Study on the potential allergen and mechanism of pseudo-allergic reactions induced by combined using of Reduning injection and penicillin G injection based on metabolomics and bioinformatics / 药学学报

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Potential components and mechanism of Liangxue Tuezi Mixture in treating Henoch-Schönlein purpura based on network pharmacology and metabolomics / 中国中药杂志

Ultra-performance liquid chromatography-quadrupole time of fight/mass spectrometry(UPLC-Q-TOF-MS) and UNIFI were employed to rapidly determine the content of the components in Liangxue Tuizi Mixture. The targets of the active components and Henoch-Schönlein purpura(HSP) were obtained from SwissTargetPrediction, Online Mendelian Inheritance in Man(OMIM), and GeneCards. A "component-target-disease" network and a protein-protein interaction(PPI) network were constructed. Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed for the targets by Omishare. The interactions between the potential active components and the core targets were verified by molecular docking. Furthermore, rats were randomly assigned into a normal group, a model group, and low-, medium-, and high-dose Liangxue Tuizi Mixture groups. Non-targeted metabolomics was employed to screen the differential metabolites in the serum, analyze possible metabolic pathways, and construct the "component-target-differential metabolite" network. A total of 45 components of Liangxue Tuizi Mixture were identified, and 145 potential targets for the treatment of HSP were predicted. The main signaling pathways enriched included resistance to epidermal growth factor receptor tyrosine kinase inhibitors, phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT), and T cell receptor. The results of molecular docking showed that the active components in Liangxue Tuizi Mixture had strong binding ability with the key target proteins. A total of 13 differential metabolites in the serum were screened out, which shared 27 common targets with active components. The progression of HSP was related to metabolic abnormalities of glycerophospholipid and sphingolipid. The results indicate that the components in Liangxue Tuizi Mixture mainly treats HSP by regulating inflammation and immunity, providing a scientific basis for rational drug use in clinical practice.

Study on the objectivity and biological mechanism of Psoralea corylifolia Linn.'s 'Great dryness damages the liver' / 药学学报

According to the theory of 'Xingben Dazao' of Psoralea corylifolia Linn. (BL), the susceptible syndromes and biomarkers of liver injury caused by BL were searched. Rat models of kidney-yin deficiency syndrome (M_yin) and kidney-yang deficiency syndrome (M_yang) were established, and all animal experimental operations and welfare following the provisions of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Traditional Chinese Medicine (No. YFYDW2020017). The results showed that BL significantly decreased the body weight, water intake, and urine weight of M_yin rats and increase the organ indexes of the liver, testis, adrenal gland, and spleen and the expression of alanine aminotransferase (ALT). Meantime, BL significantly increased the urine weight of M_yang rats and decreased the expression of ALT and aspartate aminotransferase (AST). Hematoxylin and eosin (HE) staining showed that BL could aggravate inflammatory infiltration of hepatocytes in rats with M_yin and alleviate liver injury in rats with M_yang. Metabolomics identified 17 BL co-regulated significant differential metabolic markers in M_yin and M_yang rats. Among them, 8 metabolites such as glutamine, quinolinate, biliverdin, and lactosylceramide showed opposite trends, mainly involving cysteine and methionine metabolism, tyrosine metabolism, tryptophan metabolism, purine metabolism, sphingolipid metabolism, glycerol phospholipid metabolism, glutamine metabolism, and other pathways. M_yin/M_yang may be the susceptible constitution of BL for liver damage or protection, which may be related to the regulation of amino acid metabolism and sphingolipid metabolism. The study can provide some experimental data support for the safe and accurate use of BL in the clinical practice of traditional Chinese medicine.

Comparison of distribution of eight components from Liangxue Tuizi Mixture between normal and Henoch-Schonlein purpura rats / 中国中药杂志

This study used UPLC-TQ-MS technology to replicate a Henoch-Schonlein purpura(HSP) model in rats by administering warm drugs by gavage and injecting ovalbumin with Freund's complete adjuvant emulsion. The distribution differences and characteristics of eight major components(ferulic acid, caffeic acid, neochlorogenic acid, cryptochlorogenic acid, benzoyl oxypaeoniflorin, tracheloside, loganin, and paeoniflorin) in rat liver, lung, heart, spleen, and kidney tissues were determined after oral administration of the Liangxue Tuizi Mixture at a dose of 42 g·kg~(-1) in both normal physiological and HSP states at 0.5, 1, 2, 6, and 12 hours. The results showed that the distribution patterns of the eight components of Liangxue Tuizi Mixture in the tissues of normal and HSP model rats were different. The main component, paeoniflorin, in Moutan Cortex and Paeoniae Radix Alba had higher content in all tissues. The eight components were predominantly distributed in the liver, lung, and kidney tissues, followed by spleen and heart tissues.

hiPSCs and organoids: prediction of arrhythmogenic risks for optimized traditional Chinese medicine / 中国中药杂志

Accurate assessment of the risks associated with traditional Chinese medicine(TCM), such as the potential to induce serious cardiovascular adverse reactions including cardiac arrhythmias, is crucial. This article introduced the pharmacological evaluation strategies for cardiac safety and the progress in cardiac organ research, with a focus on discussing the application prospects of human induced pluripotent stem cells(hiPSCs) and organoids in assessing the risks of TCM-induced cardiac arrhythmias. Compared with traditional animal models, hiPSCs and organoid models provide better reference and predictive capabilities, allowing for more accurate simulation of human cardiac responses. Researchers have successfully generated various cardiac tissue models that mimic the structure and function of the heart to evaluate the effects of TCM on the heart. The hiPSCs model, by reprogramming adult cells into pluripotent stem cells and differentiating them into cardiac cells, enables the generation of personalized cardiac tissue, which better reflects individual differences and drug responses. This provides guidance for the assessment of TCM cardiac toxicity risks. By combining organoid model with cardiac safety pharmacology strategies such as electrocardiogram monitoring and ion channel function assessment, the impact of TCM on the heart can be comprehensively evaluated. In addition, the application of the Comprehensive in Vitro Proarrhythmia Assay(CiPA) approach improves the accuracy of evaluation. Applying the CiPA approach to TCM research reveals potential risks and provides a scientific basis for the clinical application and industrial development of TCM. In conclusion, organoid model and cardiac safety pharmacology evaluation strategies provide important tools for assessing the cardiac toxicity risks of TCM. The combination of hiPSCs model, comprehensive assessment methods, and the CiPA strategy enables an accurate assessment of the risks of TCM-induced cardiac arrhythmias, thus providing a scientific basis for the safe use and international recognition of TCM in clinical practice. This contributes to ensuring the safety and efficacy of TCM and promoting its clinical application and global acceptance.

Serum metabolomics of chronic obstructive pulmonary disease with lung-Qi deficiency syndrome / 中国中药杂志

The present study analyzed the potential biomarkers of chronic obstructive pulmonary disease(COPD) with lung-Qi deficiency syndrome by non-targeted metabolomics and explored the biological basis of this syndrome. Blood samples of 96 COPD patients with lung-Qi deficiency syndrome(COPD with lung-Qi deficiency syndrome group) and 106 healthy people(healthy control group) were collected, and the metabolic profiles of both groups were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Multivariate statistical analysis and differential metabolite screening were carried out by using Progenesis QI and Simca-P. Metabolic pathways were constructed through the MetaboAnalyst. Seven potential biomarkers, such as L-cystathionine, protoporphyrinogen Ⅸ, and citalopram aldehyde, were identified. Compared with the results in the healthy control group, the content of citalopram aldehyde, N1-methyl-2-pyridone-5-carboxamide, and 11β,17β-dihydroxy-4-androsten-3-one was significantly up-regulated, while that of the other four compounds such as L-cystathionine, dihydrotestosterone, protoporphyrinogen Ⅸ, and D-urobilinogen was down-regulated. These potential biomarkers involved six metabolic pathways, including cysteine and methionine metabolism, porphyrin and chlorophyll metabolism, drug metabolism of cytochrome P450, steroid hormone biosynthesis, glycine, serine, and threonine metabolism, and nicotinate and nicotinamide meta-bolism. This study is expected to provide a certain scientific basis for the research on traditional Chinese medicine syndrome of COPD with lung-Qi deficiency syndrome from the molecular biology level.

Study on alleviating effect of Glycyrrhizae Radix et Rhizoma on Psoraleae Fructus-induced liver injury based on network pharmacology and cell experiments / 中国中药杂志

This study was designed to explore the alleviating effect and mechanism of Glycyrrhizae Radix et Rhizoma against Psora-leae Fructus-induced liver injury based on network pharmacology and cell experiments. The active components of Glycyrrhizae Radix et Rhizoma and Psoraleae Fructus were first retrieved from the Encyclopedia of Traditional Chinese Medicine(ETCM), Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Comparative Toxicogenomics Database(CTD), and literature and further screened by SwissADME. The obtained 25 potential toxic components of Psoraleae Fructus and 29 flavonoids in Glycyrrhizae Radix et Rhizoma were input into the SwissTargetPrediction for target predication. A total of 818 targets related to liver injury were screened out based on GeneCards and MalaCards, and 91 common targets of Psoraleae Fructus, Glycyrrhizae Radix et Rhizoma, and liver injury were obtained from Venny. STRING was applied for constructing the PPI network, and Metascape for analyzing the biological processes and signaling pathways that common targets participated in. Cytoscape was used to construct the component-target-disease network and component-target-pathway network for Glycyrrhizae Radix et Rhizoma against Psoraleae Fructus-induced liver injury. The predicted core targets were proto-oncogene tyrosine-protein kinase(SRC), phosphatidylinositol 4,5-bisphosphate 3-kinase subunit alpha(PIK3 CA), RAC-alpha serine/threonine-protein kinase(AKT1), etc, with PI3 K-AKT signaling pathway, MAPK signaling pathway, apoptosis, Toll-like receptor signaling pathway, and NF-κB signaling pathway mainly involved. Following the scree-ning of the main toxic and pharmacodynamic components, the pharmacodynamic effects were investigated by cell experiments. The results showed that licochalcone A was mainly responsible for alleviating coryfolin-induced liver injury, licochalcone B for coryfolin-and psoralidin-induced liver injury, and echinatin for corylifolinin-and bakuchiol-induced liver injury. The preliminary revealing of the alleviating effect of Glycyrrhizae Radix et Rhizoma on Psoraleae Fructus-induced liver injury and the prediction of related mechanisms will provide reference for further mechanism research and reasonable clinical compatibility.

Effect of Shaoyaotang on Inflammatory Cytokines and Intestinal Flora in Rats with Dampness-heat Diarrhea / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Shaoyaotang on diarrhea， inflammation， and intestinal flora in rats with dampness-heat diarrhea and explore the mechanism of therapeutic principle "treating incontinent syndrome with dredging method" of Shaoyaotang. MethodThe dampness-heat diarrhea model was induced by high temperature， high humidity， high sugar and fat diet， and pathogenic factors. The rats were divided into normal group， model group （normal saline）， Shaoyaotang group （5.62 g·kg-1）， Rhei Radix et Rhizoma （RRER）-free Shaoyaotang group （5.15 g·kg-1）， and RRER group （0.01 g·kg-1）. The rats were treated correspondingly for five days， twice a day in the morning and evening. The diarrhea index was used to evaluate the antidiarrheal effect of each group three hours after the administration in the evening. The levels of tumor necrosis factor （TNF）-α， interleukin （IL）-1β， IL-2， and IL-6 in the serum were detected by enzyme-linked immunosorbent assay （ELISA） three hours after the last administration. The structure of intestinal flora in feces was characterized by 16sDNA. ResultCompared with the model group， the Shaoyaotang group， the RRER-free Shaoyaotang group， and the RRER group showed reduced diarrhea index （P<0.01）， with the onset rates ranking as the Shaoyaotang group>the RRER-free Shaoyaotang group>the RRER group. Those three groups with drug intervention all showed decreased levels of inflammatory factors （P<0.01）， especially the Shaoyaotang group， and no significant difference was observed between the RRER group and the RRER-free Shaoyaotang group. The abundance of pathogenic bacteria and conditioned pathogens （e.g. Escherichia-Shigella， Prevotella， Enterorhabdus， and Bacteroides） was reduced and the proliferation of probiotics （such as Ruminococcus， Turicibacter， and Lachnospiraceae） was increased in the groups with drug intervention （P<0.01）. For the structure of intestinal flora， the RRER group and the Shaoyaotang group were close to the normal group， and the RRER-free Shaoyaotang group was different from the other three groups （P<0.01）. ConclusionShaoyaotang can improve the outcome of rats with dampness-heat diarrhea through anti-inflammation and regulation of intestinal flora disorders. RRER in the prescription plays a key role in reducing the abundance of harmful bacteria and promoting the proliferation of probiotics， which is the key of Shaoyaotang in promoting the re-balance of intestinal flora. It also confirms the scientificity of treating dampness-heat diarrhea with RRER following the therapeutic principle "treating incontinent syndrome with dredging method".

Antipyretic activity and potential mechanism of Indigo Naturalis on 2,4-dinitrophenol-induced fever rat model / 中国中药杂志

As an effective antipyretic medicine,Indigo Naturalis has a long history of application in the field of Chinese medicine.The content of organics,mainly indigo and indirubin,is about 10%. However,the active ingredients and mechanism of its antipyretic effect have not yet been fully elucidated. In view of this,they were investigated in this study with the rectal temperature change as an indicator and 2,4-dinitrophenol-induced fever rats as subjects. The content of PGE2 and c AMP in the hypothalamus and the serum levels of TNF-α,IL-1β and IL-6 were determined by ELISA. Moreover,the plasma samples of fever rats were analyzed by metabonomics in combination with UPLC-Q-TOF-MS for the exploration of potential biomarkers and the discussion on the antipyretic mechanism of Indigo Naturalis and its active ingredients. The results showed that the rising trend of rectal temperature in rats was suppressed 0. 5 h after the treatment with Indigo Naturalis,organic matter,indigo or indirubin as compared with the rats of model group( P < 0. 05),among which Indigo Naturalis and organic matter had better antipyretic effect. ELISA results showed that organic matter and indigo can inhibit the expression of PGE2 and c AMP( P<0. 01),while Indigo Naturalis and organic matter were effective in curbing the increase in TNF-α( P<0. 05). A total of 21 endogenous metabolites were identified from the plasma samples of the Indigo Naturalis,organic matter,indigo and indirubin groups,which were mainly involved in glycerophospholipid metabolism.

Study on effect of Schisandra Chinensis Fructus-Glycyrrhizae Radix Et Rhizoma containing serum on lipid accumulation in hepatocytes andits mechanism / 中国药理学通报

Aim To study the effect of drug-containing serum of Schisandra Chinensis Fructus and compatible with Glycyrrhizae Radix Et Rhizoma -on lipid accumulation in hepatocytes and explore the related mechanism. Methods SD rats were given Schisandra Chinensis Fructus (SF, 3.9 g • kg"1), Schisandrae Chinensis Fructus-Glycyrrhizae Radix Et Rhizoma (SG, 1 : 1, 1 '• 1. 5, the extract 3. 9 g • kg"1 in crud of Schisandrae Chinensis Fructus), once per day, the drug-containing serum was prepared after seven days of continuous administration. Conventional cultivation of human normal hepatocytes (L02 cells) in vitro, cells were divided into blank control group, SF group, and SG(1 : 1 and 1 : 1.5) group. After 48 hours' treatment , lactate dehydrogenase ( LDH) release was detected by the kit, the levels of intracellular triglyceride (TG) and total cholesterol (TC) were detected by biochemical method. The mRNA expression levels of PPAR-a, PPAR-7, Fabpl/2, SREBPlc, ACCa and FAS were detected by the real-time reverse tran scrip- tion polymerase chain reaction ( RT-PCR ). Results The biochemical results showed that compared with the blank group, the content of TG and TC in SF group increased significantly (P < 0. 05 ) , the mRNA expres sion of PPAR-a and PPAR-7 in SF group was significantly reduced, and the mRNA expression of SREBPlc and ACCa markedly increased ( P < 0.05, P < 0.01). When compared with SF group, the levels of TG and TC in SG (1 : 1) group were significantly reduced (P <0. 05) , the mRNA expressions of Fabpl/2 and FAS in SG (1 : 1) group were significantly reduced, while the mRNA expression of SREBPlc significantly increased ( P < 0. 05, P < 0. 01 ). TC content in SG (1 : 1.5) group significantly decreased (P < 0.05 ) and the mRNA expression of PPAR-7, SREBP1 c in SG (1 : 1.5) significantly increased, but the Fabpl/2 and FAS markedly decreased (P <0. 05, P < 0. 01). Conclusions SF containing serum can significantly increase the content of TG and TC in hepatocytes , and the SG containing serum can significantly improve the elevated TG and TC contents and reduce lipid accumulation. The mechanism may be related to the regulation of mRNA expression of PPAR-a, PPAR- 7, Fabpl/2, SREBPlc, ACCa and FAS.

Influence of Schisandrae Fructus and compatible with Glycyrrhiza on level of serum lipids and synthesis pathway of triglyceride / 中国药理学通报

Aim To investigate the influence of Schisandrae Fructus ( Wuweizi in Chinese) and com¬patible with Glycyrrhiza ( Gancao in Chinese ) on the levels of serum lipids and their influence on liver syn¬thesis pathway of triglyceride ( TG ). Methods ICR mice were divided, according to weight randomized block method, into four groups; normal control group ( Control, C ), Schisandrae Fructus ethanolic extract group (SF) , Schisandrae Fructus compatible with Gly¬cyrrhiza ethanolic extract (SG) 1 : 1 and 1 : 1.5. The control group was intragastrically given normal saline (10 mL • kg-1), SF group, SG 1 : 1 and 1 : 1. 5 group were given the extract 3. 9 g • kg"1 in crude of Schisandrae Fructus for 10 days. The levels of TG, to¬tal cholesterol (TC) , low-density lipoprotein-cholester¬ol ( LDL-C ) and high-density lipoprotein-cholesterol ( HDL-C ) were detected by biochemical method, as well as alanine aminotransferase (ALT) activity. The activities of liver fatty acid synthase (FAS) and acctyl-COA carboxylase ( ACC ), and levels of GPAT, acy- CoA oxidase ( ACO ) were detected by enzyme immu¬noassay ( ELISA ). The protein expressions of sterol regulatory element-binding protein-lc (SREBP-lc) and peroxisome proliferator-activiated receptor-a ( PPARa ) were detected by immunohistochemistry technique. Results Compared with C group, the lev¬els of TG and TC increased significantly, the level of serum LDL-C decreased significantly, the activities of liver ACC and GPAT level increased markedly, the protein expression of SREBP-1 c was markedly up-regu¬lated, and the protein expression of PPARa was evi¬dently down-regulated in SF group. When compared with SF group, the levels of serum TG and ACO, the activities of serum ALT and GPAT apparently de¬creased in SG 1 : 1 group. The protein expression of SREBP-1 c in SG 1 : 1 and 1 : 1.5 group was signifi¬cantly down-regulated, and the protein expression of PPARa was markedly up-regulated. Conclusions High dose of SF can increase the serum TG and TC levels , and the mechanisms may be related to that SF can promote the expression of liver SREBP-lc, in¬crease the activities and levels of FAS, ACC and GPAT in TG synthesis pathway, and down-regulate protein expression of PPARct and ACO for promoting liver TG synthesis. Compatible with Glycyrrhiza can significantly improve the elevated blood lipids and the proteins in the TG synthesis pathway.

Analysis of Chemical Components in Supernatant and Precipitate of Sanajon Oral Liquid Based on UPLC-Q-TOF-MSE Technology / 中国实验方剂学杂志

Objective:To analyze the main chemical components in the supernatant and precipitate of Sanajon oral liquid, so as to provide basis for establishing its quality standard and precipitation control technology. Method:UPLC-Q-TOF-MSE was used to analyze the chemical components in the supernatant and precipitate of this oral liquid. The analysis was performed on Waters ACQUITY UPLC BEH C18 column (2.1 mm×100 mm, 1.7 μm) with the mobile phase of 0.1% formic acid solution (A) and acetonitrile (B) for gradient elution (0-1 min, 2%B; 1-2 min, 2%-5%B; 2-4 min, 5%-7%B; 4-6 min, 7%-24%B; 6-10 min, 24%-42%B; 10-12 min, 42%-54%B; 12-15 min, 54%-76%B; 15-18 min, 76%-100%B), the flow rate was set to 0.3 mL·min-1, the column temperature was 30 ℃, the injection volume was 2 µL. The mass spectrographic analysis was used with electrospray ionization (ESI), sample MS data was acquired by time-dependent MSE in negative ion mode, the collection range was m/z 50-1 200 (supernatant) and m/z 50-3 000 (precipitate). Then the chemical constituents were identified by the information of retention time, accurate relative molecular mass and secondary mass spectrum fragment. Result:Totally 61 compounds were identified in the supernatant, including tannins, phenolic acids, flavonoids, amino acids, organic acids, fatty acids, etc. Totally 15 compounds were identified in the precipitate, including tannins, phenolic acids, flavonoids, fatty acids, etc. Conclusion:The hydrolyzed tannin of Sanajon oral liquid may be the potential material basis of its precipitate, and its precipitate is likely to be a complex precipitate mainly composed of ellagic acid and tanned red. The established UPLC-Q-TOF-MSE can quickly and comprehensively analyze the chemical composition of Sanajon oral liquid, which can provide a scientific basis for the researches of its material basis, precipitation mechanism and quality control.

Comparative study on the effect of Danggui-Chuanxiong herb pair on vasoactive substances and adhesion molecules in the serum of acute blood stasis in rats using PLS-DA and multi-attribute comprehensive index methods / 药学学报

We evaluated the effects of Danggui-Chuanxiong (GX) herb pair with different proportions (1∶0, 3∶2, 1∶1, 2∶3, 0∶1) and preparation methods (water extract W, alcohol extract A, and water-alcohol extracts WA) on vasoactive substances and endothelial cell adhesion molecules in the serum of acute blood stasis in rats. An acute blood stasis model was co-replicated by ice water bath and subcutaneous injection of epinephrine hydrochloride in rats. The expressions of vasoactive substances (arachidonic acid metabolites, coagulation-fibrin system index) and adhesion molecules in the serum were detected by enzyme linked immunosorbent assay method; the Spearman method was used to analyze the correlation of those detection indicators; the partial least squares-discriminant analysis and multi-attribute comprehensive index method were used to comprehensively evaluate the total effect of GX herb pair samples with different proportions and preparation methods on vasoactive substances and adhesion molecules. The experimental scheme was approved by the Animal Experimental Ethics Committee of the First Affiliated Hospital of Henan University of Chinese Medicine. The results showed that GX 1∶1_WA had the strongest effect on the improvement of vasoactive substances and adhesion molecules in the serum of acute blood stasis in rats (the total effect value was 6.96). When extraction method was same, the overall effect of GX 1∶1 had better effect than that of other proportions; when the proportion of GX was same, the total effects of GX_WA and GX_A were better than GX_W. The combination of Danggui and Chuanxiong can significantly improve the expressions of vasoactive substances and adhesion molecules in the serum of blood stasis in rats. But the action strength of GX herb pairs was different when the proportions and preparations of GX herb pair were different. These findings provide a basis for clinical rational application of GX herb pair, and lay the foundation for in-depth research on GX herb pair for treatment of blood stasis related diseases.

Screening of serum susceptibility biomarkers in patients with mild liver function abnormalities based on non-targeted metabolomics / 中国中药杂志

In the present study,non-targeted metabolomics technique was used to screen potentially susceptibility biomarkers in patients with mild liver function abnormalities during long-term use of Chinese herbal compound. According to the inclusion and exclusion criteria,we collected 7 cases of patients with abnormal liver function during the period of complete taking Chinese herbal medicine( 60 days),and 18 cases of patients with normal liver function in re-examination from the reproductive medicine center in our hospital. Ultra performance liquid chromatography coupled with time-of-flight mass spectrometry( UPLC-Q-TOF/MS~E) technique combined with Progenesis QI software was used to analyze the differential biomarkers in serum of patients with wild liver function abnormalities and normal liver function. 11 potential biomarkers such as bilirubin,pantothenic acid,hippuric acid,sphingomyelin,palmitic acid,and oleic acid were tentatively identified. Metabolic disorders in patients with herbal-induced mild liver abnormality were mainly related to two pathways: pantothenic acid and coenzyme A biosynthesis and linoleic acid metabolism. It could provide a reference for the early warning of mild liver function abnormalities of patients that may be caused by long-term use of Chinese medicine compound in clinical application,and will lay a foundation for further understanding the endogenous substance changes in different levels of liver injury.

Analysis of adverse reactions' factors to Danhong injection--nested case control study by using hospital centralized monitoring data / 中国中药杂志

To study the adverse reactions' factors to Danhong injection in the real world. A multi-center, large sample and prospective hospital centralized monitoring method was adopted, and 30 888 cases of Danhong injection from 37 national 3A hospitals were collected to carry out a nested case control design study. These cases were divided into adverse reaction group and non-adverse group. Single factor logistic regression and multiple factor logistic regression were used to analyze data, and investigate the correlation between adverse reaction and gender, allergy history, methods of administration, and combined drug use. One hundred and eight cases of adverse reactions in 30 888 patients were determined, with an incidence of 0.35%. The results showed that Danhong injection combined with other medication(potassium mendoxine magnesium, thymic peptide, celecoxib, fumarate bisoprolol) with history of adverse reactions including scephalosporin allergy and proprietary Chinese medicine allergies had more adverse reactions than the control group(<0.05, estimated coefficient>0), indicating that these six factors were the risk factors for the adverse reaction of Danhong injection. The adverse reaction of Danhong injection combined with the aspirin was less than that in the control group(<0.05, estimated coefficient<0), indicating that the aspirin was a non-risk factor for the adverse reaction of Danhong injection. All the above results indicate that the adverse factors to Danhong injection include scephalosporin allergy, patent Chinese medicine allergy, Danhong injection combined with medication(potassium mendoxine magnesium, thymic peptide, celecoxib, fumarate bisoprolol), suggesting special attention shall be paid in clinical application.

Quality consistency evaluation of Fuzi formula granules using determination of multi-component contents by HPLC-MS/MS method / 中国中药杂志

To establish HPLC-MS/MS method for simultaneous determination of 14 toxic or active components in Fuzi formula granules, and further analyze the quality consistency of 29 batches of formula granules by considering the cluster analysis (CA), principal component analysis (PCA), and partial least squares discriminant analysis (PLS-DA) and other chemometrics methods. Phenomenonex Gemini C18 column (4.6 mm×150 mm, 5 μm) was used with 0.1% formic acid solution (A) -acetonitrile (B) as the mobile phase. The mass spectrum was scanned by ESI⁺ multiple reaction monitoring (MRM) mode. The contents of aconitine, mesaconitine, hypaconitine, Indaconitine, benzoylaconine, benzoylmesaconine, benzoylhypaconitine, aconine, fuziline, neoline, talatisamine, songorine, higenamine and salsoline were determined. The results showed that 14 compounds had a good linear relationship within their respective concentration range (R²>0.990 0). The limit of quantification was 2.07-7.71 mg·L⁻¹, and the average recovery was 96.07%-102.2%. The content determination results demonstrated that all batches of Fuzi formula granules had very low hypertoxic ingredients and high safety, while the content of active ingredients was greatly different. CA and PCA results showed that there were significant differences in the formula granules between two manufacturers; even though the different batches of samples from the same manufacturer had certain differences, but the difference in manufacturer A was less than that of B. Further PLS-DA showed that the content of cardiotonic substance salsola in the formula granules from manufacturer A was generally higher, while the contents of analgesic and anti-inflammatory substances benzoylmesaconitine and fuziline were generally lower than those in the products from manufacturer B. In conclusion, the safety of Fuzi formula granules was assured well, but the consistency needed to be improved. We recommend that all manufacturers establish strict standard for decoctions in the production process, and form a unified standard method to produce better Fuzi formula granules.

Study progress on chemical compounds, pharmacological action and clinical application of Naoxintong capsule / 中国中药杂志

Naoxintong capsule (NXTC) is an oral Chinese preparation produced by modern technology, derived from the classic preparation of Buyang Huanwu decoction which was recorded by WANG Qing-ren (Qing dynasty) in Yilingaicuo Juanxia Tanweilun. NXTC is composed of 16 herbs including insect herbs and some blood circulation herbs, with the effects of supplementing Qi and activating blood circulation, dispersing blood stasis and dredging collaterals. In clinical application, it is mainly used for stroke, cerebral infarction, vascular dementia, ischemic cerebrovascular disease, transient ischemic attack, coronary heart disease, angina pectoris, ischemic cardiomyopathy, diabetic cardiomyopathy, myocardial infarction, chronic heart failure, chronic complications of diabetes, essential hypertension, hyperlipidemia and other cardiovascular and cerebrovascular diseases, and has achieved good therapeutic effect on above diseases or their concurrent diseases. Its clinical efficacy is mainly achieved through the improvement in related links of brain protection, neuroprotection, cardioprotection, hemorheology, et al. Nearly 200 chemical constituents identified in NXTC are important pharmacological basis for its functions. At present, however, most of its pharmacological basic researches are focused on plant herbs, and the three kinds of insect herbs remain to be further studied. The researches on clinical effectiveness are more comprehensive; the safety study of long-term application in real world is ongoing by our team, and its results are yet to be published after finishing the study. Through the systematic and comprehensive combing and elaboration of the research progresses on the chemical compositions, pharmacological action and clinical application of NXTC, it can provide a reference for the in-depth study of this preparation, with a great significance for the quality control, secondary development and internationalization promotion of NXTC.

Correlation analysis on idiosyncratic hepatotoxicity of Zhuangguguanjie Wan and 27 cytokines based on related visualization / 中草药

Objective: To analyze the correlation of idiosyncratic hepatotoxicity of Zhuangguguanjie Wan (ZGW) with 27 cytokines. Methods: After 12 h fasting, SD rats were ig with ZGW at a single dose of 3.8 g/kg, and injected with lipopolysaccharide (LPS) at a dosage of 2.8 mg/kg via tail vein after 2 h. The rats were anesthetized with chloral hydrate after 10 h LPS administration, and then the blood samples were collected from the inferior vena cava and liver tissue was also obtained. Alanine aminotransferase (ALT) activity in serum and levels of 27 cytokines in liver tissue were tested. Correlation analysis of ALT and cytokines were performed using R 3.2.4 software. Results: Correlation analysis showed that there was a high positive correlation between ALT and macrophage inflammatory protein-1α (MIP-1α) or vascular endothelial growth factor (VEGF). There was a strong correlation among interleukin-18 (IL-18), interferon-inducible protein-10 (IP-10), interleukin-1α (IL-1α), and interleukin-1β (IL-1β). However, eotaxin regulated upon activation of normal T cell expression and secreted factor (RANTES), which has their own independence. Conclusion: Idiosyncratic liver injury induced by ZGW has a strong positive correlation with MIP-1α and VEGF, which provides a new experimental evidence for clinical medication safety and risk prevention of ZGW.

Expert consensus on prescription comment of Chinese traditional patent medicine for promoting the rational use of drugs in Beijing / 中国中药杂志

With the growth of number of Chinese patent medicines and clinical use, the rational use of Chinese medicine is becoming more and more serious. Due to the complexity of Chinese medicine theory and the uncertainty of clinical application, the prescription review of Chinese patent medicine always relied on experience in their respective, leading to the uncontrolled of clinical rational use. According to the traditional Chinese medicine (TCM) theory and characteristics of the unique clinical therapeutics, based on the practice experience and expertise comments, our paper formed the expert consensus on the prescription review of Chinese traditional patent medicine for promoting the rational use of drugs in Beijing. The objective, methods and key points of prescription review of Chinese patent medicine, were included in this expert consensus, in order to regulate the behavior of prescription and promote rational drug use.

Cytokine analysis of Zhuangguguanjie wan-induced idiosyncratic liver injury based on mathematical modeling / 药学学报

In this study, we used a mathematic-based modeling system to screen the cytokines that are sensitive to Zhuangguguanjie wan (ZGW)-induced idiosyncratic liver injury. The values of 27 cytokines were used as the data source in rat liver of lipopolysaccharide (LPS) + ZGW group. The alanine aminotransferase (ALT) activity value of liver function indexes was used as the outcome evaluation index of liver injury. Cytokines of ZGW-induced idiosyncratic liver injury were screened using Logistic regression, random forest method, LASSO Logistics regression and method of combining rule discovery algorithm with LASSO, and cytokines filtered out were revalued in THP1 macrophage. Susceptible cytokine combinations:interleukin-1β (IL-1β), epidermal growth factor (EGF) and interleukin-18 (IL-18) closely related to ZGW-induced idiosyncratic liver injury were obtained after preliminary screening analysis. The result of revalued in THP1 showed that the ethanolic extract of ZGW (EtZ) combined with IL-1β or IL-18 synergistically enhanced tumor necrosis factor-α (TNF-α) secretion in THP1 macrophage, and EtZ combined with IL-1β significantly enhanced interleukin-6 (IL-6) secretion in THP1 macrophage, but EtZ combined with EGF markedly inhibited IL-6 secretion in THP1 macrophage. The results suggest that the sensitive cytokines that can be characterized in the ZGW-induced idiosyncratic liver injury are IL-1β and IL-18, which provides a basis for screening the ZGW-induced idiosyncratic liver injury patients, and a new experimental evidence for clinical safety medication and risk prevention of ZGW.