Phytomedicine最新文献

{"title":"Targeting STING and protecting mitochondrial function with Nephropathy Ⅱ decoction to alleviate renal fibrosis","authors":"Yujiu Gao ,&nbsp;Tingting Wei ,&nbsp;Linjie Mu ,&nbsp;Chen Liu ,&nbsp;Yini Zeng ,&nbsp;Xingrong Guo ,&nbsp;Yong Zhang ,&nbsp;Zhengzhong Yuan ,&nbsp;Jinguo Cheng","doi":"10.1016/j.phymed.2025.156785","DOIUrl":"10.1016/j.phymed.2025.156785","url":null,"abstract":"<div><h3>Background</h3><div>Nephrology II Decoction (NED), a compound from traditional Chinese medicine, has been used in the clinical treatment of chronic kidney disease (CKD) for a long time. However, the specific active ingredients and the mechanisms by which they operate are not yet fully understood.</div></div><div><h3>Objective</h3><div>The study aims to explore how NED eases CKD, with an emphasis on its influence on stimulator of interferon genes (STING)-mediated mitochondrial balance within kidney cells.</div></div><div><h3>Methods</h3><div>Various CKD mouse models, including folic acid nephropathy (FAN), unilateral ureteral obstruction (UUO), and bilateral renal ischemia-reperfusion injury (bIRI), were administered with NED via oral gavage for three weeks. This study evaluated kidney function, pathological alterations, and fibrosis markers (fibronectin, collagen I, TGF-β, α-SMA) were assessed. Bulk RNA-sequencing of kidney tissues identified key targets, with molecular docking, dynamics simulations, and microscale thermophoresis were used to predict active components and pathways. These components and pathways were confirmed in renal tissues from CKD mice and renal tubular cells induced by folic acid. Additionally, oxidative stress induced by Tert‑butyl hydroperoxide (t-BHP) in HK2 cells was used to replicate CKD-induced renal fibrosis <em>in vitro</em>.</div></div><div><h3>Results</h3><div>NED significantly improved renal function, reduced pathological damage, and decreased fibrosis in mice with CKD. Bulk RNA-seq identified STING as a pivotal target, and molecular docking demonstrated a strong binding affinity between NED's active components and murine STING. NED inhibited the cGAS/STING/TBK1/IRF3/IFN-β pathway, thereby alleviating renal fibrosis. It also corrected defects in mitochondrial oxidative phosphorylation, diminished inflammatory responses, and reduced apoptosis in fibrotic kidneys. <em>In vitro</em>, NED prevented mitochondrial DNA leakage induced by t-BHP, preserved mitochondrial function, and suppressed STING activation. STING inhibitor C176 effectively reduced fibrosis in both FAN mice and folic acid -induced cells, whereas the STING agonist DMXAA intensified fibrosis. There were potential interactions observed when DMXAA was combined with NED.</div></div><div><h3>Conclusions</h3><div>This study clarified the anti-fibrotic mechanisms of NED through the cGAS/STING pathway, highlighting STING as a primary target and the involvement of mitochondrial phosphorylation. NED appears to be a promising candidate for the treatment of CKD and reductions of renal fibrosis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156785"},"PeriodicalIF":6.7,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868325","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":"A comprehensive pharmacology study reveals the molecular mechanisms underlying the antidepressant effects of Gastrodiae Rhizoma","authors":"Pei Liu ,&nbsp;Zhihuang Zhao ,&nbsp;Haili Zhang ,&nbsp;Chenghong Xiao ,&nbsp;Meidan Wang ,&nbsp;Chengyan Yang ,&nbsp;Yu-e Liu ,&nbsp;Lulu Wang ,&nbsp;Hui He ,&nbsp;Yangyan Ge ,&nbsp;Yan Fu ,&nbsp;Tao Zhou ,&nbsp;Zili You ,&nbsp;Jinqiang Zhang","doi":"10.1016/j.phymed.2025.156761","DOIUrl":"10.1016/j.phymed.2025.156761","url":null,"abstract":"<div><h3>Background</h3><div>Gastrodiae Rhizoma (GR) and its extract have been widely used in the treatment of depression, but the underlying mechanism of its antidepressant effects is unclear due to its numerous components.</div></div><div><h3>Purpose</h3><div>Revealing the cellular and molecular mechanisms underlying the antidepressant effects of GR through a comprehensive pharmacology-based in vivo and in vitro investigation.</div></div><div><h3>Methods</h3><div>A mouse model of depression was established using chronic mild stress (CMS) procedure, and the antidepressant effects of GR were evaluated using systematic behavior. Metabolites in GR decoction and in mouse brain were identified by UPLC-QTOF-MS technology. Core components and targets of GR against MDD were screened based on network pharmacology analysis and molecular docking. The mechanism through which GR mitigated MDD was explored using transcriptome analysis, immunohistochemistry and western blotting in vitro and in vivo.</div></div><div><h3>Results</h3><div>A total of 273 components were identified in the GR decoction, out of which 15 were detected in the brain of depressed mice treated with the GR decoction. We further identified nine key active ingredients, six essential targets, and fifth signaling pathways associated with the therapeutic effects of GR against MDD. We confirmed that the active ingredients of GR can target the neural stem/precursor cells (NSPCs) in the hippocampus of depressed mice to promote neurogenesis, as evidenced by a significant increase in the numbers of DCX⁺ cells, BrdU⁺ cells, BrdU⁺-DCX⁺ cells, and BrdU⁺-NeuN⁺ cells within the hippocampus of GR-treated mice compared to salinetreated mice under CMS exposure. Moreover, we have identified that the key active constituents of GR, namely gastrodin and parishin C, exert a targeted effect on EGFR to activate PI3K-Akt signaling in NSPCs, thereby facilitating proliferation and differentiation of NSPCs.</div></div><div><h3>Conclusion</h3><div>The antidepressant effect of GR involves the facilitation of PI3K/Akt-mediated neurogenesis through gastrodin and parishin C targeting EGFR in NSPCs.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156761"},"PeriodicalIF":6.7,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting mitochondrial DNA-STING-NF-κB Axis-mediated microglia activation by cryptotanshinone alleviates ischemic retinopathy","authors":"Wanlu Qiu ,&nbsp;Zhihua Zheng ,&nbsp;Jiaojiao Wang ,&nbsp;Youran Cai ,&nbsp;Jiami Zou ,&nbsp;Ziqing Huang ,&nbsp;Pinglian Yang ,&nbsp;Weile Ye ,&nbsp;Mei Jin ,&nbsp;Dongmei Zhang ,&nbsp;Peter J Little ,&nbsp;Qing Zhou ,&nbsp;Zhiping Liu","doi":"10.1016/j.phymed.2025.156779","DOIUrl":"10.1016/j.phymed.2025.156779","url":null,"abstract":"<div><h3>Background</h3><div>Ischemic retinopathy, a leading cause of vision impairment, involves oxidative stress and dysregulated inflammation, with microglia playing a key role. Cryptotanshinone (CTS), a bioactive compound from <em>Salvia miltiorrhiza</em>, exhibits anti-inflammatory and antioxidant properties and thus has the potential for development as a therapeutic agent. However, the actual mechanism of action of CTS in ischemic retinopathy is not known. Overactivation of the STING pathway in microglia is critical in ischemic retinopathy pathogenesis and a potential target of CTS.</div></div><div><h3>Purpose</h3><div>This study aimed to explore whether CTS alleviates ischemic retinopathy by modulating microglial STING signaling.</div></div><div><h3>Methods</h3><div>Oxygen-induced retinopathy (OIR) mice and hypoxia-induced microglial cells were used. CTS efficacy in ischemic retinopathy was evaluated at multiple stages using fluorescein fundus angiography, electroretinogram, H&amp;E staining, and Western blotting of relevant proteins. Network pharmacology and RNA sequencing identified STING as a key target. Furthermore, surface plasmon resonance (SPR), molecular docking, and site-directed mutagenesis were systematically employed to elucidate the precise binding interface between CTS and the STING protein. STING activation and knockout models were employed to further investigate the mechanisms of action of CTS.</div></div><div><h3>Results</h3><div>CTS treatment reduced microglial activation and pathological retinal angiogenesis, and protected both retinal function and structure in OIR mice. Network pharmacology, RNA sequencing, and experimental validation demonstrated a significant link between the protective effect of CTS and the inhibition of STING signaling. Mechanistically, CTS suppressed cytosolic mtDNA release, blocked STING translocation from the ER to the Golgi, and enhanced lysosomal STING degradation. These CTS-mediated effects were abolished by STING activation and absent in <em>Sting</em>-deficient OIR mice. Notably, CTS combined with anti-VEGF therapy showed synergistic efficacy in suppressing pathological retinal neovascularization.</div></div><div><h3>Conclusion</h3><div>CTS, a natural inhibitor of STING, alleviated ischemic retinopathy by inhibiting the mtDNA-STING-NF-κB signaling pathway via multifaceted mechanisms in microglia.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156779"},"PeriodicalIF":6.7,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868323","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":"The extract of chrysanthemum flos mitigates post-stroke sarcopenia by inhibiting PANoptosis and restoring muscle homeostasis","authors":"Hu Qi ,&nbsp;Xiongwei Zhang ,&nbsp;Zeyang Zhang ,&nbsp;Yuanlin Gao ,&nbsp;Dan Tian ,&nbsp;Ge Zhao ,&nbsp;Zhiqiang Xie ,&nbsp;Jiuseng Zeng ,&nbsp;Lihong Zhang ,&nbsp;Nan Zeng ,&nbsp;Ruocong Yang","doi":"10.1016/j.phymed.2025.156784","DOIUrl":"10.1016/j.phymed.2025.156784","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Sarcopenia and muscle weakness are prevalent complications of ischemic stroke (IS), with limited pharmacological options. This study identifies high-dose extracts of Chrysanthemum Flos (ECF) as a potential therapy for post-stroke muscle dysfunction by targeting PANoptosis—a pro-inflammatory programmed cell death pathway. Through its anti-inflammatory and antioxidant properties, ECF attenuates muscle atrophy and enhances functional recovery, offering novel insights into ISS treatment.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;To evaluate the therapeutic efficacy of high-dose ECF in ischemic stroke-induced sarcopenia (ISS) and elucidate its regulatory role in PANoptosis-mediated muscle degeneration and protein homeostasis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Preparation of a rat middle cerebral artery occlusion (MCAO) model using intravascular wire thrombus blockade. Cerebral injury was assessed using laser speckle contrast imaging, triphenyltetrazolium chloride (TTC) staining, and Zea-Longa neurological scoring. ECF's effects on muscle function were evaluated through gait analysis, muscle morphology (length and weight), grip strength, electromyography, and H&amp;E staining. RNA sequencing was conducted to elucidate transcriptomic alterations and enriched pathways associated with ECF in ISS. PANoptosis-mediated myofiber and L6 cell damage was analyzed by flow cytometry (FC), immunofluorescence (IF), immunohistochemistry (IHC), and western blotting (WB). ECF composition and quality were validated using liquid chromatography-mass spectrometry (LC-MS).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;ISS rats showed 83 % reductions in endurance, grip strength, and EMG signals compared to sham (&lt;em&gt;p&lt;/em&gt; &lt; 0.01), which improved to 70 % of normal after ECF treatment. ECF significantly increased muscle fiber area, alleviated mitochondrial damage, and improved sarcomere structure (&lt;em&gt;p&lt;/em&gt; &lt; 0.001). RNA-seq identified TNF signaling and PANoptosis (apoptosis, pyroptosis, necroptosis) as key drivers of ISS-induced muscle injury. The TNF-targeted inhibitor R7050 further confirmed TNF-α as a critical activator of Z-DNA binding protein 1 (ZBP1). ECF treatment significantly reduced tissue inflammation (&lt;em&gt;p&lt;/em&gt; &lt; 0.01) and inhibited ZBP1 expression (&lt;em&gt;p&lt;/em&gt; &lt; 0.01). Following ISS, key PANoptosis-related proteins, including ZBP1, Gasdermin D N-terminal fragment (GSDMD-N), Cleaved-Caspase3, Caspase6, Caspase8, phosphorylated mixed-lineage kinase domain-like (p-MLKL), Phosphorylated Receptor-Interacting Protein Kinase 1 (p-RIPK1), Phosphorylated Receptor-Interacting Protein Kinase 3 (p-RIPK3), and NOD-like receptor family pyrin domain containing 3 (NLRP3), were significantly upregulated (&lt;em&gt;p&lt;/em&gt; &lt; 0.05), while ECF-H treatment significantly suppressed their expression (&lt;em&gt;p&lt;/em&gt; &lt; 0.05, &lt;em&gt;p&lt;/em&gt; &lt; 0.01). Additionally, ECF significantly promoted the expression of muscle protein synthesis factors (myogenic differentiati","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156784"},"PeriodicalIF":6.7,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891853","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":"Natural products and ferroptosis: A novel approach for heart failure management","authors":"Zeyu Zhang ,&nbsp;Zhihua Yang ,&nbsp;Shuai Wang ,&nbsp;Xianliang Wang ,&nbsp;Jingyuan Mao","doi":"10.1016/j.phymed.2025.156783","DOIUrl":"10.1016/j.phymed.2025.156783","url":null,"abstract":"<div><h3>Background</h3><div>The discovery of ferroptosis has brought a revolutionary breakthrough in heart failure treatment, and natural products, as a significant source of drug discovery, are gradually demonstrating their extraordinary potential in regulating ferroptosis and alleviating heart failure symptoms. In addition to chemically synthesized small molecule compounds, natural products have attracted attention as an important source for discovering compounds that target ferroptosis in treating heart failure.</div></div><div><h3>Purpose</h3><div>Systematically summarize and analyze the research progress on improving heart failure through natural products' modulation of the ferroptosis pathway.</div></div><div><h3>Methods</h3><div>By comprehensively searching authoritative databases like PubMed, Web of Science, and China National Knowledge Infrastructure with keywords such as “heart failure”, “cardiovascular disease”, “heart disease”, “ferroptosis”, “natural products”, “active compounds”, “traditional Chinese medicine formulas”, “traditional Chinese medicine”, and “acupuncture”, we aim to systematically review the mechanism of ferroptosis and its link with heart failure. We also want to explore natural small-molecule compounds, traditional Chinese medicine formulas, and acupuncture therapies that can inhibit ferroptosis to improve heart failure.</div></div><div><h3>Results</h3><div>In this review, we not only trace the evolution of the concept of ferroptosis and clearly distinguish it from other forms of cell death but also establish a comprehensive theoretical framework encompassing core mechanisms such as iron overload and system xc-/GSH/GPX4 imbalance, along with multiple auxiliary pathways. On this basis, we innovatively link ferroptosis with various types of heart failure, covering classic heart failure types and extending our research to pre-heart failure conditions such as arrhythmia and aortic aneurysm, providing new insights for early intervention in heart failure. Importantly, this article systematically integrates multiple strategies of natural products for interfering with ferroptosis, ranging from monomeric compounds and bioactive components to crude extracts and further to traditional Chinese medicine formulae. In addition, non-pharmacological means such as acupuncture are also included.</div></div><div><h3>Conclusion</h3><div>This study fills the gap in the systematic description of the relationship between ferroptosis and heart failure and the therapeutic strategies of natural products, aiming to provide patients with more diverse treatment options and promote the development of the heart failure treatment field.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156783"},"PeriodicalIF":6.7,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874355","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":"Gastrodin attenuates hypercholesterolaemia through regulating the PCSK9/LDLR signalling pathway by suppressing HNF-1α and activating FoxO3a","authors":"Yaowen Zhang ,&nbsp;Lan Han ,&nbsp;Qiyuan Ning ,&nbsp;Xixi Zhang ,&nbsp;Menglian Zhang ,&nbsp;Jinyong Peng ,&nbsp;Hao Chen ,&nbsp;Zhiwei Zhao ,&nbsp;Dandan Wang","doi":"10.1016/j.phymed.2025.156778","DOIUrl":"10.1016/j.phymed.2025.156778","url":null,"abstract":"<div><h3>Background</h3><div>Hypercholesterolaemia is a prevalent etiological factor of cardiovascular diseases (CVDs). Gastrodin (Gas), the paramount active constituent in <em>Gastrodia elata</em> Bl<em>.</em>, has lipid-lowering and anti-inflammatory properties for the treatment of CVDs. Nevertheless, the underlying mechanism responsible for hypolipidemic efficacy remains to be elucidated. The signalling pathwayof PCSK9/LDLR is a key signalling pathway that regulates cholesterol metabolism.</div></div><div><h3>Purpose</h3><div>This investigation elucidated whether Gas has an inhibitory effect on hypercholesterolaemia and whether this effect is associated with the regulation of the PCSK9/LDLR signalling pathway.</div></div><div><h3>Methods</h3><div>We induced hypercholesterolaemia of mice by feeding them a high-fat diet (HFD) for 12 weeks to analyse the therapeutic effects and related pathways of Gas <em>in vivo. In vitro</em>, western blotting, qRT-PCR, molecular docking, and transfection were employed to verify the molecular mechanism of action of Gas in the treatment of hypercholesterolaemia.</div></div><div><h3>Results</h3><div>Gas exhibited potent therapeutic effects against hypercholesterolaemia in HFD mice. Moreover, the HFD-induced hepatic lipid accumulation and liver damage were attenuated by Gas. Mechanistically, Gas decreased the expression of PCSK9 via inhibiting the JAK2/STAT3 signalling pathway to suppress HNF-1α and promote FoxO3a. In addition, Gas increased LDLR transcription via SREBP2 activation.</div></div><div><h3>Conclusion</h3><div>Collectively, our data provide new insights into the prevention and treatment of hyperlipidaemia by Gas.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156778"},"PeriodicalIF":6.7,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868392","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":"Semen Ziziphi Spinosae alleviates cardiomyocyte apoptosis in rats with coronary heart disease via the AMPK/SIRT1/PGC-1α signaling pathway activation","authors":"Anqi Bi,&nbsp;Rihong Liu,&nbsp;Min Xie,&nbsp;Bosai He,&nbsp;Tingxu Yan,&nbsp;Yiyang Du,&nbsp;Ying Jia","doi":"10.1016/j.phymed.2025.156743","DOIUrl":"10.1016/j.phymed.2025.156743","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Coronary heart disease (CHD) represents a significant cardiovascular condition, with its occurrence increasing as a result of alterations in lifestyle and dietary habits. Semen Ziziphi Spinosae (SZS) is commonly utilized for the management of disorders associated with the nervous system, including conditions like depression and insomnia. Recent research has revealed its potential therapeutic properties for cardiovascular issues. Nevertheless, there exists a limited amount of research addressing the mechanisms involved.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This research seeks to explore the protective effects that SZS has on cardiac tissue, specifically within the framework of CHD. By conducting this investigation, the study aims to uncover the various mechanisms that play a role in these protective effects. This understanding could yield significant insights into how SZS may result in the preservation and enhancement of cardiac health in patients affected by CHD.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Study design&lt;/h3&gt;&lt;div&gt;The study innovatively combines multiple advanced techniques. It first integrates UPLC-Q-TOF/MS analysis and network pharmacology to identify SZS components. In vitro experiments were conducted using H9c2 rat cardiomyocytes, and in vivo experiments used a CHD model in SD rats. Multiple assays were performed for multi - level and multi - dimensional validation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;In the initial stage, the primary components of SZS and their possible mechanisms for combating CHD were examined through UPLC-Q-TOF/MS analysis in conjunction with network pharmacology approaches.&lt;/div&gt;&lt;div&gt;For the in vitro investigation, an ischemia-hypoxia model was established utilizing H9c2 rat cardiomyocytes. The CCK-8 assay was used to assess myocardial injury markers. TUNEL staining and Western blot techniques were employed to confirm the impact of SZS treatment on apoptosis in H9c2 cells. The expression levels of proteins associated with the AMPK/SIRT1/PGC-1α signaling pathway were measured using RT-qPCR and Western blotting, and the results were validated with the AMPK inhibitor, compound C.&lt;/div&gt;&lt;div&gt;In the in vivo segment, a model of coronary heart disease (CHD) in SD rats was established through the administration of a high-fat emulsion diet combined with pituitrin injections. Cardiac function in the rats was evaluated through electrocardiograms and echocardiograms. Pathological changes in the heart were observed utilizing TTC and H&amp;E staining. Kits were implemented to measure the serum biochemical indicators in the rats.RT - qPCR and Western blotting were employed to measure the expression levels of proteins related to the AMPK/SIRT1/PGC - 1α signaling pathway.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The study identified 67 in vitro components, 27 blood - absorbed components, and 12 metabolic components of SZS. Network pharmacology analysis suggested the AMPK/SIRT1/PGC - 1α signaling pathway as a key mechanism.","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156743"},"PeriodicalIF":6.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844385","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":"Berbamine targets the FKBP12-rapamycin-binding (FRB) domain of the mTOR complex to promote microglial autophagy and ameliorate neuroinflammation in Alzheimer’s disease","authors":"Pingyuan Ge ,&nbsp;Siqi Guo ,&nbsp;Pingping Wang ,&nbsp;Peng Zhou ,&nbsp;Zhishu Tang ,&nbsp;Nianyun Yang ,&nbsp;Rui Guo ,&nbsp;Qingqing Xiao ,&nbsp;Xin Chai ,&nbsp;Qichun Zhang ,&nbsp;Huaxu Zhu","doi":"10.1016/j.phymed.2025.156771","DOIUrl":"10.1016/j.phymed.2025.156771","url":null,"abstract":"<div><h3>Background</h3><div>Berbamine (BBM), a natural bisbenzylisoquinoline alkaloid, has demonstrated promising effects in ameliorating pathological process and inflammation response in central neuronal system (CNS). Alzheimer’s disease (AD), primarily characterized by amyloid-beta (Aβ)-containing extra-cellular plaques and abnormal “autophagy-brake regulation” of neuroinflammation, currently lacks of effective therapeutic options. Therapeutics of BBM on AD is indeed intriguing, and the potential targets and mechanisms are vague yet.</div></div><div><h3>Purpose</h3><div>This study is designed to elucidate the therapeutic potential of BBM on AD, focusing particularly on its ability to enhance autophagy, induce microglial M2 polarization, and to uncover the underlying molecular mechanisms and implicated targets.</div></div><div><h3>Methods</h3><div>The therapeutic efficacy of BBM was systematically investigated in APP/PS1 mice, with a focus on its potential to enhance autophagy, induce M2 polarization in microglia, and facilitate the clearance of Aβ plaques. Cognitive function was rigorously assessed through a series of behavioral tests, including the Morris Water Maze and Object Location Task. Immunofluorescence was employed to visualize the spatial distribution of inflammatory cytokines and autophagic markers within the brain parenchyma. Quantitative measurements of these cytokines were obtained using enzyme-linked immunosorbent assay (ELISA). Western blotting was utilized to analyze protein profiles associated with autophagy and microglial phenotypes. Additionally, chemo-proteomics and molecular docking techniques were applied to identify the key molecular targets of BBM.</div></div><div><h3>Results</h3><div>BBM treatment significantly ameliorated cognitive dysfunction and reduced Aβ plaque deposition in APP/PS1 transgenic mice. Notably, BBM promoted microglial polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, accompanied by attenuation of neuroinflammation. Mechanistically, BBM exerted its effects through inhibition of mTOR signaling via direct interaction with the FKBP12-rapamycin-binding domain, thereby restoring autophagic flux and facilitating M2 microglial polarization. The mTOR activator MHY1485 abrogated the beneficial effects of BBM, highlighting the pivotal role of mTOR inhibition in its mechanism of action.</div></div><div><h3>Conclusions</h3><div>BBM promotes M2 microglial polarization and restores autophagic flux in AD by inhibiting mTOR signaling, representing a novel dual-modulatory mechanism for AD intervention. These findings highlight BBM’s ability to target mTOR and intersecting pathways, offering a promising disease-modifying therapeutic approach for AD and other neurodegenerative disorders.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156771"},"PeriodicalIF":6.7,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868391","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":"Neixiao-ruanmai decoction No 2 improves carotid atherosclerosis by modulating gut microbiota and inhibiting TLR4/NF-κB pathway activation","authors":"Hanrui Ji ,&nbsp;Zhizhi Dong ,&nbsp;Yanan Yang ,&nbsp;Wenqiang Cui ,&nbsp;Jingbo Han ,&nbsp;Yibin Hu ,&nbsp;Haonan Chen ,&nbsp;Chongxuan Qiao ,&nbsp;Qingxiao Li ,&nbsp;He Li ,&nbsp;Shengxian Wu","doi":"10.1016/j.phymed.2025.156775","DOIUrl":"10.1016/j.phymed.2025.156775","url":null,"abstract":"<div><h3>Background</h3><div>Carotid atherosclerosis(CAs) plaques are challenging to reverse. Neixiao-Ruanmai Decoction No 2(NXRMT No 2), a Traditional Chinese Medicine (TCM) decoction, has shown potential in treating CAs. However, while preliminary clinical trials have confirmed the efficacy of NXRMT No 2 in improving CAs, the comparative effectiveness of long-term versus short-term treatment courses remains unclear, and the underlying mechanisms of this decoction are not yet fully understood.</div></div><div><h3>Methods</h3><div>We conducted clinical trials, animal studies, 16S rRNA sequencing, metabolomics and fecal microbiota transplantation.</div></div><div><h3>Result</h3><div>Clinical research results indicate that NXRMT No 2(24 weeks of treatment) reduced total plaque area by 22.02%, maximum plaque thickness by 7.91%, and maximum plaque area by 21.29%. NXRMT No 2 improves patients’serum inflammatory levels, with a 24-week treatment course demonstrated superior efficacy compared to the 12-week treatment. Animal experiments demonstrated that NXRMT No 2 improved CAs progression, modulated the gut microbiota, inhibited the intestinal Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway and activated the expression of intestinal tight junction proteins.</div></div><div><h3>Conclusion</h3><div>NXRMT No 2 significantly attenuates CAs progression, with its primary mechanism likely related to modulating the gut microbiota to counteract the TLR4/NF-κB pathway and protect the intestinal barrier. This study provides evidence-based support for the use of NXRMT No 2 in treating CAs, offers guidance on optimal treatment duration for patients, and contributes to the development of traditional Chinese medicine formulations that improve CAs by modulating the gut microbiota—a significant advance in the prevention and treatment of CAs.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156775"},"PeriodicalIF":6.7,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868326","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":"Artemisinin alleviates ischemic stroke injury and promotes neurogenesis through PPARγ-mediated M2 polarization of microglia","authors":"Lin Li ,&nbsp;Huiqin Hu ,&nbsp;Weifeng Jiang,&nbsp;Shihui Mao,&nbsp;Zheng Yang,&nbsp;Ting Lan,&nbsp;Xiaowei Hu,&nbsp;Yan Fang,&nbsp;Lanxi Xu,&nbsp;Jiadong Xu,&nbsp;Yan Yang,&nbsp;Weiru Jiang,&nbsp;Lisheng Chu","doi":"10.1016/j.phymed.2025.156769","DOIUrl":"10.1016/j.phymed.2025.156769","url":null,"abstract":"<div><h3>Background</h3><div>Ischemic stroke (IS) remains a challenge in clinical treatment due to limited therapeutic options. While artemisinin (ART), an antimalarial drug, shields against acute IS via anti-inflammatory, antioxidant, and anti-apoptotic properties, the long-term benefits and specific underlying mechanisms have not been fully elucidated. Here, we investigate whether ART ameliorates IS injury and promotes neurogenesis by activating the peroxisome proliferator-activated receptor γ (PPARγ)-dependent M2 microglial polarization.</div></div><div><h3>Methods</h3><div>The experimental models included transient middle cerebral artery occlusion/reperfusion (MCAO/R) in rats and oxygen-glucose deprivation/reoxygenation (OGD/R) in primary microglial cultures to simulate IS. The therapeutic effects of ART were evaluated by neurological functions and infarct volume. PPARγ inhibitor T0070907 (T007) was intraperitoneally injected 24 h following MCAO/R at a dose of 2 mg/kg in vivo and a concentration of 10 μM for 30 min before OGD in vitro. We utilized real-time quantitative polymerase chain reaction (RT-qPCR) along with Western blot analyses to detect the microglia markers and PPARγ. The proliferation and differentiation of neural stem cells (NSCs) both in vivo and in vitro were assessed via immunofluorescence labeling. The neurogenic potential of ART-treated microglia was investigated by conditioned medium. The levels of brain-derived growth factor (BDNF) and insulin-like growth factor-1 (IGF-1) in microglia were measured by immunofluorescence staining and enzyme-linked immunosorbent assay (ELISA).</div></div><div><h3>Results</h3><div>ART treatment significantly alleviated short- and long-term neurological deficits and reduced cerebral infarct volume in rats with IS. Experiments conducted both in vivo and in vitro experiments illustrated that ART directed microglia away from the pro-inflammatory M1 state towards the anti-inflammatory M2 state, enhanced neurogenesis, and upregulated the expression of PPARγ, BDNF, and IGF-1. In addition, the conditioned medium from ART-exposed microglia stimulated the proliferation and neuronal differentiation of primary NSCs. However, these positive effects were effectively counteracted by the use of PPARγ inhibitor T0070907 (T007).</div></div><div><h3>Conclusion</h3><div>Our findings demonstrate that ART ameliorates IS injury and promotes neurogenesis mainly through PPARγ-mediated microglia M2 polarization. Therefore, ART can be considered a potential therapeutic drug for IS.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156769"},"PeriodicalIF":6.7,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868322","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}