Phytomedicine最新文献

{"title":"A multicenter, randomized, double-blind, placebo-controlled trial to evaluate the effect of Tongmai Yangxin pill on ventricular remodeling in acute anterior STEMI patients after primary PCI.","authors":"Yongxia Wang, Xinlu Wang, Jianru Wang, Chunjie Li, Guoan Zhao, Chaoyang Zheng, Xiaochi Shi, Xiaolong Wang, Ke Wang, Wei Wu, Zhenpeng Zhang, Hengliang Liu, Hao Zhou, Fei Lin, Xiaofen Ruan, Jia Zhao, Shichao Wang, Xingyuan Li, Shanshan Nie, Xiaohui Li, Jinyu Huang, Heng Sun, Linping Pian, Wei Xing, Bin Li, Rui Yu, Zuoying Xing, Yankun Song, Yutian Luo, Duolao Wang, Yanming Xie, Junhua Zhang, Mingjun Zhu","doi":"10.1016/j.phymed.2024.156133","DOIUrl":"10.1016/j.phymed.2024.156133","url":null,"abstract":"<p><strong>Background: </strong>Acute ST-segment elevation myocardial infarction (STEMI) is a severe form of coronary heart disease and a leading cause of mortality and morbidity. This can mainly be ascribed to adverse ventricular remodeling (VR). However, the efficacy of existing treatment strategies for STEMI is not entirely satisfactory. Tongmai Yangxin Pill (TMYX), a patented traditional Chinese medicine (TCM), has been approved for treating various cardiovascular diseases.</p><p><strong>Purpose: </strong>The purpose was to assess the effect of TMYX on VR in acute STEMI patients undergoing primary percutaneous coronary intervention (PPCI).</p><p><strong>Study design: </strong>A multicenter, randomized, double-blinded, and placebo-controlled trial conducted across 11 hospitals in China.</p><p><strong>Method: </strong>A total of 270 patients with acute anterior STEMI, undergoing PPCI within 10 days of symptom onset were enrolled and randomly assigned to receive either a placebo or TMYX, in addition to guideline-directed treatments for STEMI. The primary endpoint was a change in left ventricular end-diastolic volume index (LVEDVI) at 12 weeks.</p><p><strong>Result: </strong>Among the 270 randomized patients, 218 (TMYX: 109 and placebo: 109) were included in the per-protocol analysis. At 4 and 12 weeks, TXMY significantly improved LVEDVI than the placebo group ([-2.17(-9.24, 8.28) vs. 3.76(-2.38, 11.48), p < 0.05] and [-1.17 (-12.19, 12.88) vs. 4.46 (-2.89, 11.99), p < 0.05]). Changes in left ventricular end-diastolic volume (LVEDV) at 4 weeks were superior in the TMYX group than the placebo group (-4.37 (-17, 13.99) vs. 7.41 (-4.56, 21.79), p < 0.05). Cardiac magnetic resonance imaging (CMRI) showed that left ventricular ejection fraction (LVEF) was significantly greater in the TMYX group than in the placebo group at 4 weeks. There were no statistically significant differences between groups for left ventricular end-systolic volume (LVESV), left ventricular end-systolic volume index (LVESVI), 6 min walking distance (6MWD), and major adverse cardiac and cerebrovascular events (MACCEs) (p > 0.05).</p><p><strong>Conclusion: </strong>TMYX, as an adjunctive therapy in addition to STEMI guideline-directed treatments, significantly delayed VR in patients with acute anterior STEMI undergoing PPCI within 10 days of symptom onset.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"156133"},"PeriodicalIF":6.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569421","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":"Comparative efficacy of Chinese tonic medicines for treating sepsis or septic shock: A systematic review and Bayesian network meta-analysis of randomized controlled trials.","authors":"Rui Yang, Cheng Hu, Yuxin Zhuo, Qingyuan Tan, Yuxin Shen, Kun Jiang, Qing Xia, Lihui Deng","doi":"10.1016/j.phymed.2024.156295","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156295","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Sepsis or septic shock is a life-threatening medical emergency with a poor prognosis and a high economic burden for both individuals and healthcare resources. Evidence suggests that Chinese tonic medicines (CTMs), as adjuvant treatments, are effective in treating this disease. Nevertheless, the ongoing discourse regarding the optimal CTMs persists. This study was conducted to further explore the comparative effectiveness of CTMs for patients with sepsis or septic shock.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We systematically searched Pubmed, Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature (CBM), Chinese National Knowledge Infrastructure (CNKI), Wanfang database, VIP database from inception to November 15, 2023. Primary outcomes encompassed the delta Sequential Organ Failure Assessment (ΔSOFA) score at day 7 after interventions and 28-day mortality. Secondary outcomes included delta serum lactate (ΔLac) and delta mean arterial pressure (ΔMAP) levels at day 7 after interventions, as well as the duration of vasoactive drug administration. The safety outcome was adverse drug reactions or adverse drug events (ADRs/ADEs). The risk ratio (RR) and mean difference (MD) with a 95 % confidence interval (95 %CI) were selected as effect measures. The Bayesian network meta-analysis was conducted by R version 4.2.2 software. The surface under the cumulative ranking curve (SUCRA) values were used to rank each treatment. The Cochrane Risk of Bias V.2.0 tool was employed to assess the within-study risk of bias. The CINeMA (Confidence in Network Meta-Analysis) web application was utilized to assess the quality of evidence. This protocol was prospectively registered in PROSPERO (CRD4202348572).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 45 randomized controlled trials (RCTs) involving 3433 patients were identified in this study. Seven CTMs including Shenfu injection (SF), Shenmai injection (SM), Sini decoction (SN), Shenfu and Shengmai granules (SF+SGM), Shengmai injection (SGM), Yiqifumai injection (YQFM), and Shenqifuzheng injection (SQFZ) were involved. Regarding the ΔSOFA score, interventions combining SM with Western medicine (WM) (MD, -2.77; 95 %CI, -3.28 to -2.27), YQFM+WM (MD, -1.76; 95 %CI, -2.73 to -0.79), SGM+WM (MD, -1.11; 95 %CI, -1.88 to -0.34), and SF+WM (MD, -0.98; 95 %CI, -1.17 to -0.78) demonstrated superiority over WM alone. According to the SUCRA values, SM+WM (99.28 %) achieved the highest ranking for the ΔSOFA score. Concerning 28-day mortality, SM+WM (RR, 0.51; 95 %CI, 0.35 to 0.72) and SF+WM (RR, 0.73; 95 %CI, 0.65 to 0.83) exhibited a superior effect in reducing 28-day mortality. Based on the SUCRA values, SM+WM (82.49 %) secured the top ranking for 28-day mortality. Among the secondary outcomes, SM+WM (MD, -2.50; 95 %CI, -4.15 to -0.83; SUCRA, 94.27 %) emerged as the most favorable in reducing serum lactate levels. SF+WM (MD, 10.78; 95 %CI, 3.11 to 18.71; SCURA, 78.3 %) exhibit","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"156295"},"PeriodicalIF":6.7,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792356","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":"Andrographolide attenuates SARS-CoV-2 infection via an up-regulation of glutamate-cysteine ligase catalytic subunit (GCLC).","authors":"Jarinya Chaopreecha, Nut Phueakphud, Ampa Suksatu, Sucheewin Krobthong, Suwimon Manopwisedjaroen, Nattawadee Panyain, Suradej Hongeng, Arunee Thitithanyanont, Patompon Wongtrakoongate","doi":"10.1016/j.phymed.2024.156279","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156279","url":null,"abstract":"<p><strong>Background: </strong>Andrographolide is a medicinal compound which possesses anti-SARS-CoV-2 activity. A number of cellular targets of andrographolide have been identified by target predictions and computational studies.</p><p><strong>Purpose: </strong>However, a potential cellular target of andrographolide has never been explored in SARS-CoV-2 infected lung epithelial cells. We aimed to identify cellular pathways involved in andrographolide-mediated anti-SARS-CoV-2 activity.</p><p><strong>Methods: </strong>The viral infection was determined by immunofluorescence staining, enzyme-linked immunosorbent assay and focus-forming assay. Proteomic analysis was employed to identify cellular pathways and key proteins controlled by andrographolide in the human lung epithelial cells Calu-3 infected by SARS-CoV-2. Immunofluorescence staining was used to test protein expression and localization. Western blot and realtime PCR were utilized to elucidate gene expression. Cellular glutathione level was examined by a reduced/oxidized glutathione assay. An ectopic gene expression was delivered by plasmid transfection.</p><p><strong>Results: </strong>Gene ontology analysis indicates that proteins involved in nuclear factor erythroid 2-related factor 2 (NRF2)-regulated pathways were differentially expressed by andrographolide. Notably, andrographolide increased expression and nuclear localization of the transcription factor NRF2. In addition, transcriptional expression of GCLC and glutamate-cysteine ligase modifier subunit (GCLM), which are NRF2 target genes, were induced by andrographolide. We further find that infection of SARS-CoV-2 resulted in a reduction of glutathione level in Calu-3; the effect that was rescued by andrographolide. Moreover, andrographolide also induced expression of the glutathione producing enzyme GCLC in SARS-CoV-2 infected lung epithelial cells. Importantly, an ectopic over-expression of GCLC or treatment of N-acetyl-L-cysteine in Calu-3 cells led to a decrease in SARS-CoV-2 infection.</p><p><strong>Conclusion: </strong>Collectively, our findings suggest the interplay between GCLC-mediated glutathione biogenesis induced by andrographolide and the anti-SARS-CoV-2 activity. The glutathione biogenesis and recycling pathways should be further exploited as a targeted therapy against SARS-CoV-2 infection.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"156279"},"PeriodicalIF":6.7,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780693","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":"Jiawei Qi Gong Wan improves liver fibrosis and inflammation in PCOS mice via the Akt2-FoxO1 and YAP/TAZ signaling pathways","authors":"Jie Li ,&nbsp;Ruqun Zheng ,&nbsp;Yingyan Shen ,&nbsp;Yuxuan Zhuo ,&nbsp;Lingjing Lu ,&nbsp;Jinlong Song ,&nbsp;Jing Li ,&nbsp;Maohua Lai ,&nbsp;He Zhu ,&nbsp;Min Hu ,&nbsp;Hongxia Ma ,&nbsp;Juan Li","doi":"10.1016/j.phymed.2024.156294","DOIUrl":"10.1016/j.phymed.2024.156294","url":null,"abstract":"<div><h3>Background</h3><div>Metabolic disorders in polycystic ovary syndrome (PCOS) patients have attracted increasing attention, and nonalcoholic fatty liver disease (NAFLD) in particular has been the focus of much research due to its high incidence and potential harm in patients with PCOS. However, little is known about whether PCOS is associated with more severe NAFLD histopathology. Although Jiawei Qi Gong Wan (JQGW) is widely used clinically, its specific effects and mechanisms on the liver remain unclear.</div></div><div><h3>Purpose</h3><div>The aim of this study was to explore the mechanism of JQGW in improving metabolic abnormalities in the liver in PCOS mice in order to support the development of therapies to prevent PCOS complications.</div></div><div><h3>Methods</h3><div>A mouse model of PCOS was established by subcutaneously implanting letrozole tubes. The effect of JQGW on liver metabolism in mice was observed by measuring biochemical indicators in serum. Liver morphological changes were observed using hematoxylin and eosin staining along with Sirius red staining, while Western blotting and qRT-PCR were used to quantify the expression of genes and proteins related to liver fibrosis and inflammation processes. Network pharmacology was used to analyze the key factors that JQGW may target in improving liver fibrosis in PCOS mice, and the results were verified by Western blotting of liver tissue from PCOS mice.</div></div><div><h3>Results</h3><div>PCOS mice had obvious liver metabolic dysfunction, inflammation, and fibrosis, all of which could be reversed by JQGW. Network pharmacology functional enrichment revealed that the overlapping targeted genes were enriched mainly in insulin resistance-related pathways and androgen-related pathways. We verified related proteins and found that JQGW improved liver fibrosis and inflammation in PCOS mice mainly by regulating the Akt2-FoxO1 and YAP/TAZ signaling pathways.</div></div><div><h3>Conclusion</h3><div>JQGW can improve liver metabolic function in a letrozole-induced PCOS mouse model by inhibiting liver fibrosis and inflammation, and it acts mechanistically by regulating the Akt2-FoxO1 and YAP/TAZ signaling pathways. Our findings thus provide a valuable reference for the advancement of therapeutic strategies aimed at addressing PCOS patients with abnormal liver metabolism.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"Article 156294"},"PeriodicalIF":6.7,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142756889","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":"Isobicyclogermacrenal ameliorates hippocampal ferroptosis involvement in neurochemical disruptions and neuroinflammation induced by sleep deprivation in rats.","authors":"Ao Yan, Zhejin Li, Yuanwei Gao, Fanglong Hu, Shuo Han, Fengjie Liu, Zhongcheng Liu, Jinting Chen, Chunmao Yuan, Chengyan Zhou","doi":"10.1016/j.phymed.2024.156306","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156306","url":null,"abstract":"<p><strong>Background: </strong>Sleep deprivation (SLD) is a widespread condition that disrupts physiological functions and may increase mortality risk. Valeriana officinalis, a traditional medicinal herb known for its sedative and hypnotic properties, contains isobicyclogermacrenal (IG), a newly isolated active compound. However, research on the therapeutic potential of IG for treating SLD remains limited.</p><p><strong>Methods: </strong>In this study, IG was extracted and characterized from Valeriana officinalis, and an SLD model was established in rats using p-chlorophenylalanine (PCPA). Behavioral tests and pathological studies were conducted to assess the effects of IG on SLD, and transcriptomic and metabolomic analyses were utilized to investigate its underlying mechanisms.</p><p><strong>Results: </strong>IG administration significantly improved the cognitive performance of SLD rats in behavioral tests and ameliorated histological injuries in the hippocampus and cerebral cortex. IG treatment increased the levels of brain-derived neurotrophic factor (BDNF) and neurotransmitters such as serotonin (5-HT) in SLD rats. Additionally, IG directly targets TFRC, thereby improving iron metabolism in the hippocampus. Comprehensive transcriptomic and metabolomic analyses revealed that the improvements from IG stemmed from the mitigation of abnormalities in iron metabolism, cholesterol metabolism, and glutathione metabolism, leading to reduced oxidative stress, ferroptosis, and neuroinflammation in the hippocampus caused by SLD.</p><p><strong>Conclusions: </strong>Collectively, these findings suggest that IG has the potential to ameliorate neurological damage and cognitive impairment caused by SLD, offering a novel strategy for protection against the adverse effects of SLD.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"156306"},"PeriodicalIF":6.7,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794979","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":"Study on the anti-Parkinson's disease activity mechanism and preparation of panaxadiol.","authors":"Lei Xu, Zhongjin Zhang, Ziqi Feng, Sixiang Niu, Lixia Yang, Baoguo Xiao, Xiao-Ming Jin, Cungen Ma, Huijie Fan, Shengnan Xiao, Zhi Chai","doi":"10.1016/j.phymed.2024.156296","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156296","url":null,"abstract":"<p><strong>Background: </strong>Traditional Chinese medicine offers unique and valuable resources for the exploration of novel approaches to disease treatment. Panaxadiol, an active compound derived from the transformation of ginsenosides. It has a variety of pharmacological activities. However, there is a lack of research regarding its effects on Parkinson's disease (PD).</p><p><strong>Purpose and study design: </strong>This study investigates the activity and mechanism of panaxadiol in the treatment of PD both in vivo and in vitro. In addition, a new method has been developed to extract panaxadiol.</p><p><strong>Results: </strong>The results showed that in vitro, panaxadiol can reduce the viability and cytotoxicity of BV2 cells induced by LPS, and inhibit the production of pro-inflammatory factors through the TLR4/MyD88/NF-κB pathway. In vivo, panaxadiol can improve motor and intestinal dysfunction in PD mice and repair the loss of DA neurons. Further studies have shown that panaxadiol treatment alleviates damage to the blood-brain barrier (BBB), inhibits neuroinflammation in the substantia nigra (SN), and further reduces damage to DA neurons. Subsequently, it was found that panaxadiol alleviated peripheral inflammation and significantly restored the intestinal microbial community. Further mechanistic studies found that panaxadiol treatment inhibited the TLR4/MyD88/NF-κB signaling pathway and its downstream pro-inflammatory products in the SN. In addition, Additionally, the response surface method was employed to identify the optimal conditions for extracting panaxadiol using a deep eutectic solvent (NADES).</p><p><strong>Conclusion: </strong>In summary, this study has found for the first time that panaxadiol can effectively improve the symptoms of PD by regulating neuroinflammation, repairing the BBB, and gut microbiota. Meanwhile, adopting a green extraction process significantly increases the content of panaxadiol, providing a new direction for the development of PD candidate drugs.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"156296"},"PeriodicalIF":6.7,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780784","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":"Qingfei Yin alleviates Streptococcus pneumoniae pneumonia by promoting complete autophagy to suppress necroptosis.","authors":"Tong Tian, Zhilong Xue, Xiaozhou Sun, Lizhong Ding, Renshuang Zhao, Zhongtian Wang, Jiaqi Wu, Xiao Li, Yiquan Li, Liping Sun","doi":"10.1016/j.phymed.2024.156280","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156280","url":null,"abstract":"<p><strong>Background: </strong>Bacterial pneumonia is most prevalent among all pneumonia types, with Streptococcus pneumoniae being the main pathogen. Qingfei Yin (QFY) is a traditional Chinese medicine formula used in the clinical treatment of bacterial pneumonia. Previous studies have confirmed the multi-target and -effect characteristics of QFY in treating S. pneumoniae pneumonia.</p><p><strong>Purpose: </strong>The purpose of this study was to explore the mechanism underlying QFY in treating pneumonia produced by S. pneumoniae.</p><p><strong>Methods: </strong>First, an in vivo model of S. pneumoniae-induced pneumonia was established in mice and evaluated the efficacy of QFY by hematoxylin-eosin (HE) staining and measuring cytokine levels in bronchoalveolar lavage fluid. Next, single-cell transcriptomics was used to identify the targeted cell subtypes, signaling pathways, and biological processes affected by QFY. Finally, the findings were validated using a pneumolysin (PLY) -induced mouse lung epithelial cells (TC-1) model in vitro using western blot analysis, immunofluorescence (IF), acridine orange (AO) staining, and propidium iodide (PI) staining.</p><p><strong>Results: </strong>QFY was shown to alleviate lung inflammation and reduce the TNF-α and IL-6 levels in bronchoalveolar lavage fluid in vivo. A total of 113,353 cells were classified using single-cell transcriptomics and 12 major cell types were identified. By single-cell transcriptomics, QFY was confirmed to primarily target lung epithelial cells. Differentially expressed genes were shown to be enriched in autophagy and necroptosis signaling pathways, and the key differentially expressed gene, Sequestosome 1 (p62/SQSTM1), was identified. PLY was shown to induce RIPK1-dependent necroptosis and incomplete autophagy in TC-1 cells. QFY was shown to promote complete autophagy by downregulating the expression of p62, thereby reducing phosphorylation of RIPK1 and MLKL, and alleviating necroptosis in S. pneumoniae-induced lung epithelial cell death.</p><p><strong>Conclusion: </strong>This study demonstrated that QFY can effectively alleviate S. pneumoniae pneumonia. The mechanism of action may be that QFY promotes complete autophagy by downregulating p62 expression, thereby alleviating necroptosis of S. pneumoniae-induced lung epithelial cells and reducing lung injury. It provides a scientific basis for clinical prevention and treatment of S. pneumoniae pneumonia.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"156280"},"PeriodicalIF":6.7,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786422","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":"Kechuan Decoction mitigates apoptosis of airway epithelial cells by improving lipid metabolism disorders and mitochondria dysfunction in HDM-induced asthma.","authors":"Binshu Zhao, Chen Shi, Xuan Wang, Zhengpeng Sun, Yuyuan Ruan, Xi Wang, Zhitong Zhang, Tong Xie, Jinjun Shan, Jin Wang, Guiying Qian","doi":"10.1016/j.phymed.2024.156299","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156299","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The airway epithelium serves as the first line of defense between the lung's internal environment and the external environment, functioning through physical barriers and mucus-ciliary clearance to protect against external allergens and other harmful substances. Airway epithelial damage is a common feature of asthma, and research has shown that apoptosis plays a significant role in airway injury and inflammation in asthma. Although Kechuan Decoction (KCD) has demonstrated clinical efficacy in treating pediatric asthma, its precise mechanism of action remains unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To elucidate the therapeutic mechanism of KCD in mitigating apoptosis of airway epithelial cells (AECs) in a house dust mite (HDM)-induced asthma mouse model.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;To evaluate the effects of KCD on asthma-associated airway inflammation and AECs apoptosis, an asthma model was established in C57BL/6 J mice using HDM. The major chemical constituents of KCD were analyzed using LC-MS. Subsequently, we utilized network pharmacology approaches to predict the potential targets and mechanisms of KCD in asthma. Additionally, we conducted lipidomics analysis of lung tissue and mitochondria in the lung was conducted using LC-MS. Finally, the mechanisms underlying the effects of KCD on AECs apoptosis in asthmatic mice were investigated through Western blotting, qPCR, and Transmission electron microscopy (TEM) examination techniques.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The efficacy of KCD has been shown to improve lung function, reduce airway inflammation, and prevent apoptosis of AECs in a HDM-induced asthma model. Through the use of UPLC-LTQ-Orbitrap-MS, we identified 24 potential active components of KCD. Network pharmacology analysis revealed that KCD shares 102 core targets with asthma. GO enrichment analysis, in conjunction with a literature review, indicated that the targets of KCD treatment for AECs apoptosis primarily focus on the mitochondrial membrane. Furthermore, lipidomics analysis of lung tissue and mitochondria in the lungs of mice with HDM-induced asthma revealed disruptions in lipid metabolism, with a decrease in phosphatidylcholine (PC) content in asthmatic mice, which was effectively restored by KCD treatment. KCD reinstates the expression of START domain-containing protein 7 (StarD7) and START domain-containing protein 10 (StarD10) in lung tissue, leading to increase in PC within the mitochondrial membrane. This regulation indirectly influences mitochondrial fusion and fission proteins, promoting mitochondrial membrane stability and reducing cytochrome c (Cyt c) release into the cytoplasm. Ultimately, this process helps mitigate mitochondria-mediated apoptosis of AECs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;KCD can restore the content of PC in the mitochondria of AECs by regulating StarD7 and StarD10. It also restores proteins associated with mitochondrial fusion and fission, stabilizing mitoch","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"156299"},"PeriodicalIF":6.7,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822562","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":"Sarsasapogenin stimulates angiogenesis and osteogenesis coupling to treat estrogen deficiency-induced osteoporosis by activating the GPX4/SLIT3/ROBO1 axis.","authors":"Fang Wang, Fanxuan Zhang, Bingfeng Lin, Wenlong Xiao, Xuchen Wang, Nani Wang","doi":"10.1016/j.phymed.2024.156297","DOIUrl":"https://doi.org/10.1016/j.phymed.2024.156297","url":null,"abstract":"<p><strong>Background: </strong>Promoting the coupling of osteogenesis and angiogenesis is a crucial strategy for the treatment of postmenopausal osteoporosis (PMOP). Estrogen deficiency induces ferroptosis, which is closely associated with the pathophysiology of PMOP. Sarsasapogenin (SAR) is a natural sapogenin with anti-oxidative effects. However, it is unclear whether SAR has a protective role against the impaired osteogenesis and angiogenesis coupling in PMOP. In this study, we evaluated the efficacy of SAR in estrogen deficiency-induced osteoporosis and explored the underlying mechanisms.</p><p><strong>Methods: </strong>Bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) were utilized to assess the in vitro effects of SAR on the coupling of osteogenesis and angiogenesis. In vivo experiments involved bilateral ovariectomy (OVX)-induced osteoporosis in mice and glutathione peroxidase 4 (GPX4)-knockout (KO) mice. Mice were orally administered SAR (5 or 10 mg/kg/d) for a duration of 12 weeks. The direct target of SAR was investigated through molecular docking, a cellular thermal shift assay, and surface plasmon resonance. Additionally, RNA sequencing was employed to elucidate the underlying mechanisms.</p><p><strong>Results: </strong>SAR treatment improved cell viability and osteogenic differentiation while inhibiting ferroptosis in iron dextran-induced BMSCs. Furthermore, SAR enhanced the production of slit guidance ligand 3 (SLIT3) in these cells, which stimulated angiogenesis by activating its receptor, roundabout human homolog 1 (ROBO1), in HUVECs. An in vitro model of ferroptosis induced by erastin demonstrated that SAR promoted the coupling of osteogenesis and angiogenesis by upregulating the BMSCs-SLIT3/HUVECs-ROBO1 axis. Activation of GPX4 was identified as a contributing factor to the effects of SAR on this coupling. Transfection of GPX4 small interfering RNA (siRNA) in BMSCs negated the impact of SAR on the BMSCs-SLIT3/HUVECs-ROBO1 axis. Additionally, SAR was found to directly interact with GPX4, enhancing protein stability, with an equilibrium dissociation constant of 44.6 μM. Notably, SAR did not increase SLIT3, ROBO1, or indicators of osteogenesis or angiogenesis in GPX4-KO mice.</p><p><strong>Conclusions: </strong>These findings underscore the significance of restoring the GPX4/SLIT3/ROBO1 axis in promoting the coupling of angiogenesis and osteogenesis. SAR mitigates PMOP, in part, by activating the BMSCs-SLIT3/HUVECs-ROBO1 axis, with GPX4 serving as an upstream signaling modulator responsible for SLIT3 production. Our observations provide experimental evidence supporting the clinical application of SAR in the treatment of PMOP.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"156297"},"PeriodicalIF":6.7,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786426","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":"Exploring the mechanism of Taohong Siwu Decoction in treating ischemic stroke injury via the circDnajc1/miR-27a-5p/C1qc signaling axis","authors":"Yumeng Li ,&nbsp;Qingping Ye ,&nbsp;Jingjing Li ,&nbsp;Lijuan Zhang ,&nbsp;Chao Yu ,&nbsp;Sujun Xue ,&nbsp;Shuangping Li ,&nbsp;Xianchun Duan ,&nbsp;Daiyin Peng","doi":"10.1016/j.phymed.2024.156305","DOIUrl":"10.1016/j.phymed.2024.156305","url":null,"abstract":"<div><h3>Background</h3><div>Ischemic stroke (IS) is the most prevalent type of cerebrovascular disease. Taohong Siwu Decoction (THSWD) has been demonstrated to have neuroprotective benefits during Cerebral Ischemia-Reperfusion Injury (CIRI). Whether THSWD mitigates CIRI by modulating the circDnajc1/miR-27a-5p/C1qc signaling axis is not known.</div></div><div><h3>Objective</h3><div>Examine how THSWD provides neuroprotective benefits in reducing the damage wrought by IS.</div></div><div><h3>Methods</h3><div>We employed middle cerebral artery occlusion/reperfusion (MCAO/R) rat model and oxygen glucose deprivation/re-oxygenation (OGD/R) in <em>vitro</em> model. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blot (WB), and immunofluorescence analyses (IF) were utilized to detect microglial activation markers TMEM119, CD11b, and Iba1, inflammatory mediators CCL2, CCL6, IL1, IL6, IL10, and TNF-α, as well as circDnajc1, miR-27a-5p, C1qc, C3, and C5aR.</div></div><div><h3>Conclusion</h3><div>Our data suggest that THSWD can mitigate inflammatory response, inhibit microglial activation and neuron apoptosis, and exert neuroprotective effects by regulating the circDnajc1/miR-27a-5p/C1qc signaling axis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"136 ","pages":"Article 156305"},"PeriodicalIF":6.7,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759135","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}