Phytomedicine最新文献

{"title":"Ginkgo biloba extract alleviates deltamethrin-induced testicular injury by upregulating SKP2 and inhibiting Beclin1-independent autophagy.","authors":"Huating Wang, Fan Yang, Junhua Ye, Xueyan Dai, Huan Liao, Chenghong Xing, Zhou Jiang, Chengcheng Peng, Feiyan Gao, Huabin Cao","doi":"10.1016/j.phymed.2024.156245","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156245","url":null,"abstract":"<p><strong>Background: </strong>Male infertility is a worldwide concern that is associated with a decline in sperm quality. Environmental pollutants such as deltamethrin (DM) have harmful effects on male reproductive organs. By maintaining intracellular redox homeostasis, ginkgo biloba extract (GBE) can alleviate male reproductive dysfunction. However, research on the mechanisms by which GBE alleviates reproductive toxicity induced by DM is limited.</p><p><strong>Purpose: </strong>In this study, we investigated whether GBE can alleviate DM-induced testicular and Sertoli cell reproductive toxicity by modulating SKP2 and Beclin1, thus providing a theoretical basis for the development of novel therapeutic approaches.</p><p><strong>Study design: </strong>We explored the role of GBE in mitigating DM-induced testicular damage, with a specific focus on the intricate involvement of ubiquitination and autophagy.</p><p><strong>Methods: </strong>An experimental model was constructed using ICR male mice and the TM4 cell line. Tissue, cellular, and sperm morphological changes were observed through methods such as Hematoxylin and Eosin (H&E) staining, Periodate-Schiff (PAS) staining, ultrastructural observation, immunohistochemistry, and immunofluorescence. Enzyme and hormone levels were measured, and gene and protein levels were detected using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting techniques.</p><p><strong>Results: </strong>In vivo experiments showed that DM exposure led to decreased sex hormone levels, increased seminiferous tubule diameter and impaired spermatogenesis. Meanwhile, DM exposure was found to decrease ubiquitination levels, leading to mitochondrial damage and further escalation of mitochondrial autophagy. Furthermore, in the DM-induced cell model, the upregulation of Beclin1 expression was associated with the inhibition of the ubiquitin‒proteasome system (UPS) and SKP2, thereby exacerbating autophagy. However, GBE has demonstrated notable efficacy in alleviating the reproductive toxicity induced by DM.</p><p><strong>Conclusion: </strong>Our findings highlighted that SKP2 is a key regulator of Beclin1-independent autophagy and that GBE exerts therapeutic effects by upregulating SKP2 and inhibiting Beclin1 activation, which ameliorates autophagy and reduces DM-induced testicular damage.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"156245"},"PeriodicalIF":6.7,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648371","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":"Corrigendum to \"Mitigating phospholipid peroxidation of macrophages in stress-induced tumor microenvironment by natural ALOX15/PEBP1 complex inhibitors\".","authors":"Xiang Luo, Dong-Dong Li, Zi-Chun Li, Zi-Xuan Li, De-Hua Zou, Feng Huang, Guan Wang, Rong Wang, Yun-Feng Cao, Wan-Yang Sun, Hiroshi Kurihara, Lei Liang, Yi-Fang Li, Wen Jin, Yan-Ping Wu, Rong-Rong He","doi":"10.1016/j.phymed.2024.156207","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156207","url":null,"abstract":"","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":" ","pages":"156207"},"PeriodicalIF":6.7,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the mechanism of Ling-Gui-Zhu-Gan decoction in metabolic cardiomyopathy via inhibiting ferroptosis.","authors":"Chuan-Zhi Zhao, Hui-Min Ding, Zi-Qing Hu, Lan Zhou, Yong-Qin Du, Peng Zhou, Liang Wang","doi":"10.1016/j.phymed.2024.156234","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156234","url":null,"abstract":"<p><strong>Objective: </strong>This study was to investigate the mechanism of Ling-Gui-Zhu-Gan decoction (LGZGD) in regulating lipid metabolism and thus inhibiting ferroptosis.</p><p><strong>Methods: </strong>UPLC for the determination of the main chemical composition of LGZGD. A HF-induced rat model of metabolic cardiomyopathy was established. Echocardiography was used to detect cardiac function. Serum lipid levels, myocardial injury markers, and lipid peroxidation levels were detected. Pathological changes were detected. Lipid deposition was assessed by oil red O, and the mitochondrial ultrastructure was observed by electron microscopy. Mechanistically, PLIN5, CD36, ATGL, GPX4, ACSL4, FPN1, DRP1, MFF, FIS1, and OPA1 expressions were examined. After PA-induced H9c2 cells established, apoptosis, myocardial injury markers, and lipid peroxidation levels were detected and lipid deposition levels were assessed. The expressions of PLIN5, CD36, ATGL, GPX4, ACSL4 and FPN1 were detected. H9c2 cardiomyocytes with transient knockdown of PLIN5 and overexpression of PLIN5 were constructed and treated with drug administration and modeling, and the apoptosis level was detected by flow cytometry, the levels of lipid peroxidation and ROS were detected by fluorescence, and the protein and gene expressions of ACSL4 and GPX4 were detected. Results The main active components of LGZGD were liquiritin, isoliquiritin, cinnamic acid, cinnamaldehyde, glycyrrhizic acid, and atractylenolide III. LGZGD significantly improved cardiac dysfunction, lowered lipid level and lipid deposition, reduced CK, NT-proBNP and MDA levels, restored SOD levels, and improved inflammatory cell infiltration as well as collagen fiber deposition. LGZGD decreased the expression of PLIN5, CD36, ACSL4, and increased the expression of ATGL, GPX4, and FPN1. LGZGD also decreased the gene expression of DRP1, MFF, FIS1, and increased OPA1 expression. LGZGD significantly ameliorated PA-induced apoptosis, decreased lipid deposition, lowered lipid peroxidation levels and CK level, decreased PLIN5, CD36, and ACSL4 expressions, and increased ATGL, GPX4, and FPN1 expressions. LGZGD reversed cardiomyocyte injury aggravated by transient knockdown of PLIN5, decreased apoptosis levels, lipid peroxidation levels, ROS levels, and ACSL4 expressions, and increased GPX4 expression. LGZGD enhanced cardiomyocyte protection after overexpression of PLIN5, reduced apoptosis levels, lipid peroxidation level and ROS level, decreased ACSL4 expression, and increased GPX4 expression.</p><p><strong>Conclusion: </strong>PLIN5 interferes with lipid peroxidation, regulates mitochondrial function, and inhibits HF-induced ferroptosis in cardiomyocytes. LGZGD ameliorates impairment of cardiac structural function in model rats through PLIN5-mediated ferroptosis pathway, and has the effect of preventing metabolic cardiomyopathy.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"156234"},"PeriodicalIF":6.7,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639576","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":"Gnetupendin A protects against ischemic stroke through activating the PI3K/AKT/mTOR-dependent autophagy pathway.","authors":"Danyang Mu, Jingyu Liu, Yan Mi, Dequan Wang, Libin Xu, Yuxin Yang, Yueyang Liu, Dong Liang, Yue Hou","doi":"10.1016/j.phymed.2024.156233","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156233","url":null,"abstract":"<p><strong>Background: </strong>Autophagy has been recently emerged as a prominent factor in the pathogenesis of ischemic stroke (IS) and is increasingly being considered as a potential therapeutic target for IS. Gnetum parvifolium has been identified as a potential therapeutic agent for inflammatory diseases such as rheumatism and traumatic injuries. However, the pharmacological effects of Gnetupindin A (GA), a stilbene compound isolated from Gnetum parvifolium, have not been fully elucidated until now.</p><p><strong>Objective: </strong>Here we identified the therapeutic potential of GA for IS, deeply exploring the possible mechanisms related to its regulation of autophagy.</p><p><strong>Methods: </strong>The mouse model of middle cerebral artery occlusion-reperfusion (MCAO/R) and the oxygen-glucose deprivation reperfusion (OGD/R)-exposed cells served as models to study the protection of GA against IS. The adeno-associated virus (AAV) encoding shAtg5, in conjunction with autophagy inhibitor 3-Methyladenine (3-MA) were utilized to explore the role of GA in regulating autophagy following IS. Molecular docking, CETSA, and DARTS were used to identify the specific therapeutic target of GA. PI3K inhibitor LY294002 was employed to test the participation of PI3K in GA-mediated autophagy and neuroprotective effects following IS.</p><p><strong>Results: </strong>Our findings revealed that treatment with GA significantly alleviated the brain infract volume, edema, improved neurological deficits and attenuated apoptosis. Mechanistically, we found that GA promoted autophagic flow both in vivo and in vitro after IS. Notably, neural-targeted knockdown of Atg5 abolished the neuroprotective effects mediated by GA. Inhibition of autophagy using 3-MA blocked the attenuation on apoptosis induced by GA. Moreover, molecular docking, CETSA, and DARTS analysis demonstrated that GA specifically targeted PI3K and further inhibited the activation of PI3K/AKT/mTOR signaling pathway. LY294002, which inhibits PI3K, reversed GA-induced autophagy and neuroprotective effects on OGD/R-treated cells.</p><p><strong>Conclusion: </strong>We demonstrated, for the first time, that GA protects against IS through promoting the PI3K/AKT/mTOR-dependent autophagy pathway. Our findings provide a novel mechanistic insight into the anti-IS effect of GA in regulating autophagy.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"156233"},"PeriodicalIF":6.7,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648377","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 compound K restrains hepatic fibrotic response by dual-inhibition of GLS1 and LDHA.","authors":"Wen-Hui Wu, Ya-Lan Yang, Ting Wang, Xiao-Meng Sun, Meng-Guang Wei, Xin-Yue Zhou, Li-Zeng Zhu, Gaoxiang Ma, Baolin Liu, Lian-Wen Qi, Qun Liu","doi":"10.1016/j.phymed.2024.156223","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156223","url":null,"abstract":"<p><strong>Background: </strong>Liver fibrosis is a dynamic process marked by the accumulation of extracellular matrix due to hepatic stellate cells (HSCs) activation. Ginsenoside compound K (CK), a rare derivative of its parent ginsenosides, is known to significantly ameliorate metabolic disorders.</p><p><strong>Purpose: </strong>The aim of this study was to elucidate the protective effects of CK against liver fibrosis with a focus on metabolic regulation.</p><p><strong>Methods: </strong>We established liver fibrosis models in mice using carbon tetrachloride (CCl₄) challenge, bile duct ligation, or a methionine-choline deficient diet, with continuous oral administration of CK at specified doses and intervals. Simultaneously, we examined the impact of CK on metabolic regulation in cultured HSCs and investigated the associated mechanisms.</p><p><strong>Results: </strong>CK was found to alleviate liver injury and curb fibrotic responses in mouse models, as well as decrease elevated levels of liver enzyme. Metabolomic analysis in vitro highlighted the crucial roles of pyruvate and glutamine metabolism in metabolic remodeling. Immunohistochemical staining indicated significantly elevated expressions of lactate dehydrogenase A (LDHA) (p = 0.014) and glutaminase 1 (GLS1) (p = 0.024) in liver cirrhosis patients. Comparable alterations were noted in the liver of model mice and in cultured HSCs. Molecular docking and bio-layer interferometry demonstrated that CK interacts with and inhibits the activities of LDHA and GLS1. As expected, CK attenuated glycolysis and glutaminolysis, reducing HSC growth dependently on lactate and α-ketoglutarate (α-KG). Upon HSC activation, metabolism is reprogrammed with Myc as a key regulator, transcriptionally controlling LDHA, GLS1, and glutamine transporters SLC1A5 and SLC38A5. CK inhibited Myc induction, integrating glycolysis and glutaminolysis regulation to counteract the fibrotic response.</p><p><strong>Conclusion: </strong>CK inhibited LDHA and GLS1 activities, thereby inhibiting hepatic fibrosis. These findings offer new insights into the role of ginsenosides in liver protection, especially regarding metabolic disorders.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"156223"},"PeriodicalIF":6.7,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676533","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":"DanShen Decoction targets miR-93-5p to provide protection against MI/RI by regulating the TXNIP/NLRP3/Caspase-1 signaling pathway.","authors":"Mingtai Chen, Raoqiong Wang, Lishang Liao, Yuanyuan Li, Xingyu Sun, Hao Wu, Qi Lan, Ziwen Deng, Ping Liu, Tengfei Xu, Hua Zhou, Mengnan Liu","doi":"10.1016/j.phymed.2024.156225","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156225","url":null,"abstract":"<p><strong>Background: </strong>Bone marrow mesenchymal stem cells (BMSCs) derived exosomes have demonstrated potential therapeutic efficacy on myocardial ischemia/reperfusion injury (MI/RI). This study has explored the underlying mechanisms of Danshen decoction (DSD) pretreated BMSCs-exosomes to treat MI/RI in vivo and in vitro.</p><p><strong>Methods: </strong>Extracellular vesicles extracted from BMSCs were identified, miRNA sequencing was performed to screen the effects of DSD, and verified to target TXNIP in vivo. After MI/RI modeling, rats were treated with BMSCs-exosomes pretreated with DSD or miRNA inhibitor. BMSCs-exosomes, DSD-pretreated BMSCs-exosomes, and miRNA inhibitor/anti-miRNA-pretreated BMSCs-exosomes were used to treat H9c2 cells or MI/RI rats. CCK-8, Tunnel staining, and flow cytometry were performed to measure cell viability. LDH, CK, CK-MB were detected to evaluate cell injury. MDA, SOD, and ROS were used to confirm oxidative stress. Furthermore, IL-1β, IL-18, cleaved-caspase-1, pro-caspase-1, NLRP3, TXNIP, and GSDMD were quantified for the TXNIP/NLRP3/Caspase-1 signaling activation. In addition, echocardiography was used to observe the heart function, and H&E stain was performed to detect pathological injury.</p><p><strong>Results: </strong>Following DSD pretreatment, there was a marked elevation in the expression levels of miR-93-5p, miR-16-5p, and miR-15b-5p, with miR-93-5p exhibiting the highest baseMean value. The administration of a miR-93-5p inhibitor yielded effects counteractive to those observed with DSD treatment, leading to reduced cell proliferation, heightened oxidative stress (as indicated by increased levels of SOD and ROS, alongside a decrease in MDA), and enhanced cell apoptosis. Furthermore, DSD effectively mitigated the miR-93-5p-induced upregulation of key inflammatory and apoptotic markers, including IL-1β, IL-18, caspase-1, NLRP3, TXNIP, and GSDMD. Notably, exosomes derived from DSD-pretreated BMSCs demonstrated a capacity to alleviate cardiac damage.</p><p><strong>Conclusion: </strong>DSD may target miR-93-5p within BMSC-derived exosomes to confer protection against cardiac damage by inhibiting the activation of the TXNIP/NLRP3/Caspase-1 signaling pathway, thereby mitigating cardiomyocyte pyroptosis. This study provides a theoretical foundation for the application of DSD in the treatment of MI/RI.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"156225"},"PeriodicalIF":6.7,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639574","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":"Flavonoids from Rhododendron nivale Hook. f ameliorate alcohol-associated liver disease via activating the PPARα signaling pathway","authors":"Xiao Guo ,&nbsp;Chen Liu ,&nbsp;Zhen Dong ,&nbsp;Gang Luo ,&nbsp;Qien Li ,&nbsp;Meizhou Huang","doi":"10.1016/j.phymed.2024.156215","DOIUrl":"10.1016/j.phymed.2024.156215","url":null,"abstract":"<div><h3>Background</h3><div>Flavonoids are increasingly recognized for their potent antioxidant properties and potential therapeutic roles in the management of alcohol-associated liver disease (ALD). Extracts derived from <em>Rhododendron nivale Hook. f.</em> (FRN) have been shown to influence glutathione metabolism in aging animal models, exhibiting notable antioxidant effects. However, the specific impact of FRN on ALD remains insufficiently explored.</div></div><div><h3>Hypothesis/Purpose</h3><div>This study seeks to elucidate the efficacy of FRN in alleviating the pathology associated with ALD, delving into the underlying molecular mechanisms that facilitate its protective effects.</div></div><div><h3>Study Design</h3><div>We employed network pharmacology to predict the functional roles and pathway enrichments associated with FRN targets. Both a murine model of ALD and in vitro cellular models were utilized to clarify the mechanistic basis by which FRN mitigates ALD.</div></div><div><h3>Methods</h3><div>FRN was extracted and characterized according to well-established methodologies outlined in our previous studies. Potential functions and pathways implicated by FRN were predicted through network pharmacology analyses. A combination of liver transcriptomics, targeted lipidomics, molecular biology techniques, and antagonists of relevant targets were employed to investigate the mechanisms through which FRN exerts its protective effects in ALD.</div></div><div><h3>Results</h3><div>Network pharmacology identified multiple target genes modulated by FRN, particularly those within critical ALD-related signaling pathways, such as PPARα signaling and fatty acids (FAs) degradation. Notably, treatment with FRN in the ALD murine model led to a significant attenuation of hepatic lipid accumulation and a restoration of serum AST and ALT to baseline ranges. Subsequent validation through liver transcriptomics and molecular biology techniques revealed an upregulation of PPARα expression concomitant with a downregulation of ACSL1 in FRN-treated ALD mice. Targeted lipidomic and bioinformatic analyses demonstrated that FRN substantially reduced the accumulation of long-chain fatty acids in hepatocytes. Importantly, the reversal of FRN's protective effects on lipid accumulation through the PPARα antagonist GW6471 provides compelling evidence for the critical role of PPARα signaling modulation in mediating the beneficial impact of FRN on ALD.</div></div><div><h3>Conclusion</h3><div>Our research highlights FRN's capacity to alleviate ALD through PPARα pathway activation, paving the way for innovative treatment strategies. This underscores the significance of natural compounds in pharmacotherapy, suggesting that FRN may provide an effective alternative for managing ALD.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156215"},"PeriodicalIF":6.7,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142655776","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":"Diammonium glycyrrhizinate alleviates iron overload-induced liver injury in mice via regulating the gut-liver axis","authors":"Yu Liu ,&nbsp;Xiaohong Li ,&nbsp;Ziwei Guo ,&nbsp;Guangyan Li ,&nbsp;Lu He ,&nbsp;Huan Liu ,&nbsp;Shuang Cai ,&nbsp;Taoguang Huo","doi":"10.1016/j.phymed.2024.156216","DOIUrl":"10.1016/j.phymed.2024.156216","url":null,"abstract":"<div><h3>Background</h3><div>Evidence indicates a close association between iron overload (IO) and the pathogenesis of chronic liver diseases, highlighting the potential for interventions targeted at IO to impede or decelerate the progression of chronic liver diseases. Diammonium glycyrrhizinate (DG), the medicinal form of glycyrrhizic acid, a principal constituent of licorice, has been clinically employed as a hepatoprotective agent; however, its protective effect against IO-induced liver injury and underlying molecular mechanisms remain elusive.</div></div><div><h3>Purpose</h3><div>The aim of the present study is to investigate the hepatoprotective effect of DG against IO-induced liver injury with a focus on the gut-liver axis.</div></div><div><h3>Study design and methods</h3><div>Animal models of IO-induced liver injury and DG treatment have been established in <em>vivo</em>. Iron deposition, liver injury, intestinal barrier damage, and liver inflammation were assessed in mice treated with iron dextran or DG. The microbiome composition in feces was analyzed using 16S rRNA full-length sequencing. Bile acids (BAs) profiles in feces were detected by UPLC-Q-TOF-MS technique, and the expression levels of receptors, enzymes or transporters involved in BAs metabolism were also determined.</div></div><div><h3>Results</h3><div>DG partially reduced the iron deposition and the levels of ferrous ion in the livers of mice with IO, thereby mitigating oxidative damage. DG also improved gut microbiota dysbiosis, repaired intestinal barrier damage, inhibited endotoxin translocation to the liver, and subsequently suppressed TLR4/NF-κB/NLRP3 pathway-mediated liver inflammation caused by IO. Moreover, DG modulated BAs metabolism disorder in IO mice, reducing the accumulation of BAs in the liver.</div></div><div><h3>Conclusion</h3><div>DG alleviates IO-induced liver injury in mice by regulating the gut-liver axis. This study provides novel insights into the underlying mechanisms through which DG ameliorates liver injury caused by IO.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156216"},"PeriodicalIF":6.7,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639575","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":"Cellular and molecular mechanisms elicited by natural products, including dietary supplements, against neurological disorders.","authors":"Rajeev K Singla, Rohit Sharma, Bairong Shen","doi":"10.1016/j.phymed.2024.156236","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156236","url":null,"abstract":"","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"156236"},"PeriodicalIF":6.7,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644408","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":"Siling decoction ameliorates adenine-induced renal fibrosis in rats by the AKT/IKKβ/NFκB signaling pathway","authors":"Lianlin Zeng ,&nbsp;Yu Lin ,&nbsp;Haixu Chen ,&nbsp;Xiaomei Li ,&nbsp;Dengwei Xie ,&nbsp;Yangan Li ,&nbsp;Kehui Hu","doi":"10.1016/j.phymed.2024.156228","DOIUrl":"10.1016/j.phymed.2024.156228","url":null,"abstract":"<div><h3>Objective</h3><div>Investigating how Siling decoction (SLD) mitigates fibrosis in rats with chronic kidney disease CKD (chronic kidney disease) through network pharmacology analysis and experimental verification.</div></div><div><h3>Methods</h3><div>Initially, the primary active components and their target actions of SLD (Fuling, Zhuling, Zexie, and Baizhu) were identified by the TCMSP database and liquid chromatography mass spectrometry (LC-MS). Treatment targets for renal fibrosis were screened through databases such as GeneCard, OMIM, PharmGkb, and GEO. Subsequently, a drug-disease-target network was constructed and subjected to PPI analysis. Intersecting targets underwent GO and KEGG pathway enrichment analyses. Renal fibrosis model was induced by adenine gavage, then treat with SLD. Masson, Sirius red, immunohistochemistry, and Western blot were used to detect renal function and fibrosis-related indicators. The mechanism was further validated in vitro experiments.</div></div><div><h3>Results</h3><div>Network pharmacology analysis identified 100 common targets associated with the active components of SLD, including core genes such as AKT1 and CCND1. GO enrichment analysis revealed that the top three biological processes impacted include response to xenobiotic stimulus, response to nutrient levels and response to oxidative stress. These processes involved cellular components such as membrane raft, membrane microdomain and synaptic membrane, with molecular functions predominantly associated with ubiquitin-like protein ligase binding, ubiquitin protein ligase binding, DNA-binding transcription factor binding, and RNA polymerase II-specific DNA binding transcription factor binding. KEGG pathway enrichment analysis indicated potential involvement of pathways like Lipid and atherosclerosis, PI3K-AKT signaling pathway, and prostate cancer are likely involved in the anti-fibrotic effect of SLD. Notably, the highlighted was the AKT/IKKβ/NFκB signaling pathway as a key mechanism. These findings were further confirmed in vivo and in vitro.</div></div><div><h3>Conclusion</h3><div>The SLD effectively ameliorates adenine-induced chronic kidney disease fibrosis in rats, potentially by inhibiting the AKT/IKKβ/NFκB signaling pathway.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156228"},"PeriodicalIF":6.7,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648513","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}