Role of jianxin granules in heart failure: evidence from network pharmacology, molecular docking and experimental verification.

BACKGROUND: Jianxin (JX) granules is a traditional Chinese medicine widely used in the treatment of heart failure (HF), but the mechanism is unclear. This study aimed to investigate the mechanism of JX granules in the treatment of HF based on network pharmacology analysis and in-vivo experiments. METHODS: A series of network pharmacology methods was employed to ascertain potential targets and critical pathways implicated in the therapeutic action of JX granules against HF. Subsequently, molecular docking was utilized to investigate the binding affinity of key active constituents within JX granules to these targets. In-vivo experiments, echocardiography, hematoxylin and eosin, Masson's trichrome assay, and western blot analysis were conducted to validate the efficacy and mechanism of JX granules in treating rats with HF. RESULTS: A total of 122 active components, 896 drug targets, 1216 HF-related targets, and 136 targets pertinent to drug-disease interactions were identified. 151 key targets and 725 core clusters were detected through protein-protein interaction network analysis. Among these, interleukin 6 (IL-6), vascular endothelial growth factor a (VEGFA), and serine/threonine kinase 1 (AKT1) were core hub genes. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis revealed the critical pathways, including epidermal growth factor receptor (EGFR), advanced glycation end products (AGEs) and their receptors (RAGE) pathway, along with hypoxia-inducible factor 1 (HIF-1) signaling pathway. Molecular docking studies demonstrated high binding affinities between key targets and the pivotal active ingredients of Danshenol A, salvianolic acid B, and arachidonic acid. Furthermore, animal studies corroborated that JX granules improve cardiac function and reduce myocardial fibrosis, potentially by modulating the expression of IL-6, VEGFA, and p-AKT1. CONCLUSIONS: The bioactive components within JX granules, such as Danshenol A, salvianolic acid B, and arachidonic acid may exert therapeutic effects on HF through modulation of IL-6, VEGFA, and AKT1 gene expression. This study provides a scientific basis for subsequent clinical application of JX granules and an in-depth investigation of their mechanisms of action.

Mechanistic study of the anti-excitatory amino acid toxicity of Bushen Zhichan decoction for Parkinson's disease based on the transcriptional regulation of EAAT1 by YY1.

ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Zhichan decoction (BSZCF) is derived from Liuwei Dihuang Pill, a famous Chinese herbal formula recorded in the book Key to Therapeutics of Children's Diseases. It has been widely used as a basic prescription for nourishing and tonifying the liver and kidneys to treat Parkinson's disease (PD), but its mechanism remains to be explored. AIM OF THE STUDY: BSZCF, a Chinese herbal formula comprising five herbs: Rehmannia glutinosa (Gaertn.) DC., Dioscorea oppositifolia L., Cornus officinalis Siebold & Zucc., Fallopia multiflora (Thunb.) Haraldson and Cistanche tubulosa (Schenk) Wight, is used clinically to treat PD. In vivo and in vitro experiments were designed to elucidate the mechanism of BSZCF in the protection of dopamine (DA) neurons and the treatment of PD. The toxicity of excitatory amino acids (EAA) may be attenuated by inhibiting the transcription factor Yin Yang 1 (YY1) and up-regulating the expression of excitatory amino acid transporter 1 (EAAT1). MATERIALS AND METHODS: IN VIVO: After 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was intraperitoneally injected into specific pathogen free (SPF) C57BL/6J mice, model mice were intragastrically given adamantane hydrochloride tablets (AHT) or different doses of BSZCF for 14 days. Both open field and pole-climbing tests were conducted to assess behavioral changes. In vitro: 1-Methyl-4-phe-nylpyridiniumiodide (MPP+)-injured human neuroblastoma cells (SH-SY5Y) were utilized to construct PD cell models. Primary astrocytes were transfected with EAAT1 and YY1 lentiviruses for EAAT1 gene knockout and YY1 gene knockout astrocytes, respectively. The high performance liquid chromatography-mass spectrometry (HPLC-MS) analysis of BSZCF was performed to control the quality of blood drugs. The optimal concentration and time of PD cell models treated by BSZCF were determined by the use of Cell Counting Kit-8 (CCK8). Enzyme-linked immunosorbent assay (ELISA) was used for measuring glutamate (Glu) in the peripheral blood and cells of each group. Western blotting (WB) and real-time quantitative polymerase chain reaction (qPCR) were used to detect tyrosine hydroxylase (TH), dopamine transporters (DAT), EAAT1 and YY1 protein and mRNA. After the blockade of EAAT1, immunofluorescence (IF) assay was used to detect the TH protein in each group. RESULTS: In vivo research showed that BSZCF improved the behavioral symptoms of PD mice, and reduced the death of DA neurons and the level of Glu. The mechanism may be related to the decrease of YY1 expression and the increase of EAAT1 levels. In vitro experiments showed that the anti-excitatory amino acid toxicity of BSZCF was achieved by inhibiting YY1 expression and regulating EAAT1. CONCLUSIONS: By inhibiting YY1 to increase the expression of EAAT1 and attenuating the toxicity of Glu, BSZCF exerts the effect of protecting DA neurons and treating PD-like symptoms in mice.

Design and Implementation of a Chain-Type Direct Push Drilling Rig for Contaminated Sites.

For sites where volatile organic compounds are present, the direct push method, in combination with other sensors for investigation, is a powerful method. The investigation process is an integrated drilling and sensing process, but the trajectory of the probe carrying the sensor is ambiguous. This paper explores and introduces the application of a chain-type direct push drilling rig by designing and building a chain-type direct push miniature drilling rig. This rig allows for indoor experimental studies of direct push trajectories. The chain-type direct push drilling model is proposed based on the mechanism of chain transmission. The drilling rig provides a steady direct thrust through the chain, which is driven by a hydraulic motor. In addition, the drilling tests and results described prove that the chain could be applied to direct push drilling. The chain-type direct push drilling rig can drill to a depth of 1940 mm in single-pass and up to 20,000 mm in multiple passes. The test results also indicate that it drills a total length of 462.461 mm and stops after 87.545 s of operation. The machine can provide a drilling angle of 0-90° and keep the borehole angle fluctuating within 0.6° with the characteristics of strong adjustability, flexibility, continuity, stability, and low disturbance, which is of great value and significance for studying the drilling trajectory of direct push tools and obtaining more accurate investigation data.

Prospective randomized controlled trial study of Luofengning granule in the treatment of unstable angina.

INTRODUCTION: Although the current western treatment plans for unstable angina (UA) has been optimized in past decades, UA still is a common phenotype of acute coronary syndrome and significantly influence the quality of life and endanger lives. In China, the clinical application of Chinese herb medicine is considered as an effective approach to treating UA and widely recognized by patients. In clinical practices, we found Luofengning granule (LFN-G) could improve clinical manifestations of patients with UA, but there is lack of rigorous proof of evidence-based medicine. This trial aims to further evaluate the efficacy of LFN-G in the treatment of UA. METHODS: A prospective, open-label, randomized, placebo-controlled clinical will be performed. A total of 60 patients diagnosed with UA will be randomly allocated to either the treatment group or the control group with a 1:1 ratio. The participants in the treatment group will receive LFN-G treatment and the participants in the control group will receive placebo. Meanwhile, both groups continue to undergo standard western medicine treatments. The duration of interventions is 4 weeks. The primary endpoint is the incidence of major cardiac adverse events, defined as a composite of recurrent angina, acute myocardial infarction (AMI), severe arrhythmia, heart failure, and cardiac death. Secondary outcomes include Seattle angina scale score, Chinese medicine syndromes and electrocardiograph (at weeks 0, 1, 2, 4), myocardial nuclides perfusion, measurement of wall motion score index and left ventricular ejection fraction, serum inflammation factors such as C-reactive protein, high sensitive-C-reactive protein, interleukin-6, matrix metalloproteinase-9, and so on (at weeks 0, 4). In addition, some biochemical indexes of blood and hematological indexes will be used to assess the safety of treatments. Any adverse effects of the treatment will be recorded. DISCUSSION: The results of this trial will provide compelling evidence of the efficacy and safety of LFN-G for treatment of UA and preliminarily reveal the potential mechanism of how LFN-G acts. Finally, it will widen treatment options for patients with UA.

[Characteristic spectrum and decoction process of classical prescription Qingwei San].

In this experiment, by determination of the HPLC characteristic spectrum of the classical prescription Qingwei San decoction, the contents of isoferulic acid, palmatine and paeonol in Qingwei San decoction and the extraction rate were investigated. The factors such as the crushing degree of decoction pieces, the amount of decocting water, the decocting time, the filter material and the decocting container involved in Qingwei San decoction process were examined to make a detailed comparison of Qingwei San's decoction processes during the development.HPLC characteristic spectrum method of Qingwei San was established, and then the decoction process parameters of Qingwei San were optimized, with the similarity of characteristic spectrum, the concentration of the index components and the extraction rate as indexes. The decoction process of Qingwei San was determined as follows: Qingwei San decoction pieces were weighed according to the prescription amount and pulverized into the most coarse powder; the powder was put in a ceramic pot, added with 225 mL water, heated to boiling, cooked for 50 minutes with gentle heat(100 W), and filtered with a layer of 300 mesh nylon cloth.The similarity of Qingwei San's characteristics pectrum of different decoction methods was all above 0.9, and the concentration of isoferulic acid, palmatine and paeonol in Qingwei San under determined decoction process was 40.74, 26.73, 65.73 µg·mL~(-1), respectively, with an extraction rate of 33.80%.The characteristic spectrum determined in this experiment can better express the information and index components of Qingwei San, and if combined with the extraction rate information, it can provide the general information, index component content and extraction information. The decoction process after detailed investigation can better reflect the quality of Qingwei San decoction, with easier control and operation. It can provide a basis for the subsequent research and development of Qingwei San decoction standard, and can also provide experimental basis and reference for the decoction process research of other classical prescriptions.

Two New Eudesmane Sesquiterpenoids from the Flowers of Chrysanthemum indicum.

The flowers of Chrysanthemum indicum, i.e. Ye-ju-hua recorded in the Chinese Pharmacopoeia, has been widely used in China as an important heat-clearing and detoxifying herb for the treatment of inflammation, headache, and vertigo. A phytochemical investigation of this herb has led to the isolation of two new eudesmane sesquiterpenoids, 7-epi-eudesm-4(15),11(13)-diene-1ß,3ß-diol (1) and 7-epi-1ß-hydroxy-ß-eudesmol (2). The molecular structures of these new sesquiterpenoids were established based on the comprehensive spectroscopic analyses, including NMR, MS, and IR, and comparing with the literatures.

[Analysis on quality value transmitting of substance benchmarks of Linggui Zhugan Decoction].

By preparing 10 batches of the material reference of Linggui Zhugan Decoction,the methodology of the characteristic spectrum of the material reference was created. The creaming rate range,the contents and the transfer rate range of cinnamaldehyde,glycyrrhizin and glycyrrhizic acid,the characteristic peaks and the similarity range of the characteristic spectrum of Linggui Zhugan Decoction were determined to clarify key quality attributes of the material reference of Linggui Zhugan Decoction. In the 10 batches of the material reference of Linggui Zhugan Decoction,the similarity of characteristic spectrum was higher than 0. 9. Furthermore,after summarizing the characteristic peak information,we knew that Fuling had two characteristic peaks,Guizhi had six characteristic peaks,Baizhu had two characteristic peaks and Gancao had 11 characteristic peaks. The average creaming rate of the material reference of the ten batches was( 12. 13 ± 0. 35) %. The average content of cinnamaldehyde was 0. 32%,the average transfer rate was 10. 69%,the content of cinnamaldehyde in the different batches was between 0. 22% and 0. 42%,and the transfer rate was between 7. 48% and13. 90%. The average content of glycyrrhizin was 0. 84%,the average transfer rate was 50. 39%,the content of glycyrrhizin in the different batches was between 0. 42% and 1. 26%,and the transfer rate was between 35. 27% and 65. 51%. The average content of glycyrrhizic was 1. 88%,the average transfer rate was 40. 74%,the content of glycyrrhizic in the different batches was between 0. 94% and2. 82%,and the transfer rate was between 28. 52% and 52. 96%. In this paper,the quality value transmitting of substance benchmarks of Linggui Zhugan Decoction was analyzed by the combination of characteristic spectrum,creaming rate and the content of index component. A scientific and stable method was preliminarily established,which provided scientific basis for the quality control and formulation development of Linggui Zhugan Decoction.

Sesquiterpenoids with Various Carbocyclic Skeletons from the Flowers of Chrysanthemum indicum.

A phytochemical investigation of the flowers of Chrysanthemum indicum yielded sesquiterpenoids 1-25 with various carbocyclic skeletons, including 10 new (1-10) and 15 known (11-25) analogues. The structures were elucidated via their physical data, while the absolute configuration of compounds 6, 8, and 10 was assessed via electronic circular dichroism analysis. The evaluation of the effect of sesquiterpenoids on porcine epidemic diarrhea virus (PEDV) replication showed that compounds 1-5, 12, 14, 16, 17, 19, and 21 increased cell viability against cell death in PEDV-injected cells. Compounds 2, 12, and 17 were selected and investigated for their inhibition of proteins required for PEDV replication. Compounds 2 and 17 significantly reduced PEDV nucleocapsid and spike protein synthesis compared with azauridin as a positive control.

Effect of Yang-activating and stasis-eliminating decoction from Traditional Chinese Medicine on intestinal mucosal permeability in rats with ulcerative colitis induced by dextran sulfate sodium.

OBJECTIVE: To evaluate the effect of decoction prepared with Yang-activating and stasis-eliminating medicinals from Traditional Chinese Medicine (TCM) on the intestinal mucosal permeability in rats with ulcerative colitis induced by dextran sulfate sodium (DSS). METHODS: Totally 55 male Wistar rats (body weight of 170-190 g) were randomly divided into the blank group (n = 10) and the model duplication group (n = 45). The blank group was not intervened, while the other was modeled with 5% dextran sulfate sodium by gavaging in a dosage of 4 mL per day to induce ulcerative colitis, a total of 7 days. Then, the model rats were divided into model blank group, mesalazine group and TCM group, and each group was consisted of 15 rats. They were given retention enema 10 min with normal saline, mesalazine enema (0.036 g/mL), and Yang-activating and stasis-eliminating decoction [0.54 g/mL of a decoction boiled by Puhuang (Pollen Typhae), Xiebai (Bulbus Allii Macrostemonis) and Wulingzhi (Faeces Trogopteri)] for 10 days respectively. Afterwards, all of the rats were evaluated by disease activity index (DAI), histological changes of distal colon, expression of occludin protein and ultrastructure of intestinal epithelial cells. Furthermore, ratio of lactulose to mannitol (L/M) discharged in urine was evaluated. RESULTS: Comparing the results between TCM and model control groups, scores of DAI and histological lesions decreased significantly (P = 0.000 < 0.01), ultrastructures of intestinal epithelial cells and tight junctions were more complete. The expression of occludin protein (P = 0.001 < 0.01) increased while the L/M value decreased significantly (P = 0.000 < 0.01) in TCM group. There was no statistical difference between the TCM and mesalazine groups in results of each item (P > 0.05). CONCLUSION: The decoction prepared with Yang-activating and stasis-eliminating TCM medicianls can restore intestinal mucosal epithelial cells and tight junctions the model rats with ulcerative colitis; it can reduce histological lesions and protect the permeability of intestinal mucosa barrier in the rats as well.

Chrysindins A-D, polyacetylenes from the flowers of Chrysanthemum indicum.

Four new polyacetylenes, namely chrysindins A-D, together with 6 known polyacetylenes, were isolated from the flowers of Chrysanthemum indicum. Their structures were established on the basis of comprehensive spectroscopic analyses. Chrysindins A and B bear a novel carbon skeleton.

Sesquiterpenoids from Inula britannica.

Phytochemical investigation of the flowers of Inula britannica led to the isolation of nineteen sesquiterpenoids (1- 19), including britanlins E-J ( 2, 3, 5, 8, 13, and 14, respectively) and known sesquiterpenoids (1, 4, 6, 7, 9- 12, and 15- 19). The structures of these isolates were elucidated by detailed spectroscopic analyses and comparison to the previously reported spectroscopic data. The absolute configurations of compounds 12, 15, 17, and 19 were determined by X-ray single crystal diffraction analyses and chemical transformations.

Limonoids and quinoline alkaloids from Dictamnus dasycarpus.

Phytochemical investigation on Dictamnus dasycarpus (Rutaceae) has led to the isolation of four new secondary metabolites (2, 6, 9, and 10) along with twelve known phytochemicals (1, 3- 5, 7, 8, 11-16). Compound 4 was isolated as a natural product for the first time. The structures of compounds 1-16 were elucidated by extensive spectroscopic analyses and comparison with previously reported spectroscopic data. The structures of 8 and 13 were further confirmed based on X-ray data analyses. The absolute configuration of compounds 8-12 were studied based on the CD spectra analyses.

Phytochemicals and biological activities of Gentiana species.

Gentiana, a cosmopolitan and important genus of the Gentianaceae family, comprises over 300 species distributed among the world. Phytochemical investigations on the title genus have led to characterization of almost two hundred secondary metabolites. Some of them have shown promising bioactivities. Herein, we have summarized the phytochemical and pharmacological progress of this genus. This review covers the period 1960-June, 2009.