Phytomedicine最新文献

{"title":"Qingxin Jieyu Granule alleviates myocardial infarction through inhibiting neutrophil extracellular traps via activating ANXA1/FPR2 axis","authors":"Mingzhu Qi , Helan Huang , Zhuohang Li , Jianye Quan , Jingbo Wang , Fengyu Huang , Xinzhuo Zhang , Peiping Chen , An Liu , Zhuye Gao , Ruina Bai , Chang Chen , Xiaohui Su , Xiangying Kong","doi":"10.1016/j.phymed.2024.156147","DOIUrl":"10.1016/j.phymed.2024.156147","url":null,"abstract":"<div><h3>Background</h3><div>Myocardial infarction (MI), representing the most severe manifestation of coronary artery disease (CAD), stands as a primary concern in the prevention and management of cardiovascular diseases. Clinical evidence demonstrates that Qingxin Jieyu Granule (QXJYG) is efficacious in treatment of MI patients. However, the mechanisms underlying its therapeutic effects remain to be elucidated.</div></div><div><h3>Purpose</h3><div>This study aimed to evaluate the effects of QXJYG on MI and investigate its underlying mechanisms.</div></div><div><h3>Materials and methods</h3><div>The MI model in rats was developed through ligating the left anterior descending (LAD) artery. The effect of QXJYG on cardiac function impairment in MI rats was assessed by echocardiography, while the improvement of cardiomyocyte morphology and myocardial fibrosis after treatment with QXJYG was evaluated through hematoxylin-eosin (H&E) staining and Masson staining. The chemical constituents of QXJYG in blood were identified by using the UPLC-Q-TOF/MS technique. Furthermore, the molecular mechanism underlying the QXJYG therapeutic effect in MI was postulated based on the disease gene-drug target network analysis. Other technical methods such as ELISA, immunohistochemical staining, Western Blot analysis and application of pharmacological inhibitors were employed to verify the effectiveness of QXJYG in treating MI and explore its potential molecular targets.</div></div><div><h3>Results</h3><div>The cardiac function in experimental rats post-MI was significantly impaired, as evidenced by an enlarged infarction area, disordered arrangement of cardiomyocytes, and aggravated myocardial fibrosis. QXJYG treatment significantly enhanced the cardiac function and reduced the pathological damage of the cardiac tissue in MI rats. Through the network pharmacology analysis, we identified that FPR2 might be a potential target of QXJYG in its cardiac protection role. QXJYG markedly downregulated the level of neutrophil extracellular traps (NETs) in MI rats, specifically manifested as a significant reduction in the Histone-DNA level and expression of myeloperoxidase (MPO) and citrullinated histone H3 (CitH3) proteins. Furthermore, QXJYG upregulated the levels of ANXA1 and FPR2 proteins in MI rats. The level of FPR2 was markedly reduced in MI rats upon administration of WRW4, a specific inhibitor of FPR2, which was associated with exacerbated MI injury and an elevated level of NETs. When WRW4 was co-administered with QXJYG, the cardioprotective effects of QXJYG on MI were significantly diminished. However, the addition of DNase I did not result in significant changes of the outcomes in MI rats after QXJYG intervention.</div></div><div><h3>Conclusion</h3><div>QXJYG treatment alleviates cardiac tissue injury in MI rats by inhibiting NETs through activating the ANXA1/FPR2 axis. The findings extend our understanding of the therapeutic effectiveness of QXJYG and offer a scie","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156147"},"PeriodicalIF":6.7,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442528","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":"Diosmin reduces the stability of Snail and Cyclin D1 by targeting FAK to inhibit NSCLC progression","authors":"Chenkang Ma ,&nbsp;Mengxia Dan ,&nbsp;Ying Wang ,&nbsp;Chenying Shu ,&nbsp;Min Jiao ,&nbsp;Yuna Shao ,&nbsp;Huiling Zhang ,&nbsp;Chang Li ,&nbsp;Yuanyuan Zeng ,&nbsp;Jianjie Zhu ,&nbsp;Jian-an Huang ,&nbsp;Jianjun Li ,&nbsp;Zeyi Liu","doi":"10.1016/j.phymed.2024.156135","DOIUrl":"10.1016/j.phymed.2024.156135","url":null,"abstract":"<div><h3>Background</h3><div>In different tumours, focal adhesion kinase (FAK), a nonreceptor tyrosine kinase, is upregulated and hence, it represents a promising target for cancer therapy. However, the development of FAK kinase inhibitors has faced a number of challenges. It is therefore imperative that new, effective FAK kinase inhibitors be identified promptly.</div></div><div><h3>Methods</h3><div>Small molecules that target FAK were identified through molecular docking and validated through surface plasmon resonance (SPR) and cell thermal shift analysis. We investigated the pharmacological effects of FAK kinase inhibitors using CCK-8, colony formation, EdU, and Transwell assays and cell cycle analysis. The molecular mechanism was determined via methods such as coimmunoprecipitation, RNA pull-down and RNA immunoprecipitation.</div></div><div><h3>Results</h3><div>Here, we confirmed that diosmin (Dio) is an inhibitor of FAK and demonstrated its anti-proliferative and anti-metastatic effects in lung adenocarcinoma. Mechanistically, Dio inhibited tumour proliferation and metastasis by impeding the catalytic activity of FAK. Dio activated the ubiquitin proteasome pathway to induce Cyclin D1 degradation, while inhibiting tumour proliferation and reversing the epithelial mesenchymal transition (EMT) process by reducing the mRNA stability of Snail, thereby inhibiting cancer metastasis. In addition, the inhibitory effect of Dio on lung adenocarcinoma was validated in a mouse xenograft model.</div></div><div><h3>Conclusion</h3><div>These results support the tumour-promoting role of FAK in lung adenocarcinoma by stabilizing Cyclin D1 and Snail and suggest that Dio is a promising candidate for FAK inhibition.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156135"},"PeriodicalIF":6.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142425006","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":"Shikonin induces ferroptosis in osteosarcomas through the mitochondrial ROS-regulated HIF-1α/HO-1 axis","authors":"Congcong Lu ,&nbsp;Zhen Zhang ,&nbsp;Yuhao Fan ,&nbsp;Xiyu Wang ,&nbsp;Jin Qian ,&nbsp;Zhenyu Bian","doi":"10.1016/j.phymed.2024.156139","DOIUrl":"10.1016/j.phymed.2024.156139","url":null,"abstract":"<div><h3>Background</h3><div>The most common malignant bone tumour is osteosarcoma, which has an unsatisfactory prognosis and unsatisfactory treatment. Ferroptosis shows promise as an effective OS therapy. A substance extracted from the <em>Lithospermum erythrorhizon</em>, Shikonin (SHK), inhibits a number of tumours, including ovarian, gastric, and lung cancers. However, whether SHK induces OS ferroptosis and its mechanisms are not clear.</div></div><div><h3>Purpose</h3><div>Our study is aimed at investigating whether SHK causes ferroptosis and elucidating its molecular mechanism.</div></div><div><h3>Methods</h3><div>Cell counting Kit-8, cell cycle and cell apoptosis assay were utilised to assess therapeutic effect of SHK against OS. Normal cells, including H9C2, AML-12 and HK-2, haematoxylin and eosin staining and mice serum biomarker tests were used to assess SHK biosafety. Malondialdehyde (MDA) levels, the glutathione (GSH)/oxidized glutathione (GSSG) ratio, reactive oxygen species (ROS), lipid peroxide (LPO), and intracellular Fe²⁺ detection, quantitative reverse transcription PCR (qRT-PCR), Western blotting (WB) and rescue experiments were employed to confirm whether SHK induced ferroptosis in OS cells. Molecular docking, cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) assay were used to evaluate the direct binding between SHK and hypoxia-inducible factor-1α (HIF-1α). Protein stability and degradation analysis, small RNA interference, flow cytometry, qRT-PCR, and WB were used to investigate the molecular mechanism of ferroptosis. In vivo xenografts of nude mouse was used to study the anti-OS effect of SHK.</div></div><div><h3>Results</h3><div>SHK significantly reduced OS cell viability and induced apoptosis and G2/M arrest. SHK increased intracellular levels of MDA, ROS, LPO, and Fe²⁺ while simultaneously reducing the GSH/GSSG ratio and GPX4 and SLC7A11 expression. CETSA and DARTS results demonstrated that SHK did not bind targetly to HIF-1α. Instead, mitochondrial ROS (MitoROS) promoted HIF-1α expression, resulting in HO-1 overexpression, excess Fe²⁺ production, ROS accumulation and GPX depletion, and ferroptosis. Furthermore, inhibition of MitoROS using Mito-TEMPO downregulated HIF-1α/HO-1 axis and mitigated the SHK-induced ferroptosis. In vivo, SHK effectively suppressed OS growth with favourable biosafety, confirming the molecular mechanism underlying SHK-induced ferroptosis in OS.</div></div><div><h3>Conclusion</h3><div>We observe that HIF-1α/HO-1 axis is the crucial factor in SHK-induced OS ferroptosis. Importantly, we demonstrate that HIF-1α is indirectly regulated by MitoROS rather than SHK bound directly to HIF-1α. Our research suggest that SHK is a potential drug candidate for OS treatment and may help in identifying novel therapeutic targets for OS.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156139"},"PeriodicalIF":6.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445953","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":"Cannabiorcol as a novel inhibitor of the p38/MSK-1/NF-κB signaling pathway, reducing matrix metalloproteinases in osteoarthritis","authors":"Youngsic Jeon ,&nbsp;Jiyool Kim ,&nbsp;Hyukjoon Kwon ,&nbsp;Young Joo Yeon ,&nbsp;Taejung Kim ,&nbsp;Jungyeob Ham ,&nbsp;Young-Joo Kim","doi":"10.1016/j.phymed.2024.156141","DOIUrl":"10.1016/j.phymed.2024.156141","url":null,"abstract":"<div><h3>Background</h3><div>The bioactivity and potential medicinal applications of cannabiorcol, a lesser-known derivative of <em>Cannabis sativa,</em> require further investigation. Osteoarthritis (OA) is a chronic joint condition marked by gradual degradation of the cartilage and commonly associated with elevated levels of matrix metalloproteinases (MMPs). However, the influence of cannabiorcol on OA and its underlying mechanisms remains unclear.</div></div><div><h3>Methods</h3><div><em>In silico</em> analysis investigated the key transcription factors that regulate <em>MMP</em> expression. A chondrocyte cell model [interleukin (IL)-1β and IL-1⍺-treated C20A4 cell line] was established and treated with cannabiorcol. Associated cytotoxicity was assessed using a WST-8 assay. A monoiodoacetate-induced OA rat model was established and treated with cannabiorcol. Protein translocation and transactivation analyses were conducted using immunofluorescence and dual-luciferase reporter assays, respectively. Western blotting and real-time PCR analyzed relevant markers to examine cannabiorcol's effects on OA and its fundamental mechanisms.</div></div><div><h3>Results</h3><div>Cannabiorcol inhibits the expression of IL-1β-induced MMPs compared to other cannabis-related compounds. <em>In silico</em> analysis revealed that the nuclear factor-kappa β (NF-κβ) and mitogen-activated protein kinase (MAPK) pathways are associated with MMP expression as key regulators. <em>In vitro</em>, cannabiorcol inhibits the NF-κB and p38 MAPK pathways independently cannabinoid receptors and transient receptor potential vanilloids. <em>In vivo</em>, cannabiorcol reduces MMP expression and ameliorates monoiodoacetate-induced OA traits in rats.</div></div><div><h3>Conclusion</h3><div>Cannabiorcol inhibits IL-1β-induced MMP expression <em>in vitro</em> and alleviates OA in an MIA-induced OA rat model by reducing MMP expression and inhibiting the p65/p38 axis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156141"},"PeriodicalIF":6.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142425224","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":"Laoxianghuang polysaccharide promotes the anti-inflammatory cytokine interleukin-10 in colitis via gut microbial linoleic acid.","authors":"Yuwei Zhang, Yiren Yang, Jiangping Song, Wenqing Yu, Yaqian Li, Denghong Liu, Jie Gao, Bei Fan, Fengzhong Wang, Yang Zheng","doi":"10.1016/j.phymed.2024.156136","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156136","url":null,"abstract":"<p><strong>Background: </strong>Our previous study found that the polysaccharide from Laoxianghuang (LP), fermented fruit of bergamot (traditional Chinese medicine and food), can alter gut microbiota and regulate short-chain fatty acids (SCFAs) in vitro. Nevertheless, there is a paucity of reports on the impact of LP on gut microbiota in vivo.</p><p><strong>Purpose: </strong>To analyze the structures of LP, investigate the influence of LP on the damaged intestinal barrier in DSS-induced colitis mice, and further explore its potential mechanisms.</p><p><strong>Methods: </strong>We analyzed the physicochemical properties of purified LP by HPLC, SEM, and FT-IR spectrum. Then, to assess the effect of LP in DSS-induced colitis mice, we observed the damage to the colon tissue, measured inflammatory cytokines and tight junction protein expression through RT-qPCR as well as immunofluorescent staining, and investigated the influence of LP on altering gut microbiota and metabolites using 16 s rRNA sequencing and HPLC-MS/MS. Ultimately, the impact of linoleic acid on inflammatory cytokines was confirmed by the LPS-induced RAW264.7 cells.</p><p><strong>Results: </strong>LP, mainly galactoglucan, could inhibit weight loss and colon shortening, decrease levels of tumor necrosis factor-α (TNF-α), increase levels of interleukin-10 (IL-10) and the intestinal acetic acid and butyric acid, and promote the expression of tight junction proteins ZO-1 and Claudin-1. Meanwhile, LP enhanced the abundance of beneficial bacteria including Romboutsia, Eubacterium_coprostanoligenes_group, and Akkermansia, and regulated linoleic acid metabolism to increase the linoleic acid level. In vitro cell experiment proved that linoleic acid could elevate the level of IL-10 and inhibit inflammatory responses.</p><p><strong>Conclusions: </strong>Our results suggested that LP effectively alleviated colitis by promoting the anti-inflammatory cytokine interleukin-10 via gut microbiota-mediated linoleic acid metabolism.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"156136"},"PeriodicalIF":6.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506416","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":"Astilbin alleviates hepatic fibrosis through PXR-PINK1/Parkin pathway: A new strategy by regulating hepatic stellate cells-macrophage crosstalk","authors":"Jia-Yi Dou ,&nbsp;Mei-Jie Zhou ,&nbsp;Mei-Yan Xuan ,&nbsp;Jia Guo ,&nbsp;Sai-Hu Liu ,&nbsp;Li-Hua Lian ,&nbsp;Zhen-Yu Cui ,&nbsp;Ji-Xing Nan ,&nbsp;Yan-Ling Wu","doi":"10.1016/j.phymed.2024.156144","DOIUrl":"10.1016/j.phymed.2024.156144","url":null,"abstract":"<div><h3>Background</h3><div>Astilbin (ATB), a natural dihydroflavonol compound, exists in many plants, processed and functional foods. ATB has multiple pharmacological effects, such as antioxidant, lipid-lowering, and hepatoprotective. However, its anti-hepatic fibrosis and mechanisms remain unclearly elucidated.</div></div><div><h3>Purpose</h3><div>This study explored the effect of ATB against the hepatic fibrosis and its regulation of hepatic microenvironment by regulating hepatic stellate cells-macrophage crosstalk.</div></div><div><h3>Method</h3><div>Thioacetamide (TAA) was intraperitoneal injected to establish hepatic fibrosis mice, and treated with ATB or curcumin by gavage, respectively. Hepatic stellate cells (HSCs) were stimulated with TGF-β or conditioned medium (CM) from LPS-induced THP-1, then cultured with ATB, PXR agonist or antagonist.</div></div><div><h3>Results</h3><div>In TAA-induced mice, ATB improved histopathological changes, serum transaminases increase; alleviated extracellular matrix (ECM) deposition, epithelial-mesenchymal transformation (EMT), inflammatory infiltration, PTEN induced kinase 1 (PINK1)/Parkin-mediated mitophagy and activated pregnane X receptor (PXR) expression. <em>In vitro</em>, ATB significantly reduced ECM, inflammatory cytokines release, mitophagy, EMT, and activated PXR expression. ATB could increase PXR and decrease PINK1/Parkin, functioning as a PXR agonist. PXR deficiency in LX-2 could degrade the regulation of ATB on ECM, inflammation, EMT, and mitophagy. CM from LPS-induced THP-1 activated LX-2 and resulted in PXR decreasing, while ATB could regulate the crosstalk between HSCs and macrophages. Deficiency of PXR, whether in LX-2 or in macrophages, all weakened the inhibitory effect of ATB on α-SMA, EMT, inflammatory cytokines, and PINK1/Parkin signaling.</div></div><div><h3>Conclusion</h3><div>ATB ameliorated hepatic fibrosis by inhibiting HSCs activation, inflammation and EMT through PXR-mediated PINK1/Parkin signaling. Especially, ATB targeted the hepatic microenvironment between hepatic stellate cells and macrophages, which might be a promising strategy for the treatment of hepatic fibrosis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156144"},"PeriodicalIF":6.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142424630","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":"Total alkaloids of Aconitum carmichaelii Debx alleviate cisplatin-induced acute renal injury by inhibiting inflammation and oxidative stress related to gut microbiota metabolism","authors":"Xi Yang ,&nbsp;Yijing Xin ,&nbsp;Yanzhi Gu ,&nbsp;Youlei Wang ,&nbsp;Xingjiang Hu ,&nbsp;Guanghui Ying ,&nbsp;Qiao Zhang ,&nbsp;Xuelin He","doi":"10.1016/j.phymed.2024.156128","DOIUrl":"10.1016/j.phymed.2024.156128","url":null,"abstract":"<div><h3>Background</h3><div>Cisplatin-induced acute kidney injury (AKI) is a complex and serious clinical issue, representing a major cause of hospital-acquired AKI. Alkaloids are the main active constituents of <em>Aconitum carmichaelii</em> Debx, which exhibit protective effects in several kidney disease models and against other acute organ injuries. However, its activity and mechanism of action in AKI treatment remain unclear.</div></div><div><h3>Purpose</h3><div>This study aimed to elucidate the effect of <em>Aconitum carmichaelii</em> Debx (ACA) in a model of cisplain-induced AKI and comprehensively investigate its underlying mechanisms.</div></div><div><h3>Methods</h3><div>The major alkaloids in ACA were analyzed using high-performance liquid chromatography. Blood urea nitrogen (BUN) and serum creatine levels were measured using automated biochemical instruments. 16S rRNA sequencing, short-chain fatty acid (SCFA) analysis, fecal microbiota transplantation (FMT), non-targeted metabolomics, and transcriptomics were performed to systematically identify prospective biomarkers after ACA treatment. Anti-inflammatory and anti-oxidative stress activities were monitored using ELISA and western blotting.</div></div><div><h3>Results</h3><div>Four main compounds (fuziline, neoline, talatisamine, and songorine) were identified in ACA. ACA significantly alleviated cisplatin-induced AKI by reducing (BUN) and serum creatine levels and improving histopathological scores. Moreover, ACA balanced cisplatin-mediated confoundments in microbial composition and function, including decreasing the levels of <em>Escherichia-Shigella, Clostridium,</em> and <em>Ruminococcus</em>, as well as increasing <em>Ligilactobacillus, Anaerotruncus, Bacteroides</em> and <em>Desulfovibrio</em> levels, accompanied by uremic toxin reduction, and augmenting serum SCFAs. The FMT experiments further confirmed that ACA exerts anti-AKI effects by affecting gut microbiota. A multi-omics study has shown that ACA regulates glutathione and tryptophan metabolism and mediates pathways that trigger inflammatory responses. Finally, ACA reduced serum levels of inflammatory factors (IL-1β, IL-6, and TNF-α), restored enzymes of the antioxidative system (SOD and CAT) and GSH values, and decreased monoester diterpene alkaloid levels in the kidney by inhibiting the expression of NF-κB pathway-related proteins and increasing Nrf2/HO-1 pathway-related protein expression.</div></div><div><h3>Conclusion</h3><div>ACA protects against cisplatin-induced AKI through its anti-inflammatory and antioxidant functions, which may be associated with the restoration of gut microbiota metabolism. ACA is a potential drug for AKI and other forms of organ damage related to the disruption of the gut microbiota.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156128"},"PeriodicalIF":6.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506419","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":"Jia Wei Qingxin Lotus Seed Drink ameliorates epithelial mesenchymal transition injury in diabetic kidney disease via inhibition of JMJD1C/SP1/ZEB1 signaling pathway","authors":"Jiarun Xie ,&nbsp;Haoyu Lin ,&nbsp;Fuhua Jin ,&nbsp;Yanyu Luo ,&nbsp;Peiyuan Yang ,&nbsp;Jianda Song ,&nbsp;Wang Yao ,&nbsp;Wenming Lin ,&nbsp;Daijiao Yuan ,&nbsp;Anna Zuo ,&nbsp;Jia Sun ,&nbsp;Ming Wang","doi":"10.1016/j.phymed.2024.156142","DOIUrl":"10.1016/j.phymed.2024.156142","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Diabetic kidney disease (DKD) is one of the most common microvascular complications in patients with diabetes mellitus. In this condition, renal tubular epithelial mesenchymal transition (EMT) is an important factor accelerating the progression of DKD and a major cause of renal fibrosis and end-stage renal disease. However, the therapeutic effect is unsatisfactory because of the lack of effective drugs. Jia Wei Qingxin Lotus Seed Drink (QISD) is a traditional Chinese medicine compound formula that has shown to be effective in the clinical treatment of DKD. However, the potential of QISD in DKD-EMT treatment has yet to be fully explored.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This study aimed to investigate the role of QISD in ameliorating DKD-EMT injury and its mechanism.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The active ingredients of QISD were identified &lt;em&gt;via&lt;/em&gt; ultra-performance liquid chromatography-mass spectrometry/mass spectrometry (UHPLC-MS/MS). A DKD mouse model was constructed by high-fat diet feeding and intraperitoneal injection of STZ (60 mg/kg), and QISD (14.46, 28.92, and 57.84 g/kg/day) was administered by gavage for 12 consecutive weeks. Dapagliflozin (1 mg/kg/d) was used as a positive control. Renal pathological damage was observed by HE, PAS, and Masson staining. The expression levels of EMT-related proteins and pathway proteins were detected &lt;em&gt;via&lt;/em&gt; immunohistochemistry, RT-qPCR, and western blot. In &lt;em&gt;in vitro&lt;/em&gt; experiments, EMT injury was induced in human kidney tubular epithelial cells (HK-2) by using lipopolysaccharide (LPS). A combination of CCK8 assay, wound healing assay, small-molecule inhibitor intervention, and overexpression lentiviral transfection was used to investigate the effects of QISD on cell migration ability, adhesion ability, fibrotic factor formation, and mesenchymal properties.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Animal experiments showed that QISD improved blood glucose, body weight, symptoms of excessive drinking and eating, and renal pathological injury in mice, reduced extracellular matrix deposition, delayed renal EMT injury, and inhibited the activation of the histone demethylase JMJD1C. UHPLC-MS/MS and molecular docking indicated that baicalin, wogonoside, oroxylin A-7-O-β-D-glucuronide, and glulisine A found in QISD could bind to JMJD1C. The ameliorating effect of QISD on DKD-EMT injury might be related to JMJD1C. The improvement of DKD-EMT injury by QISD was accompanied by the reduction of SP1 and ZEB1 expression. The SP1 overexpression not only reversed the therapeutic effect of JIB-04, an inhibitor of JMJD1C, on DKD-EMT but also exacerbated the expression of ZEB1 and downstream EMT-related factors. Thus, QISD might affect the expression of the epithelial marker E-cadherin by inhibiting the JMJD1C/SP1/ZEB1 signaling pathway, consequently preventing the transformation of epithelial cells to mesenchymal cells and ameliorating DKD-EMT injury.&lt;/div&gt;&lt;/div&gt;&lt;di","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156142"},"PeriodicalIF":6.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626406","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":"A neolignan enantiomer from Piper hancei with anti-neuroinflammatory effect by attenuating NF-κB signaling pathway","authors":"Qian Lan ,&nbsp;Shuang He ,&nbsp;Jin-Long Liu ,&nbsp;Yan Wang ,&nbsp;Dong Liang","doi":"10.1016/j.phymed.2024.156140","DOIUrl":"10.1016/j.phymed.2024.156140","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;In the traditional “Yao” ethno-medicine system, &lt;em&gt;Piper hancei&lt;/em&gt; Maxim. is used to treat rheumatism, wind-cold, and inflammation. Previous studies indicate that lignans obtained from &lt;em&gt;P. hancei&lt;/em&gt; stems have anti-neuroinflammatory potential in LPS-stimulated microglial cells. However, identification of the lignan enantiomers and the precise mechanism by which they work to reduce inflammation is yet to be explored.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;To identify the active anti-neuroinflammatory lignan enantiomers isolated from &lt;em&gt;P. hancei&lt;/em&gt; stems and to elucidate the mechanism of action both &lt;em&gt;in vitro&lt;/em&gt; and &lt;em&gt;in vivo&lt;/em&gt;.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The lignan enantiomers from &lt;em&gt;P. hancei&lt;/em&gt; stems were isolated and elucidated using various chromatographic and spectroscopic methods. The anti-neuroinflammatory potential of all the compounds was initially screened by measuring nitric oxide (NO) inhibition in LPS-stimulated BV-2 microglial cells. Then anti-neuroinflammatory efficacy of the most active compound was assessed with LPS-stimulated microglial cell model, microglia-induced neuronal injury SH-SY5Y cell model, and LPS-intracerebroventricular injection neuroinflammation mouse model. The underlying mechanism was further explored by qRT-PCR analysis, Western blot analysis, and immunofluorescence staining experiments to understand the intervention pathway.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Phytochemical analysis of &lt;em&gt;P. hancei&lt;/em&gt; stems resulted in the isolation of 13 pairs of neolignan enantiomers (&lt;strong&gt;1&lt;/strong&gt;–&lt;strong&gt;13&lt;/strong&gt;), including 4 new pairs named piperhancin D–G (&lt;strong&gt;1&lt;/strong&gt;–&lt;strong&gt;4&lt;/strong&gt;). All right-handed (+) and left-handed (–) enantiomers of each pair (&lt;strong&gt;1&lt;/strong&gt;–&lt;strong&gt;13&lt;/strong&gt;) were isolated successfully. Notably, (&lt;strong&gt;+&lt;/strong&gt;)&lt;strong&gt;-&lt;/strong&gt;futoquinol (&lt;strong&gt;5&lt;/strong&gt;) demonstrated significant anti-neuroinflammatory activity without cytotoxicity, unlike its inactive enantiomer (–)-&lt;strong&gt;5&lt;/strong&gt; in LPS-stimulated microglial cells. The representative compound (&lt;strong&gt;+&lt;/strong&gt;)&lt;strong&gt;-5&lt;/strong&gt; effectively suppressed pro-inflammatory cytokines in LPS stimulated BV-2 cells and mouse brains, and alleviated microglia-induced neuronal damage in SH-SY5Y cells. Behavioral tests showed that (&lt;strong&gt;+&lt;/strong&gt;)&lt;strong&gt;-5&lt;/strong&gt; alleviated the LPS-induced cognitive dysfunction in mice. Furthermore, the compound was able to reduce LPS-induced neuronal damage and microglial activation in mouse brains. A mechanistic study demonstrated that (&lt;strong&gt;+&lt;/strong&gt;)&lt;strong&gt;-5&lt;/strong&gt; hindered the nuclear translocation of NF-κB p65 and downregulated the pro-inflammatory mediators to relieve neuroinflammation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;This is the first example of both &lt;em&gt;in vitro&lt;/em&gt; and &lt;em&gt;in vivo&lt;/em&gt; study on the anti-neuroinflammatory effects and underlying mechanism of the neolignan enantiomers is","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156140"},"PeriodicalIF":6.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142424635","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":"Targeted apoptosis of senescent cells by valproic acid alleviates therapy-induced cellular senescence and lung aging","authors":"Wentao Sun ,&nbsp;Yue Gao ,&nbsp;Yubing Wu ,&nbsp;Wei Wu ,&nbsp;Chaofan Wang ,&nbsp;JiaXiao Chen ,&nbsp;Changjiao Luan ,&nbsp;Ming Hua ,&nbsp;Weili Liu ,&nbsp;Weijuan Gong ,&nbsp;Xingjie Ma","doi":"10.1016/j.phymed.2024.156131","DOIUrl":"10.1016/j.phymed.2024.156131","url":null,"abstract":"<div><h3>Background</h3><div>Accumulation of senescent cells in tissues and their downstream effect programs have emerged as key drivers of aging and age-associated pathologies. Recent progresses in senotherapeutics indicated that either selectively killing senescent cells with senolytics or suppressing the senescence-associated secretory phenotype (SASP) secretion using senomorphics contributes to extending of the healthy lifespan and alleviating numerous age-related disorders in mice.</div></div><div><h3>Purpose</h3><div>However, the potential side-effects and long-term cytotoxicity of the above novel compounds have not yet been determined. Therefore, it seems to be more efficient to explore new senotherapeutical functions from approved drugs.</div></div><div><h3>Methods</h3><div>The effects of valproic acid (VPA), a derivative of valine, in cellular senescence were evaluated by senescence-associated β galactosidase (SA-β-Gal) staining, flow cytometry and western blot (WB). The cell viability was tested using CCK-8 kits. Cell apoptosis was detected by Annexin V-EGFP/PI apoptosis detection kit. Cell autophagy was checked using GFP-RFP-LC3 ratiometric plasmid. The roles of VPA in lung aging were investigated by <em>in vivo</em> experiments using H&amp;E and Masson staining, WB, as well as electronic microscope strategies.</div></div><div><h3>Results</h3><div>Here we identified VPA was able to induce an over-accumulation of reactive oxygen species (ROS) (&gt;1.5 times increasing) and apoptosis (&gt;2 times increasing) of senescent cells. Mechanistically, VPA activated the phospholipid modifying enzyme membrane-bound O-acyltransferase domain-containing protein 1 (MBOAT1), which was repressed during senescence, then promoted mitochondrial autophagy and apoptosis. In addition, VPA was also found to alleviate therapy induced abnormal mitochondria and lung aging phenotype (&gt;1.5 times decreasing of lung fibrosis markers and &gt;2.5 times increasing of naïve/memory CD4+ or CD8+ T cells) <em>in vivo</em>.</div></div><div><h3>Conclusion</h3><div>Taken together, our study demonstrated that VPA was able to selectively kill senescent cells both <em>in vitro</em> and <em>in vivo</em>, and thus shedding light on new functions and novel potential application of VPA in anti-aging and anti-age-associated diseases.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156131"},"PeriodicalIF":6.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142425223","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}