Phytomedicine最新文献

{"title":"Autocrine and paracrine LIF signals to collaborate sorafenib-resistance in hepatocellular carcinoma and effects of Kanglaite Injection","authors":"Yingying Shao ,&nbsp;Weiling Pu ,&nbsp;Ranran Su ,&nbsp;Yu Wang ,&nbsp;Shuangshuang Yin ,&nbsp;Hao Zhong ,&nbsp;Lifeng Han ,&nbsp;Haiyang Yu","doi":"10.1016/j.phymed.2024.156262","DOIUrl":"10.1016/j.phymed.2024.156262","url":null,"abstract":"<div><h3>Background</h3><div>Sorafenib (SFN) is the first-line medicine for advanced hepatocellular carcinoma (HCC). However, Sorafenib resistance is a main challenge of therapeutic efficacy, and the mechanisms have not been fully clarified.</div></div><div><h3>Purpose</h3><div>The purpose of this study was to investigate the therapeutic potential and mechanism of action of LIF in modulating the microenvironment of SFN resistance as well as Kanglaite Injection (KLTI) in ameliorating SFN resistance in HCC and to guide future research directions for drug combination for HCC.</div></div><div><h3>Methods</h3><div>Established SFN-resistance HCC cell line was used to study the relationship between resistance and immunosuppression in HCC-tumor microenvironment (TME). <em>In vivo</em> macrophage and natural killer (NK) cells depletion were achieved by clodronate liposomes (CL) and anti-NK1.1. <em>In vitro</em> multiple cell co-culture systems were used to determine the effects of KLTI on SFN-resistant. Likewise, flow cytometry, qRT-PCR, Western blot, and immunohistochemistry analysis were performed for further mechanistic investigation.</div></div><div><h3>Results</h3><div>Tumor associated-macrophages (TAMs) and NK cells mediated SFN-resistance in murine HCC. In the case of SFN resistance, the paracrine-leukemia inhibitory factor (LIF) by M2-like TAMs increased and potently suppressed NK cells proliferation and cytotoxicity, which finally inducing NK cells exhaustion and malignancy of HCC metastasis. Meanwhile, SFN resistance led to the increased autocrine-LIF of tumor cells, and further promoted the protective autophagy and activation of the acquired drug-resistant pathway PI3K/Akt/mTOR. KLTI could ameliorate the resistance of tumor immune microenvironment (TIME) and enhance the sensitivity of HCC to SFN by regulating LIF and macrophage-NK cell interaction.</div></div><div><h3>Conclusions</h3><div>Our findings verify the therapeutic effects of targeting LIF in SFN-resistance, uncover the potential mechanism for the increased sensitivity to SFN and sought to elucidate how this intervention might contribute to overcoming SFN resistance. KLTI is a promising immunomodulatory drug by regulating LIF and macrophage-NK cell interaction, which could be a potential combination partner for HCC treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"Article 156262"},"PeriodicalIF":6.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142706562","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":"Jinwu Jiangu capsule attenuates rheumatoid arthritis via the SLC7A11/GSH/GPX4 pathway in M1 macrophages","authors":"Yi Ling ,&nbsp;Yuzheng Yang ,&nbsp;Nina Ren ,&nbsp;Hui Xu,&nbsp;Changming Cheng,&nbsp;Daomin Lu,&nbsp;Qiuyi Wang,&nbsp;Xueming Yao,&nbsp;Wukai Ma","doi":"10.1016/j.phymed.2024.156232","DOIUrl":"10.1016/j.phymed.2024.156232","url":null,"abstract":"<div><h3>Background</h3><div>JinWu JianGu capsule (JWJGC) is a Chinese herbal medicine that alleviates the clinical manifestations of rheumatoid arthritis (RA). However, the mechanism of action requires further investigation..</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the anti-inflammatory effects of JWJGC on RA via the regulation of reactive oxygen species (ROS) and ferroptosis.</div></div><div><h3>Materials and methods</h3><div>JWJGC was administered to rats with collagen-induced arthritis (CIA) via oral gavage for 28 days. In vitro, M1 macrophages were pre-treated with JWJGC-containing serum. After assessing joint swelling and physiologic, the M1/M2 macrophage ratio was detected in CIA rats. The levels of ROS markers were assessed in the serum and cell supernatants. Liquid chromatography-tandem mass spectrometry analyses were employed to check lipid metabolism, and changes in mitochondrial morphology during ferroptosis were detected by transmission electron microscopy. Western blotting, immunofluorescence, immunohistochemistry, and qRT-PCR were performed to validate these results.</div></div><div><h3>Results</h3><div>JWJGC ameliorated CIA by reducing ROS levels in rats. It also restored the balance of the M1/M2 macrophage ratio and reduced the levels of macrophage-related inflammatory markers. Additionally, JWJGC affected lipid metabolism to alleviate inflammation by downregulating lipids associated with ferroptosis. It attenuated ferroptosis by modulating glutathione (GSH)/ Glutathione peroxidase 4(GPX4) expression in CIA rats. In vitro, JWJGC targeted M1 macrophages via the solute carrier family 7a member 11 (SLC7A11)/GSH/GPX4 signaling pathway.</div></div><div><h3>Conclusions</h3><div>This study showed that JWJGC improved RA, primarily through the integrated regulation of the SLC7A11/GSH/GPX4 pathway in M1 macrophages. These findings provide an innovative therapeutic basis for RA treatment and expanding the clinical applications of JWJGC.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156232"},"PeriodicalIF":6.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639578","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":"Honey-fried licorice in the treatment of arrhythmia: Structure elucidation and the mechanism of antiarrhythmic activity","authors":"Yushu Wang ,&nbsp;Yuxin Li ,&nbsp;Wenxin Xia ,&nbsp;Mengxin Tao ,&nbsp;Yuanyuan Zhang ,&nbsp;Lin Dong ,&nbsp;Tingting Li ,&nbsp;Xueyan Fu","doi":"10.1016/j.phymed.2024.156259","DOIUrl":"10.1016/j.phymed.2024.156259","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Aim of the study&lt;/h3&gt;&lt;div&gt;To evaluate the therapeutic mechanism of Honey-fried licorice on arrhythmia, to explore the distribution of main components of Honey-fried licorice &lt;em&gt;in vivo&lt;/em&gt; before and after processing, and to elucidate the active ingredient of Honey-fried licorice on arrhythmia.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and methods&lt;/h3&gt;&lt;div&gt;UPLC-Q-TOF/MS were used to analyze the common and different components of raw and honey-fried licorice before and after processing. Yin deficiency syndrome was established by continuous irritability and water platform sleep deprivation, and then ventricular arrhythmia model was established by injection of calcium chloride into the tail vein. Applying the electrocardiograph changes in heart rate in rats. Subsequently, ELISA and histopathological examinations were conducted to assess the therapeutic effects of honey-fried licorice on arrhythmia. Metabonomics analysis was employed to predict key regulatory pathways involved in the treatment response. Finally, RT-PCR and enzyme activity assays were utilized to verify the expression and function of key genes and proteins, providing insights into the underlying mechanisms.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The heart rate of rats increased after injection of Cacl&lt;sub&gt;2&lt;/sub&gt; solution into the tail vein. Honey-fried licorice has a certain improvement effect on heart injury and tachycardia, and its mechanism may be through the obvious correction effect on SOD, MDA, LDH, Na+-K+-ATPase, CaM and CAMK2 in the arrhythmia model. Under pathological conditions, Metabonomics revealed that the heart was highly exposed to glycyrrhetic acid 3-O-glucuronide, isoformononetin, araboglycyrrhizin, 18β-glycyrrhetinic acid, liquiritigenin, licoflavonol and isoliquiritigenin are known to have anti-arrhythmic effects through immune regulation and oxidation. Notably, both PCR and ELISA analyses indicated that honey-fried licorice may effectively treat arrhythmia, potentially through the modulation of the arachidonic acid pathway.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;These results suggested that honey-fried licorice could protect against arrhythmia and alleviate oxidative stress and tissue damage caused by arrhythmia. Through correlation analysis and metabolomics, it was found that glycyrrhetic acid 3-O-glucuronide, isoformononetin, araboglycyrrhizin, 18β-glycyrrhetinic acid, liquiritigenin, licoflavonol and isoliquiritigenin can be used as the active ingredient of honey-fried licorice in the treatment of arrhythmia. Moreover, our results suggested that the therapeutic effect of honey-fried licorice on arrhythmia may be linked to the regulation of the arachidonic acid pathway. This study elucidates the mechanisms by which honey-fried licorice treats arrhythmia from a metabolic perspective, highlighting its role in \"tonifying the spleen and stomach, supplementing qi, and replenishing the pulse.\" These findings provide a foundation for the further application of honey-frie","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"Article 156259"},"PeriodicalIF":6.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695734","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":"Guizhi Shaoyao Zhimu decoction inhibits neutrophil extracellular traps formation to relieve rheumatoid arthritis via gut microbial outer membrane vesicles","authors":"Haixin Ye ,&nbsp;Hao Wang ,&nbsp;Bingqi Han ,&nbsp;Keshan Chen ,&nbsp;Xing Wang ,&nbsp;Fopei Ma ,&nbsp;Lifang Cheng ,&nbsp;Songyuan Zheng ,&nbsp;Xueqin Zhao ,&nbsp;Junqing Zhu ,&nbsp;Juan Li ,&nbsp;Mukeng Hong","doi":"10.1016/j.phymed.2024.156254","DOIUrl":"10.1016/j.phymed.2024.156254","url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid arthritis (RA) is a common autoimmune disease with a high disability rate. Accumulating studies suggest that neutrophil extracellular traps (NETs) play a crucial role in the pathogenesis of RA and targeting NETs has emerged as a potential therapeutic strategy for RA. As a traditional Chinese medicine, Guizhi-Shaoyao-Zhimu Decoction (GSZD) has exhibited good efficacy in the treatment of rheumatoid arthritis (RA), while the underly mechanism especially the possibility that GSZD alter NETs formation to relieve RA remains unknown.</div></div><div><h3>Purpose</h3><div>Our study aimed to investigate relationship between GSZD and NETs in RA treatment and revealed underlying mechanism.</div></div><div><h3>Methods</h3><div>We constructed collagen-induced arthritis (CIA) model and treated CIA mice with GZSY to validate therapeutic effects of GSZD and examine whether GZSD could inhibit NETs formation in RA. And 16S rRNA sequencing and Fecal microbiota transplantation (FMT) experiment were performed to determine whether GSZD could reduce NETs formation to alleviate RA in gut microbiota-associated manner and identify crucial bacterium in response to GSZD administration. CIA mice treated with effective bacteria and its outer membrane vesicles (OMVs) with oral administration to investigate protective effect against RA and NETs regulative efficiency. We utilized small interfering RNA in vivo and vitro to silence gene mediating effect of GZSD-gut microbiota-NETs.</div></div><div><h3>Results</h3><div>GSZD could inhibit NETs formation and relive arthritis in CIA mice. Additionally, GSZD alter gut microbiota composition and significantly increase intestinal <em>Parabacteroides goldsteinii</em> (<em>P.goldsteinii</em>) abundance. Mechanistically, <em>P.goldsteinii</em> enriched by GSZD secreted outer membrane vesicles (OMVs) to translocate into joints and activate Cav-1-Nrf2 axis, leading to reduced NETs formation and alleviate arthritis. In clinical, the abundance of <em>P.goldsteinii</em> exhibited negative correlation with NETs indexes and RA disease activities.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that GSZD inhibits NETs formation to relieve RA in <em>P.goldsteinii-</em>Cav-1-Nrf2 associated manner, which could provide new sight of the prevention and treatment of RA.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"Article 156254"},"PeriodicalIF":6.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142706564","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 YOXINTINE for depression: A double-blinded, randomized, placebo-controlled, phase 2 clinical trial","authors":"Zaiquan Dong ,&nbsp;Qi Shen ,&nbsp;Hanwen Zhu ,&nbsp;Zirong Yang ,&nbsp;Jianqin Lv ,&nbsp;Ruizhi Feng ,&nbsp;Xue Bai ,&nbsp;Guoping Huang ,&nbsp;Yueqiang Hu ,&nbsp;Liya Pan ,&nbsp;Guijun Zhao ,&nbsp;William Jia ,&nbsp;Xue Wang","doi":"10.1016/j.phymed.2024.156204","DOIUrl":"10.1016/j.phymed.2024.156204","url":null,"abstract":"<div><h3>Background</h3><div>YOXINTINE contains &gt;98 % of 20(S)-protopanaxadial (PPD), a metabolic product of ginsenosides with pre-clinical neuroprotective activity. Animal experiments and previous studies have shown that PPD has good antidepressant effect and safety.</div></div><div><h3>Purpose</h3><div>To evaluate YOXINTINE in treating depression compared with a placebo in Chinese patients.</div></div><div><h3>Study Design</h3><div>This was a multicenter, double-blinded, randomized, placebo-controlled, phase 2 clinical trial.</div></div><div><h3>Methods</h3><div>The study included 178 randomized (1:1:1) Chinese patients with depression. Patients were randomly assigned to receive oral YOXINTINE at doses of 200 or 400 mg or a placebo administered twice daily for 8 weeks. The primary outcome was assessed by measuring changes in the Montgomery–Asberg Depression Rating Scale (MADRS) total score. All adverse reactions were recorded. All demographic and baseline characteristics were comparable.</div></div><div><h3>Results</h3><div>The changes in MADRS total scores from baseline were −10.43 for the placebo group, −16.24 for the 200 mg YOXINTINE group, and −13.60 for the 400 mg YOXINTINE group. The differences in MADRS total score changes compared with the placebo were −5.81 (95 % CI: −7.69, −3.92; P &lt; 0.0001) and −3.17 (95 % CI: −5.08, −1.25; P = 0.0013) for the 200 mg and 400 mg groups, respectively. The results indicated a significantly greater MADRS score reduction in the 200 mg group (P = 0.0058, 95 % CI: 0.78, 4.51). Adverse event incidence was comparable among all groups.</div></div><div><h3>Conclusion</h3><div>Oral YOXINTINE is safe and significantly improves depressive symptoms. PPD may exhibit antidepressant properties through mechanisms distinct from monoamine reuptake inhibition.</div></div><div><h3>Registration number</h3><div>ChiCTR2300070568</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"Article 156204"},"PeriodicalIF":6.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142706118","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":"Cryptotanshinone alleviates immunosuppression in endometriosis by targeting MDSCs through JAK2/STAT3 pathway","authors":"Linling Xie ,&nbsp;Yu Zhong ,&nbsp;Yi Chen ,&nbsp;Yishu Wang ,&nbsp;Peiyi Xian ,&nbsp;Shanjia Liu ,&nbsp;Xiaoyan Xin ,&nbsp;Yanfen Chen ,&nbsp;Yongge Guan ,&nbsp;Kunyin Li","doi":"10.1016/j.phymed.2024.156227","DOIUrl":"10.1016/j.phymed.2024.156227","url":null,"abstract":"<div><h3>Background</h3><div>Endometriosis (EMS), a well-recognized chronic inflammatory disorder, characterized by significant immune dysregulation, in which myeloid-derived suppressor cells (MDSCs) are essential for facilitating immunosuppression and driving to disease progression. Cryptotanshinone (CTS) is an active compound capable of modulating MDSC-mediated immunosuppression; however, its therapeutic effects and mechanisms in the treatment of EMS remain unclear.</div></div><div><h3>Purpose</h3><div>This study aims to investigate the therapeutic potential of CTS in modulating MDSCs through JAK2/STAT3 signaling pathway and to evaluate its effects on immune microenvironment and endometriotic lesion growth in EMS.</div></div><div><h3>Methods</h3><div>Transcriptomic data (GSE141549) and single-cell RNA sequencing data (GSE213216) were analyzed to compare immune cell populations in control endometrium (CE), eutopic endometrium (EuE) and ectopic endometrium (EcE) of patients with EMS. Network pharmacology analysis, surface plasmon resonance (SPR) and cellular thermal shift assay (CETSA) were utilized to explore the molecular mechanism of CTS's effects on MDSCs. A C57BL/6J EMS mice model was established to evaluate CTS's influence on MDSC-mediated immune response in vivo. Flow cytometry and immunofluorescence were used to analyze the immune cell populations, particularly MDSCs and CD8⁺ T cells. Ex vivo bone marrow (BM)-derived MDSCs were prepared to investigate the modulatory activities of CTS on the frequency and function of MDSCs. The impacts of CTS on JAK2/STAT3 pathway were further examined by western blot.</div></div><div><h3>Results</h3><div>Bioinformatic analysis revealed that, among the three progression stages (CE, EuE, and EcE), the EcE stage exhibited a relatively elevated level of MDSCs and a reduced level of CD8⁺ T cells. Network pharmacological analysis, along with SPR and CETSA identified that CTS potentially modulates MDSCs in EMS by targeting the JAK2/STAT3 pathway. In vivo studies demonstrated that a relatively high dose of CTS treatment (60mg/kg) effectively inhibited lesion growth, reduced the population of MDSCs, and enhanced CD8⁺ T cell infiltration. Ex vivo experiments showed that CTS decreased the BM-derived MDSC frequency and rescued the suppressive ability of MDSC upon CD8⁺ T cells in a dose-dependent manner. Further mechanism analysis confirmed that CTS modulates the expression of immunosuppressive genes and proteins associated with MDSCs through JAK2/STAT3 pathway.</div></div><div><h3>Conclusion</h3><div>This study is the first to demonstrate that CTS is a promising natural compound for EMS treatment by inhibiting MDSC accumulation and modulating MDSC-mediated immune responses. Its therapeutic efficacy is linked to the modulation of the JAK2/STAT3 signaling pathway.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"Article 156227"},"PeriodicalIF":6.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142706560","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":"Salvianolic acid B alleviated myocardial ischemia-reperfusion injury via modulating SIRT3-mediated crosstalk between mitochondrial ROS and NLRP3","authors":"Xiao-Hong Wei ,&nbsp;Jie Chen ,&nbsp;Xue-Fen Wu ,&nbsp;Qian Zhang,&nbsp;Gui-Yang Xia,&nbsp;Xin-Yu Chu,&nbsp;Huan Xia,&nbsp;Sheng Lin,&nbsp;Hong-Cai Shang","doi":"10.1016/j.phymed.2024.156260","DOIUrl":"10.1016/j.phymed.2024.156260","url":null,"abstract":"<div><h3>Background</h3><div>Mitochondrial ROS (mtROS) accumulation and NLRP3 inflammasome activation are critical in the pathogenesis of myocardial ischemia-reperfusion injury (MIRI). However, their upstream regulatory mechanisms and interaction remain inadequately understood.</div></div><div><h3>Purpose</h3><div>The study aims to investigate the therapeutic effect of Salvianolic acid B (Sal B) on MIRI and elucidate its potential molecular mechanism, mainly focusing on the role of SIRT3.</div></div><div><h3>Methods</h3><div>SIRT3 was knocked down (SIRT3^KD) and overexpressed (SIRT3^OE) using small interfering RNA and plasmid, respectively. The role of SIRT3 in the cardioprotective effect of Sal B was explored using MIRI rat models and H9c2 cell hypoxia/reoxygenation (H/R) models. SIRT3, NLRP3 inflammasome proteins, and MnSOD expression were analyzed by Western blot and immunofluorescence staining. MtROS levels were assessed with mitochondrial superoxide indicators (MitoSOX™ Red). ELISA was utilized to measure the levels of LDH, CK-MB, cTnT, and markers of inflammation and oxidative stress. The interaction between SIRT3 and Sal B was studied through biolayer interferometry, cellular thermal shift assay and molecular docking.</div></div><div><h3>Results</h3><div>Our findings revealed significantly decreased SIRT3 level, enhanced MnSOD acetylation, and activated NLRP3 inflammasome in myocardium after MIRI and H9c2 cardiomyocytes exposed to H/R conditions. SIRT3^KD promoted MnSOD acetylation and NLRP3 expression, aggravating mtROS accumulation and inflammation. Conversely, SIRT3^OE significantly inhibited MnSOD acetylation and NLRP3 inflammasome activation. In <em>vitro</em> studies confirmed the crosstalk between mtROS and NLRP3, demonstrating that mtROS scavenger inhibited NLRP3 inflammasome activation induced by H/R and SIRT3^KD, and the NLRP3 inhibitor suppressed MnSOD acetylation in H/R and SIRT3^KD cardiomyocytes. Interestingly, Sal B was found to bind and upregulate SIRT3, reduce the expression of Acy-MnSOD, NLRP3, ASC, Caspase-1, and GSDMD, inhibit oxidative stress and inflammatory response, decrease myocardial infarct size and ST-segment elevation, and restore myocardial morphology. However, the protective effect of Sal B against MIRI was nullified by a specific SIRT3 inhibitor.</div></div><div><h3>Conclusion</h3><div>This study unveils that the SIRT3-mediated interplay between mtROS and the NLRP3 inflammasome is pivotal in the pathogenesis of MIRI. Furthermore, it highlights Sal B as a novel therapeutic agent that alleviates MIRI by targeting SIRT3, offering new insights into MIRI treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"Article 156260"},"PeriodicalIF":6.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695736","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":"Mulberry leaf benefits the intestinal epithelial barrier via direct anti-oxidation and indirect modulation of microbiota in pigs","authors":"Hui Yan ,&nbsp;Shurui Yan ,&nbsp;Zaiyao Li ,&nbsp;Tingting Zhang ,&nbsp;Jun He ,&nbsp;Bing Yu ,&nbsp;Jie Yu ,&nbsp;Junqiu Luo ,&nbsp;Aimin Wu ,&nbsp;Junning Pu ,&nbsp;Quyuan Wang ,&nbsp;Huifen Wang ,&nbsp;Xingyu Liu ,&nbsp;Daiwen Chen","doi":"10.1016/j.phymed.2024.156217","DOIUrl":"10.1016/j.phymed.2024.156217","url":null,"abstract":"<div><h3>Background</h3><div>Diarrhea and intestinal dysfunction commonly occur in young mammals, causing malnutrition and growth retardation in both human and livestock. As the traditional Chinese herb, mulberry leaf contains various bioactive compounds and showed several health benefits, such as regulating glucose and lipid metabolism, and modulating gut microbiota. Mulberry leaf exhibits the potential to modulate redox homeostasis and improve gut health, but the function and underlying mechanisms remains elucidative.</div></div><div><h3>Purpose</h3><div>To investigate the benefit of mulberry leaf on intestinal barrier in weanling pigs, illustrate the possible involvement of Keap1-Nrf2 mediated anti-oxidation and gut microbiota.</div></div><div><h3>Methods</h3><div>Chemical compositions of mulberry leaf powder (MLP) and mulberry leaf extract (MLE) were determined. The effects of MLP on growth performance, intestinal barrier integrity, anti-oxidative capacity, immune function and gut microbiota were evaluated in weaned pigs. The regulation of redox homeostasis by MLE and the involvement of Keap1-Nrf2 signaling were further determined in H₂O₂ induced oxidative stress (OS) model in IPEC-J2 cells via determining reactive oxygen species (ROS) production by flow cytometry and related protein abundance by western blot analysis.</div></div><div><h3>Results</h3><div>In weanling pigs, MLP reduced diarrhea incidence, and increased villus height, intestinal integrity and expression of tight junctions in intestinal mucosa. The improvement of intestinal barrier by MLP was associated with the enhancement in anti-oxidative capacity and the changes in gut microbiota and related short chain fatty acids production. Our study further revealed the direct regulation of MLE on tight junction expressions and ROS production to alleviate H₂O₂ induced OS in IPEC-J2 cells via the activating Keap1-Nrf2 signaling pathway.</div></div><div><h3>Conclusions</h3><div>Mulberry leaf in diet improved epithelial barrier via the direct anti-oxidation through the activation of Keap1-Nrf2 signaling pathway and the indirect modulation of gut microbiota in weaned pigs.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156217"},"PeriodicalIF":6.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688655","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":"Bushen Huoxue Yiqi formula alleviates cardiac fibrosis in ischemic heart failure through SIRT1/Notch1 pathway-mediated EndMT.","authors":"Cong Chen, Jie Wang, Chengzhi Hou, Wenjing Lian, Xueying Zhu, Jun Hu, Chao Liu","doi":"10.1016/j.phymed.2024.156252","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156252","url":null,"abstract":"<p><strong>Background: </strong>Cardiac fibrosis plays a crucial role in the development of heart failure (HF) following myocardial infarction (MI). Endothelial-mesenchymal transition (EndMT) is one of the key drivers of cardiac fibrosis and subsequent cardiac dysfunction. The traditional Chinese medicine formula Bushen Huoxue Yiqi Formula (BHYF) is an effective prescription for treating HF, significantly improving cardiac function in patients. However, the underlying mechanisms of BHYF's efficacy remain inadequately understood.</p><p><strong>Objective: </strong>This study aims to determine whether BHYF ameliorates HF by inhibiting cardiac fibrosis and to elucidate the intrinsic mechanisms involved.</p><p><strong>Methods: </strong>A post-MI HF model was established by ligating the left anterior descending coronary artery in rats, and human umbilical vein endothelial cells (HUVEC) were stimulated with hypoxia/reoxygenation (H/R) in vitro. Active compounds in BHYF were identified using HPLC. Cardiac function and morphology were assessed using echocardiography, TTC staining, HE staining, Masson's trichrome, and Sirius Red staining. The mechanism of action of BHYF was evaluated using Western blotting, immunohistochemistry, and immunofluorescence.</p><p><strong>Results: </strong>A total of 98 compounds, including glycosides, phenolic compounds, carboxylic acids, and others, were identified or preliminarily identified. BHYF improved cardiac function and myocardial damage in rats with MI-induced HF and mitigated cardiac fibrosis by inhibiting EndMT. Mechanistically, BHYF treatment inhibited EndMT by modulating the SIRT1/Notch1 pathway, thereby exerting anti-fibrotic effects in the heart.</p><p><strong>Conclusion: </strong>Targeting EndMT based on the SIRT1/Notch1 pathway, BHYF may represent a novel antifibrotic therapeutic strategy, providing a scientific basis for the development of new cardiovascular drugs.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"156252"},"PeriodicalIF":6.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682486","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":"Huang-Lian-Jie-Du decoction alleviates cognitive impairment in high-fat diet-induced obese mice via Trem2/Dap12/Syk pathway","authors":"Jia-Yi Zheng ,&nbsp;Rui-Kang Pang ,&nbsp;Jiang-Hong Ye ,&nbsp;Shan Su ,&nbsp;Jia Shi ,&nbsp;Yu-Hui Qiu ,&nbsp;Hua-Feng Pan ,&nbsp;Ru-Yu Zheng ,&nbsp;Xin-Rui Hu ,&nbsp;Qi-Wen Deng ,&nbsp;Xiao-Xiao Li ,&nbsp;Ye-Feng Cai ,&nbsp;Shi-Jie Zhang","doi":"10.1016/j.phymed.2024.156248","DOIUrl":"10.1016/j.phymed.2024.156248","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Cognitive impairment induced by a high-fat diet (HFD) is common, but its mechanism is largely unknown. Huang-Lian-Jie-Du (HLJD) decoction is a classical and powerful prescription in China. It consists of four medicinal plants and is widely used in traditional Chinese medicines (TCM). Studies have shown that HLJD decoction is effective in treating obesity, depression, and so on. However, the therapeutic mechanism of HLJD is still poorly understood.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;Our study aimed to explore whether inflammatory factors and Trem2/Dap12/Syk pathway are involved in this process and whether HLJD treatment can repair cognitive impairment in HFD-induced obesity.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;To obtain the obese mice, male mice were treated with HFD (60 Kcal% fat) for 16 weeks. After an additional eight weeks, HLJD decoction was administered orally at doses of 4 and 8 g/kg daily for eight weeks. The mice were then subjected to four behavior tests. Aβ42, total Tau, inflammatory-related, and microglial dysregulation-related markers expression were measured. Molecular docking analysis was also conducted to predict the interaction of the chemical constituents of HLJD with human TREM2, DAP12, and SYK. HLJD at doses of 12.5, 25, and 50 µg/mL or limonin at concentrations of 12.5, 25, and 50 µM were used to treat BV2 cells for 24 h. CCK8 assay and Trem2, Dap12, Syk, and p-Syk expression were measured.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Our study revealed that cognitive impairment was evident in mice treated with HFD, indicating the impact of obesity on cognitive function. The expression of Aβ42 and total Tau in the hippocampus (HIP) was significantly higher in obese (HFD-V) mice compared to normal control (NC-V) mice. The &lt;em&gt;Il6, Il1b&lt;/em&gt;, and &lt;em&gt;Il10&lt;/em&gt; mRNA expression levels were also markedly increased in the HIP of obese mice. Furthermore, Trem2, Dap12, p-Syk, and Iba1 expression were elevated in the HIP of obese mice. Importantly, HLJD treatment was found to repair cognitive impairment and lower the protein expression of Aβ42, Tau, Trem2, Dap12, p-Syk, and the expression of &lt;em&gt;Il6, Il1b&lt;/em&gt;, and &lt;em&gt;Il10&lt;/em&gt; mRNA in HIP of HFD-V mice. The increased expression of Trem2, Dap12, p-Syk, and Iba1 in HIP after HFD consumption could be reduced after receiving HLJD decoction. The compound Limonin showed a well-predicted binding energy with TREM2, DAP12, and SYK. BV2 cells with HLJD or limonin detected the mRNA expressions of &lt;em&gt;Trem2/Dap12&lt;/em&gt;. HLJD at 25 and 50 µg/mL decreased Trem2, Dap12, and p-Syk protein levels in BV2 cells.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;These results reveal that HLJD treatment could alleviate cognitive impairment in HFD-induced obese mice by controlling the activation of the Trem2/Dap12 pathway and reducing Syk phosphorylation in HIP microglia. HLJD and limonin suppressed Trem2/Dap12/Syk signaling pathway in BV2 cells. HLJD therapy might represent a novel treatment","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156248"},"PeriodicalIF":6.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142655778","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}