of GE and its active compounds were assessed through chemotaxis assays, targeted metabolomics, and LC-QQQ-MS analysis. Key neurotransmitter levels, including l-Leucine (l-Leu), l-Phenylalanine (l-Phe), γ-aminobutyric acid (GABA), and Acetylcholine (ACh), were quantified. The study also utilized principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) to investigate metabolic biomarkers.</div></div><div><h3>Results</h3><div>Parishin E (BG E) was identified as the most effective compound in reducing Aβ levels and modulating key biomarkers associated with learning and memory impairments. LC-QQQ-MS analysis showed that BG E restored neurotransmitter levels closer to those of healthy controls. GE extracts (100 μg/ml) and the positive control Huperzine A (Hup A, 8 μg/ml) significantly delayed paralysis in AD C. elegans models. PCA and OPLS-DA analyses confirmed that BG E normalized metabolic biomarkers and key neurotransmitter levels associated with AD.</div></div><div><h3>Conclusion</h3><div>These findings highlight the therapeutic potential of Gastrodia elata, particularly its active compound Parishin E (BG E), in mitigating learning and memory impairments in Alzheimer’s disease. This study provides a foundation for further validation in advanced models and supports the development of natural therapeutics for neurological disorders.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156876"},"PeriodicalIF":6.7,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144107597","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}