Chinese Medicine
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2024
·Vol. 19
·期 1
·1-16
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IF 5.3
Rao Chang,Hu Ruixue,Hu Yongxin,Jiang Yan,Zou Xu,Tang Huilan,Chen Xing,He Xiaoli,Hu Guang
Background Salvia miltiorrhiza (Danshen, DS) and Radix Paeoniae Rubra (Chishao, CS) herbal pair (DS-CS) is a famous traditional Chinese combination which has been used as antithrombotic formular for centuries. However, there is still lack of sufficient scientific evidence to illustrate its underlying mechanisms. The purpose of this study is to investigate the antithrombotic effects of DS-CS extract in zebrafish and explore its possible mechanism of action. Methods The quality of traditional Chinese medicines DS and CS granules was evaluated using High Performance Liquid Chromatography (HPLC). Subsequently, the therapeutic effect of the DS-CS combination and its components, Salvianolic Acid A (SAA) and Paeoniflorin (PF), in various concentrations on thrombosis was experimentally validated. Moreover, the interaction between DS-CS and the thrombosis disease targets was analyzed through network pharmacology, predicting the potential antithrombotic mechanism of DS-CS. Molecular docking and in vivo zebrafish experiments were conducted to validate the predicted targets, with qRT-PCR utilized for target validation. Results DS-CS exhibited anti-thrombotic effect in zebrafish with concentrations ranging from 25 to 300 μg/mL. The co-administration of PF and SAA at 25 μg/mL each revealed a synergistic antithrombotic effect exceeding that of individual components when contrasted with PHZ treatment. Protein–protein interaction (PPI) analysis identified key genes, including Albumin (ALB), Proto-oncogene tyro-sine-protein kinase Src (SRC), Matrix metalloproteinase-9 (MMP9), Caspase-3 (CASP3), Epidermal growth factor receptor (EGFR), Fibroblast growth factor 2 (FGF2), Vascular endothelial growth factor receptor 2 (KDR), Matrix metalloprotein-ase-2(MMP2), Thrombin (F2), and Coagulation factor Xa (F10), associated with the antithrombotic action of PF and SAA. Furthermore, KEGG pathway analysis indicated involvement of lipid metabolism and atherosclerosis pathways. Molecular docking revealed strong binding of PF and SAA to pivotal hub genes, such as SRC, EGFR, and F10. The experimental findings demonstrated that DS-CS could upregulate the mRNA expression levels of EGFR while inhibiting F10 and SRC mRNA levels, thereby ameliorating thrombotic conditions. Conclusion This research provided valuable insights into the potential mechanisms underlying the antithrombotic activity of DS-CS. Our findings suggested that PF and SAA could be the key active ingredients responsible for this activity. The antithrombotic effects of DS-CS appeared to be mediated through the regulation of mRNA expression of SRC, EGFR, and F10. These results enhanced our understanding of DS-CS's therapeutic potential and lay the groundwork for future studies to further elucidate its mechanisms of action.
研究领域:
药理学
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分子生物学
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中医药
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网络药理学
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斑马鱼模型
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产品关联
DOI
PubMed
高影响因子
Frontiers in Cellular and Infection Microbiology
·
2021
·
IF 5.293
Liu Yali,Zhou Mingyue,Yang Ming,Jin Chen,Song Yonggui,Chen Jingbin,Gao Meng,Ai Zhifu,Su Dan
Pulsatilla chinensis (Bunge) Regel is a commonly used Chinese medicine for clearing away heat and detoxification, cooling blood, stopping dysentery, and anti-inflammatory effects. Pulsatilla chinensis saponins (PRS) have been identified to be responsible for producing these pharmacological activities. Studies have shown that Pulsatilla decoction has a good therapeutic effect on ulcerative colitis (UC), however, the therapeutic effect of PRS on UC has not been reported. Therefore, the purpose of this study was to investigate the possible anti-UC activity of PRS using a dextran sulfate sodium (DSS)-induced rat model, and further study the mechanism of PRS in the treatment of UC. The fecal and colon samples were collected from rats to monitor the changes in the composition and diversity of the intestinal flora, and pathological colon sections were also made to examine the mesenteric hemorheological characteristics. The results showed that PRS significantly reduced the mesenteric blood flow in UC rats and significantly alleviated the inflammatory response, which indicates that saponins are involved in the anti-UC effects of PRS. At the same time, it is also suggested that the regulation of intestinal flora by Pulsatilla chinensis saponins is an important pathway for its anti-UC activity, which may be ascribed to the increase in beneficial bacteria like norank_F_Muribaculaceae and norank_F_norank_O_Clostridia_UCG-014, and decrease in the harmful Bacteroides.
研究领域:
药理学
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微生物学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2017
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IF 2.981
Zhongcheng Ke,Gang Wang,Lei Yang,Huihui Qiu,Hao Wu,Mei Du,Juan Chen,Jie Song,Xiaobin Jia,Liang Feng
Ethnopharmacological relevance Radix paeoniae rubra , also known as chishao (CS), is a frequently used traditional Chinese medicine that can promote blood circulation to remove blood stasis . It has been widely used for the prevention and treatment of cardiovascular diseases in China. Although terpene glycoside (TG), the major component in CS, has been shown to possess cardioprotective properties, the mechanism underlying CS-TG's preventive effect against myocardial ischemia injury is unknown. This study was conducted to explore the protective and curative effects of CS-TG against isoproterenol (ISO)-induced myocardial ischemic injury in rats and investigate the underlying myocardial protective mechanisms. Materials and methods A rat model of ISO-induced myocardial ischemia was established to evaluate the protective effect of CS-TG in ameliorating heart injury. Myocardial ischemia was induced by administering ISO (40 mg/kg/d) subcutaneously for 2 days. Serum was collected and analyzed for the levels of different cardiac biomarkers, and heart tissues were isolated and prepared for ATP analysis, glycogen content determination, histopathology assay, and ultrastructure observation. The regulatory effects of CS-TG on myocardial apoptosis in rats were studied by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and the levels of cleaved caspase-3, Bax, and Bcl-2 were detected by western blotting . Furthermore, in vitro experiments were conducted to examine whether the CS-TG's cardioprotective effects were linked to the inhibition of apoptosis via activation of the phosphoinositide-3-kinase/serine-threonine kinase AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. Results CS-TG (300 mg/kg/d) significantly decreased serum levels of creatine kinase and lactate dehydrogenase in ISO-induced myocardial ischemic rats. Analysis of ATP and glycogen contents, myocardial ultrastructure, and pathological examination showed that CS-TG (300 mg/kg/d) significantly improved energy metabolism and alleviated myocardial injury in vivo. In addition, the expression of p-AKT and p-mTOR in rats subjected to CS-TG significantly elevated, while the levels of caspase-3 and Bax/Bcl-2 dramatically reduced. Moreover, treatment with LY294002 , a PI3K inhibitor, abrogated CS-TG (200 μg/mL) induced down-regulation of cleaved caspase-3, Bax/Bcl-2 in the serum. Conclusions CS-TG protects the heart from ISO-induced myocardial ischemia, potentially by improving cardiac energy metabolism and inhibiting cardiomyocyte apoptosis via activation of the PI3K/AKT/mTOR signaling pathway. Thus, CS -TG might be a potential therapeutic candidate for the prevention and treatment of myocardial ischemia.
研究领域:
药理学
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心脏病学
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中医
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Nutrients
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2024
·Vol. 16
·期 24
·4409
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IF 4.8
Tingyu Wen,Guang Xin,Qilong Zhou,Tao Wang,Xiuxian Yu,Yanceng Li,Shiyi Li,Ying Zhang,Kun Zhang,Ting Liu,Beiwei Zhu,Wen Huang
Background: Radix Paeoniae Rubra (RPR), an edible and medicinal Traditional Chinese Medicine (TCM), is extensively employed in therapeutic interventions of cardiovascular and cerebrovascular diseases. However, the curative effect of RPR on ischemic stroke remains ambiguous. This work integrated network pharmacology, molecular docking, and experimental validation to explore the mechanisms of RPR in treating ischemic stroke. Methods: In this study, we preliminarily elucidated the therapeutic effect and mechanism of RPR on ischemic stroke through network pharmacology, molecular docking analysis, and experimental verification. Results: The results indicated that RPR improved the neurological deficit scores, decreased the size of infarcts, and reduced brain edema symptoms in the tMCAO mice model. Furthermore, through network pharmacology and molecular docking, four core targets (MAPK3, TNF-α, MAPK14, and JNK) closely related to RPR’s treatment of ischemic stroke were identified, exhibiting strong affinity with two key active components of RPR: albiflorin (AF) and β-sitosterol (BSS). The Western blot showed the potential mechanism of RPR treatment for ischemic stroke by regulating the MAPK signaling pathway. Moreover, RPR and its main active ingredients exhibited a significant inhibitory effect on platelets. Conclusion: In conclusion, this study revealed that RPR alleviates ischemic injury by activating the MAPK signaling pathway, and its protective effect may partly stem from inhibiting platelet activation. This work may provide a scientific basis for the development and utilization of RPR as a natural edible material to prevent ischemic stroke and anti-platelet therapy.
研究领域:
药理学
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神经科学
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分子生物学
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传统中药学
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产品关联
DOI
PubMed
高影响因子
ELECTROPHORESIS
·
2015
·Vol. 36
·期 19
·2433-2441
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IF 3.028
Chunye Liu,Xuejiao Zhang,Hui Jing,Yanqing Miao,Lingzhi Zhao,Yan Han,Cuixia Cui
Oriented covalent immobilized β 2 -adrenergic receptor (β 2 -AR) CE (OIRCE) was developed to determine the interactions between a set of natural extracts of Radix Paeoniae Rubra (NERPR) and β 2 -AR, and to predict the activity of NERPR. The inner capillary surface is chemically bonded with stable β 2 -AR coating via microwave-assisted technical synthesis. The modified capillaries were characterized via infrared spectroscopy and fluorescence microscopy. Furthermore, the bonding amounts of β 2 -AR were first obtained via fluorescence spectroscopy method. In determining the amount of bonded β 2 -AR, the regression equation A = 576 707C + 35.449 and the correlation coefficient 0.9995 were obtained. This result revealed an excellent linear relationship in the range of 2 × 10 −4 mg/mL to 1 × 10 −3 mg/mL. The normalized capacity factor ( K RCE ) was obtained using OIRCE in evaluating drug–receptor interactions. Related theories and equations were used to calculate K RCE values from apparent migration times of a solute and EOF. The order of K RCE and the binding constant ( K b ) values between drugs and β 2 -AR was well consistent. The results confirmed that the OIRCE and K RCE values can be effectually used to investigate drug-receptor interactions, and OIRCE has the potential to predict drug activity and to select leading compounds from natural chemicals.
研究领域:
药学
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分析化学
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药物发现
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产品关联
DOI
PubMed
高影响因子
CURRENT MICROBIOLOGY
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2025
·Vol. 82
·期 10
·1-12
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IF 2.6
Chen Chaoheng,Huang Yilan,Liao Yanke,Lan Sugui,Liang Zining,Yuan Jing,Tan Qiang
This study aimed to investigate the underlying mechanism of action and further identify main active ingredient by which Radix Paeoniae Rubra extracts (RPRE) inhibited the cross-resistance to tetracycline (TET), piperacillin (PIP), and gentamicin (GEN) mediated by Rhizoma Coptidis extracts (RCE) in Staphylococcus aureus (SA). Treatment with mixed solutions of RCE and RPRE resulted in disappearance of TET, PIP, or GEN resistance compared to what was shown with RCE treatment alone. Fifteen relevant resistant genes ( smrB , bmr3 , nhoA , BTN44_15030 , clpL , hisG , norA , fmtA_1 , emrB_1 , BTN44_07590 , paiA , icaR , BTN44_13995 , HMPREF0776_1664 and vraG ) were significantly downregulated compared to the RCE-induced mutants. RPRE was sequentially fractionated using macroporous resin and silica gel column chromatography, and all resulting eluates exhibited the antibacterial activity against Staphylococcus ATCC 25923. When exposed to RCE combined with either 30% EE or DCM:MeOH(5:1) eluates, no significant cross-resistance to the tested antibiotics was observed in the induced isolates. Similarly, the expression levels of the fifteen resistant genes were markedly reduced. Furthermore, gallic acid (GA) was identified in the two aforementioned eluates using HPLC–MS. After selection with a mixed solution of RCE and GA, the induced strains displayed no cross-resistance to the tested antibiotics, and the expression of the resistant genes was significantly decreased. These results suggest that GA is a key active ingredient in RPRE responsible for suppressing RCE-mediated cross-resistance to TET, PIP, and GEN in SA.
研究领域:
药理学
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微生物学
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分子生物学
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植物学
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抗菌药物耐药性
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产品关联
DOI
PubMed
高影响因子
ULTRASONICS SONOCHEMISTRY
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2022
·
IF 9.336
Yu Zhao,Haofang Wan,Jiehong Yang,Yan Huang,Yu He,Haitong Wan,Chang Li
Natural deep eutectic solvent (NaDES) is widely applied in the extraction of nutrients from natural resources as a greener alternative for fossil solvent. In the present work, 27 different NaDESs were screened for the extraction of paeoniflorin (PF) and galloyl paeoniflorin (GPF) from Radix Paeoniae Rubra (RPR). After screening and extraction parameter optimization, the extraction yields of PF and GPF reached up to 182.8 mg/g and 77.4 mg/g with the selected NaDES, ChCl-Sor. Furthermore, the antioxidant activity in vitro and neuroprotectivity in vivo of the ‘ready-to-use’ extracts were evaluated comprehensively. Especially in vivo , the cerebral ischemic/ reperfusion injury model was established in rats and the protective effects of the RPR extracts were determined. The results not only proved that NaDES is a valuable green extraction media, but also indicated the safety and potential pharmaceutical application of NaDES based ‘ready-to-use’ extracts from medical plants.
研究领域:
药理学
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神经科学
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绿色化学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）