摘要：
Traumatic brain injury (TBI) has become a leading cause of mortality, morbidity and disability worldwide. Hydroxysafflor yellow A (HSYA) is effective in treating TBI, but the potential mechanisms require further exploration. We aimed to reveal the mechanisms of HSYA against acute TBI by an integrated strategy combining metabolomics with network pharmacology. A controlled cortical impact (CCI) rat model was established, and neurological functions were evaluated. Metabolomics of brain tissues was used to identify differential metabolites, and the metabolic pathways were enriched by MetaboAnalyst. Then, network pharmacology was applied to dig out the potential targets against TBI induced by HSYA. The integrated network of metabolomics and network pharmacology was constructed based on Cytoscape. Finally, the obtained key targets were verified by molecular docking. HSYA alleviated the neurological deficits of TBI. Fifteen potentially significant metabolites were found to be involved in the therapeutic effects of HSYA against acute TBI. Most of these metabolites were regulated to recover after HSYA treatment. We found 10 hub genes according to network pharmacology, which was partly consistent with the metabolomics findings. Further integrated analysis focused on 4 key targets, including NOS1, ACHE, PTGS2 and XDH, as well as their related core metabolites and pathways. Molecular docking showed high affinities between key targets and HSYA. Region-specific metabolic alterations in the cortex and hippocampus were illuminated. This study reveals the complicated mechanisms of HSYA against acute TBI. Our work provides a novel paradigm to identify the potential mechanisms of pharmacological effects derived from a natural compound. (C) 2021 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.
摘要：
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Ginsenoside CK (GCK) serves as the potential anti-colorectal cancer (CRC) protopanaxadiol (PPD)-type saponin, which could be mainly bio-converted to yield PPD by gut microbiota. Meanwhile, the anti-CRC effects of GCK could be altered by gut microbiota due to their different diversity in CRC patients. We aimed to investigate the bioconversion variation of GCK mediated by gut microbiota from CRC patients by comparing with healthy subjects.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Gut microbiota profiled by 16S rRNA gene sequencing were collected from healthy volunteers and CRC patients. GCK was incubated with gut microbiota in vitro. A LC-MS/MS method was validated to quantify GCK and PPD after incubation at different time points.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The bioconversion of GCK in healthy subjects group was much faster than CRC group, as well as the yield of PPD. Moreover, significant differences of PPD concentration between healthy subjects group and CRC group could be observed at 12h, 48h and 72h check points. According to 16S rRNA sequencing, the profiles of gut microbiota derived from healthy volunteers and CRC patients significantly varied, in which 12 differentially abundant taxon were found, such as<jats:italic>Bifidobacterium</jats:italic>,<jats:italic>Roseburia</jats:italic>,<jats:italic>Bacteroides</jats:italic>and<jats:italic>Collinsella</jats:italic>. Spearman’s correlation analysis showed bacteria enriched in healthy subjects group were positively associated with the biotransformation of GCK, while bacteria enriched in CRC group displayed non correlation character. Among them,<jats:italic>Roseburia</jats:italic>which could secrete<jats:italic>β</jats:italic>-glycosidase showed the strongest positive association with the bioconversion of GCK.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The bioconversion of GCK in healthy subjects was much faster than CRC patients mediated by gut microbiota, which might alter the anti-CRC effects of GCK.</jats:p></jats:sec>
期刊：
Frontiers in Neuroscience,2020年14:532068 ISSN：1662-4548
通讯作者：
Wang, Y;Zhang, W;Ding, CS
作者机构：
[Zhou, Yan-Tao; Zheng, Fei] Hunan Univ, Coll Elect & Informat Engn, Changsha, Peoples R China.;[Luo, Jie-Kun; Hu, En; Wang, Yang; Tang, Tao; Li, Teng; Li, Peng-Fei] Cent South Univ, Inst Integrated Tradit Chinese & Western Med, Xiangya Hosp, Lab Ethnopharmacol, Changsha, Peoples R China.;[Zhang, Wei] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha, Peoples R China.;[Ding, Chang-Song] Hunan Univ Chinese Med, Sch Informat, Changsha, Peoples R China.
通讯机构：
[Zhang, W ; Ding, CS ] H;[Wang, Y ] C;Cent South Univ, Inst Integrated Tradit Chinese & Western Med, Xiangya Hosp, Lab Ethnopharmacol, Changsha, Peoples R China.;Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha, Peoples R China.;Hunan Univ Chinese Med, Sch Informat, Changsha, Peoples R China.
关键词：
Traumatic Brain Injury;Hippocampus and cortex;Metabolomics;LC-MS/MS;Subacute phase
摘要：
本文分析了脑缺血再灌注炎症反应的发生机制,提出了中西医结合防治思路。脑缺血再灌注后,发生一系列级联反应,大量相关炎症因子释放后引发细胞炎症反应,使神经元发生不可逆死亡。最新研究表明,微小RNA（miRNA）与环状RNA（circRNA）关系密切,有望成为脑缺血再灌注治疗新靶点和依据。并通过GeneCards数据库,收集抗脑缺血再灌注炎症反应的作用靶点,运用Srting数据库及Cytoscape软件构建靶点PPI网络。采用DAVID数据库并结合Cytoscape软件对共同靶点进行基因组百科全书（Kyoto Encyclopedia of Genes and Genomes,KEGG）富集分析得到可视化通路富集图,运用Origin软件绘制热图。由于脑缺血再灌注炎症反应发生机制复杂,目前无法通过有效准确的方法进行治疗。中医药防治脑缺血再灌注损伤炎症反应具有一定优势,本文运用阴阳学说理论分析中医病因病机,提出在防治该病的过程中,不仅要对其病因病机进一步探索,更要进一步结合病理生理及现代科学技术发挥中医药的特色与优势,实现中西医结合精准治疗。
期刊：
Evidence-Based Complementary and Alternative Medicine,2020年2020:1-12 ISSN：1741-427X
通讯作者：
Wang, Y
作者机构：
[Wang, Yang; Luo, Jiekun; Yang, Zhaoyu; Zheng, Piao; Wang, Y; Cui, Hanjin; Tang, Tao] Cent South Univ, Xiangya Hosp, Dept Integrated Tradit Chinese & Western Med, Inst Integrat Med, Changsha 410008, Hunan, Peoples R China.;[Tian, Xuefei; Zheng, Piao; Zhang, Wei] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;[Zhou, Jing] Shanxi Prov Hosp Tradit Chinese Med, Shanxi Prov Inst Tradit Chinese Med, Taiyuan 030012, Shanxi, Peoples R China.;[Zheng, Jun] Cent South Univ, Coll Chem & Chem Engn, Changsha 410083, Hunan, Peoples R China.
通讯机构：
[Wang, Y ] C;Cent South Univ, Xiangya Hosp, Dept Integrated Tradit Chinese & Western Med, Inst Integrat Med, Changsha 410008, Hunan, Peoples R China.
摘要：
<jats:p>As a bioactive absorbed compound of rhubarb, Rhein is applied for the treatment of brain injury. However, the underlying pharmacological mechanisms remain unclear. In this study, we aimed to explore antineuroinflammatory functions and underlying mechanisms of Rhein in vitro. BV2 microglia cells were chosen and irritated by LPS. The influence of Rhein on cell viability was determined using MTT assay. We finely gauged the proinflammatory cytokines of TNF-<jats:italic>α</jats:italic> and IL-1<jats:italic>β</jats:italic> through tests of immunofluorescence staining, ELISA, RT-qPCR, and western blot. Additionally, mediators including IL-6, IL-12, iNOS, and IL-10 were surveyed by ELISA. Furthermore, protein levels of the underlying signaling pathways (PI3K/Akt, p38, ERK1/2, and TLR4/NF-<jats:italic>κ</jats:italic>B) were tested adopting western blot. We found that Rhein reduced the secretion of pivotal indicators including TNF-<jats:italic>α</jats:italic> and IL-1<jats:italic>β</jats:italic>, effectively restraining their mRNA and protein expression in LPS-activated BV2 microglial cells. Besides, Rhein treatment demoted the production of IL-6, IL-12, and iNOS and promoted the excretion of IL-10. Subsequent mechanistic experiments revealed that Rhein obviously downregulated the phosphorylation levels of PI3K, Akt, p38, and ERK1/2 and simultaneously upregulated the PTEN expression. In addition, Rhein antagonized the increase of TLR4, p-I<jats:italic>κ</jats:italic>B<jats:italic>α</jats:italic>, and NF-<jats:italic>κ</jats:italic>B. In summary, Rhein suppresses neuroinflammation via multiple signaling pathways (PI3K/Akt, p38, ERK1/2, and TLR4/NF-<jats:italic>κ</jats:italic>B) in LPS-stimulated BV2 microglia cells. This study highlights a natural agent for prevention and treatment of neuroinflammation.</jats:p>
摘要：
Gut microbiota dysbiosis is a risk factor for colorectal cancer (CRC) in inflammatory bowel disease (IBD). In this study, the effects of Panax notoginseng saponins (PNS) on colitis-associated CRC progression were evaluated on an azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model. In vivo, PNS significantly relieved AOM/DSS-induced colon tumorigenesis and development by reducing the disease activity index (DAI) scores and colon tumor load. The 16S rRNA data of fecal samples showed that the microbiome community was obviously destructed, while PNS could recover the richness and diversity of gut microbiota. Especially, PNS could increase the abundance of Akkermansia spp. which was significantly decreased in model group and negatively correlated with the progression of CRC. Moreover, ginsenoside compound K (GC-K) was evaluated on the effects of human CRC cells, which was the main bio-transformed metabolite of PNS by gut microbiota. Our data showed that PNS played important role in the prevention of the progression of CRC, due to their regulation on the microbiome balance and microbial bio-converted product with anti-CRC activity.
摘要：
AIMS: Altered activities of long noncoding RNAs (lncRNAs) have been associated with cancer development, and lncRNA FOXD1-AS1 (FOXD1-AS1) is the antisense transcript of the gene encoding for FOXD1, known for its role as an oncogene in several tumor types including glioma. However, the role of FOXD1-AS1 in the differentiation and progression of glioma is not well known. METHODS: Expression profile chip and qPCR were used to screen and identify FOXD1-AS1. Glioma cells were transfected with siRNA or eukaryotic expression vector to observe FOXD1-AS1 function in vitro and in vivo. Dual luciferase reporter gene analysis, Western blot, and ChIRP-MS were used to detect microRNAs and protein that combine with FOXD1-AS1. RESULTS: FOXD1-AS1 was upregulated and directly correlated with the glioma grade, and it was localized in both the nucleus and the cytoplasm of the glioma cell. FOXD1-AS1 silencing caused tumor suppressive effects via inhibiting cell proliferation, migration, and apoptosis, while FOXD1-AS1 overexpression resulted in opposite effects. Additionally, in vivo experiments showed that FOXD1-AS1 knockdown reduced tumor volume and weight. More importantly, mechanical studies revealed that FOXD1-AS1 targeted both miR339-5p and miR342-3p (miR339/342). Furthermore, protein eukaryotic translation initiation factor 5 subunit A (eIF5a) resulted a direct target of FOXD1-AS1. CONCLUSIONS: These data indicated that FOXD1-AS1, a miR339/342 target, affected biological processes via protein eIF5a; thus, it might be considered as a new therapeutic target for glioblastoma.
摘要：
Panax notoginseng saponins (PNS) are the major components of Panax notoginseng, with multiple pharmacological activities but poor oral bioavailability. PNS could be metabolized by gut microbiota in vitro, while the exact role of gut microbiota of PNS metabolism in vivo remains poorly understood. In this study, pseudo germ-free rat models were constructed by using broad-spectrum antibiotics to validate the gut microbiota-mediated transformation of PNS in vivo. Moreover, a high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was developed for quantitative analysis of four metabolites of PNS, including ginsenoside F1 (GF1), ginsenoside Rh2 (GRh2), ginsenoside compound K (GCK) and protopanaxatriol (PPT). The results showed that the four metabolites could be detected in the control rat plasma, while they could not be determined in pseudo germ-free rat plasma. The results implied that PNS could not be biotransformed effectively when gut microbiota was disrupted. In conclusion, gut microbiota plays an important role in biotransformation of PNS into metabolites in vivo.
摘要：
<jats:p>Although the compatibility of Astragali Radix (AR) and Angelicae Sinensis Radix (ASR) has favorable effect on promoting hematopoiesis in traditional Chinese medicine (TCM), the main active components and pharmacological mechanism are unknown. We investigated the five active components and its mechanisms <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo</jats:italic>. Five active components of Astragalus glycosides (AST), Formononetin (FRM), Ferulic acid (FRA), Calycosin (CAL), and Calycosin-7-glucoside (CLG), which could be absorbed in intestinal tract, were detected in this study. The peripheral blood, hematopoietic growth factors (HGFs), and hematopoietic progenitor cells (HPCs) colony were observed to evaluate the effect of these five active components promoting hematopoiesis. Furthermore, hematopoietic stem cell (HSC) proliferation, aging, cycle, and related proteins were detected to explore the mechanism of these five components promoting HSC proliferation. <jats:bold>i)</jats:bold> The <jats:italic>in vivo</jats:italic> experiments showed that the combination of the five active components could remarkably increase the number of RBCs, WBCs, PLTs, and content of Hb in peripheral blood and the area of bone marrow hematopoietic tissue, as well as thrombopoietin (TPO), erythropoietin (EPO), granulocyte-macrophage colony stimulating factor (GM-CSF), and colony of CFU-GM, CFU-MK, CFU-E, and BFU-E in serum. Each of these five components promoted the recovery of RBCs and Hb, and increased TPO, CFU-MK, and CFU-E. All components except for AST increased the CFU-GM. FRA increased the number of WBCs, the area of bone marrow hematopoietic tissue, and BFU-E. FRA and AST promoted PLT recovery. FRA and CAL improved the content of GM-CSF. FRA, CAL, and CLG improved the content of EPO. <jats:bold>ii)</jats:bold> The <jats:italic>in vitro</jats:italic> experiments showed that FRA, FRM, and AST significantly promoted cell proliferation, reduced the positive rate and G0/G1 cells, and increased G2/M + S cells and the expression of cyclin D1 and CDK4 proteins in aging HSCs. Furthermore, the combination of five components had the best effect. Taken together, the five active components of AST, FRM, FRA, CAL, and CLG were the main pharmacodynamic substances of the AR-ASR compatibility, which promoted hematopoiesis. The combination of them had a synergistic effect. The mechanism of promoting hematopoiesis may be relevant to regulating cyclin-related proteins, promoting cell cycle transformation, and promoting HSC proliferation.</jats:p>
