Phytomedicine最新文献

{"title":"Neuroprotective role of geniposide-loaded UMSC nanovesicles in depression via P2ry12 downregulation","authors":"Guoxiang Duan ,&nbsp;Tianyu Zou ,&nbsp;Xue Wu ,&nbsp;Yiming Zhang ,&nbsp;Hongmei Liu ,&nbsp;Cheng Mei","doi":"10.1016/j.phymed.2025.156581","DOIUrl":"10.1016/j.phymed.2025.156581","url":null,"abstract":"<div><h3>Background</h3><div>Depression is a prevalent mental disorder characterized by persistent low mood, loss of interest, and cognitive impairment. Oxidative stress and inflammation play crucial roles in its pathogenesis. Novel therapeutic strategies targeting these mechanisms are needed to improve treatment outcomes.</div></div><div><h3>Purpose</h3><div>The purpose of this study is to gauge the therapeutic effectiveness of geniposide (GEN)-loaded umbilical cord-derived mesenchymal stem cell membrane biomimetic nanovesicles (CSPG@UMSC NPs) targeting the P2ry12 factor for depression management, considering its association with oxidative stress and inflammatory pathways.</div></div><div><h3>Study Design</h3><div>A combination of <em>in vitro</em> neuronal cell culture experiments and an <em>in vivo</em> chronic unpredictable mild stress (CUMS) mouse model was used to assess the effects of CSPG@UMSC NPs.</div></div><div><h3>Methods</h3><div><em>In vitro</em> investigations involved culture and characterization of CSPG@UMSC NPs and transcriptome sequencing analysis to identify DEGs in neurons. <em>In vivo</em> experiments utilized a depression mouse model treated with CSPG@UMSC NPs, followed by behavioral tests, biomarker analysis, and histological assessments.</div></div><div><h3>Results</h3><div>CSPG@UMSC NPs successfully downregulated P2ry12 expression, leading to improved neuronal activity, decreased inflammation, reduced cell apoptosis, and lowered reactive oxygen species levels in both <em>in vitro</em> and <em>in vivo</em> settings.</div></div><div><h3>Conclusion</h3><div>CSPG@UMSC NPs loaded with GEN inhibit oxidative stress and inflammation by downregulating P2ry12. This research unveils, for the initial instance, the vital role of P2ry12 in depression and proposes a novel nano-therapy strategy based on MSCs and GEN, offering new insights and potential clinical applications for the treatment of depression.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156581"},"PeriodicalIF":6.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620652","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":"Mixtures of EGCG, bamboo leaf flavonoids, and broccoli seed water extracts exhibit anti-glycation and skin-protective effects","authors":"Chang Sun ,&nbsp;Zibin Liu ,&nbsp;Mengmeng Feng ,&nbsp;Junbo Wang ,&nbsp;Yanfei Jiang ,&nbsp;Chunyue Zhao","doi":"10.1016/j.phymed.2025.156592","DOIUrl":"10.1016/j.phymed.2025.156592","url":null,"abstract":"<div><h3>Background</h3><div>Skin aging is a multifaceted process. Glycation significantly contributes to skin aging and the development of complications. Researchers are currently investigating various substances, particularly those from natural sources, to combat skin glycation.</div></div><div><h3>Purpose</h3><div>This study aimed to comprehensively evaluate the anti-glycation effect of a new natural combination, EBB, which includes (-)-epigallocatechin-3 gallate (EGCG), bamboo leaf flavonoids, and broccoli seed water extracts, using cell and animal models and to explore its potential anti-glycation mechanism.</div></div><div><h3>Methods</h3><div>The components of EBB were identified using HPLC and UHPLC-MS/MS. Additionally, a glycation cell model induced by glyceraldehyde, advanced glycation end products (AGEs), and methylglyoxal was established in HaCaT cells to evaluate the efficacy of EBB in alleviating glycation. Differential genes, signalling pathways, and biological processes were analysed through RNA sequencing to explore the mechanisms of the anti-glycation effects of EBB, which were further validated using qRT-PCR and Western blotting. Finally, the protective effects of EBB against glycation and skin damage were assessed in zebrafish and mouse <em>in vivo</em> models through histological studies and the measurement of various skin physiological parameters.</div></div><div><h3>Results</h3><div>Glucoraphanin, Sinapine and orientin were identified in EBB, which effectively reduced the formation of AGEs and decreased the expression level of the RAGE protein in HaCaT cells. Transcriptomic analyses revealed that EBB regulated the expression of 576 differentially expressed genes. These genes were enriched in various biological processes, such as chronic inflammation and immune responses, and participated in the regulation of multiple signalling pathways, including TNF. Glycation upregulated the expression of the ROS1 gene and protein, while EBB reversed this effect. Furthermore, EBB attenuated the glycation response by downregulating the expression levels of proteins such as p-p38, p-ERK1/2, p-p65, and TNF-α. Additionally, the reduction of AGE accumulation by EBB was confirmed in a zebrafish model. Similarly, histological analyses of mouse skin tissue and various physiological parameters demonstrated that EBB significantly mitigated damage induced by glycation.</div></div><div><h3>Conclusions</h3><div>Our results show that EBB effectively inhibited glycation reactions. The mechanism of action may involve the reduction of inflammation by downregulating the expression levels of RAGE and ROS1, thereby decreasing the accumulation of AGEs in keratinocytes and alleviating skin damage. This paves the way for the potential application of EBB as a valuable anti-glycation functional ingredient in the food and cosmetic industries.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156592"},"PeriodicalIF":6.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609482","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":"Metabolomics based analysis reveals the therapeutic effects of Incarvillea arguta (Royle) Royle aqueous extract against alcohol-induced liver injury","authors":"Zi-Ge Feng ,&nbsp;Zang-Jia Geng ,&nbsp;Qin Song ,&nbsp;Hu Hu ,&nbsp;Xiao-Yan Tan ,&nbsp;Shang-Yu Zeng ,&nbsp;Rong-Yu Zhou ,&nbsp;Xiao Ma ,&nbsp;Yue Liu ,&nbsp;Yi Zhang","doi":"10.1016/j.phymed.2025.156639","DOIUrl":"10.1016/j.phymed.2025.156639","url":null,"abstract":"<div><h3>Background</h3><div>Alcohol-induced liver injury (ALI) poses a significant threat to global human health. The Chinese Yi medicine Liangtoumao (LTM), which originated from the whole plant of <em>Incarvillea arguta</em> Royle (Royle), has been widely used by the Yi ethnic group to prevent and treat ALI and other liver diseases. However, its effectiveness and mechanisms are still under-researched.</div></div><div><h3>Purpose</h3><div>The objective of our research is to investigate the chemical composition of LTM aqueous extract, evaluate its potential therapeutic intervention effect on ALI, and explore its mechanisms in rat models.</div></div><div><h3>Methods</h3><div>The chemical components and constituents of LTM aqueous extract migrating to the blood were analyzed by UPLC-Q-TOF/MS. Sprague–Dawley rats subjected to chronic binge alcohol exposure were utilized to establish chronic ALI models and evaluate the therapeutic effects of LTM aqueous extract. Serum and spatial metabolomics analyses were used to investigate potential mechanisms.</div></div><div><h3>Results</h3><div>A total of 60 chemical components in LTM aqueous extract were identified, with 67 absorbed into the blood, including 29 original compounds and 38 metabolites. Treatment with LTM aqueous extract remarkably alleviated hepatic lesions in livers of ALI rats, improved liver function, reduced oxidative stress and inflammation. Serum metabolomics and hepatic spatial metabolomics identified 30 and 215 differential metabolites, respectively. Metabolic pathways of glyoxylate and dicarboxylate, glycerophospholipid, linoleic acid, taurine and hypotaurine, and cysteine and methionine were closely related to the hepaprotective effects of LTM.</div></div><div><h3>Conclusion</h3><div>Our research confirmed significant effects of LTM on ALI prevention and treatment for the first time. Metabolomic findings revealed that LTM significantly influences various aspects of lipid metabolism. This study supports expanded mechanism investigations of LTM and explores its possibility as a potential ALI therapy.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156639"},"PeriodicalIF":6.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620646","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":"Combined metabolomics and network pharmacology to elucidate the mechanisms of Huiyang Shengji decoction in treating diabetic skin ulcer mice","authors":"Jia Chen ,&nbsp;Baoquan Qu ,&nbsp;Danyang Yang ,&nbsp;Yazhuo Wang ,&nbsp;Haoyue Zhu ,&nbsp;Zhengchun Wang ,&nbsp;Xiawei Zhang ,&nbsp;Huike Ma ,&nbsp;Ning Zhao ,&nbsp;Li Zhao ,&nbsp;Lijiaming Zhou ,&nbsp;Xiujuan He ,&nbsp;Ping Li","doi":"10.1016/j.phymed.2025.156569","DOIUrl":"10.1016/j.phymed.2025.156569","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic skin ulcer is a clinical disorder of glucose metabolism that has a long treatment period and is prone to recurrent episodes. Huiyang Shengji decoction (HYSJD) is an effective traditional Chinese medicine for its clinical treatment, but its metabolic effects in patients with diabetic skin ulcers have not been well studied.</div></div><div><h3>Purpose</h3><div>Our study aimed to investigate the mechanism of pharmacological treatment of HYSJD in treating diabetic skin ulcers.</div></div><div><h3>Methods</h3><div>The potential mechanism underlying diabetic wound treatment by HYSJD was screened using network pharmacology. Ultra-high performance liquid chromatography-MS/MS metabolomics analysis and correlation analysis were performed to investigate potential target pathways and genes. Furthermore, the db/db diabetic wound tissues and RAW264.7 macrophage inflammation model verified the mechanism using molecular biology experiments.</div></div><div><h3>Results</h3><div>In network pharmacology, HYSJD played a mainly therapeutic effect by regulating PI3K/AKT signaling pathway, EGFR tyrosine kinase inhibitor resistance, metabolic pathway, and other related metabolic-related pathways. Metabolomics analysis disclosed that L-lysine content increased, while those of linoleic and deoxycholic acids decreased in plasma between the HYSJD-treated group and the control group, participating in biotin metabolism. Among them, PPARγ played an important role. The experiments conducted in db/db mice indicated that HYSJD facilitates VEGF secretion and PPARγ expression. <em>In vitro</em> experiments have revealed that HYSJD inhibits macrophage ROS production, augments mitochondrial ATP production, elevates mitochondrial membrane potential, and diminishes the mitochondrial ECAR rate. Furthermore, these effects culminate in promoting M2 macrophage polarization through PPARγ activation. The molecular docking results revealed that the active compounds from HYSJD were capable of binding to PPARγ protein primarily through hydrogen bonding interactions. Notably, all binding energies were found to be lower than –3 kcal/mol, indicating strong and favorable interactions between the active compounds and the target receptor.</div></div><div><h3>Conclusions</h3><div>The findings suggested that HYSJD regulates biotin metabolism by reducing excess levels of linoleic and deoxycholic acids and increasing levels of L-lysine, which in turn promotes diabetic wound healing by promoting M2 macrophage polarization through PPARγ up-regulation. These findings indicated that HYSJD is a decoction that can effectively treat diabetic skin ulcers.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156569"},"PeriodicalIF":6.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683046","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":"Shenqi granules enhance recovery from cerebral ischemia-reperfusion injury by modulating tryptophan and tyrosine metabolism and activating NFE2L2/NRF2","authors":"Hai-Xin Liu ,&nbsp;Ming-Kuan Yang ,&nbsp;Yu-Chang Li ,&nbsp;Cai-Xia Liu ,&nbsp;Gai-Ping Li ,&nbsp;Xiang-Long Meng ,&nbsp;Ke Pei ,&nbsp;Shi-Yuan Wen","doi":"10.1016/j.phymed.2025.156623","DOIUrl":"10.1016/j.phymed.2025.156623","url":null,"abstract":"<div><h3>Background</h3><div>Stroke is a multifaceted physiological event linked to imbalances in gut microbiota and disruptions in metabolic pathways. Traditional Chinese medicines, leveraging the gut-brain axis, have been shown to significantly ameliorate ischemic stroke. However, the specific role and molecular mechanism of Shenqi granules (SQF) in enhancing the recovery from ischemic stroke remain to be elucidated.</div></div><div><h3>Purpose</h3><div>This study aims to explore the therapeutic effects of SQF on rats with cerebral ischemia-reperfusion injury (CIRI) and its regulatory effects on the gut microbiota, providing a basis for the clinical rational use of drugs in ischemic stroke.</div></div><div><h3>Methods</h3><div>The study conducted a comprehensive biological assessment of SQF's role in improving CIRI at the whole-animal level. Subsequently, Weighted Gene Co-expression Network Analysis (WGCNA) and network pharmacology analysis were used for component analysis and target prediction. Then, the therapeutic targets of SQF were further validated through molecular docking and molecular experiments. Finally, an integrated omics approach combining fecal untargeted metabolome and 16S rRNA sequencing was employed to state the anti-CIRI effects of SQF and its potential mechanisms.</div></div><div><h3>Results</h3><div>SQF alleviates cerebral infarct volume and improves cognitive functions in MCAO rats. Network pharmacology analysis shows 20 potential active ingredients of SQF could target 13 target proteins. Further employing WGCNA, our study identified four key targets of SQF in the treatment of ischemic stroke. Based on molecular docking and molecular experiments, SQF improves CIRI by activating NFE2L2/NRF2. Serum metabolomics analysis identified six metabolites related to the tryptophan and tyrosine metabolic pathways, which interact with NFE2L2/NRF2 protein. Fecal metabolome and microbiome reveal that SQF's protective effect on CIRI is linked to the tryptophan metabolism and tyrosine metabolism and gut microbiome modulation. In particular, metabolites related to tryptophan and tyrosine metabolism, such as kynurenic acid and dopamine, may exert their protective effects by interacting with NFE2L2/NRF2.</div></div><div><h3>Conclusion</h3><div>This pioneering study unveils the therapeutic potential of SQF in addressing CIRI, highlighting the pivotal role of NFE2L2/NRF2 upregulation in its mechanism of action. Furthermore, SQF demonstrates its efficacy in restoring gut microbiota balance by modulating the metabolism of tryptophan and tyrosine in CIRI. By elucidating the intricate interplay among constituents, targets, metabolites, and gut microbiota, this research offers novel insights into the multifaceted mechanisms underlying SQF's therapeutic impact on CIRI.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156623"},"PeriodicalIF":6.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578314","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":"Herbal-based Xuebijing injection ameliorated vascular endothelial dysfunction via inhibiting ACLY/MYB/RIG-I axis in sepsis-associated lung injury","authors":"Jiayin Cui ,&nbsp;Yunxin Deng ,&nbsp;Xuechuan Li ,&nbsp;Liya Gao ,&nbsp;Jinrong Li ,&nbsp;Zuxian Li ,&nbsp;Hongping Qu ,&nbsp;Yufeng Chu ,&nbsp;Yuchao Gu ,&nbsp;Mei Meng ,&nbsp;Ranran Li","doi":"10.1016/j.phymed.2025.156573","DOIUrl":"10.1016/j.phymed.2025.156573","url":null,"abstract":"<div><h3>Background</h3><div>Excessive endothelial pro-inflammatory response is an early hallmark of sepsis-induced acute lung injury (ALI). Xuebijing (XBJ), a traditional Chinese medicine, is widely used in clinical practice to treat sepsis.</div></div><div><h3>Purpose</h3><div>This study aims to investigate the molecular mechanisms underlying the beneficial effects of XBJ.</div></div><div><h3>Methods</h3><div>Plasma samples from septic patients treated with or without XBJ were collected and analyzed. The mouse model of sepsis was established by intraperitoneal injection of LPS (10 mg/kg). XBJ (10 ml/kg) was administrated intraperitoneally twice before LPS challenge and one time after LPS challenge. The severity of lung injury and the levels of inflammation and coagulation were evaluated. <em>In vitro</em>, HUVEC were used to explore the mechanisms of XBJ and its compounds in regulating the ACLY/MYB/RIG-I axis.</div></div><div><h3>Results</h3><div>XBJ significantly reduced the plasma levels of endothelial cell (EC) damage-related markers in septic patients. The <em>in vivo</em> and <em>in vitro</em> data demonstrated that XBJ alleviated LPS-induced lung injury and reduced the levels of inflammation and coagulation activation in ECs. XBJ inhibited the phosphorylation-dependent activation of ATP citrate lyase (ACLY), thereby suppressing the acetylation-dependent nuclear translocation of the transcription factor MYB. The expression of retinoic acid inducible gene I (RIG-I) was downregulated, leading to the inhibition of NF-κB signaling and EC pro-inflammatory and coagulation activation, which further alleviated sepsis-associated ALI. Moreover, XBJ compounds Quercetin, Ferulic Acid, Kaempferol and Paeoniflorin all showed inhibitory effects on the activation of the downstream MYB/RIG-I signaling by binding to ACLY protein.</div></div><div><h3>Conclusion</h3><div>Our study revealed a novel regulatory mechanism of XBJ in sepsis-induced EC dysfunction and ALI. The compounds in XBJ inhibited the activity of ACLY, thereby inhibiting the expression of RIG-I by reducing the acetylation of transcription factor MYB, leading to the alleviation of EC activation and lung injury induced by sepsis. Our findings provide a theoretical basis for the clinical application of XBJ and shedding light on novel therapeutic targets for treating sepsis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156573"},"PeriodicalIF":6.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620647","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":"Enhancing temozolomide efficacy in GBM: The synergistic role of chuanxiong rhizoma essential oil","authors":"Gang Ke ,&nbsp;Pengyi Hu ,&nbsp;Hui Xiong ,&nbsp;Jing Zhang ,&nbsp;Huixin Xu ,&nbsp;Chuanyu Xiao ,&nbsp;Yu Liu ,&nbsp;Ming Cao ,&nbsp;Qin Zheng","doi":"10.1016/j.phymed.2025.156575","DOIUrl":"10.1016/j.phymed.2025.156575","url":null,"abstract":"<div><h3>Background</h3><div>Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a poor prognosis. Temozolomide (TMZ), the standard first-line chemotherapy drug is limited by severe toxicity and the development of drug resistance.</div></div><div><h3>Purpose</h3><div>To explore the potential of Chuanxiong Rhizoma (CR), a traditional Chinese medicine, in enhancing the efficacy of TMZ against GBM, especially in TMZ-resistant cells under hypoxic conditions.</div></div><div><h3>Study Design</h3><div>This study combines in vitro experiments, network pharmacology modeling, molecular docking, and in vivo validation to explore how the essential oil from the blood-activating and stasis-removing Chinese medicine CR (CEO) ameliorate the hypoxic tumor microenvironment and synergizes with TMZ to treat GBM</div></div><div><h3>Methods</h3><div>The impact of CEO combined with TMZ on the growth, migration, invasion, and apoptosis of glioma U251 cells, including TMZ-resistant variants, was assessed in vitro under both normoxic and hypoxic conditions. Network pharmacology was applied to predict the biological processes and signaling pathways affected by CEO. Western blot analysis was conducted to evaluate the expression of hypoxia-inducible factor-1α (HIF-1α), matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor A (VEGFA). In vivo, the efficacy of Ligustilide (LIG), a key component of CEO, was tested in combination with TMZ using a mouse model of GBM.</div></div><div><h3>Results</h3><div>In vitro experiments revealed that the combination of CEO and TMZ significantly inhibited cell growth, migration, and invasion, and induced apoptosis in both TMZ-resistant and non-resistant U251 cells under hypoxic conditions. Network pharmacology suggested that CEO's effects are closely linked to oxygen-related biological processes, with the HIF-1 signaling pathway being a key target. Western blot confirmed that CEO downregulated the expression of HIF-1α, MMP-9, and VEGFA. This suggests that CEO can regulate the expression of these proteins through the HIF-1 signaling pathway, alleviating the TMZ resistance caused by the tumor microenvironment and thereby enhancing the sensitivity of glioma cells to TMZ. In vivo, LIG synergized with TMZ to inhibit tumor growth and enhance the sensitivity of TMZ-resistant GBM.</div></div><div><h3>Conclusion</h3><div>Our findings indicate that the combination of CEO and TMZ is a promising therapeutic strategy for GBM, particularly in overcoming TMZ resistance.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156575"},"PeriodicalIF":6.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620860","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":"Artemetin targets the ABCG2/RAB7A axis to inhibit mitochondrial dysfunction in asthma","authors":"Ningpo Ding ,&nbsp;Qiaoyun Bai ,&nbsp;Zhiguang Wang ,&nbsp;Yihua Piao ,&nbsp;Liangchang Li ,&nbsp;Hongmei Piao ,&nbsp;Guanghai Yan ,&nbsp;Yilan Song","doi":"10.1016/j.phymed.2025.156600","DOIUrl":"10.1016/j.phymed.2025.156600","url":null,"abstract":"<div><h3>Background</h3><div>Artemetin, a natural flavonoid, is well-known for its significant anti-inflammatory and antioxidant properties, but its mechanisms in asthma are still unclear.</div></div><div><h3>Purpose</h3><div>This study aims to explore the therapeutic potential of Artemetin in mitigating airway inflammation and mitochondrial dysfunction via ABCG2/RAB7A signaling pathway.</div></div><div><h3>Methods</h3><div>An HDM-induced mouse asthma model and HDM-treated BEAS-2B cell model were established, methods utilized included bioinformatics, molecular docking, Drug Affinity Responsive Target Stability (DARTS), and Cellular Thermal Shift Assay (CETSA), flow cytometry, Western blot, co-immunoprecipitation (CO-IP), immunohistochemistry, and immunofluorescence staining.</div></div><div><h3>Results</h3><div>Artemetin significantly alleviates the proportion of eosinophils and pro-inflammatory cytokines in BALF, IgE levels in serum, airway epithelial mucus secretion, inflammatory cell infiltration and collagen fiber deposition. ABCG2 was identified as a core binding target of Artemetin. When Artemetin was labeled with Biotin, further experiments confirmed its interaction and upregulation of ABCG2. Overexpression of ABCG2 (OV-ABCG2) enhances antioxidant capacity by upregulating Nrf2, HO-1, SOD and CAT, mitigating mitochondrial oxidative stress (mtROS), improving mitochondrial membrane potential (MMP), and reducing DRP1-mediated mitochondrial fission while enhancing MFN2-mediated fusion. Furthermore, ABCG2 was found to interact with and downregulate RAB7A. Both Artemetin and siRNA-RAB7A notably inhibit p-DRP1 and mitochondrial translocation of DRP1, thereby promoting mitochondrial fusion, reducing mtROS and increasing MMP. KEGG pathway enrichment revealed that ABCG2 is closely linked to apoptosis. Artemetin, OV-ABCG2, and RAB7A knockdown all alleviated HDM-induced PANoptosis by decreasing ZBP1, GSDMD, Caspase-8, FADD, BAX and RIPK1 while increasing anti-apoptotic protein Bcl-2.</div></div><div><h3>Conclusion</h3><div>Artemetin significantly improves airway inflammation, oxidative stress, and mitochondrial dysfunction in asthma by modulating the ABCG2/RAB7A axis and PANoptosis. Artemetin presents new possibilities for adjunctive therapy in the management of asthma.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156600"},"PeriodicalIF":6.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620650","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":"Stachydrine hydrochloride reduces NOX2 activity to suppress oxidative stress levels to improve cardiac insufficiency","authors":"Mengwei Fu ,&nbsp;Shuting Guo ,&nbsp;Songru Yang ,&nbsp;Kaijing Yang ,&nbsp;Rongshan Li ,&nbsp;Xiaoli Shan ,&nbsp;Pei Zhao ,&nbsp;Chen Zhang ,&nbsp;Wei Guo ,&nbsp;Ming Xu ,&nbsp;Huihua Chen ,&nbsp;Rong Lu","doi":"10.1016/j.phymed.2025.156621","DOIUrl":"10.1016/j.phymed.2025.156621","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Oxidative stress is a significant cause in the occurrence of cardiac insufficiency. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase2 (NOX2)-derived reactive oxygen species (ROS) play a pivotal role in oxidative stress-induced excitation-contraction decoupling. Stachydrine hydrochloride (Sta) reduces pressure overload-induced cardiac insufficiency, which may be related to the NOX2-ROS pathway, as demonstrated by our earlier research. However, the mechanism through which Sta specifically affects NOX2 remains unknown.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;In order to investigate whether Sta plays a cardioprotective role by inhibiting NOX2 activity, we explored the specific mechanism by which Sta improves cardiac function by affecting NOX2-mediated oxidative stress in this study.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Molecular docking and cellular thermal shift assay (CETSA) were performed to verify whether Sta can bind to individual subunits of NOX2. We induced models of cardiac insufficiency in the compensatory phase (cardiac hypertrophy) by phenylephrine (PE) &lt;em&gt;in vivo&lt;/em&gt; and &lt;em&gt;in vitro&lt;/em&gt; and treated with Sta and GSK2795039 (NOX2 inhibitor). Cardiac function and structure were observed by echocardiography analysis. We detected the expression and localization of NOX2 subunits and calcium channel proteins, also detected the activities of ROS and NOX2, SOD, and GSH, and observed intracardiac calcium homeostasis and systolic-diastolic function in cardiomyocytes. Secondly, we used adenovirus and adeno-associated virus transfection for cardiac-specific overexpression of NOX2 &lt;em&gt;in vivo&lt;/em&gt; and &lt;em&gt;in vitro&lt;/em&gt; respectively, and also treated with Sta to observe NOX2 activation indexes and ROS levels, cardiac function and cardiomyocyte function in mice.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Prior to our investigation, we discovered that Sta could bind to NOX2 through molecular docking and CETSA. The findings demonstrated that Sta decreased the expression levels of gp91&lt;sup&gt;phox&lt;/sup&gt; and p67&lt;sup&gt;phox&lt;/sup&gt;, as well as the phosphorylation levels of p47&lt;sup&gt;phox&lt;/sup&gt;, and by preventing p67&lt;sup&gt;phox&lt;/sup&gt; and p47&lt;sup&gt;phox&lt;/sup&gt; from translocating across cell membranes. NOX2 activity inhibition by Sta suppresses ROS production. Sta reduced ROS-induced oxidation of Ca&lt;sup&gt;2+&lt;/sup&gt;/calmodulin protein kinase II and modulated excitatory-contractile coupling via sarcoplasmic reticulum calcium pumps. Cardiac-specific overexpression of gp91&lt;sup&gt;phox&lt;/sup&gt; promotes membrane translocation of p67&lt;sup&gt;phox&lt;/sup&gt; and p47&lt;sup&gt;phox&lt;/sup&gt;, increases NOX2 activity, and promotes ROS generation. Sta inhibition of gp91&lt;sup&gt;phox&lt;/sup&gt; overexpression reduced the membrane translocation of p67&lt;sup&gt;phox&lt;/sup&gt; and p47&lt;sup&gt;phox&lt;/sup&gt;, decreased NOX2 activity and oxidative stress levels, and restored excitatory-contractor-coupled myocardial function.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Our study innovatively verified the key role ","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156621"},"PeriodicalIF":6.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620651","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":"Quercetin protected the gut barrier in ulcerative colitis by activating aryl hydrocarbon receptor","authors":"Qiuzhu Wei ,&nbsp;Haixu Jiang ,&nbsp;Jia Zeng ,&nbsp;Jie Xu ,&nbsp;Honglin Zhang ,&nbsp;Enfan Xiao ,&nbsp;Qingyi Lu ,&nbsp;Guangrui Huang","doi":"10.1016/j.phymed.2025.156633","DOIUrl":"10.1016/j.phymed.2025.156633","url":null,"abstract":"<div><h3>Background</h3><div>Ulcerative colitis (UC) is characterized by abdominal pain and bloody diarrhoea and restoring the gut barrier is the core goal of UC treatment. Activation of aryl hydrocarbon receptor (Ahr) was reported to effectively alleviate symptoms and repair the gut barrier damage. Neutrophil extracellular traps (NETs) have been recognized as potential targets in the treatment of UC. Ahr activation has been found to be capable of upregulating Nqo1, thereby reducing the production of reactive oxygen species (ROS), which is important in the formation of NETs. Quercetin (QUE), which is derived from natural plants and herbs used in traditional Chinese medicine (TCM), is able to strengthen gut barrier function by activating Ahr.</div></div><div><h3>Purpose</h3><div>The aim of this study is to investigate how QUE suppresses NETs in UC and activates Ahr in neutrophils.</div></div><div><h3>Methods</h3><div>In this study, the dextran sulfate sodium (DSS)-induced UC model was used. Histopathological assessments were performed in the paraffin slides of tissues after H&amp;E, PAS, Masson and alcian blue staining. The concentration of cytokines was also detected using cytometric beads array kits. Based on the transcriptomic analysis of colon tissues, western blot (WB) analysis, immunohistochemistry (IHC) assays and immunofluorescence (IF) assays were conducted to validate the significantly regulated genes and pathways. <em>In vitro</em>, the binding of quercetin to Ahr was calculated by molecular dynamic simulations (MDS) and biolayer interferometry (BLI) analysis. Primary neutrophils isolated from mice were cocultured with LPS or PMA with or without quercetin. The regulated genes were detected using WB, real-time quantitative PCR, enzyme-linked immunosorbent assay (ELISA) and IF analysis. The agonists and antagonist of Ahr were used as the control.</div></div><div><h3>Results</h3><div>After the administration of quercetin, colon inflammation and gut barrier disruption was significantly prevented through inhibiting the NF-κB pathway and upregulating the expression of Ahr/Arnt and Nqo1. The transcriptomic analysis and IHC assays showed that inflammation and NETs were greatly decreased by QUE treatment. <em>In vitro</em>, quercetin inhibited LPS-induced inflammatory responses through NF-κB pathway. Furthermore, MDS and BLI analysis revealed that QUE is an agonist of AHR. QUE activated Ahr translocation and reduced ROS production via regulation of Arnt and Nqo1.</div></div><div><h3>Conclusion</h3><div>This study proved that quercetin greatly improved gut barrier function in the DSS-induced colitis model by regulating NET formation and that quercetin was able to activate Ahr and upregulate Arnt in neutrophils to regulate NET formation.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156633"},"PeriodicalIF":6.7,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620762","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}