Phytomedicine最新文献

{"title":"Polysaccharide from Pyrus pashia Buch ameliorates DSS-induced colitis in mice via MAPKP38/NF-κB P65 and SCFAs/ERK/MSK signaling pathways","authors":"Yan Zhang ,&nbsp;Jiaxin Han ,&nbsp;Jiaqi Gao,&nbsp;Qin Ge,&nbsp;Huiying Zhang,&nbsp;Jing Shi,&nbsp;Hui Wang","doi":"10.1016/j.phymed.2025.156561","DOIUrl":"10.1016/j.phymed.2025.156561","url":null,"abstract":"<div><h3>Purpose</h3><div>In this experiment, we investigated the effect of <em>Pyrus pashia Buch</em> on the relevant inflammatory disease indexes, intestinal microbiota, and short-chain fatty acids in mice with dextran sodium sulfate (DSS)-induced ulcerative colitis.</div></div><div><h3>Methods</h3><div>The anti-inflammatory effect of PPBP was assessed by measuring inflammatory markers (ELISA), colonic pathological changes (H&amp;E), qPCR of relevant gene expression, 16S rRNA sequencing of intestinal contents, and short-chain fatty acids (SCFAs).</div></div><div><h3>Results</h3><div><em>Pyrus pashia Buch</em> polysaccharide (PPBP) alleviated the main symptoms of UC (Weight down, reduced diet, increased disease activity index) and ameliorated pathological damage to colonic tissues by reducing the release of cytokines TNF-α, IL-6, IL-1β, and iNOS. Furthermore, PPBP enhanced the expression of tight junction proteins (ZO-1, Occludin, and Claudin-1) and elevated intestinal mucin MUC2 and MUC3 levels. qPCR analysis showed that PPBP activated MAPK/NF-κB and verified that it regulated the MAPK signaling pathway through the SCFA-ERK-MSK pathway and downregulated the phosphorylation levels of p38 and p65. Using the 16S rRNA method to analyze the level of microbial changes in the mouse gut, it was shown that <em>Pyrus pashia Buch</em> polysaccharide (PPBP) restored the intestinal microbial diversity and species richness in the UC model, and gas chromatography-mass spectrometry analysis demonstrated that <em>Pyrus pashia Buch</em> polysaccharide (PPBP) was able to increase beneficial short chain fatty acids.</div></div><div><h3>Conclusion</h3><div>PPBP is a resourceful edible herb. By studying the mechanism of action of P38/IκBα/P65 in MAPK/NF-κB and SCFA with ERK/MSK in MAPK, we have demonstrated that PPBP can attenuate inflammatory responses to repair intestinal mucosal damage, balance abnormalities in the intestinal microbiota, and improve the function of the damaged intestinal barrier. It provides preliminary experiments for developing PPBP as an IκBα stabilizer and P65 inhibitor.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156561"},"PeriodicalIF":6.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550275","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":"Baicalein inhibits hepatitis B virus through the coiled coil domain containing protein 88A (CCDC88A)-dependent autophagy pathway","authors":"Yi-jun Niu ,&nbsp;Xin Ai ,&nbsp;Xiao-tong Lin ,&nbsp;Wei-ming Xu ,&nbsp;Su-ya Lao ,&nbsp;Zi-chen Tian ,&nbsp;Hai-yan Zhu ,&nbsp;Wei Zhou ,&nbsp;Hai Huang ,&nbsp;Xun-long Shi","doi":"10.1016/j.phymed.2025.156577","DOIUrl":"10.1016/j.phymed.2025.156577","url":null,"abstract":"<div><h3>Background</h3><div>Chronic infection with the hepatitis B virus (HBV) represents a significant global health concern. Baicalein, a naturally occurring flavone derived from the roots of <em>Scutellaria baicalensis</em> Georgi, has exhibited both anti-inflammatory and antiviral activities. <em>S. baicalensis</em> is extensively utilized in traditional Chinese medicine for the treatment of various liver disorders, including hepatitis. However, the specific anti-HBV effects of baicalein have not been fully elucidated.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the inhibitory effects of baicalein on HBV and to elucidate its underlying mechanisms.</div></div><div><h3>Materials and Methods</h3><div>The levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were measured using enzyme-linked immunosorbent assay (ELISA) kits. Quantification of HBV DNA was performed using quantitative real-time polymerase chain reaction (qRT-PCR). Western blot analysis was conducted to evaluate proteins involved in autophagy, lysosomal acidification, and autophagy-related signaling pathways. Immunofluorescence microscopy was utilized to assess autophagic flux and lysosomal acidification.</div></div><div><h3>Results</h3><div>Baicalein demonstrated significant inhibition of HBsAg, HBeAg, and HBV-DNA secretion in both in vivo and in vitro environments. Subsequent investigations revealed that baicalein disrupted the intracellular trafficking of the hepatitis B virus by inhibiting the CCDC88A-AKT-mTOR (Coiled coil domain containing protein 88A- protein kinase B-mammalian target of rapamycin) signaling pathway. Additionally, baicalein induced autophagy in HepG2 (Human hepatocellular carcinoma cell line 2) and HepG2.215 cell models. The anti-hepatitis B antigen effect of baicalein was partially attenuated when both early and late stages of autophagy were inhibited. A significant correlation was identified between the phosphorylation of AMPKα and the enhanced autophagy observed in baicalein-treated cells.</div></div><div><h3>Conclusions</h3><div>This study elucidates a novel mechanism by which baicalein inhibits the hepatitis B virus (HBV). Specifically, baicalein exerts its antiviral effects by activating autophagy and suppressing the CCDC88A-AKT-mTOR signaling pathway.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156577"},"PeriodicalIF":6.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520694","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":"Polyphenol extract ameliorates diabetes-related atherosclerosis through HIF-1 signaling pathway in APOE−/− mice: Possible synergism with atorvastatin","authors":"Yang Yang ,&nbsp;Shengxiang Chen ,&nbsp;Guanjin Shi ,&nbsp;Shanshan Huang ,&nbsp;Ningning Cui ,&nbsp;Le Tan ,&nbsp;Xuefeng Yang","doi":"10.1016/j.phymed.2025.156572","DOIUrl":"10.1016/j.phymed.2025.156572","url":null,"abstract":"<div><h3>Background</h3><div>Diabetes mellitus promotes atherosclerosis (AS), a major cause of cardiovascular disease. Statins, clinical drugs for AS treatment, may increase the risk of diabetes and induce hepatotoxicity. Polyphenols can alleviate AS by exerting anti-inflammatory and antioxidant effects, and play a role in liver protection. However, the effects of polyphenol extract (PE) on diabetic AS and whether PE can assist atorvastatin in managing diabetic AS with additional benefits remain poorly understood.</div></div><div><h3>Purpose</h3><div>This study aims to investigate the synergistic effects of a type of PE with atorvastatin on diabetic AS, as well as explore the anti-atherogenic mechanisms of PE.</div></div><div><h3>Methods</h3><div>Polyphenol constituents in PE were identified using UPLC-MS/MS. Streptozocin -induced diabetic ApoE^−/⁻ mice were orally administered 350 and 700 mg/kg of PE, 10 mg/kg of atorvastatin, or 5 mg/kg of atorvastatin+700 mg/kg of PE for 10 weeks. Atherosclerotic lesions and plaque stability were evaluated using Oil Red O staining, Sirius red staining, and immunofluorescence. Inflammation and oxidative stress were determined using the corresponding markers. Hepatic pathological changes were assessed using hematoxylin and eosin staining. Network pharmacology prediction, molecular docking, microscale thermophoresis (MST) and western blotting were used to explore the anti-atherosclerotic mechanisms of PE.</div></div><div><h3>Results</h3><div>The polyphenolic constituents of PE mainly consist of flavonoids and phenolic acids. PE treatment effectively mitigated atherosclerotic lesions in diabetic mice, particularly at high dose. Co-treatment with a half-dose of atorvastatin and PE did not restrain the anti-atherosclerotic effects of atorvastatin treatment, whereas the combination better relieved hyperglycemia, inflammation, oxidative stress, and liver damage in diabetic AS compared to that with atorvastatin alone. In addition, network pharmacology, molecular docking, MST and western blotting results indicated that PE ameliorated diabetic AS, possibly by targeting the AKT/mTOR/HIF-1 signaling pathway.</div></div><div><h3>Conclusion</h3><div>The PE demonstrated efficacy against diabetic AS and cooperated with atorvastatin for some additional benefits, especially in liver protection, indicating that PE has the potential to be developed as a supplement for the management of diabetes-related AS.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156572"},"PeriodicalIF":6.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520684","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":"SIRT3 suppresses vascular endothelial senescence via DHRS2 and contributes to the anti-vascular aging effect of Bazi Bushen capsule","authors":"Yuan Zhao ,&nbsp;Chunmei Zhang ,&nbsp;Chen Zhang ,&nbsp;Xuehui Zheng ,&nbsp;Yan Qi ,&nbsp;Binghui Kong ,&nbsp;Yunlong Hou ,&nbsp;Yun Ti ,&nbsp;Peili Bu","doi":"10.1016/j.phymed.2025.156571","DOIUrl":"10.1016/j.phymed.2025.156571","url":null,"abstract":"<div><h3>Aims</h3><div>Vascular and endothelial aging are significant causes of chronic diseases among the elderly. This study investigated the specific mechanism by which sirtuin 3 (SIRT3) regulates vascular endothelial senescence and the beneficial role of Bazi Bushen capsule (BZBS) in preventing vascular aging.</div></div><div><h3>Methods</h3><div>Human umbilical vein endothelial cells and mouse aortic endothelial cells were cultured with D-galactose (D-gal) to induce aging and evaluate the beneficial effects of the SIRT3-dehydrogenase/reductase member 2 (DHRS2) axis on the inhibition of vascular endothelial aging. d-Gal was injected intraperitoneally into wild-type and Sirt3 knockout mice, while BZBS was administered orally. Histochemical staining, immunohistochemistry, and western blotting assays were used to explore the beneficial effects of BZBS against aging-associated vascular remodelling. Endothelial cell function assays were used to evaluate the role of BZBS in suppressing endothelial aging <em>in vitro</em>.</div></div><div><h3>Results</h3><div>SIRT3 deacetylated DHRS2 and modulated the translation of DHRS2. The SIRT3-DHRS2 axis played an important role in preserving mitochondrial homeostasis and reducing reactive oxygen species generation through suppressing endothelial nitric oxide synthase (eNOS) translocating to mitochondria and eNOS-Thr495 phosphorylation mediated by protein kinase C δ (PKCδ). BZBS mitigated vascular remodelling and relieved endothelial oxidative stress via the SIRT3-DHRS2 axis.</div></div><div><h3>Conclusion</h3><div>SIRT3 activates DHRS2-PKCδ to stop aging in endothelial cells by inhibiting uncoupled eNOS translocating to mitochondria. BZBS rescued vascular aging and endothelial dysfunction via the SIRT3-DHRS2 axis. Revealing a protective mechanism by which SIRT3 inhibits endothelial senescence, this study provides evidence for BZBS in delaying vascular aging.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156571"},"PeriodicalIF":6.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549536","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":"Tianma Gouteng Decoction improve neuronal synaptic plasticity and oligodendrocyte apoptosis in Parkinson's disease mice","authors":"Tong Lei ,&nbsp;Gaoshuang Fu ,&nbsp;Xin Xue ,&nbsp;Hongjun Yang","doi":"10.1016/j.phymed.2025.156553","DOIUrl":"10.1016/j.phymed.2025.156553","url":null,"abstract":"<div><h3>Background</h3><div>Parkinson's disease (PD) is a complex and multifactorial disorder of the nervous system. Tianma Gouteng Decoction (TGD) is a clinical prescription of traditional Chinese medicine for PD, but its neuroprotective effects and mechanisms for PD are poorly understood.</div></div><div><h3>Purpose</h3><div>The aim of this study was to explore the mechanism of TGD in the treatment of PD.</div></div><div><h3>Study design</h3><div>Serum pharmacochemistry, single cell sequencing, network pharmacology, and validation experiment were combined to study the effect of TGD in PD model.</div></div><div><h3>Methods</h3><div>TGD water extract and its distribution in serum of PD mice were analyzed by secondary metabolomics. The crossing blood-brain barrier components and targets were preliminarily identified. Target cells and pathways of TGD were analyzed by network pharmacology and single cell sequencing.</div></div><div><h3>Results</h3><div>TGD treatment improved the movement disorders in MPTP-induced PD mice, restoring dopaminergic neurons in the substantia nigra region and suppressing the expression of α-synuclein. We identified 1272 components in TGD, among which 73 were distributed in the serum of PD mice after oral administration. Network pharmacological analysis demonstrated that these components were involved in the regulation of apoptosis, and 15 of them could across the blood-brain barrier and bind to PD pathological proteins. Single nucleus RNA sequencing analysis identified 18 cell subpopulations, and TGD treatment restored the neuron-oligodendrocyte crosstalk. Neurons were identified as the most widely responding target cells, while oligodendrocytes were the core response target cells to TGD therapy. After treatment, the apoptosis of oligodendrocytes was inhibited, and the secretion of trophic factor was enhanced, facilitating the improvement of neuronal synaptic plasticity and neuroinflammation.</div></div><div><h3>Conclusion</h3><div>This study systematically elucidates the molecular mechanism of TGD improving movement disorders, which is helpful to provide new ideas for drug development of PD.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156553"},"PeriodicalIF":6.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526915","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":"Astragali Radix-Curcumae Rhizoma normalizes tumor blood vessels by HIF-1α to anti-tumor metastasis in colon cancer","authors":"Yan Liang ,&nbsp;Tingting Su ,&nbsp;Shijiao Zhu ,&nbsp;Ruolan Sun ,&nbsp;Jiahui Qin ,&nbsp;Zengyaran Yue ,&nbsp;Xu Wang ,&nbsp;Zhongqing Liang ,&nbsp;Xiying Tan ,&nbsp;Yong Bian ,&nbsp;Fan Zhao ,&nbsp;Decai Tang ,&nbsp;Gang Yin","doi":"10.1016/j.phymed.2025.156562","DOIUrl":"10.1016/j.phymed.2025.156562","url":null,"abstract":"<div><h3>Background</h3><div>Abnormal tumor blood vessels can significantly promote the malignant progression of tumors, prompting researchers to focus on drugs that normalize these vessels for clinical treatment. The combination of the Qi-tonifying drug <em>Astragali Radix</em> and the blood-activating drug <em>Curcumae Rhizoma</em>, referred to as AC, exhibited significant anti-tumor metastasis effects. However, the association between the anti-tumor metastasis effect of AC and its potential role in regulating tumor vascular remodeling warrants further exploration.</div></div><div><h3>Purpose</h3><div>This study aimed to elucidate the mechanism through which AC induces tumor blood vessel normalization in colon cancer (CC).</div></div><div><h3>Methods</h3><div>The potential active components of AC were identified through UPLC-MS/MS. An orthotopic transplantation model of CC was established in BALB/c mice using the CT26-Lucifer cell line, and the effects of AC were evaluated using IVIS imaging, hematoxylin and eosin (H&amp;E) staining, and immunohistochemistry. Network pharmacology and molecular biology analyses were employed to identify the potential direct targets of AC. Subsequently, RT-PCR and Western blotting techniques were utilized to validate the findings obtained from network pharmacology. Furthermore, ELISA and other methodologies were used to investigate glycolysis-related indicators, along with immunofluorescence technology to demonstrate changes in vascular leakage and perfusion characteristics associated with blood vessel normalization.</div></div><div><h3>Results</h3><div>We identified HIF-1α as a potential direct target of AC. This interaction influences the glycolytic processes in both tumor cells and tumor-associated endothelial cells (TECs) by directly binding to HIF-1α and modulating its nuclear translocation, thereby determining the integrity of TEC junctions. Mechanistically, AC directly regulates the key enzyme PFKFB3 in glycolysis by modulating HIF-1α expression and inhibiting its nuclear translocation. This action reduces tumor glycolytic flux, decreases the internalization of VE-cad, and influences the expression of downstream matrix metalloproteinases (MMPs), thereby strengthening the adherens and tight junctions between TECs and restoring vascular integrity.</div></div><div><h3>Conclusion</h3><div>This study presents novel findings that AC can regulate glycolysis through the inhibition of HIF-1α nuclear translocation, thereby promoting the normalization of tumor blood vessels and effectively inhibiting tumor metastasis. These results suggested that AC may serve as an effective therapeutic agent for normalizing tumor blood vessels.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156562"},"PeriodicalIF":6.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526913","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":"Exploring the therapeutic potential of HAPC in COVID-19-induced acute lung injury","authors":"Zhichen Pu ,&nbsp;Lingling Li ,&nbsp;Yan Zhang ,&nbsp;Yinping Shui ,&nbsp;Jun Liu ,&nbsp;Xiaohu Wang ,&nbsp;Xiaogan Jiang ,&nbsp;Liqin Zhang ,&nbsp;Hui Yang","doi":"10.1016/j.phymed.2025.156563","DOIUrl":"10.1016/j.phymed.2025.156563","url":null,"abstract":"<div><h3>Background</h3><div>Acute lung injury (ALI) is one of the critical complications of coronavirus disease 2019 (COVID-19), which significantly impacts the survival of patients.</div></div><div><h3>Purpose</h3><div>In this study, we screened COVID-19-related target genes and identified and optimized potential drugs targeting these genes for the treatment of COVID-19.</div></div><div><h3>Study design</h3><div>In this study, bioinformatic analyses were conducted and subsequently identified and optimized potential drugs targeting these genes for the treatment of COVID-19 were carried out.</div></div><div><h3>Methods</h3><div>Firstly, we analyzed the targets gene in patients with COVID-19 using single-cell data analysis. We performed structural modifications on Chicoric acid (CA) and combined it with hyaluronic acid to enhance the targeted activity towards Cluster of differentiation 44 (CD44). Poly (sodium-p styrenesulfonate) (PSS) was used to form a PSS-coated CA+hyaluronic acid nanocomplex (HA-P). Subsequently, <em>Lactobacillus murinus</em> conidia cell wall (CW) was encapsulated to prepare PSS-coated CA + hyaluronic acid + Lactobacillus murinus conidia cell wall (HAPC) nanocomplexes.</div></div><div><h3>Results</h3><div>The expression of APPL1 expression in macrophage of COVID-19 patients was up-regulation. CA was found to bind to the APPL1 protein and inhibit its ubiquitination. HAPC effectively targeted ALI through the highly efficient interaction between CD44 and Hyaluronic acid (HA). HAPC alleviated the symptoms of ALI and restored epithelial function in mice with ALI. HAPC induced the Adaptor protein containing a pH domain, PTB domain and leucine zipper motif 1 (APPL1)/ liver kinase B1 (LKB1)/ AMP-activated protein kinase (AMPK) pathway by inactivating the NOD - like receptor protein 3 (NLRP3) pathway in ALI. CA interacted with the APPL1 protein and prevented its ubiquitination. HAPC facilitated the interaction between APPL1 and LKB1 to induce the AMPK/NLRP3 pathway. It promoted the formation of LKB1 at GLU-67, ARG-72, ARG-314, ASP-316, and GLN-312 and APPL1 at ARG-106, ASP-115, LYS-124, ASN-119, and GLU-120.</div></div><div><h3>Conclusion</h3><div>Altogether, HAPC nanocomplexes exerted anti-inflammatory effects on ALI by promoting the interaction between APPL1 and LKB1 to induce the AMPK/NLRP3 pathway, and may be one new therapeutic strategie for ALI.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156563"},"PeriodicalIF":6.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512677","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":"Hua Zheng San Ji Fang suppresses liver cancer progression by inhibiting TYRO3 expression via the ERK signaling pathway","authors":"Zhuang Xiong ,&nbsp;Xiaodan Sui ,&nbsp;Yu Bai ,&nbsp;Yangyang Liu ,&nbsp;Yan Leng ,&nbsp;Song Wang ,&nbsp;Boyang Su ,&nbsp;Zhiyuan Liu ,&nbsp;Tiejun Liu","doi":"10.1016/j.phymed.2025.156497","DOIUrl":"10.1016/j.phymed.2025.156497","url":null,"abstract":"<div><h3>Background</h3><div>Liver cancer poses a significant global health challenge owing to its increasing incidence and associated mortality rates. Traditional Chinese Medicine (TCM) has garnered attention for its potential in oncology, with formulations such as Hua Zheng San Ji Fang (HZSJF) exhibiting antineoplastic effects. HZSJF is clinically employed in China for cancer treatment; however, its molecular mechanisms in liver cancer remain elusive. TYRO3 plays a key role in tumor progression via the ERK signaling pathway, rendering it a potential therapeutic target. However, the effect of HZSJF on TYRO3 expression and its downstream signaling in liver cancer remains unexplored.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the molecular mechanisms through which HZSJF alleviates liver cancer progression, focusing on its regulation of TYRO3 and the ERK signaling pathway.</div></div><div><h3>Methods</h3><div>TYRO3 expression in liver cancer and para-carcinoma tissues was analyzed using immunohistochemistry, reverse transcription-quantitative PCR, and western blotting. Liver cancer cells were used to investigate HZSJF-regulated pathways. Transcriptome sequencing was used to identify HZSJF-targeted genes. Cell proliferation, apoptosis, invasion, and migration were assessed using EdU, YO-PRO-1/PI staining, and transwell assays. ERK signaling involvement was examined using a specific inhibitor and validated <em>in vivo</em> using subcutaneous nude mouse tumor models.</div></div><div><h3>Results</h3><div>HZSJF significantly inhibited TYRO3 expression and ERK pathway activation, reducing proliferation, invasion, and migration while promoting apoptosis. The ERK inhibitor corroborated the pathway's role in the antitumor effects of HZSJF. HZSJF suppressed tumor growth and TYRO3 expression <em>in vivo</em>.</div></div><div><h3>Conclusion</h3><div>HZSJF alleviated liver cancer progression through the ERK signaling pathway by inhibiting TYRO3 expression, presenting a potential therapeutic approach.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156497"},"PeriodicalIF":6.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512298","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":"Efficacy and safety of Shexiang Baoxin Pill in patients with angina and non-obstructive coronary arteries: A multicenter, randomized, double-blind, placebo-controlled, phase Ⅳ clinical trial","authors":"Zhiqing He ,&nbsp;Na Li ,&nbsp;Wei Zhang ,&nbsp;Xianhao Meng ,&nbsp;Jingping Wang ,&nbsp;Lihong Gong ,&nbsp;Bing Liu ,&nbsp;Mingqi Zheng ,&nbsp;Zhuo Shang ,&nbsp;Jianjiang Xu ,&nbsp;Piqiao Jiang ,&nbsp;Qingxia Zhao ,&nbsp;Boning Xu ,&nbsp;Chun Liang","doi":"10.1016/j.phymed.2025.156556","DOIUrl":"10.1016/j.phymed.2025.156556","url":null,"abstract":"<div><h3>Introduction</h3><div>Solid evidence generated from large studies supporting the recommendation of Shexiang Baoxin Pill (MUSKARDIA) as a promising treatment for angina and nonobstructive coronary arteries (ANOCA) populations is lacking.</div></div><div><h3>Objective</h3><div>To evaluate the efficacy and safety of MUSKARDIA in patients with ANOCA.</div></div><div><h3>Methods</h3><div>In this randomized, double-blind, placebo-controlled, phase IV trial, we enrolled 239 patients with ANOCA at 11 centers across China between May 2021 and July 2023. Patients were randomly assigned in a 1:1 ratio to receive MUSKARDIA or placebo (orally 4 pills thrice daily) based on conventional treatment for 12 weeks. The primary endpoint was the change in angina-related outcomes, assessed using the Seattle Angina Questionnaire (SAQ) scores for the treatment groups at week 12.</div></div><div><h3>Results</h3><div>Among 239 randomized patients with ANOCA, 236 (MUSKARDIA group, <em>n</em> = 117; placebo group, <em>n</em> = 119) completed treatment and endpoint assessments. At week 12, patients in the MUSKARDIA group showed better angina-related outcomes, with a more rapid increase in SAQ scores, than those in the placebo group (all <em>p</em> &lt; 0.0001). Statistically significant differences favoring MUSKARDIA over placebo were observed for change in angina attack frequency compared with baseline at week 12 (<em>p</em> &lt; 0.0001). Meanwhile, according to the Canadian Cardiovascular Society grading of angina, the change in angina pectoris severity, compared with baseline, was significantly reduced in MUSKARDIA group compared with placebo group at week 12 (<em>p</em> &lt; 0.0001). The percentage of patients who did not use sublingual nitroglycerin was noticeably higher in MUSKARDIA group than that in placebo group (84.16 % <em>vs.</em> 58.33 %; <em>p</em> &lt; 0.001). The incidence of adverse events did not differ significantly between the two groups, and no serious adverse events occurred.</div></div><div><h3>Conclusion</h3><div>This randomized, placebo-controlled clinical trial firstly confirmed that MUSKARDIA was an effective, safe, and well-tolerated treatment for patients with ANOCA in clinical settings. This study was registered at ClinicalTrials.gov (NCT04897126).</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156556"},"PeriodicalIF":6.7,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512678","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":"Aristolochic acid IVa ameliorates arthritis in SKG Mice by regulating macrophage polarization and Th17/Treg balance","authors":"Qin-wen Gao ,&nbsp;Wei-ying Liu ,&nbsp;Mirza Jawad ,&nbsp;Lei Ci ,&nbsp;Yi-yi Cao ,&nbsp;Jing Xi ,&nbsp;Jia-ying Wu ,&nbsp;Yu-yang Lei ,&nbsp;Yu-shi Hu ,&nbsp;Xin-yue You ,&nbsp;Xin-yu Zhang ,&nbsp;Jian Fei ,&nbsp;Yang Luan","doi":"10.1016/j.phymed.2025.156557","DOIUrl":"10.1016/j.phymed.2025.156557","url":null,"abstract":"<div><h3>Background</h3><div>Aristolochic acids (AAs)-containing herbs have been used as medicinal remedies for thousands of years. However, exposure to AAI and AAII increases the risk of nephropathy and cancers. Our previous study identified AAIVa, an analogue without carcinogenicity or nephrotoxicity, exerted anti-inflammatory effects.</div></div><div><h3>Purpose</h3><div>To explore AAIVa's anti-inflammatory mechanisms and assess its therapeutic potential in arthritis.</div></div><div><h3>Methods and results</h3><div>In this study, we employed <em>in vitro</em> assays on RAW 264.7 cells and explored the underlying mechanisms of AAIVa's anti-inflammatory effect through transcriptome analysis, identifying macrophage polarization-associated genes, IL-17 signaling, and Rheumatoid Arthritis (RA) pathway. Also, we used BALB/cAnSmoc-Zap70^{em(W163C)Smoc} (SKG) mice, a model that spontaneously develops chronic arthritis closely resembling human RA, and revealed AAIVa's therapeutic potential in arthritis. AAIVa-treatment (10 mg/kg, <em>i.g.</em>) for 4 weeks protected SKG mice from mannan-accelerated arthritis symptoms, reducing inflammation and improving bone microstructure. We further isolated bone marrow-derived macrophages (BMDMs) and spleen primary cells from SKG and BALB/c mice to evaluate the impact of AAIVa on macrophage polarization and T cell differentiation. We found that AAIVa induced M2 macrophage polarization in BMDMs, and mitigated lipopolysaccharide-stimulated inflammation by increasing Tregs and decreasing Th17 cells. Subsequently, the elevation of M2 macrophages, increased Tregs expression and decreased Th17 cells in the ankle joints of SKG mice supported our <em>in vitro</em> observation.</div></div><div><h3>Conclusion</h3><div>We provide first evidence that AAIVa exerts anti-arthritis effects, likely through modulation of macrophage polarization and restoration of the Th17/Treg balance. Our findings highlight AAIVa's mechanism of action and AAIVa's potential as a therapeutic candidate for autoimmune arthritis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156557"},"PeriodicalIF":6.7,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534447","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}