Phytomedicine最新文献

{"title":"Corrigendum to Peanut (Arachis hypogaea L.) seeds and by-products in metabolic syndrome and cardiovascular disorders: A systematic review of clinical studies Phytomedicine 123 (2024) 155170.","authors":"Yandra Cervelim Nunes, Gian de Oliveira Santos, Nathália Mendes Machado, Alda M M B Otoboni, Lucas Fornari Laurindo, Anusha Bishayee, Carmela Fimognari, Anupam Bishayee, Sandra Maria Barbalho","doi":"10.1016/j.phymed.2024.155870","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.155870","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular diseases (CVDs) are the leading causes of death worldwide. The main risk factors are hypertension, diabetes, obesity, and increased serum lipids. The peanut (Arachis hypogaea L.), also known as the groundnut, goober, pindar, or monkey nut, belongs to the Fabaceae family and is the fourth most cultivated oilseed in the world. The seeds and skin of peanuts possess a rich phytochemical profile composed of antioxidants, such as phenolic acids, stilbenes, flavonoids, and phytosterols. Peanut consumption can provide numerous health benefits, such as anti-obesity, antidiabetic, antihypertensive, and hypolipidemic effects. Accordingly, peanuts have the potential to treat CVD and counteract its risk factors.</p><p><strong>Purpose: </strong>This study aims to critically evaluate the effects of peanuts on metabolic syndrome (MetS) and CVD risk factors based on clinical studies.</p><p><strong>Method: </strong>This review includes studies indexed in MEDLINE-PubMed, COCHRANE, and EMBASE, and the Preferred Reporting Items for a Systematic Review and Meta-Analysis guidelines were adhered to.</p><p><strong>Results: </strong>Nineteen studies were included and indicated that the consumption of raw peanuts or differing forms of processed foods containing peanut products and phytochemicals could improve metabolic parameters, such as glycemia, insulinemia, glycated hemoglobin, lipids, body mass index, waist circumference, atherogenic indices, and endothelial function.</p><p><strong>Conclusion: </strong>We propose that this legume and its products be used as a sustainable and low-cost alternative for the prevention and treatment of MetS and CVD. However, further research with larger sample sizes, longer intervention durations, and more diverse populations is needed to understand the full benefit of peanut consumption in MetS and CVD.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":" ","pages":"155870"},"PeriodicalIF":6.7,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142732079","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":"Bushen Jianpi Tiaoxue Decoction (BJTD) ameliorates oxidative stress and apoptosis induced by uterus ageing through activation of the SIRT1/NRF2 pathway","authors":"Jiacheng Zhang ,&nbsp;Hangqi Hu ,&nbsp;Yutian Zhu ,&nbsp;Yuxin Jin,&nbsp;Haolin Zhang,&nbsp;Ruiwen Fan,&nbsp;Yang Ye,&nbsp;Xiyan Xin,&nbsp;Dong Li","doi":"10.1016/j.phymed.2024.156288","DOIUrl":"10.1016/j.phymed.2024.156288","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Uterus ageing is a crucial factor contributing to decreased fertility in older women and is also implicated in menstrual disorders, endometritis, and adenomyosis. Bushen Jianpi Tiaoxue Decoction (BJTD) is a traditional Chinese medicine formulation used to ameliorate endocrine disorders in the female reproductive system and finds extensive application in ageing-related endometrial diseases. However, the mechanisms underlying its improvement of uterus ageing have not been thoroughly investigated.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;To explore the potential components and mechanisms of BJTD in ameliorating uterus ageing through network pharmacology, &lt;em&gt;in vivo&lt;/em&gt;, and &lt;em&gt;in vitro&lt;/em&gt; experiments.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Morphological changes were observed using hematoxylin and eosin staining, collagen deposition was assessed using Masson staining, and apoptotic-related molecules were detected using Western blot. After determining the modeling doses, BJTD intervention was administered at two doses, and the expression of oxidative stress and apoptosis-related genes and proteins was measured. The levels of cellular apoptosis were evaluated using the TUNEL assay kit and Annexin V/FITC-PI assay kit. The main components of BJTD were determined by UPLC-MS, and the potential targets and mechanisms of BJTD action were explored using network pharmacology and molecular docking. BJTD-Containing Serum (BJTD-S) was extracted and applied &lt;em&gt;in vitro&lt;/em&gt; experiments using human endometrial stroma cells (hESC) to preliminarily identify the pathways affected.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;We demonstrated that modeling with 600 mg/kg/day D-Gal for 5 weeks significantly increased collagen deposition in uterine tissues, particularly in the glands and stroma. Additionally, it significantly elevated the levels of TNF-α and IL-1β and increased the expression of p53 and BAX while decreasing BCL-2 expression. BJTD significantly reduced the increased levels of TNF-α and IL-1β induced by D-Gal, and modulated oxidative stress markers such as SOD, MDA, GSH-Px, and T-AOC. BJTD also inhibited the cascade activation of apoptosis induced by D-Gal, suppressing the expression of cleaved-Caspase 8, cleaved-Caspase 3, and BAX. SIRT1 is a potential target of BJTD action. &lt;em&gt;In vitro&lt;/em&gt; experiments showed that BJTD-S significantly improved D-Gal-induced apoptosis in hESC cells, and the expression levels of SIRT1, NRF2, and HO-1 were significantly decreased in D-Gal-induced hESC, and BJTD-S significantly increased their expression.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;BJTD can ameliorate oxidative stress and cell apoptosis levels in D-Gal-induced uterine aging, and its active ingredients can activate the SIRT1/NRF2 pathway to exert its effects. Importantly, our study provides novel insights into the molecular mechanisms by which traditional Chinese medicine influence uterus ageing. By specifically targeting the SIRT1/NRF2 pathw","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"Article 156288"},"PeriodicalIF":6.7,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759217","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":"Toosendanin alleviates acute lung injury by reducing pulmonary vascular barrier dysfunction mediated by endoplasmic reticulum stress through mTOR","authors":"Xiaocheng Mao ,&nbsp;Cheng Wang ,&nbsp;Hong Tang ,&nbsp;Xiaohua Liu ,&nbsp;Caihui Wei ,&nbsp;Fang Yin ,&nbsp;Tianmei Fu ,&nbsp;Yangyang Fang ,&nbsp;Kuai Yu ,&nbsp;Zhanglin Zhang ,&nbsp;Chenggao Wu ,&nbsp;Hongfei Liu ,&nbsp;Aiping Le","doi":"10.1016/j.phymed.2024.156277","DOIUrl":"10.1016/j.phymed.2024.156277","url":null,"abstract":"<div><h3>Background</h3><div>Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe clinical conditions with limited treatment options. Toosendanin (TSN), a triterpenoid compound with anti-inflammatory effects, has unclear efficacy in ALI.</div></div><div><h3>Purpose</h3><div>This study aimed to evaluate TSN's protective effects on ALI and the related mechanisms.</div></div><div><h3>Methods</h3><div>Lipopolysaccharide (LPS)-induced ALI models were developed in vivo and in vitro. Endothelial permeability was measured using Evans Blue dye; lipid reactive oxygen species (ROS) and apoptosis were assessed using flow cytometry. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined, and cell viability was measured. mRNA and protein expression were quantified using qRT-PCR and Western blotting. Network pharmacology and surface plasmon resonance were used to identify and validate TSN's targets.</div></div><div><h3>Results</h3><div>TSN reduced endothelial permeability and LPS-induced ALI. It lowered ROS levels, lipid peroxidation, endoplasmic reticulum (ER) stress, and apoptosis, both in vitro and in vivo. Network pharmacology identified mTOR as a key target of TSN, and surface plasmon resonance analysis confirmed TSN's direct binding to mTOR, underscoring mTOR's role in TSN's protective effects against ALI. Western blotting showed that TSN inhibits mTOR and its phosphorylation. In vitro, the mTOR activator MHY1485 reversed TSN's protective effects, increasing ER stress, apoptosis, and endothelial permeability. In vivo, TSN and rapamycin synergistically protected against ALI.</div></div><div><h3>Conclusion</h3><div>This study is the first to demonstrate that TSN protects against ALI by targeting the mTOR pathway, regulating ER stress and apoptosis and mitigating endothelial damage. These findings suggest a novel approach for ALI treatment and underscore TSN's potential clinical value.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"Article 156277"},"PeriodicalIF":6.7,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142747554","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":"Xibining inhibition of the PI3K-AKT pathway reduces M1 macrophage polarization to ameliorate KOA synovial inflammation and nociceptive sensitization","authors":"Lishi Jie ,&nbsp;Li Zhang ,&nbsp;Houyu Fu ,&nbsp;Junfeng Kang ,&nbsp;Zeling Huang ,&nbsp;Zaishi Zhu ,&nbsp;Songjiang Yin ,&nbsp;Peng Wu ,&nbsp;Peimin Wang ,&nbsp;Wei Mei ,&nbsp;Xiaochen Li","doi":"10.1016/j.phymed.2024.156281","DOIUrl":"10.1016/j.phymed.2024.156281","url":null,"abstract":"<div><h3>Background</h3><div>Pain is the most critical symptom of knee osteoarthritis(KOA), which seriously affects the quality of life of patients. Xibining (XBN), a traditional herbal compound, has achieved good results in the clinical treatment of KOA, and its mechanism of action is worth exploring in depth.</div></div><div><h3>Objective</h3><div>In vivo and in vitro models of KOA were constructed, and the potential drug action mechanism of XBN in improving osteoarthritis pain was explored in combination with transcriptomics.</div></div><div><h3>Methods</h3><div>In vitro experiments were also conducted to explore the effects of different treatments of BMDMs on TRP channels in DRG neurons by constructing a coculture system of BMDMs and DRG neurons. The specific mechanism by which XBN affects BMDMs was explored via participatory transcriptomics.</div></div><div><h3>Results</h3><div>Our results showed that KOA aggravated macrophage infiltration in synovial tissues and DRG tissues and increased the transcriptional and translational levels of TRPA1, TRPV1, and TRPM8 in synovial tissues and DRG tissues; XBN treatment improved inflammation in synovial tissues and macrophage infiltration in DRG tissues, and it decreased the transcriptional and translational levels of TRPA1, TRPV1, and TRPM8, consistent with the results of behavioral tests to improve nociceptive sensitization induced by KOA. The results from in vitro experiments showed that promoting macrophage M1-type polarization exacerbated TRP channel activation in DRG neurons and that XBN acted by inhibiting macrophage M1-type polarization. A reference transcriptome study showed that XBN may play a role in inhibiting M1 macrophage-type polarization in KOA by suppressing the PI3K-AKT pathway in BMDMs. We verified the conclusions obtained from transcriptomics via in vitro experiments. We place greater emphasis on the role that the intrinsic immune system plays in the area of pain control in osteoarthritis.</div></div><div><h3>Conclusion</h3><div>XBN improve KOA nociceptive sensitization by modulating the PI3K/Akt signaling pathway, attenuating the level of synovial inflammation and inhibiting M1-type macrophage polarization in synovial and DRG tissues in KOA mice.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"Article 156281"},"PeriodicalIF":6.7,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142747555","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":"S6K/FLNC/ITGβ3 signaling pathway regulates osteoclastogenesis and the inhibition of osteoclastogenesis by columbianadin","authors":"Qiu Wei ,&nbsp;Zi-Chang Niu ,&nbsp;Xiao-Yu Fu ,&nbsp;Ming-Hui OuYang ,&nbsp;Xiao-Tong Guo ,&nbsp;Jin Li ,&nbsp;Yan-Xu Chang ,&nbsp;Hao-Ping Mao ,&nbsp;Xiu-Mei Gao","doi":"10.1016/j.phymed.2024.156276","DOIUrl":"10.1016/j.phymed.2024.156276","url":null,"abstract":"<div><h3>Background</h3><div>Over-activation of osteoclastogenesis is a significant factor contributing to bone loss, leading to increased resorption of bone. Columbianadin (CBN), a compound derived from Angelicae Pubescentis Radix, has traditionally been used in Chinese medicine to treat bone-related disorders. However, the specific effects of CBN on bone loss are still poorly understood.</div></div><div><h3>Study design</h3><div>This study aims to identify a novel target for inhibiting osteoclast differentiation and to elucidate the effects and underlying mechanisms of CBN on osteoclastogenesis.</div></div><div><h3>Methods</h3><div>We employed a transcriptomics approach to identify genes that undergo significant changes during osteoclast differentiation. These findings were validated using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot (WB) analysis. Subsequently, we utilized adenoviral transfection to investigate the effects of target genes on osteoclast differentiation. Additionally, we employed proteomics to elucidate the signaling pathways that regulate osteoclast differentiation. We examined the effect of CBN on S6K/FLNC/ITGβ3 signaling pathway and osteoclast differentiation.</div></div><div><h3>Results</h3><div>Our results revealed a dramatic increase in filamin C (FLNC) levels during osteoclast differentiation. Inhibition of FLNC expression significantly suppressed markers of osteoclast differentiation such as tartrate-resistant acid phosphatase (TRAP), nuclear factor-activated T cell 1 (NFATc1), and c-Fos, as well as inhibited the activity of bone resorption. We further conducted a proteomic analysis and found S6 K protein might be involved in this process. Then we utilized an S6K-specific inhibitor (PF-4,708,671) and demonstrated that inhibiting the S6 K protein reduced FLNC expression and the interaction between FLNC and integrin β3 (ITGβ3) in osteoclasts. Finally, we found that CBN inhibited osteoclast differentiation and bone loss in ovariectomized mice by targeting the S6K/FLNC/ITGβ3 signaling pathway.</div></div><div><h3>Conclusion</h3><div>FLNC was identified as a critical protein in osteoclastogenesis. The S6K/FLNC/ITGβ3 signaling pathway played a significant role in osteoclast differentiation and bone loss. Furthermore, CBN exhibited anti-osteoporotic effects by inhibiting the S6K/FLNC/ITGβ3 signaling pathway.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"Article 156276"},"PeriodicalIF":6.7,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142747558","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 promoted ferroptosis by activating mitochondrial dysfunction to inhibit colorectal cancer and synergistically enhanced the efficacy of PD-1 inhibitors.","authors":"Wang Haoyue, Sun Kexiang, Tan Wei Shan, Gao Jiamin, Yuan Luyun, Wen Junkai, Deng Wanli","doi":"10.1016/j.phymed.2024.156224","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156224","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;A controlled type of cell death called ferroptosis is linked to increased reactive oxygen species (ROS), lipid peroxidation, and iron buildup. Furthermore, evidence indicates that ferroptosis may act as an immunogenic form of cell death with potential physiological functions in tumors and immunosuppression. Inducing ferroptosis in tumor cells may have the potential to complement cancer immunotherapy strategies. The development of colorectal cancer (CRC) and the poor efficacy of immunotherapy are associated with the crosstalk of cellular ferroptosis. Currently, Icariin (ICA), the main bioactive component extracted from Epimedium, has been shown to inhibit a variety of cancers. However, the specific role and potential mechanism of ICA in regulating ferroptosis in CRC remains unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;The aim of this investigation was to clarify the mechanism underlying the anti-CRC cancer properties of ICA and how it induces ferroptosis to enhance immunotherapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;To evaluate cell viability, the Cell Counting Kit-8 (CCK-8) test was utilized. The transwell test and the wound healing assay were used to assess cell migration. A subcutaneous graft tumor model was constructed with C57BL/6 mice using MC38 colorectal cancer cell lines. The inhibitory effect of ICA on CRC, ferroptosis level and immunomodulatory effects were detected by serum biochemical assay, cytokine assay, hematoxylin-eosin (H&E) staining, immunofluorescence staining, CyTOF mass spectrometry flow screening and Western blotting. Western blotting, proteomics, molecular docking and microscale thermophoresis (MST) were used to forecast and confirm ICA's binding and interaction with HMGA2, STAT3, and HIF-1α. Moreover, the levels of lipid peroxidation and ferroptosis were assessed through the use of the C11-BODIPY fluorescent probe, the FerroOrange fluorescent probe, the iron level, the malondialdehyde (MDA) and reduced glutathione (GSH) assay kit, and Western blotting analysis. To assess alterations in mitochondrial structure and membrane potential, transmission electron microscopy (TEM) and JC-1 immunofluorescence were employed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;It was demonstrated in the current study that ICA treatment inhibits CRC and enhances anti-PD-1 therapy efficacy by inciting ferroptosis. As shown in vitro, ICA inhibits CRC cell proliferation, migration, and apoptosis. As demonstrated in vivo, ICA has a dose-dependent tumor suppressor effect when combined with anti-PD-1, it can significantly inhibit tumor growth, increase the expression of serum TNF-α, IFN-γ, and granzyme B, and promote CD69&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt; T, CD69&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt;Tem, CD69&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt;Teff, TCRβ&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt; T, TCRβ&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt; T, TCRβ&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt;Tem, TCRβ&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt;Teff. The inhibitory effect of ICA on CRC was associated with the binding of HMGA2","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"156224"},"PeriodicalIF":6.7,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792375","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":"Qingke Pingchuan granules alleviate airway inflammation in COPD exacerbation by inhibiting neutrophil extracellular traps in mice","authors":"Mengxin Cheng ,&nbsp;Xi Yan ,&nbsp;Yu Wu ,&nbsp;Zijian Zeng ,&nbsp;Yutian Zhang,&nbsp;Fuqiang Wen,&nbsp;Jun Chen,&nbsp;Tao Wang","doi":"10.1016/j.phymed.2024.156283","DOIUrl":"10.1016/j.phymed.2024.156283","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Chronic obstructive pulmonary disease (COPD) imposes a significant global health and socioeconomic burden. Exacerbations of COPD (ECOPD), characterized by heightened airway inflammation and mucus hypersecretion, adversely affect patient health and accelerate disease progression. Qingke Pingchuan (QKPC) granules, a formulation from Traditional Chinese Medicine initially prescribed for acute bronchitis, have shown unexplored potential in ECOPD management, with mechanisms of action yet to be clarified.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This study investigates the therapeutic effects of QKPC in a mouse model of ECOPD, focusing on underlying molecular mechanisms.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;COPD was induced in mice through chronic cigarette smoke (CS) exposure, followed by intratracheal administration of &lt;em&gt;Pseudomonas aeruginosa&lt;/em&gt; lipopolysaccharide (LPS) to trigger exacerbation, after which mice were treated with QKPC granules. Major compounds in QKPC were identified &lt;em&gt;via&lt;/em&gt; UHPLC-QE-MS, and high-throughput RNA sequencing of lung tissue samples identified differentially expressed genes. Transcriptomic data were integrated with network pharmacology analysis to pinpoint potential pathways, bioactive compounds, and target genes through which QKPC might attenuate ECOPD. Molecular docking, protein-small molecule binding assays, and &lt;em&gt;in vitro&lt;/em&gt; analyses further validated interactions between key compounds and target genes, shedding light on plausible signaling pathways.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;QKPC treatment led to significant reductions in airway leukocyte infiltration and goblet cell metaplasia in CS- and LPS-exposed mice, accompanied by decreased levels of inflammatory cytokines (IL-6, IL-1β, CXCL1, and TNF-α) and mucin MUC5AC in bronchoalveolar lavage fluid. The integrative transcriptomic and network pharmacology analysis identified the neutrophil extracellular trap (NET) formation pathway as a key mechanism underlying QKPC's protective effect against ECOPD. &lt;em&gt;In vitro&lt;/em&gt; assays demonstrated that epigallocatechin-3-gallate (EGCG) and quercetin, two important bioactive compounds in QKPC, significantly inhibited NETosis induced by cigarette smoke extract (CSE) plus LPS in human neutrophils. The two compounds were found to interact directly with the reactive oxidative species (ROS)-generating enzyme NOX2 and its regulatory subunit p47phox. Subsequent &lt;em&gt;in vitro&lt;/em&gt; studies further confirmed EGCG and quercetin's capacity to reduce ROS production and downregulate NOX2 and p47phox protein levels in neutrophils stimulated with CSE and LPS. Additionally, &lt;em&gt;in vivo&lt;/em&gt; studies confirmed QKPC's efficacy in reducing NET formation, oxidative stress, and NOX2/p47phox protein expression in the lung tissue of ECOPD mice.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;These findings suggest that QKPC granules alleviate airway inflammation in ECOPD, potentially through inhibition of pulmonary NET ","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"Article 156283"},"PeriodicalIF":6.7,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142747495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Casticin inhibits proliferation of Non-small cell lung cancer cells through regulating reprogramming of glucose metabolism.","authors":"Jingyi Wei, Guangyan Lei, Qiang Chen, Wen Huang, Hui Ning, Meng Yang, Jiaqi Dong, Longquan Hu, Shujia Peng, Hui Gong, Menghui Yuan, Peng Yuan","doi":"10.1016/j.phymed.2024.156278","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156278","url":null,"abstract":"<p><strong>Background: </strong>Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with poor prognosis due to its rapid progression and resistance to existing therapies. Metabolic reprogramming, particularly alterations in glucose metabolism, is a key mechanism underlying tumor growth and progression, providing potential targets for novel therapeutic strategies. Casticin (CAS), a bioactive flavonoid, has shown anticancer effects in various cancers, but its specific role in NSCLC metabolism remains unclear.</p><p><strong>Purpose: </strong>This study aims to investigate the effects of casticin on the proliferation and glucose metabolism of NSCLC cells, and to explore its underlying mechanisms.</p><p><strong>Study design and methods: </strong>We used both in vitro and in vivo models. (18)F-FDG PET/MR imaging was employed to assess the impact of casticin on glucose metabolism in A549 xenograft mice. NSCLC cell lines (A549 and H157) were treated with casticin to evaluate its effects on cell viability, glycolysis, oxidative phosphorylation, and fatty acid oxidation. Key metabolic enzyme expressions were analyzed using molecular detection techniques, and in vivo validation was performed using a subcutaneous xenograft mouse model.</p><p><strong>Results: </strong>Casticin significantly inhibited glucose metabolism and cell proliferation in a dose-dependent manner, while promoting oxidative phosphorylation without affecting lipid metabolism. The drug suppressed glycolysis by downregulating the expression of key glycolytic enzymes (GLUT1, HK2, GPI, ALDOA, ENO2, PKM2, and MCT4) through the regulation of HIF-1α. Overexpression of HIF-1α in both in vitro and in vivo models reversed the inhibitory effects of casticin, indicating that HIF-1α plays a central role in its mechanism of action.</p><p><strong>Conclusion: </strong>Casticin inhibits NSCLC cell proliferation by suppressing glycolytic reprogramming via HIF-1α regulation. These findings highlight the potential of casticin as an anticancer therapeutic, particularly in targeting glucose metabolism in NSCLC.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"156278"},"PeriodicalIF":6.7,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794978","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":"Proanthocyanidins alleviate acute alcohol liver injury by inhibiting pyroptosis via inhibiting the ROS-MLKL-CTSB-NLRP3 pathway","authors":"Yingli Jin ,&nbsp;Chunyun Wang ,&nbsp;Zhuoqun Meng ,&nbsp;Yuxin Zhang ,&nbsp;Desen Meng ,&nbsp;Jiaqi Liu ,&nbsp;Meng Yuan ,&nbsp;Shuang Guan","doi":"10.1016/j.phymed.2024.156268","DOIUrl":"10.1016/j.phymed.2024.156268","url":null,"abstract":"<div><h3>Background</h3><div>Alcoholic Liver Disease (ALD) is a hepatic disorder resulting from prolonged or excessive alcohol intake. The predominant manifestation of ALD is fatty liver, which progresses to alcoholic hepatitis as the disease worsens. Pyroptosis is a novel type of programmed cell death that is intricately linked to the inflammatory cascade, presenting a promising avenue for therapeutic intervention in the management of ALD. Oligomeric proanthocyanidins (OPCs) are polyphenols extracted from grape seeds that have anti-inflammatory and antioxidant properties. However, whether OPCs can treat ALD by suppressing pyroptosis is not completely clarified.</div></div><div><h3>Purpose</h3><div>To explore the role of OPCs in ALD to inhibit pyroptosis and its mechanism.</div></div><div><h3>Methods</h3><div>In vitro, HepG2 cells were employed to evaluate the beneficial impact of OPCs on alcohol-induced pyroptosis. MTT colorimetric method, enzyme-linked immunosorbent assay (ELISA), western blot (WB), immunofluorescence, acridine orange (AO) staining, and reactive oxygen species (ROS) assay were performed. In vivo, C57BL mice were used and gavaged with alcohol and OPCs. Hematoxylin-eosin staining (HE) staining, alanine aminotransferase (ALT), aspartate aminotransferase (AST) level assay, and WB were performed.</div></div><div><h3>Results</h3><div>The findings revealed that OPCs could reduce the alcohol-induced increase in pyroptosis-related proteins, such as pyrin domain-containing 3 protein (NLRP3), cleaved-caspase 1, gasdermin D (GSDMD-N), Interleukin-18 (IL-18), IL-1β (IL-1β). In in vitro mechanistic experiments, We discovered that OPCs ameliorate alcohol-induced pyroptosis by decreasing cathepsin B (CTSB) leakage-mediated NLRP3 activation. More significantly, we discovered that alcohol phosphorylates mixed lineage kinase domain-like protein (MLKL), enabling P-MLKL to translocate to the lysosomal membrane and induce lysosomal membrane permeabilization (LMP). OPCs might counteract the effects of alcohol by reducing the leakage of CTSB and inhibiting the phosphorylation of MLKL through the scavenging of ROS.</div></div><div><h3>Conclusions</h3><div>These results suggested that OPCs might counteract ALD by inhibiting pyroptosis through the ROS-MLKL-CTSB-NLRP3 pathway. Our study offered fresh insight into the ways in which naturally occurring chemicals shield ALD against harm.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"Article 156268"},"PeriodicalIF":6.7,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142747493","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":"Advances in the application of network analysis methods in traditional Chinese medicine research","authors":"Defu Tie ,&nbsp;Mulan He ,&nbsp;Wenlong Li ,&nbsp;Zheng Xiang","doi":"10.1016/j.phymed.2024.156256","DOIUrl":"10.1016/j.phymed.2024.156256","url":null,"abstract":"<div><h3>Objective</h3><div>This review aims at evaluating the role and potential applications of network analysis methods in the medicinal substances of traditional Chinese medicine (TCM), theories of TCM compatibility, properties of herbs, and TCM syndromes.</div></div><div><h3>Methods</h3><div>Literature was retrieved from databases, such as CNKI, PubMed, and Web of Science, using keywords, including \"network analysis,\" \"network biology,\" \"network pharmacology,\" and \"network medicine.\" The extracted literature included the biological network construction (including ingredient-target and target-disease relations), analysis of network topology characteristics (including node degree, clustering coefficient, and path length), network modularization analysis, functional annotation and so on. These studies were categorized and organized based on their research methods, application domains, and other relevant characteristics.</div></div><div><h3>Results</h3><div>Network analysis algorithms, such as network distance, random walk, matrix factorization, graph embedding, and graph neural networks, are widely applied in fields related to the properties, compatibility, and mechanisms of TCM. They effectively reflect the interactive relations within the complex systems of TCM and elucidate and clarify theories, such as the effective substances, the principles of TCM compatibility, the TCM syndromes, and the properties of TCM.</div></div><div><h3>Conclusion</h3><div>The network analysis method is a powerful mathematical and computational tool that reveals the structure, dynamics, and functions of complex systems by analyzing the elements and their relations. This approach has effectively promoted the modernization of TCM, providing essential theoretical and practical tools for personalized treatment and scientific research on TCM. It also offers a significant methodological framework for the modernization and internationalization of TCM.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"Article 156256"},"PeriodicalIF":6.7,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142747563","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}