JOURNAL OF ETHNOPHARMACOLOGY
·
2021
·
IF 4.36
Zi-Dong Qiu,Xiaoping Zhang,Xu-Ya Wei,Konstantin Chingin,Jia-Quan Xu,Wei Gao,Bin Yang,Shuang-Long Wang,Ting Tan,E-Hu Liu,Hai-Yu Xu,Guang-Hong Cui,Juan Guo,Ya-Nan Wang,Ye Shen,Yu-Jun Zhao,Huan-Wen Chen,Chang-Jiang-Sheng Lai,Lu-Qi Huang
Ethnopharmacological relevance Aconitum carmichaelii Debeaux, a famous traditional medicinal herb for collapse, rheumatic fever , and painful joints, always raises global concerns about its fatal toxicity from toxic alkaloids when improperly processed. Therefore, it is urgent to clarify the internal molecular mechanism of processing detoxification on Aconitum and develop simple and reliable approaches for clinical application, which is also of great significance to the rational medicinal use of Aconitum . Aim of the study The study aimed at developing a complete molecular mechanism exploration strategy in complex medicinal herb decocting system, clarifying the internal molecular mechanism of processing detoxification on Aconitum, and exploring valid approaches for detoxification. Materials and methods Aconiti Lateralis Radix Praeparata (Fuzi) was selected as the model for exploring the complex Aconitum detoxification mechanism using an advanced online real-time platform based on extractive electrospray ionization mass spectrometry. The methods realized the sensitive capture of dynamic trace intermediates, accurate qualitative and quantitative analysis, and real-time and long-term monitoring of multi-components with satisfactory accuracy and resistance to complex matrices. Results Components in the complex Aconitum decocting system were real-timely characterized and fat meat was discovered and verified to directionally detoxify Aconitum while reserving the therapy effect. More importantly, the dynamic detoxification mechanism in the chemically complex Aconitum decoction was molecularly profiled. A novel reaction pathway based on nucleophilic substitution reaction mechanism was proposed. As confirmed by the theoretic calculations at DFT B3LYP/6-31G (d) levels, fatty acids ( e.g. , palmitic acid) acted as a green, cheap, and high-performance catalyst and promote the decomposition of toxic diester alkaloids to non-toxic and active benzoyl-monoester alkaloids through the discovered mechanism. Conclusion The study exposed a novel detoxification molecular mechanism of Aconitum and provided an effective method for the safe use of Aconitum , which could effectively guide the development of traditional processing technology and compatibility regulation of the toxic herb and had great value to the modernization and standardization development of traditional medicine.
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高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Ze Li,Jing Yuan,Yue Dai,Yufeng Xia
Ethnopharmacological relevance For centuries, Shaoyao-Gancao-Fuzi decoction (SGFD) has been a reliable traditional Chinese medicine for treating rheumatoid arthritis (RA). Despite its long history of use, the specific active components and underlying mechanisms of its therapeutic effects have yet to be fully understood. Aim of the study The aim of this study was to investigate the active ingredients and therapeutic effects of SGFD on RA, and to further understand its underlying mechanism. Materials and methods The chemical constituents in SGFD extract and in rat serum after oral administration of SGFD were identified and evaluated using ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry (UPLC-Q-TOF/MS) together with various data-processing methods, respectively. The efficacy of SGFD was assessed by using an adjuvant-induced arthritis (AIA) rat model and lipopolysaccharide-stimulated RAW 264.7 cell. Subsequently, cell metabolomic was conducted to clarify the potential biomarkers and pathways. ELISA, RT-qPCR, and WB were used to verify the anti-arthritis mechanism of SGFD. Results A total of 65 chemical constituents were identified in SGFD. 17 active components were distinguished in rat serum samples, of which 13 may be the main active ingredients for SGFD treatment of RA. The remarkable efficacy of SGFD in reducing the symptoms of RA is evident through its ability to alleviate the redness and swelling of the affected paws, as well as reduce the infiltration of inflammatory cells. Cell experiments revealed that rat serum of SGFD reduced IL-1 β , IL-6, and TNF- α secretion in RAW 264.7 cells. 27 potential biomarkers were identified through cell metabolomics analysis. The arachidonic acid (AA) metabolism signaling pathway was activated in RA, which could be reversed by rat serum of SGFD. SGFD effectively inhibited the expression and transformation of AA by downregulating the expression of key enzymes, including phospholipase A and cyclooxygenase. Conclusion SGFD may ameliorate RA symptoms by regulating the AA-PGH 2 -PGE 2 /PGF 2α pathway. The main active components include songorine, fuziline, neoline, albiflorin, paeoniflorin, liquiritin, benzoylmesaconine, isoformononetin, liquiritigenin, isoliquiritigenin, formononetin, glycyrrhizic acid, and glycyrrhetinic acid.
研究领域:
药理学
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民族药理学
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代谢组学
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中医
·
风湿病学
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高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Xiang Bin,Geng Ruiman,Zhang Zhengkun,Ji Xuxu,Zou Jiaqiong,Chen Lihong,Liu Ji
Background: Yiyi Fuzi Baijiang powder (YFBP) is a traditional Chinese medicine used to treat colorectal cancer, although its bioactivity and mechanisms of action have not been studied in depth yet. The study intended to identify the potential targets and signaling pathways affected by YFBP during the treatment of colorectal cancer through pharmacological network analysis and to further analyze its chemical compositions and molecular mechanisms of action.Methods: The Traditional Chinese Medicine Systems Pharmacology (TCMSP), Traditional Chinese Medicine Integrated Database (TCMID), HitPredict (HIT), and Search Tool for Interactions of Chemicals (STITCH) databases were used to screen the bioactive components and promising targets of YFBP. Targets related to colorectal cancer were retrieved from the GeneCards and Gene Ontology databases. Cytoscape software was used to construct the “herb–active ingredient–target” network. The STRING database was used to construct and analyze protein–protein interactions (PPIs). Afterward, the R packages clusterProfiler and Cytoscape Hub plug-in were used to perform Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of target genes. The results of the network pharmacological analysis were also experimentally validated.Results: In total, 33 active components and 128 target genes were screened. Among them, 46 target genes were considered potential therapeutic targets that crossed the CRC target genes. The network pharmacology analysis showed that the active components of YFBP were correlated positively with CRC inflammatory target genes such as TLR4, TNF, and IL-6. The inflammation-related signaling pathways affected by the active components included the TNF-α, interleukin-17, and toll-like receptor signaling pathways. The active ingredients of YFBP, such as luteolin, β-sitosterol, myristic acid, and vanillin, may exert anti-tumor effects by downregulating SMOX expression via anti-inflammatory signaling and regulation of the TLR4/NF-κB signaling pathway.Conclusion: In the present study, the potential active components, potential targets, and key biological pathways involved in the YFBP treatment of CRC were determined, providing a theoretical foundation for further anti-tumor research.
研究领域:
药理学
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肿瘤学
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中医药
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生物信息学
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高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2023
·
IF 3.4
Taixiang Gao,Hongxiong Zhang,Qinqing Li,Feng Zhao,Nan Wang,Wenbin He,Junlong Zhang,Rui Wang
Fuzi decoction (FZD) is clinically used to treat chronic heart failure (CHF) in China, but the mechanism underlying FZD treatment in CHF remains unclear. Here, we investigated the potential mechanism underlying FZD treatment of CHF in rats. First, the compounds in FZD-containing serum of rats were identified, and 16 S rRNA sequencing and GC–MS-based untargeted metabolomics analysis were then performed. The levels of fecal short-chain fatty acids (SCFAs) were determined and compared, and fecal microbiota transplantation (FMT) was used to verify the role of the gut microbiota . Our results identified 27 in FD-containing serum. FZD increased the Firmicutes -to- Bacteroidetes ratio and the Lactobacillus abundance and affected the β diversity of the gut microbiota in rats with CHF. Differential species analysis showed that Lactobacillus and Prevotella were biomarkers of FZD treatment of CHF. Untargeted metabolomics analysis revealed that FZD affected valine , leucine and isoleucine biosynthesis; galactose metabolism; and aminoacyl-tRNA biosynthesis in rats with CHF. Furthermore, FZD significantly increased the acetic acid, propionic acid , butyric acid and isopentanoic acid levels in the feces of rats with CHF. Correlation analysis showed that the butyric acid and Lactobacillus levels had the strongest correlation in the control, sham and high-dose FZD (HFZD) groups, and many microbiota components were closely related to differentially abundant metabolites. FMT revealed that the fecal microbiota obtained from the HFZD group changed the heart rate; the brain natriuretic peptide (BNP), acetic acid, propionic acid, butyric acid, and metabolite levels; and the gut microbiota in rats with CHF. In summary, our study revealed that the mechanism of action of FZD in CHF treatment may be related to improvements in the gut microbiota, elevations in the SCFA content and the regulation of valine, leucine, and isoleucine biosynthesis; galactose metabolism; and other metabolic pathways.
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高影响因子
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
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2024
·Vol. 27
·期 5
·773-785
·
IF 1.6
Liu Kejia,Yang Xu,Zhang Guihong,Xiang Zheng
Background: Fuzi-Gancao herb couple is one of the most common herb couples involved in the TCM formula, which was used for the treatment of chronic diseases. The herb couple has a hepatoprotective effect. However, its main components and therapeutic mechanism are not yet clear. This
study aims to elucidate the therapeutic effect and mechanism of the Fuzi-Gancao herb couple on NAFLD from animal experiments, network pharmacology, and molecular docking. Methods: 60 Male C57BL/6 mice (20 g ± 2 g) were randomly divided into six groups including the blank group
(n=10) and NALFD group (n=50). The mice of the NALFD group were fed with a high-fat diet for 20 weeks to establish the NAFLD model and the NALFD mice were randomly divided into five groups including positive group (berberine), model group and F-G groups with three dosages (0.257, 0.514, 0.771
g/kg) (n=10). After 10 weeks of administration, the serum was collected for the analysis of ALT, AST, LDL-c, HDL-c, and TC, and liver tissues were collected for pathological analysis. The TCMAS database was used to collect the main components and targets of the Fuzi-Gancao herb couple. The
GeneCards database was used to collect NAFLD-related targets, and the key targets were obtained by intersecting with herbal targets. The diseasecomponent- target relationship diagram was constructed by Cytoscape 3.9.1. The obtained key targets were imported into the String database to obtain
the PPI network, and imported into the DAVID database for KEGG pathway analysis and GO analysis. Finally, the key targets and key gene proteins were imported into Discovery Studio 2019 for molecular docking verification. Results: In this study, H-E staining indicated the pathological
changes of liver tissue in Fuzi- Gancao groups were significantly improved, and the levels of AST, ALT, TC, HDL-c, and LDL-c in serum of Fuzi-Gancao groups decreased in a dose-dependent manner, compared with the model group. 103 active components and 299 targets in the Fuzi-Gancao herb couple
were confirmed in the TCMSP database and 2062 disease targets in NAFLD were obtained. 142 key targets and 167 signal pathways were screened, such as the AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, IL-17 signaling pathway, TNF signaling pathway, and so on.
The main bioactive ingredients of Fuzi-Gancao herb couple in the treatment of NAFLD are quercetin, kaempferol, naringenin, inermine, (R)-norcoclaurine, isorhamnetin, ignavine, 2,7-Dideacetyl-2,7- dibenzoyl-taxayunnanine F, glycyrol mainly involving IL6, AKT1, TNF, TP53, IL1B, VEGFA and other
core targets. Molecular docking analysis indicated that there is a good affinity between the key components and the key targets. Conclusion: This study preliminarily explained the main components and mechanism of the Fuzi- Gancao herb couple in the treatment of NAFLD and provided an idea
for subsequent research.
研究领域:
中药学
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肝脏疾病
·
生物信息学
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PHYTOMEDICINE
·
2022
·
IF 6.656
Zi-Dong Qiu,Xu-Ya Wei,Ze-Yan Chen,Juan Guo,Lu-Qi Huang,Chang-Jiang-Sheng Lai
Background The synergic action of compound prescriptions is an important feature and core advantage of traditional medicine. Ginseng-Fuzi decoction is a classic compatible phytomedicine in China, of which Ginseng can effectively reduce the toxicity of Fuzi in clinical, but the detoxification chemical mechanism is still unclear. Purpose Develop a novel method for real-time tracking and monitoring of complex substances in the decoction system of traditional Chinese medicine to uncover the detoxification effect Ginseng on Fuzi and explore the possible chemical reaction mechanism of Ginseng-Fuzi co-decoction. Methods A novel real-time monitoring system, online filtration electrospray ionization mass spectrometry, was developed for extremely complex substances analysis in the decoction of traditional medicine compounds to uncover the directionally detoxification effect and the mechanism of compatibility interaction. Results Nine key alkaloids and 7 ginsenosides in Ginseng-Fuzi decoction were simultaneously in-situ monitoring in positive ion mode or negative ion mode respectively. Both types of targeted analytes had satisfactory MS signal response for real-time qualitative and quantitative analysis with high precision (RSD < 14.04%) and low LLODs (0.002 ng/ml-10 ng/ml). Through long-term tracking analysis, the exact detoxification and synergistic effect of Ginseng-Fuzi decoction were confirmed as the concentration of main toxic alkaloids decreased ( e.g. the content of mesaconitine has been reduced by about 38%) and the main active monoester alkaloids increased obviously. More importantly, the possible molecular mechanism of the detoxification effect of Ginseng compatibility was revealed for the first time, which was the nucleophilic substitution reaction of diester alkaloids catalyzed by fatty acids. Conclusion This study revealed the exact effect of co-decoction of Ginseng and Fuzi at the molecular level and the chemical reaction mechanism of fatty acid-catalyzed degradation of toxic diester-type alkaloids. The comprehensive multi-component real-time monitoring strategy for complex traditional medicine compounds developed and implemented here has important demonstration significance for revealing the scientific connotation of the compatibility of compound traditional medicine.
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高影响因子
Analytical Methods
·
2016
·Vol. 8
·期 35
·6566-6572
·
IF 1.915
Xiaozhong Wang,Xuwen Li,Lanjie Li,Min Li,Qian Wu,Ying Liu,Jie Yang,Yongri Jin
A green and effective extraction system based on the use of an ultrasound-assisted ionic liquid aqueous two-phase system (IL-ATPS) was developed for the determination of aconitum alkaloids in lateral roots of Aconitum carmichaeli Debx (Fuzi in Chinese). IL-ATPS parameters, including the type and amount of ionic liquid, amount of salts, and pH value, as well as extraction time, were investigated. Under the optimized conditions, the recoveries of the analytes varied from 80.37 to 107.18%. The detection limits and quantification limits for the analytes were achieved within the ranges of 0.048–0.082 μg g−1 and 0.16–0.30 μg g−1, respectively. After extraction, the recovery of ionic liquids without the use of organic solvents was also confirmed. The hydrophilic ionic liquids (1-hexyl-3-methylimidazolium bromide) were converted into hydrophobic ionic liquids (1-hexyl-3-methylimidazolium hexafluorophosphate) by a metathesis reaction, and in situ liquid–liquid microextraction was triggered simultaneously. Finally, 0.1 mol L−1 HCl aqueous solution (containing 5% Tween-20) was used as the back-extraction agent to recover the ionic liquids.
研究领域:
中药学
·
分析化学
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高影响因子
危险品化学品经营许可证（带存储）