Phytomedicine最新文献

{"title":"Traditional Chinese medicine in the treatment of adverse reactions after TACE for primary hepatic carcinoma: Effect, mechanism, and potential advantages.","authors":"Huai-Bang Li, Lin Huang, Jia-Yu Ni, Ruo-Yao Lin, Sheng-Yan Xi","doi":"10.1016/j.phymed.2024.156244","DOIUrl":"10.1016/j.phymed.2024.156244","url":null,"abstract":"<p><p>Primary hepatic carcinoma is one of the most common malignant tumors. China is a major country for liver cancer, accounting for about 50 % of the patients worldwide. Although there are a variety of treatments for primary hepatic carcinoma, chemotherapy remains an important method, and transcatheter arterial chemoembolization (TACE) is a commonly used local chemotherapy. Currently, there are no effective therapeutic measures to target adverse reactions generated after chemoembolization. A new approach is needed to alleviate post-TACE syndrome. Clinical and experimental studies have shown that traditional Chinese medicine can reduce adverse reactions and improve clinical efficacy when combined with primary hepatic carcinoma treatment. This suggests that traditional Chinese medicine plays an important and irreplaceable role in alleviating adverse reactions after TACE. However, there is still a need for high-quality experimental and clinical studies to obtain evidence of effective treatment.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"156244"},"PeriodicalIF":6.7,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668871","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":"Hesperidin alleviated dendritic spines through inhibiting ferritinophagy via HERC2-NCOA4 ubiquitination in CUMS mice","authors":"Mingjia Zhang ,&nbsp;Yixuan Cui ,&nbsp;Ruiting Jia ,&nbsp;Ziling Cai ,&nbsp;Yineng Shen ,&nbsp;Wumin Yu ,&nbsp;Zixin Pang ,&nbsp;Shuning Ding ,&nbsp;Xing Gao ,&nbsp;Yike Huang ,&nbsp;Maolin Song ,&nbsp;Yahui Lou ,&nbsp;Fa Ye ,&nbsp;Haiqing Ao ,&nbsp;Aisong Zhu","doi":"10.1016/j.phymed.2024.156132","DOIUrl":"10.1016/j.phymed.2024.156132","url":null,"abstract":"<div><h3>Background</h3><div>Depression has been linked to ferritinophagy-induced synaptic damage, which affects the emotional circuitry and can ultimately lead to depressive symptoms. It has been suggested that Hesperidin might improve depression disorders. However, the relationship between the therapeutic effects of the sympathetic nervous system in alleviating depression-like behaviors and ferritinophagy is still unknown.</div></div><div><h3>Purpose</h3><div>The objective of this study is to investigate the possible impact of Hesperidin in alleviating dendritic spines through the inhibition of ferritinophagy via HERC2-NCOA4 ubiquitination in mice exposed to chronic unpredictable mild stress (CUMS).</div></div><div><h3>Methods</h3><div>C57BL/6 and NCOA4^+/+ mice were exposed to CUMS for 42 days. During the last 3 weeks of the CUMS procedure, the mice were administered Hesperidin (50, 100, 200 g/kg/d) or fluoxetine (10 mg/kg/d) once daily. Following the behavioral tests, Golgi staining, tissue iron concentration test, and perls staining were conducted to assess the therapeutic effect of Hesperidin. Additionally, ultrahigh-performance liquid chromatography-high-resolution tandem mass spectrometry (UPLC-Q-TOF/MS) and ultrahigh-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was utilized to analyze the metabolic components of Hesperidin in both blood and brain tissue. To investigate mechanism of Hesperidin, the cells were subjected to different concentrations of Hesperidin (25, 50, 100 µM), its metabolites (Eriodictyol (10, 20, 50 µM), Homoeriodictyol (0.1, 0.5, 1 µM)) and si-HERC2. Furthermore, HERC2-NCOA4 ubiquitination, and ferritinophagy-related proteins was explored through techniques such as western blot, immunofluorescence, co-immunoprecipitation, and molecular docking.</div></div><div><h3>Results</h3><div>Hesperidin has demonstrated the potential to alleviate symptoms of depression by regulating dendritic spines through the inhibition of NCOA4-ferritinophagy, while NCOA4 overexpression could reverse these results. Importantly, the content of Hesperidin metabolites (Homoeriodictyol and Eriodictyol) was relatively high in brain tissue. The Hesperidin and its metabolites, Eriodictyol and Homoeriodictyol, were able to regulate GluR2 and SYN protein expression. Additionally, they inhibited ferritinophagy involving NCOA4, P62, LC3, and FTH. but this phenomenon was reversed by si-HERC2 following Hesperidin and its metabolite administration. Furthermore, the binding of HERC2 and NCOA4 protein was found to be inhibited by Hesperidin and its metabolites.</div></div><div><h3>Conclusions</h3><div>Hesperidin alleviated dendritic spines through inhibiting ferritinophagy via HERC2-NCOA4 ubiquitination in CUMS mice.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156132"},"PeriodicalIF":6.7,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626306","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":"Wogonin mitigates microglia-mediated synaptic over-pruning and cognitive impairment following epilepsy","authors":"Yang Hu ,&nbsp;Honggang Qi ,&nbsp;Jiurong Yang ,&nbsp;Feiyu Wang ,&nbsp;Xintao Peng ,&nbsp;Xiang Chen ,&nbsp;Xinjian Zhu","doi":"10.1016/j.phymed.2024.156222","DOIUrl":"10.1016/j.phymed.2024.156222","url":null,"abstract":"<div><h3>Background</h3><div>Epilepsy, a neurological disorder characterized by recurrent abnormal neuronal discharges, leading to brain dysfunction and imposing significant psychological and economic burdens on patients. Microglia, the resident immune cells within the central nervous system (CNS), play a crucial role in maintaining CNS homeostasis. However, activated microglia can excessively prune synapses, exacerbating neuronal damage and cognitive dysfunction following epilepsy. Wogonin, a flavonoid from <em>Scutellaria Baicalensis</em>, has known neuroprotective effects via anti-inflammatory and antioxidative mechanisms, but its impact on microglial activation and synaptic pruning in neurons post-epilepsy remains unclear.</div></div><div><h3>Methods</h3><div>Synaptic density was assessed using presynaptic marker Synaptophysin and postsynaptic marker Psd-95, and microglial phagocytosis was evaluated with fluorescent microspheres. Pilocarpine-induced mouse model of status epilepticus was used to evaluate synaptic density changes of mouse hippocampus following an intraperitoneal injection of wogonin (50 and 100 mg/kg). Memory and cognitive function in mice were subsequently evaluated using the Y-maze, object recognition, and Morris water maze tests. Single-cell sequencing was employed to investigate the underlying causes of microglial state alterations, followed by experimental validation.</div></div><div><h3>Results</h3><div>Microglia were transitioned to an activated state post-epilepsy, exhibiting significantly enhanced phagocytic capacity. Correspondingly, levels of synaptophysin and Psd-95 were markedly reduced in neurons. Treatment with wogonin (100 mg/kg) significantly increased neuronal synaptic density and improved learning and memory deficits in epileptic mice. Further investigation revealed that wogonin inhibits the release of pro-inflammatory cytokines and synaptic phagocytosis of microglia by activating the AKT/FoxO1 pathway.</div></div><div><h3>Conclusions</h3><div>Wogonin could alleviate excessive synaptic pruning of epileptic neurons by microglia and improve cognitive dysfunction of epileptic mice via the AKT/FoxO1 pathway.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156222"},"PeriodicalIF":6.7,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639579","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":"Disruption of local circadian clocks in aristolochic acid-induced nephropathy in mice","authors":"Dihao Xie,&nbsp;Simin Zhong,&nbsp;Meixue Luo,&nbsp;Jiahao Xu,&nbsp;Ruoyan Zheng,&nbsp;Jiading Luo,&nbsp;Yiting Wang,&nbsp;Yongxing Guo,&nbsp;Lianxia Guo,&nbsp;Baojian Wu,&nbsp;Danyi Lu","doi":"10.1016/j.phymed.2024.156235","DOIUrl":"10.1016/j.phymed.2024.156235","url":null,"abstract":"<div><h3>Background</h3><div>Aristolochic acid I (AAI), an emerging biogenic contaminant widely present in Aristolochic plants, has been implicated in the progression of tubulointerstitial disease, known as aristolochic acid nephropathy (AAN). The circadian clock, a vital regulator of organ homeostasis, is susceptible to external chemical cues, including toxins. However, the reciprocal interactions between AAI and the circadian clock remain unexplored.</div></div><div><h3>Methods</h3><div>We initially assessed sex- and time-dependent nephropathy and behavioral responses in C57BL/6J mice exposed to AAI. Subsequently, we evaluated changes in the expression of circadian clock genes following treatment with AAI or its bioactive metabolite, aristolactam I, using real-time quantitative PCR and immunoblotting in renal tissues and cells. Additionally, real-time reporter assays were conducted on kidney explants from PER2::Luc knock-in reporter mice and <em>Per2-dLuc</em>/<em>Bmal1-dLuc</em> reporter cell lines. To further elucidate the regulatory role of circadian clocks in AAI-induced nephropathy, mice with global or kidney-specific knockout of <em>Bmal1</em>, as well as mice subjected to experimental jetlag, were utilized.</div></div><div><h3>Results</h3><div>Our findings revealed a sex-dependent nephrotoxicity of AAI, with males exhibiting greater vulnerability. AAI-induced nephropathy was accompanied by impaired spatial cognitive function, disruptions in free-running locomotor activity, altered renal expression of multiple core clock genes, and disturbances in the circadian rhythm of renal PER2::Luc activity. Notably, kidney-specific ablation of the core clock gene <em>Bmal1</em> significantly exacerbated renal injury and inflammation, whereas disruptions to the central clock, either genetically (through conventional knockout of <em>Bmal1</em>) or environmentally (mimicking jetlag), had minimal effects on AAI nephrotoxicity. Furthermore, both AAI and its bioactive metabolite aristolactam I demonstrated the ability to disrupt circadian clocks in human osteosarcoma cells (U2OS) and mouse renal tubular epithelial cells (mRTEC).</div></div><div><h3>Conclusion</h3><div>Collectively, these findings highlight the detrimental impact of aristolochic acids on local renal circadian clocks, ultimately exacerbating kidney damage. This study provides novel insights into the molecular mechanisms underlying AAI nephrotoxicity, potentially opening avenues for therapeutic interventions aimed at modulating the renal circadian clock to treat AAN.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156235"},"PeriodicalIF":6.7,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626299","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":"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}