Phytomedicine最新文献

{"title":"A comprehensive and systematic review on Curcumin as a promising candidate for the inhibition of melanoma growth: From pre-clinical evidence to molecular mechanisms of action.","authors":"Qi-Hao Guo, Ling-Yan Jian, Yihan Hu, Shu Wang","doi":"10.1016/j.phymed.2024.156073","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156073","url":null,"abstract":"<p><strong>Background: </strong>Melanoma, a highly malignant skin tumor, can develop systemic metastases during the early stage. Several studies of melanoma animal models indicate that curcumin, a natural plant extract, inhibits melanoma growth through various mechanisms. To evaluate the relationships among different experimental conditions, curcumin itself, its derivatives, and special formulations, it is necessary to conduct a systematic review and meta-analysis.</p><p><strong>Purpose: </strong>This meta-analysis aims to evaluate the potential of Curcumin as a drug for inhibiting the growth of melanoma and to determine the optimal dosage range and treatment duration for Curcumin administration.</p><p><strong>Methods: </strong>A systematic search of studies published from inception to December 2023 was conducted across six databases (PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang Data, and VIP). Methodological quality was assessed using SYRCLE's RoB tool. Study heterogeneity was assessed using Cochran's Q test and I² statistics. Publication bias risk was evaluated using a funnel plot. All analyses were performed using R (version 4.3.3). Additionally, three-dimensional effect analysis and machine learning techniques were utilized to determine the optimal dosage range and treatment duration for Curcumin administration.</p><p><strong>Results: </strong>Forty studies involving 989 animals were included. The results demonstrated that, relative to the control group, administration of Curcumin resulted in a significant reduction in tumor volume. [SMD=-3.44; 95 % CI (-4.25, -2.63); P<0.01; I² = 79 %] and tumor weight [SMD=-1.93; 95 % CI (-2.41, -1.45); P<0.01; I² = 75 %]. Additionally, Curcumin demonstrated a significant capacity to decrease the number of lung tumor nodules and microangiogenesis, as well as to extend survival time, in animal models. The results from three-dimensional effect analysis and machine learning emphasize that the optimal dosage range for Curcumin is 25-50 mg/kg, with an intervention duration of 10-20 days.</p><p><strong>Conclusion: </strong>Curcumin can inhibit the growth of melanoma, and the dose-response relationship is not linear. However, further large-scale animal and clinical studies are required to confirm these conclusions.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"156073"},"PeriodicalIF":6.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606007","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":"Taohe Chengqi decoction improves diabetic cognitive dysfunction by alleviating neural stem cell senescence through HIF1α-driven metabolic signaling","authors":"Tingting Qin ,&nbsp;Zhangxu He ,&nbsp;Hozeifa Mohamed Hassan ,&nbsp;Qiqi Wang ,&nbsp;Le Shi ,&nbsp;Yun Yu ,&nbsp;Yang Zhou ,&nbsp;Wenzhou Zhang ,&nbsp;Ziqiao Yuan","doi":"10.1016/j.phymed.2024.156219","DOIUrl":"10.1016/j.phymed.2024.156219","url":null,"abstract":"<div><h3>Objective</h3><div>Type 2 diabetes mellitus (T2DM) is characterized by numerous long-term complications, in which progressive cognitive decline represents a significant risk factor for dementia and other neurodegenerative disorders. Taohe Chengqi decoction (THCQ) is a common traditional Chinese formula for treating T2DM; however, the neuroprotective effect of THCQ on diabetes-associated cognitive dysfunction remains unclear. Hence, the present study investigated the therapeutic effects of THCQ on cognitive impairment associated with T2DM and elucidated the underlying mechanisms.</div></div><div><h3>Methods</h3><div>A stable high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM mouse model was established and received intragastrical THCQ administration. Blood and tissue samples were investigated for biochemical parameters and neuropathology, whereas hippocampal tissue underwent transcriptome analyses and the role of neural stem cell (NSC) senescence was detected both <em>in vivo</em> and <em>in vitro</em>. Network pharmacology analysis and subsequent primary NSC experiments were conducted to explore the involvement of the HIF1α signaling pathway in THCQ-mediated hippocampal NSC senescence. Furthermore, a lentivirus vector overexpressing HIF1α was used to verify the THCQ potential therapeutic effects on HIF1α/PDKs metabolic signaling that influenced NSC senescence.</div></div><div><h3>Results</h3><div>THCQ alleviated cognitive dysfunction and metabolic abnormalities in HFD/STZ mice, and relieved hippocampal neurodegeneration. Transcriptome analyses and validation experiments revealed THCQ-induced neuroprotective effects by targeting high glucose-mediated hippocampal neuropathy and NSC senescence. Bioinformatic analysis indicated that HIF1α signaling played a significant role in THCQ therapeutic outcomes; while HIF1α overexpression impaired the effects of THCQ on high glucose-induced metabolic disorders and NSC senescence.</div></div><div><h3>Conclusion</h3><div>The present study demonstrated that THCQ improved diabetic cognitive dysfunction and hippocampal neurogenesis, the effects of which were mainly attributed to the restoration of metabolic homeostasis and inhibition of NSC senescence through HIF1α signaling. Our results provide novel insights into the therapeutic framework for diabetic neuropathy and indicate that THCQ might be a promising candidate for the management of T2DM-related cognitive disorders.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156219"},"PeriodicalIF":6.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626470","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":"Icariin ameliorates Coxsackievirus B3-induced viral myocarditis by modulating the S100 calcium binding protein A6/β-catenin/c-Myc signaling pathway.","authors":"Huizhen Tian, Qigang Pan, Jianfeng Wu, Juanjuan Liao, Yuwei Wan, Ke Pei, Qiong Liu, Lingbing Zeng, Yanli Cao, Qiaofa Shi, Nanzhen Kuang, LiJuan Sun, Xiaomin Yu, Xiaotian Huang","doi":"10.1016/j.phymed.2024.156214","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156214","url":null,"abstract":"<p><strong>Background: </strong>Coxsackievirus B3 (CVB3) is a leading cause of viral myocarditis and is currently lacking specific pharmacological treatments, highlighting the critical need for therapeutic development. Icariin (ICA), a prenylated flavonol glycoside, was previously found to exhibit several pharmacological effects, but its potential to combat CVB3 remains uninvestigated.</p><p><strong>Purpose: </strong>This study aimed to elucidate the anti-CVB3 efficacy of ICA and elucidate its molecular mechanisms.</p><p><strong>Methods: </strong>CVB3-infected HeLa cells, H9C2 cells and neonate rat ventricular cardiomyocytes (NRVCs) were selected as in vitro models, and were treated with ICA at 1 and 10 μM. Additionally, BALB/c mice that were infected with CVB3 via intraperitoneal injection were chosen as in vivo model and were treated with ICA or ribavirin over 3 days. The effect of ICA against CVB3 was determined by Cell Counting Kit-8 (CCK-8) assay, western blot, real-time fluorescence quantitative PCR (RT-qPCR), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC) and flow cytometry.</p><p><strong>Results: </strong>In this study, it was found that ICA is capable of reducing CVB3 viral load both in vitro and in vivo. Mechanistic studies suggested that ICA prevents cardiomyocyte apoptosis by attenuating the S100 calcium binding protein A6 (S100A6)/β-catenin/c-Myc signaling pathway. Additionally, ICA inhibits the secretion of proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β) and CXC motif chemokine ligand 2 (CXCL2) in heart tissue, thereby mitigating CVB3-induced myocarditis. Moreover, ICA also regulates the immune response of CD4⁺ T, CD8⁺ T and Treg cells by changing the cells numbers in spleen tissue. Lastly, ICA can reduce the load of other enteroviruses (such as CVA6, CVA16 and EV71) in rhabdomyosarcoma (RD) cells as well.</p><p><strong>Conclusion: </strong>Our findings indicate that ICA provides significant protection against CVB3 infection by modulating the S100A6/β-catenin/c-Myc signaling pathway, suggesting its potential use as a novel drug against CVB3 infection in clinical application.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"156214"},"PeriodicalIF":6.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626308","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":"Integrated gut microbiome and UHPLC-MS metabolomics to reveal the prevention mechanism of pidanjiangtang granules on IGT Rats.","authors":"Yu Xie, Zirong Li, Yue Fan, Xinyi Liu, Ran Yi, Yaoyao Gan, Zixuan Yang, Shangjian Liu","doi":"10.1016/j.phymed.2024.156201","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156201","url":null,"abstract":"<p><strong>Introduction: </strong>Pidanjiangtang (PDJT) is a traditional Chinese medicine formula empirically used to treat impaired glucose tolerance (IGT) based on the \"Pidan\" theory from the classic ancient book Nei Jing. However, the mechanism of PDJT intervention for IGT remains to be studied.</p><p><strong>Objective: </strong>This study aims to explore the mechanism of PDJT granules intervention in IGT by integrating gut microbiome and UHPLC-MS untargeted metabolomics.</p><p><strong>Materials and methods: </strong>The IGT model was established in 6-week-old male Sprague-Dawley (SD) rats by feeding them a high-fat diet and using an STZ injection. The low, medium, and high doses of PDJT were used for six weeks. metformin (Glucophage) was used as the positive control drug. The efficacy of PDJT was evaluated using fasting blood glucose (FBG), blood glucose maximum (BGmax), blood lipid, and inflammatory factor levels. Finally, 16S rDNA gut microbiome sequencing with metabolomics analysis was used to explore the pharmacological mechanism of PDJT intervention in IGT.</p><p><strong>Results: </strong>PDJT could reverse the phenotype of IGT rats, reduce blood glucose levels, improve lipid metabolism disorder, and reduce inflammatory response. Gut microbiome analysis found that PDJT can improve gut microbiota composition and abundance of three phyla (Firmicutes, Bacteroidota, Desulfobacterota) and four genera (unclassified_f__Lachnospiraceae, Ruminococcus, Allobaculum, Desulfovibrio), which play an important role in the process of PDJT intervention on glucose metabolism and lipid metabolism in IGT rats. UHPLC-MS untargeted metabolomics showed that PDJT could regulate the levels of 258 metabolites in lipid metabolism pathways, inflammatory response pathways, fat and protein digestion, and absorption. The combined analysis of the two omics showed that improving the body's metabolism by gut microbes may be the possible mechanism of PDJT in treating IGT. Thus, this study provides a new method to integrate gut microbiome and UHPLC-MS untargeted metabolomics to evaluate the pharmacodynamics and mechanism of PDJT intervention in IGT, providing valuable ideas and insights for future research on the treatment of IGT with traditional Chinese medicine.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"156201"},"PeriodicalIF":6.7,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626398","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":"Damascenone inhibits osteoclastogenesis by epigenetically modulating Nrf2-mediated ROS scavenge and counteracts OVX-induced osteoporosis.","authors":"Qingliang Ma, Yinuo Xiong, Zhiwei Jie, Changzhen Li, Congyu Wang, Jingwen Cai, Yuchen Zhang, Jinghang Li, Yunhao You, Mingzheng Chang, Dapeng Zhang, Cheng Qiu, Yuhua Li, Xinyu Liu, Lianlei Wang","doi":"10.1016/j.phymed.2024.156205","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156205","url":null,"abstract":"<p><strong>Background: </strong>Bone formation and resorption regulate bone homeostasis. Excessive osteoclastogenesis enhances bone resorption and causes osteoporosis. Although medicines targeting osteoclast have been developed, these drugs have several side effects. Natural compounds have advantages in safety and efficiency, making them potential candidates for osteoporosis treatment.</p><p><strong>Purpose: </strong>This study aims to elucidate the role of damascenone (Dama) in osteoclastogenesis and osteoporosis.</p><p><strong>Study design and methods: </strong>To demonstrate the effect of Dama on osteoclast differentiation and function, we performed multiple in vitro experiments including TRAP staining, F-actin staining, bone slice resorption assay, real-time PCR, and western bolt. Further, ROS detection, network pharmacology, microscale thermophoresis assay, and ChIP assay were conducted to elucidate the underlying molecular mechanism. Finally, the in vivo effects of Dama were verified using an ovariectomy induced osteoporosis mice model.</p><p><strong>Results: </strong>Dama inhibited RANKL-induced osteoclast differentiation and bone resorptive function in vitro. The expression of osteoclast-related genes and activation of MAPKs and NF-κB signaling in osteoclast were also attenuated by Dama. Meanwhile, Dama reduced intracellular ROS level via up-regulating Nrf2 expression. Network pharmacology demonstrated that HDAC2 is the potential direct target of Dama. Dama inhibited HDAC2 function and increased H3K27ac level of Nrf2, which induced Nrf2 expression and activated ROS scavenging enzymes. Inhibiting NRF2 or activating HDAC2 attenuated the effect of Dama on osteoclastogenesis. Finally, Dama injection suppressed in vivo osteoclastogenesis and ameliorated bone loss induced by OVX.</p><p><strong>Conclusion: </strong>Dama attenuates osteoclastogenesis by epigenetically modulating Nrf2 expression and ROS scavenge. This study provides evidence for Dama being a potential treatment for osteoporosis.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"156205"},"PeriodicalIF":6.7,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639573","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":"Cycloastragenol reduces microglial NLRP3 inflammasome activation in Parkinson's disease models by promoting autophagy and reducing Scrib-driven ROS","authors":"Linjuan Feng ,&nbsp;Hsuan Lo ,&nbsp;Jiahao Zheng ,&nbsp;Weipin Weng ,&nbsp;Yixin Sun ,&nbsp;Xiaodong Pan","doi":"10.1016/j.phymed.2024.156210","DOIUrl":"10.1016/j.phymed.2024.156210","url":null,"abstract":"<div><h3>Background</h3><div>In Parkinson's disease (PD), microglial autophagy is crucial for the maintenance of cellular redox homeostasis. Meanwhile, cycloastragenol (CAG), a triterpenoid saponin and the principal active component of Astragalus, reduces the activation of NLRP3 inflammasomes. Nevertheless, the specific molecular mechanisms underlying the CAG-mitigated microglial neuroinflammation remains obscure in PD.</div></div><div><h3>Purpose</h3><div>This study explored the role of CAG in the activation of microglial NLRP3 inflammasome and the mechanisms underlying its therapeutic potential for PD treatment.</div></div><div><h3>Study design</h3><div>The effect of CAG was assessed in α-Syn-induced primary microglia and PD models.</div></div><div><h3>Methods</h3><div>AAV1/2-hsyn-SNCA (A53T) was stereo-injected into the striatum of mice to induce PD models and CAG was orally administered. The mice underwent quantitative 4D proteomics analysis and behavioral assessments. The primary microglia and neuron cultures were analyzed by western blotting, immunofluorescence, transmission electron microscopy, etc.</div></div><div><h3>Results</h3><div>CAG reduced phagocytosis-induced reactive oxygen species (ROS) by suppressing the microglial Scribble (Scrib) and p22^phox expression. Concurrently, CAG enhanced autophagy, promoted α-Syn clearance, and reduced mitochondrial damage. These synergistic effects downregulated NLRP3 inflammasome activation, in turn reducing gasdermin D cleavage, caspase-1 activation, and the release of interleukin-1β and interleukin-18. Further investigation revealed that CAG shielded neurons from α-Syn toxicity, thus attenuating behavioral impairments observed in the mouse PD model.</div></div><div><h3>Conclusion</h3><div>CAG mitigates neuroinflammation by inhibiting ROS-induced NLRP3 inflammasome activation in microglia via promoting microglial autophagy and reducing the activity of Scrib-associated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which signifies a promising alternative approach to PD management.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156210"},"PeriodicalIF":6.7,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626295","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":"Metabolic pathways, pharmacokinetic, and brain neurochemicals effects of capsaicin: Comprehensively insights from in vivo studies","authors":"Lulu Guo ,&nbsp;Wu Fan ,&nbsp;Die Li ,&nbsp;Zhilin Hao ,&nbsp;Pingping Liu ,&nbsp;Chang Liu ,&nbsp;Kun Cui ,&nbsp;Wenjuan Zhang ,&nbsp;Xingyu Liu ,&nbsp;Qidong Zhang ,&nbsp;Jian Mao ,&nbsp;Jianping Xie","doi":"10.1016/j.phymed.2024.156212","DOIUrl":"10.1016/j.phymed.2024.156212","url":null,"abstract":"<div><h3>Background</h3><div>Capsaicin (CAP), a prominent component of chili pepper known for its potent agonistic effects on TRPV1, has attracted significant attention for its diverse physiological effects. Nevertheless, there remains a paucity of data concerning its <em>in vivo</em> distribution, metabolism, pharmacodynamic properties, and influence on the metabolic profile of the brain.</div></div><div><h3>Methods</h3><div>Stable isotope tracing, <em>in vitro</em> enzyme incubation, microdialysis coupled with UHPLC-MS/MS techniques were employed to investigate the <em>in vivo</em> metabolic pathways, distribution, and pharmacokinetic properties of CAP, and the potential biases in metabolic pathways was elucidate through molecular docking. Furthermore, the effect of CAP on brain metabolic profiles was assessed using untargeted metabolomics, and spatial visualization analysis was conducted through mass spectrometry imaging.</div></div><div><h3>Results</h3><div>CAP was distributed predominantly in the kidneys, with lower content in the liver, heart, lungs, brain, and spleen following peripheral administration, and the absorption half-life in the body was about 20 min. CAP primarily underwent alkyl terminal dehydrogenation, hydroxylation, and macrocyclization metabolic pathways under the action of CYP2C9, CYP2C19 and CYP2D6, resulting in at least four metabolites. Among them, the hydroxylation products were main metabolites and the dehydrogenation product 16,17-dihydrocapsaicin could interact with the key binding sites Leu515 and Thr550 of TRPV1 like CAP. CAP quickly diffused to various brain regions and the metabolic characteristics in the striatum were relatively different from that in the blood. The distribution of CAP in the brain primarily triggered the release of neurotransmitters in areas associated with reward, cognition, and memory. Both acute and chronic exposure to CAP elevated amino acid levels in cortical regions, while producing contrasting effects on nucleotide metabolites.</div></div><div><h3>Conclusion</h3><div>This study offers an initial in-depth analysis of the distribution patterns, metabolic pathways and pharmacodynamic properties of CAP in the body and brain. These findings established a basis for further studies on CAP's pharmacology properties and its influence on the central nervous system.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156212"},"PeriodicalIF":6.7,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626366","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":"Yi-Qi-Jian-Pi-Xiao-Yu formula inhibits cisplatin-induced acute kidney injury through suppressing ferroptosis via STING-NCOA4-mediated ferritinophagy","authors":"Ji Zhu ,&nbsp;Aini Yuan ,&nbsp;Yifei Le ,&nbsp;Xiaohui Chen ,&nbsp;Jianan Guo ,&nbsp;Jing Liu ,&nbsp;Hang Chen ,&nbsp;Cai-Yi Wang ,&nbsp;Dezhao Lu ,&nbsp;Keda Lu","doi":"10.1016/j.phymed.2024.156189","DOIUrl":"10.1016/j.phymed.2024.156189","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;The kidneys are the primary excretory organs for platinum drugs, making them susceptible to damage from these drugs. Cisplatin-induced acute kidney injury (CIAKI) is the most common side effect observed in patients undergoing clinical cisplatin treatment. A traditional Chinese medicinal preparation, the Yi-Qi-Jian-Pi-Xiao-Yu formula (YQJPXY), which is a modified formulation of the classical Chinese medicine formula Buyang Huanwu Decoction, has long been used in the treatment of clinical kidney diseases. It is expected to be used to ameliorate cisplatin-induced acute kidney injury. However, the mechanism of this YQJPXY for the treatment of cisplatin-induced acute kidney injury remains unclear.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;The objective of this study is to examine the impact of the YQJPXY on the inhibition of ferroptosis in cisplatin-induced acute kidney injury and to elucidate the underlying mechanisms.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The active components of YQJPXY were analysed using UPLC-MS/MS. A comprehensive investigation was conducted to elucidate the effects and regulatory mechanisms of YQJPXY on CIAKI and ferroptosis in mice subjected to acute cisplatin treatment and in mice receiving cisplatin treatment after STING expression was inhibited using the STING inhibitor C176. The renoprotective effect of YQJPXY on cisplatin-treated mice was evaluated by measuring tissue damage, inflammation and pro-fibrosis. In addition, we employed network pharmacology and molecular docking methodologies to analyse the principal regulatory targets of YQJPXY. Furthermore, the expression of key proteins and markers of ferroptosis and iron metabolism, as well as the levels of key indicators related to STING-associated ferritinophagy, were examined by immunoblotting, immunohistochemistry, immunoprecipitation, quantitative real-time PCR (qPCR) and specific probes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The results demonstrated that YQJPXY reduced the levels of indicators of injury, inflammation and pro-fibrosis in CIAKI mice, with renoprotective effects. Network pharmacological analyses revealed that ferroptosis might be the main biological process regulated by YQJPXY. Furthermore, molecular docking results indicated that STING might be a potential regulatory target of YQJPXY. Furthermore, YQJPXY treatment resulted in a significant reduction in MDA and 4-HNE levels, as well as the inhibition of ferroptosis and improvement in iron metabolic processes. Concomitantly, YQJPXY exhibited a robust protective effect on ferroptosis and iron metabolism homeostasis, as evidenced by its inhibitory action on ferritinophagy. Validation experiments utilising the cisplatin inhibitor C176 demonstrated that YQJPXY inhibits cisplatin-induced ferroptosis in kidney via STING-mediated ferritinophagy.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;These suggest that YQJPXY alleviates cisplatin-induced acute kidney injury through suppressing ferroptosis v","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156189"},"PeriodicalIF":6.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606135","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":"Avicularin inhibits ferroptosis and improves cognitive impairments in Alzheimer's disease by modulating the NOX4/Nrf2 axis","authors":"Zixiang Li ,&nbsp;Yingying Lu ,&nbsp;Yongqi Zhen ,&nbsp;Wenke Jin ,&nbsp;Xuelan Ma ,&nbsp;Ziyue Yuan ,&nbsp;Bo Liu ,&nbsp;Xian-Li Zhou ,&nbsp;Lan Zhang","doi":"10.1016/j.phymed.2024.156209","DOIUrl":"10.1016/j.phymed.2024.156209","url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer's disease (AD) is a widespread neurodegenerative disorder for which effective therapies remain elusive, primarily due to the complexity of its underlying pathophysiology. In recent years, natural products have gained attention for their therapeutic potential in AD, owing to their multi-targeted actions and low toxicity profiles. Avicularin (Avi), a flavonoid derived from the peels of <em>Zanthoxylum bungeanum</em> Maxim., has shown promise as an anti-AD agent. However, the specific mechanisms by which Avi mitigates oxidative stress and inhibits ferroptosis in AD models remain insufficiently understood. Further investigation is required to elucidate its therapeutic potential in these pathways.</div></div><div><h3>Purpose</h3><div>Therefore, this study aims to elucidate the neuroprotective effects of Avi in AD by investigating its impact on the NOX4/Nrf2 signaling pathway, as well as its role in modulating oxidative stress and ferroptosis.</div></div><div><h3>Methods</h3><div>In this study, an <em>in vitro</em> H₂O₂-induced oxidative stress model in SH-SY5Y cells was utilized to evaluate the pharmacological efficacy and underlying mechanisms of Avi. Molecular docking, cellular thermal shift assay and bio-layer interferometry assays were conducted to identify potential molecular targets of Avi. Additionally, <em>in vivo</em> models, including scopolamine (SCOP)-induced and APP/PS1 transgenic mice, were employed to assess the cognitive effects of Avi and further explore its associated molecular mechanisms.</div></div><div><h3>Results</h3><div>Our study demonstrates that Avi effectively attenuates H₂O₂-induced toxicity in SH-SY5Y cells by reducing apoptosis and enhancing cellular antioxidant defenses. This neuroprotective effect is mediated through the inhibition of NOX4 and the promotion of Nrf2 nuclear translocation. Furthermore, Avi improves cognitive function and mitigates ferroptosis in both SCOP-induced and APP/PS1 transgenic mouse models of AD.</div></div><div><h3>Conclusion</h3><div>Avi emerges as an effective neuroprotective agent against AD, offering a promising therapeutic approach by targeting the NOX4/Nrf2 signaling axis to alleviate oxidative stress and ferroptosis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156209"},"PeriodicalIF":6.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606109","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":"Lutein, a versatile carotenoid: Insight on neuroprotective potential and recent advances","authors":"Megha Jayakanthan ,&nbsp;Janani Manochkumar ,&nbsp;Thomas Efferth ,&nbsp;Siva Ramamoorthy","doi":"10.1016/j.phymed.2024.156185","DOIUrl":"10.1016/j.phymed.2024.156185","url":null,"abstract":"<div><h3>Background</h3><div>Neurodegenerative diseases (NDDs) are a diverse group of neurological disorders with progressive neuronal loss at specific brain regions, leading to impaired cognitive functioning, loss of neuroplasticity, severe neurological impairment, and dementia. The incidence of neurodegenerative diseases is increasing at an alarming rate with current treatments struggling to barely prolong the inevitable. The desperation to discover a therapeutic agent to treat neurodegenerative diseases and to aid in the process of healthy recovery has opened a gateway into natural pigments.</div></div><div><h3>Hypothesis</h3><div>The xanthophyll pigment lutein may bear the potential as a therapeutic agent against NDDs.</div></div><div><h3>Results</h3><div>Lutein plays an important role in brain development, cognitive functioning, and improving neuroplasticity. <em>In vitro</em> and <em>in vivo</em> studies revealed the neuroprotective properties of lutein against NDDs such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and cerebral ischemia. The neuroprotective effect of lutein is evidenced by the reduction of free radicals and the simultaneous strengthening of the endogenous antioxidant systems by activating the NRF-2/ERK/AKT pathway. Further, it effectively suppressed mitochondrial aberrations, excitotoxicity, overaccumulation of metals, and its resultant complications. The immunomodulatory activity of lutein prevents neuroinflammation by hindering NF-κB nuclear translocation, regulation of NIK/IKK, PI3K/AKT, MAPK/ERK, JNK pathways, and ICAM-1 downregulation. Lutein also rescued the dysregulated cholinergic system and resolved memory defects. Along with its neuroprotective properties, lutein also improved neuroplasticity by enabling neurogenesis through increased GAP-43, NCAM, and BDNF levels.</div></div><div><h3>Conclusion</h3><div>Lutein exhibits strong neuroprotective activities against various NDDs. Though the investigations are in the exploratory phase, this review presents the consolidation of scattered evidence of the neuroprotective properties of lutein and urges its further exploration in clinical studies.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156185"},"PeriodicalIF":6.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626433","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}