Phytomedicine最新文献

{"title":"Ginkgo biloba leaf extract EGb 761® for the treatment of various diseases: Overview of systematic reviews","authors":"Katrin Pfuhlmann ,&nbsp;Anna K. Koch ,&nbsp;Jost Langhorst","doi":"10.1016/j.phymed.2025.156565","DOIUrl":"10.1016/j.phymed.2025.156565","url":null,"abstract":"<div><h3>Background</h3><div><em>Ginkgo biloba</em> leaf extract EGb 761® might have diverse therapeutic effects.</div></div><div><h3>Objective</h3><div>We conducted an overview of systematic reviews (SRs) to compile the efficacy and safety of EGb 761®.</div></div><div><h3>Methods</h3><div>The Cochrane Database of Systematic Reviews, MEDLINE (<em>via</em> PubMed), Embase (<em>via</em> OVID) and PROSPERO were searched from inception until July 25th, 2023 with an update on January 30th, 2025. SRs were included if they evaluated the efficacy and safety of oral treatment with EGb 761® under any clinical condition or in healthy subjects for clinical reasons, such as prevention, or for health promotion. Two authors carried out screening, selection, data extraction and risk of bias assessment (AMSTAR 2). The degree of overlap was quantified. The overview was registered a priori (PROSPERO: CRD42023423789).</div></div><div><h3>Results</h3><div>We screened 126 articles and included reviews on neurocognitive disorders (<em>n</em> = 13), tinnitus, macular degeneration and schizophrenia (all <em>n</em> = 1). For neurocognitive disorders, most SRs were in favor of EGb 761® regarding cognition and behavioral and/or psychological symptoms, while the results for functional activities of daily living varied. EGb 761® might have positive effects on tinnitus, macular degeneration or schizophrenia: however, more evidence is needed. In general, EGb 761® appears to be safe. Methodological quality was poor in all SRs. The overall overlap of the primary studies on neurocognitive disorders was very high, and pairwise overlap varied.</div></div><div><h3>Conclusion</h3><div>EGb 761® has been studied in various reviews, particularly regarding neurocognitive disorders and has been reported to be safe in many SRs. The results must be treated with caution due to the poor quality of the SRs.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156565"},"PeriodicalIF":6.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683114","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":"Therapeutic efficacy of Xuebijing injection in treating severe acute pancreatitis and its mechanisms of action: A comprehensive survey","authors":"Zhuo Chen ,&nbsp;Rui Zheng ,&nbsp;Huiru Jiang ,&nbsp;Xinyi Zhang ,&nbsp;Mengqi Peng ,&nbsp;Tong Jiang ,&nbsp;Xiaowei Zhang ,&nbsp;Hongcai Shang","doi":"10.1016/j.phymed.2025.156629","DOIUrl":"10.1016/j.phymed.2025.156629","url":null,"abstract":"<div><h3>Background</h3><div>Severe acute pancreatitis (SAP) is a life-threatening condition associated with high mortality and limited therapeutic options. Current management strategies focus on infection prevention, immune regulation, and anticoagulation. Xuebijing Injection (XBJ), a widely used traditional Chinese medicine-derived intravenous preparation, has shown promising therapeutic effects in SAP. Herein, we sought to evaluate clinical and preclinical evidence on XBJ to reveal its potential mechanisms of action, and provide insights to guide future research and clinical applications.</div></div><div><h3>Methods</h3><div>We conducted a comprehensive survey of studies on XBJ in the treatment of SAP across PubMed, Embase, Cochrane Library, CBM, CNKI, Wanfang and VIP databases from their inception to March 21st, 2024.</div></div><div><h3>Results</h3><div>A total of 239 studies were included, comprising 12 animal experiments, 7 systematic reviews, 220 clinical trials. Mechanistic studies suggest that XBJ downregulates the expression of inflammatory mediators, improves immune function, and alleviates oxidative stress via multiple signaling pathways, including the TLR4/NF-κB, p38-MAPK, HMGB1/TLR, TLR4/NF-κB, FPR1/NLRP3, and JAK/STAT pathways. These effects contribute to reducing organ damage. Compared to standard treatment, XBJ has more effective at reducing mortality and complications, improving overall clinical outcomes, shortening ventilator use time, and hospital stay in SAP patients.</div></div><div><h3>Conclusions</h3><div>Preclinical evidence and clinical trial data indicated that XBJ can simultaneously regulate inflammatory responses, immune function, microcirculatory disorders, oxidative stress, and apoptosis. However, further research is required to elucidate the specific mechanisms of action, clinical characteristics and safety of XBJ.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156629"},"PeriodicalIF":6.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Berbamine alleviates neuropathic pain via suppressing spinal TMEM34/SGK1/FOXO3 axis","authors":"Chang-Heng Yao ,&nbsp;Zi-Meng Zhang ,&nbsp;Shen Zhang ,&nbsp;Han Jiang ,&nbsp;Rui Wang ,&nbsp;Ji-Hua Liu ,&nbsp;Hao Xie ,&nbsp;Wen-Ling Dai","doi":"10.1016/j.phymed.2025.156619","DOIUrl":"10.1016/j.phymed.2025.156619","url":null,"abstract":"<div><h3>Background</h3><div>The pathologic mechanism of neuropathic pain (NP) is still not fully understood, and efficient and safe therapeutic options are limited.</div></div><div><h3>Purpose</h3><div>Seeking new treatment options for neuropathic pain.</div></div><div><h3>Study Design</h3><div>Exploring new therapeutic target for NP and finding analgesic medications derived from traditional Chinese medicines against the target is urgent.</div></div><div><h3>Methods</h3><div>Chronic constriction injury (CCI) model was used for behavioral assays. <em>In vitro</em> assay was conducted by using primary neurons, glial cells, as well as PC12, C6, and BV2 cells. The mechanical and thermal withdrawal threshold was assessed using Von Frey filaments and Hargreaves method. RNA sequencing (RNA-Seq), immunofluorescence, western blot, and quantitative RT-PCR were also used.</div></div><div><h3>Results</h3><div>Spinal transmembrane34 (TMEM34) was firstly found to be elevated in CCI induced NP. Knocking-down spinal TMEM34 obviously alleviated NP, while overexpressing TMEM34 promoted NP and induced allodynia in naïve rats. Furthermore, TMEM34 was expressed in spinal neurons and astrocytes but not in microglia to activate them in CCI rats. Serum and glucocorticoid inducible kinase-1 (SGK1) was similarly expressed in astrocytes and neurons, and its expression trend is compatible with that of TMEM34. p-SGK1 expression was also suppressed by blocking TMEM34 in CCI rats. In addition, TMEM34/SGK1 was found to prevent Forkhead box O3 (FOXO3) from activating neurons and astrocytes and promoting NP. Berbamine (BBM), an active compound in <em>Stephania epigaea</em> H. S. Lo, was screened to block the TMEM34/SGK1/FOXO3 axis, hence relieving NP.</div></div><div><h3>Conclusions</h3><div>Our findings highlighted the significance of TMEM34 as a critical factor in NP and found a prospective medication that inhibited TMEM34 to reduce NP.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156619"},"PeriodicalIF":6.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620648","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":"Integrative gut microbiota, metabolomics and proteomics studies unraveled the mechanism of Shaoteng decoction in treating Sjogren's syndrome","authors":"Fengtao Pang ,&nbsp;Quan Jiang ,&nbsp;Kesong Li,&nbsp;Xiaopo Tang","doi":"10.1016/j.phymed.2025.156631","DOIUrl":"10.1016/j.phymed.2025.156631","url":null,"abstract":"<div><h3>Background</h3><div>Sjögren's syndrome (SS) is a complicated autoimmune disorder, encompassing multifaceted pathogenesis of inflammatory response, immune dysregulation and metabolic abnormalities. Shaoteng Decoction (STD) is a type of traditional Chinese medicine preparation that has been shown to effectively improve inflammatory damage and immune dysfunction in patients with SS. Nevertheless, the exact mechanism has not been unspecified.</div></div><div><h3>Purpose</h3><div>This work aims to determine the mechanism of STD treatment on SS, identifying potential therapeutic targets and their relationships.</div></div><div><h3>Methods</h3><div>Non-obese diabetic mice served as a disease model. This study analyzes potential signaling pathways of STD treatment for SS through network pharmacology, and assesses the role of STD in reducing inflammatory damage using pathological staining, ELISA, and immunohistochemistry. Additionally, the study apply gut microbiota, metabolomics, and proteomics analyses to identify the key microbiota, metabolites and proteins, aiming to find potential action targets of STD. We use Western blotting and immunohistochemistry to verify the authenticity of the relevant targets and study the interactions among gut microbiota, metabolites, and proteins.</div></div><div><h3>Results</h3><div>Proteobacteria is the important intestinal bacteria, Bile Acid Biosynthesis is the main metabolic pathway, IfI30, Ndufv3, and Ndufs6 are the crucial differential expressed proteins. Moreover, there is a strong correlation among the three. STD treats SS by reducing the abundance of Proteobacteria, increasing Bile Acid Biosynthesis, decreasing IfI30 expression, and increasing the expression of Ndufv3 and Ndufs6.</div></div><div><h3>Conclusion</h3><div>STD inhibits inflammatory responses, improves immune dysregulation and energy metabolism abnormalities, and prevents the progression of SS through regulating the gut microbiota, enhancing Bile Acid Biosynthesis, and modulating proteins expression levels.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156631"},"PeriodicalIF":6.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620763","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":"Theabrownins improve burn-induced kidney injury by increasing the levels of guanidinoacetic acid and fumaric acid","authors":"You Gao ,&nbsp;Changshun Han ,&nbsp;Zhiyuan Chen ,&nbsp;Jiancheng Huang ,&nbsp;Tianyun Peng ,&nbsp;Xiaoyan Ding ,&nbsp;Hongbin Zhong ,&nbsp;Lixin Liao ,&nbsp;Chengyong He ,&nbsp;Jiyi Huang","doi":"10.1016/j.phymed.2025.156609","DOIUrl":"10.1016/j.phymed.2025.156609","url":null,"abstract":"<div><h3>Background</h3><div>Burns are a common and serious health issue, with severe burn-induced acute kidney injury (AKI) being a major factor contributing to poor recovery and increased mortality in patients. Theabrownins (TBs), bioactive compounds formed during tea leaf fermentation, have shown promising effects on reducing inflammation, combating oxidative stress, and enhancing metabolic function. However, the roles and mechanisms of TBs in burn-induced kidney injury are still not fully understood.</div></div><div><h3>Methods</h3><div>The dorsal skin of 3-month-old mice was exposed to hot water for 10 s to induce burn-related renal injury. The mice were then orally administered TBs (40 mg/kg and 400 mg/kg). After 24 h of treatment, the mice were sacrificed for tissue collection. Transcriptomic and metabolomic analyses were performed to identify the pathways modulated by TBs. Metabolomics revealed TB-associated renal metabolites, such as guanidinoacetic acid (GAA) and fumaric acid (FA). Renal tubular epithelial (HK2) cells pretreated with GAA and FA were exposed to hydrogen peroxide (H₂O₂), cisplatin (CDDP) and erastin to establish a cell injury model. Changes in the levels of relevant molecules were assessed using quantitative RT-PCR, Western blotting, and fluorescence staining.</div></div><div><h3>Results</h3><div>TB treatment significantly increased the survival rate and reduced kidney injury in mice with burn injury. Multiomics analyses and molecular experimental validation revealed that TB treatment downregulated the inflammation, apoptosis, and ferroptosis pathways in the kidneys of mice with burn injury and increased the levels of the renal metabolites GAA and FA. Cellular experiments confirmed that GAA and FA alleviated H₂O₂-, CDDP- and erastin-induced renal tubular epithelial cell injury by inhibiting apoptosis and ferroptosis.</div></div><div><h3>Conclusions</h3><div>Burns induce inflammation and kidney damage by upregulating the apoptosis and ferroptosis pathways in renal tissue. TBs alleviate burn-induced renal apoptosis and ferroptosis by increasing the levels of GAA and FA in the kidneys, thereby ameliorating kidney damage. This study innovatively and systematically evaluated the ability of TBs to ameliorate burn-induced kidney injury and, for the first time, identified the potential mechanism by which TBs ameliorate burn-induced kidney damage by increasing the levels of the metabolites GAA and FA in the kidneys.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156609"},"PeriodicalIF":6.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628024","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":"Brazilin reduces methicillin-resistant Staphylococcus aureus virulence and pathogenicity by decreasing the secretion of the α-hemolysin","authors":"Mingzhe Li ,&nbsp;Zhengyuan An ,&nbsp;Mengfei Yu ,&nbsp;Xiaoxian Zhou ,&nbsp;Zhifang Yang ,&nbsp;Zehui Chen","doi":"10.1016/j.phymed.2025.156616","DOIUrl":"10.1016/j.phymed.2025.156616","url":null,"abstract":"<div><h3>Background</h3><div>Methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) is a super-resistant bacterium with strong pathogenicity, causing broad range of infections in various tissues. α-Hemolysin (Hla) is the main virulence factor of <em>S. aureus</em>. Brazilin (BN), is a homoisoflavonoid derivative, obtained from the wood of <em>Caesalpinia echinata</em> Lam (Brazil-wood), <em>Caesalpinia sappan</em> L (Leguminosae), and <em>Caesalpinia violacea</em> Standl, has been proven to exert excellent antibacterial and anti-virulence effects against <em>S. aureus</em>. However, the underlying mechanisms remain still unclear.</div></div><div><h3>Objective</h3><div>This study aims to evaluate the inhibitory effect of BN on MRSA virulence and pathogenicity and elucidate its underlying mechanisms.</div></div><div><h3>Methods</h3><div>Rabbit erythrocytes were used to evaluate the effect of BN on hemocytolysis. The potential target of BN was screened by transcriptomic sequencing and verified by qRT-PCR, western blot (WB), and molecular interaction experiments. The effects of BN on MRSA toxicity and pathogenicity were both validated using A549 cell and mouse skin abscess model caused by MRSA.</div></div><div><h3>Results</h3><div>BN attenuated the hemolytic activity of MRSA by inhibiting Hla secretion. It was also found that BN blocks its binding to the P1 promoter of the <em>sae</em> operon, and then reduced its transcript level. Remarkably, <em>ΔsaeR</em> strain exhibits significantly reduced hemolytic activity due to impaired regulation of Hla and no extra inhibitory effect was observed in the samples treated with BN. Moreover, BN relieved A549 cell damage and mouse skin abscess induced by MRSA by inhibiting SaeR.</div></div><div><h3>Conclusion</h3><div>These findings reveal, for the first time, BN can alleviate MRSA virulence and pathogenicity by decreasing the secretion of the Hla <em>via</em> inhibiting SaeR. Overall, this study suggests that BN could be a candidate for being submitted to further studies with the aim of its development as a new antibiotic against MRSA.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156616"},"PeriodicalIF":6.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578313","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":"Schisandra total lignans ameliorate neuronal ferroptosis in 3xTg-AD mice via regulating NADK/NADPH/GSH pathway","authors":"Yuying Wu ,&nbsp;Mengying Wei ,&nbsp;Mengyao Wang ,&nbsp;Minsong Guo ,&nbsp;Hengyuan Yu ,&nbsp;Yong Chen ,&nbsp;Tengfei Xu ,&nbsp;Yuan Zhou","doi":"10.1016/j.phymed.2025.156612","DOIUrl":"10.1016/j.phymed.2025.156612","url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited treatments. <em>Schisandra</em> total lignans (STL), the primary active component of <em>Schisandra chinensis</em>, shows potential in alleviating AD-related symptoms, though the mechanisms remain unclear.</div></div><div><h3>Purpose</h3><div>Considering the promoting effect of neuronal ferroptosis on AD and the neuroprotective activity of STL, this study aimed to investigate the impact of STL on AD neuronal ferroptosis and elucidate its underlying mechanisms.</div></div><div><h3>Methods</h3><div>This study used 3xTg-AD mice and SH-SY5Y cells overexpressing APPswe as models. UHPLC/Q-TOF-MS was applied for identifying components in STL extract and the plasma of 3xTg-AD mice, as well as to detect cellular endogenous metabolites for one-carbon metabolism analysis. Behavioral tests, including the Y maze, novel object recognition, Morris water maze, and open field, were conducted to assess the cognitive function and emotional state. Histopathological examinations were performed using immunofluorescence, immunohistochemistry, Nissl staining, and transmission electron microscopy. The GSH, GSSG, NAD(H), NADP(H), and MDA levels, as well as GPX and GR activity were measured using assay kits. ROS, Fe²⁺, and lipid peroxidation levels were detected with probes. Protein expression was evaluated by Western blot. Molecular docking, molecular dynamics simulations and cellular thermal shift assay were performed to analyze the STL-NADK interactions.</div></div><div><h3>Results</h3><div>Behavioral tests indicated that STL alleviated cognitive impairments and anxiety in 3xTg-AD mice. Histological analysis showed that STL decreased hippocampal Aβ levels, inhibited hippocampal neuronal ferroptosis, and mitigated synaptic damage. Cellular assays demonstrated that STL alleviated APPswe overexpression-induced ferroptosis and synaptic damage by activating the NADK/NADPH/GSH pathway, with NADK knockdown abolishing this neuroprotective effect of STL. Computational analysis and cellular thermal shift assay identified Gomisin D as the key STL component with strong affinity for NADK, driving its neuroprotective effects.</div></div><div><h3>Conclusion</h3><div>NADK emerges as a novel potential therapeutic target for AD, with STL activating NADK, promoting NADPH and GSH production, thereby mitigating neuronal ferroptosis in AD.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156612"},"PeriodicalIF":6.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620761","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":"Interdisciplinary integration strategy reveals the anti-inflammatory efficacy and potential mechanism of Jianpi Qingre Tongluo prescription in rheumatoid arthritis","authors":"Yang Li ,&nbsp;Jian Liu ,&nbsp;Yue Sun ,&nbsp;Yuedi Hu ,&nbsp;Chengzhi Cong ,&nbsp;Yiming Chen ,&nbsp;Yanyan Fang","doi":"10.1016/j.phymed.2025.156625","DOIUrl":"10.1016/j.phymed.2025.156625","url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovitis and associated with high rates of disability and systemic damage. Jianpi Qingre Tongluo prescription (Huangqin Qingre Chubi Capsule, HQC), an herbal formula with abundant clinical applications, has played a definite role in both clinical and experimental studies of RA. However, the specific mechanisms by which HQC relieves inflammation in RA have not been fully elucidated.</div></div><div><h3>Objective</h3><div>This study aimed to elucidate the anti-inflammatory efficacy and potential molecular mechanisms of HQC in RA and provide new targets and strategies for its clinical treatment.</div></div><div><h3>Methods</h3><div>An adjuvant-induced arthritis with damp-heat pattern rat model was established to observe the <em>in vivo</em> effects of HQC. Hematoxylin-eosin and toluidine blue staining, and enzyme-linked immunosorbent assay were used to assess potential efficacy. Bioinformatics methods and molecular docking were used to predict potential targets and intervention pathways in which HQC might act on RA. Clinical samples, overexpressed / silenced genes, and pathway agonists were selected to investigate the clinical relevance and regulatory relationships of the pathways. The regulatory mechanism of HQC was confirmed in an <em>in vitro</em> co-culture of neutrophils and fibroblast-like synoviocytes (FLSs) and an <em>in vivo</em> model.</div></div><div><h3>Results</h3><div>HQC dose-dependently reversed synovial pathological injury and systemic inflammatory responses in rats <em>in vivo</em>. Integrated bioinformatics and molecular docking identified the p38 mitogen-activated protein kinase (MAPK) signaling pathway and neutrophil extracellular trap (NET) formation as the key mechanisms by which HQC exerts anti-inflammatory effects on RA. Subsequently, a high correlation between circ0005732, p38 MAPK, and clinical features of RA was confirmed in clinical samples. <em>In vitro</em> experiments demonstrated that HQC alleviated the proliferation and inflammatory response of FLSs by regulating circ0005732 expression to inhibit NET formation driven by the p38 MAPK signaling pathway. Finally, RT-qPCR and western blotting confirmed that HQC modulated circ0005732, p38 MAPK pathway, and NET formation to alleviate RA <em>in vivo</em>.</div></div><div><h3>Conclusion</h3><div>HQC exerts therapeutic effects against RA by modulating circ0005732 to inhibit p38 MAPK signaling pathway-mediated NET generation and inflammation progression.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156625"},"PeriodicalIF":6.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592905","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":"Sauchinone preserves cardiac function in doxorubicin-induced cardiomyopathy by inhibiting the NLRP3 inflammasome","authors":"Wenxu Xin ,&nbsp;Hai Yang ,&nbsp;Xinyu Heng ,&nbsp;Tao Xu ,&nbsp;Ke Zhang ,&nbsp;Yining Zhao ,&nbsp;Yankui Liu ,&nbsp;Deshen Han ,&nbsp;Yueyue Wu ,&nbsp;Wei Zhang ,&nbsp;Meiqi He ,&nbsp;Lin Pu ,&nbsp;Yicong Shen ,&nbsp;Xiuxia Qu ,&nbsp;Ning Sun ,&nbsp;Chao Ye","doi":"10.1016/j.phymed.2025.156624","DOIUrl":"10.1016/j.phymed.2025.156624","url":null,"abstract":"<div><h3>Background</h3><div>Doxorubicin (Dox)-induced cardiomyopathy (DIC) is characterized by severe myocardial damage that can progress to dilated cardiomyopathy and potentially lead to heart failure. No effective prevention or treatment strategies are available for DIC. Sauchinone, a diastereomeric lignan isolated from <em>Saururus chinensis</em>, is known for its notable anti-inflammatory effects. However, a paucity of research on sauchinone in relation to heart disease exists, particularly regarding its role in DIC, which remains unclear.</div></div><div><h3>Purpose</h3><div>This study aimed to assess the therapeutic potential of sauchinone in alleviating cardiac injury and elucidate its potential molecular mechanism in DIC.</div></div><div><h3>Methods</h3><div>Male C57BL/6J mice were used to construct chronic and acute DIC models <em>in vivo</em>. The mice were administered sauchinone intragastrically concurrently with the first injection of Dox to evaluate the therapeutic effect of sauchinone on DIC. H9c2, a rat cardiomyocyte cell line, was treated with various concentrations of sauchinone in conjunction with Dox to assess the protective effects of sauchinone on cardiomyocyte injury <em>in vitro</em>.</div></div><div><h3>Results</h3><div>Supplementation with exogenous sauchinone mitigated Dox-induced cardiac atrophy, cardiac fibrosis, and ventricular remodeling, while preserving cardiac function. Sauchinone reduced Dox-induced abnormal apoptosis both <em>in vitro</em> and <em>in vivo</em>. Additionally, sauchinone restored mitochondrial function and decreased reactive oxygen species levels, which may be attributed to its activation of nuclear factor erythroid 2-related factor 2 (NRF2) signaling, thereby attenuating Dox-induced oxidative damage. Furthermore, sauchinone significantly inhibited the activation of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome and reduced the cardiac infiltration of inflammatory factors, thereby alleviating oxidative stress and inhibiting the progression of DIC. The NLRP3 agonist nigericin abolished DIC progression, while the NLRP3 antagonist MCC950 further enhanced the beneficial effects of sauchinone on DIC progression both <em>in vivo</em> and <em>in vitro</em>.</div></div><div><h3>Conclusions</h3><div>The key novel finding of the present study is that the use of sauchinone, a diastereomeric lignan isolated from <em>Saururus chinensis</em>, effectively limits the progression of DIC. Specifically, sauchinone not only alleviates Dox-induced chronic cardiac injury but also significantly delays the progression of acute DIC. Mechanistically, inactivation of the NLRP3 inflammasome and NRF2-mediated antioxidant pathways have been identified as two critical signaling pathways regulated by sauchinone, which plays a vital role in blocking the progression of DIC. Sauchinone holds promise as a potential therapeutic approach for DIC or dilated cardiomyopathy.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156624"},"PeriodicalIF":6.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578803","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":"Bakuchiol mitigates colitis through GPR120 activation","authors":"Fangfang Xu ,&nbsp;Jixia Wang ,&nbsp;Tianyu Zhang ,&nbsp;Tao Hou ,&nbsp;Han Zhou ,&nbsp;Aijin Shen ,&nbsp;Wenyi Yu ,&nbsp;Xiaomin Xie ,&nbsp;Dian Liu ,&nbsp;Di Chen ,&nbsp;Hailong Piao ,&nbsp;Ye Fang ,&nbsp;Yanfang Liu ,&nbsp;Xinmiao Liang","doi":"10.1016/j.phymed.2025.156618","DOIUrl":"10.1016/j.phymed.2025.156618","url":null,"abstract":"<div><h3>Background</h3><div>Sishen Wan (SSW) is a traditional herbal formula widely used in China to treat inflammatory bowel disease (IBD). However, effective compound(s) and the mechanism(s) of action remain mostly unelucidated.</div></div><div><h3>Purpose</h3><div>A demonstration study was carried out to identify the main components of SSW, investigate its effects, and explore the target mechanism in the treatment of IBD.</div></div><div><h3>Study design and methods</h3><div>The main chemical species of the SSW were identified using ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS/MS) method. The therapeutic effects of bakuchiol, the main component, were further analyzed in DSS-induced colitis mice. The target of bakuchiol was predicted using virtual screening and validated using pharmacological approaches. The possible mechanisms of bakuchiol were investigated using RNA-seq and bioassays with cytokines-induced human epithelial cell lines.</div></div><div><h3>Results</h3><div>Bakuchiol was identified as the main component of the SSW. Bakuchiol displayed therapeutic potential similar to SSW in alleviating body weight loss, disease activity index (DAI) increases, colonic shortening, colonic pathological injury and inhibiting proinflammatory genes Tnf-α, Il6, Il17a and Ifn-γ expression in mice with DSS-induced colitis. Compared with the clinical drug mesalazine, bakuchiol at lower doses showed a superior effect in alleviating body weight loss, DAI increases and colonic shortening. RNA-seq revealed that bakuchiol treatment suppresses inflammation pathways, such as chemokine signaling, IL-17 signaling and TNF signaling. Pharmacological profiling at a panel of GPCRs associated with IBD showed that bakuchiol was a GPR120 agonist with an EC₅₀ value of 37.80 ± 3.10 μM. In the TNF-α-induced HT-29 cells, we found that bakuchiol maintained the barrier function partially via the activation of GPR120.</div></div><div><h3>Conclusion</h3><div>This work demonstrates that bakuchiol is instrumental in SSW and provides evidence of the therapeutic effect of bakuchiol via activation of the GPR120 receptor, suggesting that bakuchiol may represent a novel potential agent for preventing and treating IBD.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156618"},"PeriodicalIF":6.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609479","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}